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Navigating the Journey of Vitiligo: Insights from the European Health Congress 2023 in Munich

Introduction:

The European Health Congress 2023, held in Munich, served as a pivotal platform for discussions on the latest developments in health policies, the exchange of valuable information and experiences, and the exploration of economic and structural requirements within the health sector. This annual two-day event drew decision-makers from various spheres, including hospitals, clinics, insurance companies, associations, political figures, and, notably, medical professionals. Among the diverse topics covered, a panel on Vitiligo took centre stage, shedding light on the autoimmune disease and offering a unique perspective on its challenges and triumphs.

Vitiligo in the Spotlight:

Titled “Autoimmune disease Vitiligo: Visible help!” the Vitiligo discussion added a distinctive perspective to the congress. It went beyond the conventional subjects of law, politics, and public health, incorporating personal narratives from individuals directly impacted by the condition. The panel succeeded in weaving together a comprehensive narrative, ranging from cold facts and figures to the nuanced realms of psychology and emotions. This inclusive approach made the Vitiligo discussion stand out in a sea of formal presentations.

 

The Multifaceted Discussion:

What set the Vitiligo panel apart was its commitment to embracing diverse perspectives. The panellist’s, hailing from backgrounds in law, politics, public health, and support groups, collaborated with patients to provide a holistic view of the challenges posed by Vitiligo. This multidimensional approach allowed for a more profound exploration of the various facets of living with the condition, creating an atmosphere where honesty and bravery were not only encouraged but celebrated.

 

Authenticity Amidst Formality:

Despite the inherently formal nature of conferences, the Vitiligo discussion at the European Health Congress 2023 managed to break through the rigid facade. The panellists, including patients, shared personal insights, experiences, and true feelings about their journey with Vitiligo. This authenticity added a human touch to the conference, reminding attendees that, beyond the clinical aspects, individuals dealing with Vitiligo are on a deeply personal journey that involves not only physical but also emotional and psychological dimensions.

 

The European Health Congress 2023 in Munich proved to be an illuminating event, offering a stage for diverse voices to converge and share insights on health-related issues. The Vitiligo panel, with its unique blend of perspectives and emphasis on authenticity, contributed to a broader understanding of the challenges associated with autoimmune diseases. As we continue to navigate the complex landscape of healthcare, events like these play a pivotal role in fostering empathy, understanding, and a collective commitment to support those on their journey with conditions like Vitiligo.

 

Source: German Vitiligo Association

Doctors’ training on vitiligo in the D.R.C

The Association Franco-Congolaise du Vitiligo (AFCV), which was created in December 2021 with the support and sponsorship of the AFV, has been very active ever since. She recently initiated a very important training course for doctors (dermatologists, anatomical pathologists, nurses, etc.) in Haut-Katanga (province of the Democratic Republic of Congo) specifically on the subject of vitiligo.

Doctors’ interest in vitiligo

 

The European Academy of Dermatology and Venereology 2023

The European Academy of Dermatology and Venereology convened this year in Berlin, Germany, marking the largest European gathering for skin-related scientists and healthcare professionals. Over the course of three days, the congress delved into various aspects of dermatology, including a dedicated session on vitiligo that spotlighted the latest outcomes of clinical trials.

 

Among the attendees were two VIPOC representatives and board members, Mr. Georg Pliszewski from Germany, and Mr. Jean-Marie Meurant from France. Their interactions with numerous pharmaceutical delegates centered around ongoing clinical trials involving both topical and systemic treatments. Discussions also touched on upcoming research avenues exploring diverse vitiligo pathways, revealing the possibility of more than five lines of treatment.

 

The VIPOC conference slated for 2024, European Union advocacy initiatives, Vitiligo Summits across South America, Africa, and Asia, as well as patient organizations’ contributions to drug approval processes, formed integral parts of the discourse. Engaging proposals emerged during these conversations.

 

Moreover, our VIPOC delegates actively participated in the significant Vitiligo Task Force meeting, led by Prof. Nanja Van Geel from France and Prof. Julien Seneschal from France. This inclusive gathering saw the presence of scientists and dermatologists from across Europe and Mediterranean countries, with others joining virtually. The discussions encompassed international recommendations, cutting-edge developments, ongoing research related to vitiligo, and insights into the upcoming Vitiligo International Symposium (VIS 2024). Anticipation is building for the collaborative efforts shaping the future of vitiligo research and treatment on a global scale.

Mr Stephen Taylor, an active 63-year-old African American who’s not just counting his years but making them count

Meet Mr Stephen Taylor, an active 63-year-old African American who’s not just counting his years but making them count. Diagnosed with vitiligo four decades ago, he’s been on a colorful journey through life, even if his skin might tell a different story.

Retiring from General Motors after an impressive 35-year stint as a reliability engineer, Mr Taylor didn’t let vitiligo put the brakes on his passion for making things work seamlessly. While his skin may have lost its pigment, his spirit remains anything but monochrome.

In his quest for a palette of treatments, he’s tried it all – from vitamin supplements to topical immune inhibitors, and even basked under the glow of phototherapy. Yet, his skin, like a canvas refusing paint, remains 99% void of color. But don’t let that fool you; he’s not faded away. In fact, he’s boldly taken the spotlight as a member of not one, not two, but three vitiligo organizations.

As the General Secretary of the Vitiligo International Patient Organization Committee, Mr Taylor is not just a name on a roster; He is a key player and plays a crucial role in the team’s dynamics and achievements. His dedication doesn’t stop there; he’s been a stalwart member of the VStrong Vitiligo Support Community in Detroit, Michigan, for a whopping 15 years, now donning the hat of the General Secretary. And if that weren’t enough, he’s sitting on the board of directors for the Global Vitiligo Foundation, contributing his wisdom to a cause larger than himself.

This isn’t just about Mr Taylor’s journey; it’s about his commitment to ensuring others don’t face the shadows alone. As a patient advocate, his experience transcends borders – local, national, and international. His engagements with healthcare professional organizations have given him a palette of experiences, painting a unique and well-rounded picture of advocacy. Mr Stephen Taylor isn’t just living with vitiligo; he’s thriving, and in doing so, he’s helping others paint their own vibrant stories despite the stigma that might come with vitiligo.

In the symphony of life, Mr Stephen Taylor’s story is a bold note, refusing to be muted by the absence of color on his skin. His journey is a testament to the fact that life can be lived in full color, no matter the canvas it’s presented on.

Dermatologists Answer Your Top Vitiligo Questions

Living with vitiligo can mean navigating through plenty of unanswered questions involving the condition. You may be curious about how vitiligo will progress, what treatments are available, and whether dietary changes can help restore pigment.

“I’m thinking improving my diet may prove helpful during my struggle with vitiligo,” one MyVitiligoTeam member said. Another asked, “Stress makes spreading my vitiligo worse, and I’m also having hypothyroidism — what kind of things are you doing so vitiligo doesn’t spread?”

 

To get to the bottom of a few burning questions, MyVitiligoTeam partnered with the Global Vitiligo Foundation to host World Vitiligo Day in June. At the event, dermatologists Dr. Pearl Grimes, Dr. John Harris, Dr. Nada Elbuluk, and Dr. Victor Huang discussed a variety of topics that can help you understand more about the condition. Check out several of the questions that attendees asked, along with responses from the dermatologists.

Does puberty play a part in the progression of vitiligo?

“There is a cohort of kids who may progress during puberty, but it’s certainly not a universal phenomenon,” Dr. Grimes said. “I don’t even think it occurs in 50 percent of kids.”

Dr. Huang offered a similar take. “We do recognize from the epidemiology that half of people with vitiligo will present before the age of 20,” he said. “And when you look at the characteristics of vitiligo that people have, it seems to be different. There are at least some suggestions in larger cohorts that the folks with associated autoimmune conditions, such as thyroid disease, tend to be from the groups that present later, after puberty. So I think there is a difference between the folks who develop their vitiligo earlier on versus those who develop it later in life.”

Dr. Huang takes a multipronged approach to managing depigmentation, which means addressing small spots differently than those that involve larger sections of skin. That may include a combination of topical therapies (such as ointments and creams), phototherapy, and systemic steroids.

“Thankfully, now there’s this whole fourth category of investigational medicines that are available,” Dr. Huang noted. A new class of medications known as Janus kinase (JAK) inhibitors are under investigation and may be available later in 2021.

“Surgical treatments are available as well,” Dr. Huang said. “The idea being that, once the immune part has been resolved, if the fundamental problem is that we don’t have enough melanocytes in the area, we can borrow melanocytes from other normally pigmented parts of the body and replace them into the part where they’re missing.”

Is there a risk that vitiligo spots will return following treatment?

“Unfortunately, there is,” Dr. Elbuluk said. “I always tell patients that no matter how successful we are at gaining repigmentation back, because they are genetically predisposed to vitiligo, there’s always the chance that they could depigment again. And it could be in the same spots where they previously had vitiligo, and it could be in new spots.”

When Dr. Elbuluk sees people who have fully repigmented, she checks in with them every few months to review disease activity. If she sees new spots, she moves ahead with treatment again.

Is vitiligo passed on genetically in families?

“There is a genetic component to this,” Dr. Huang said. “But the way I talk to my patients about this is to mention that in the general population, about 1 percent to 2 percent of people will have vitiligo. If you have a first-degree relative — a mother, father, brother, or sister — the risk of vitiligo goes up to about 6 percent. Even when you look at identical twins, that only bumps up the risk to 26 percent or 27 percent. When you look at those numbers, the more closely related you are to someone genetically, the greater your risk is to get vitiligo.”

When Dr. Huang sees people with vitiligo who are thinking of starting a family, he reminds them that there’s a 94 percent chance that their child will not have vitiligo. “So while there is a strong genetic component, it’s not the only thing that drives vitiligo.”

Is there a specific diet that can help people manage vitiligo? Does going gluten-free help?

“This is a really popular question,” Dr. Elbuluk said. “Unfortunately, we don’t have any well-controlled studies that really allow us to give evidence-based recommendations about diet and vitiligo. But what we do know about the disease is that antioxidants can help the stabilization of vitiligo, meaning preventing progression of it. And they may even aid in repigmentation when people are doing other concomitant therapies, such as phototherapy, the topicals we use, etc. Based on what we know, I think there is a role for antioxidants, both in diets and as supplements in vitamins, in addition to the treatments that we do for vitiligo.”

Dr. Elbuluk noted that current data does not support any benefits of a gluten-free diet in people with vitiligo, unless they have celiac disease or gluten allergies in addition to vitiligo.

Does vitamin D play a role in vitiligo management?

“Vitamin D is really a powerful hormone that regulates so much in our body, and I think it does play a role in pigmentation,” Dr. Elbuluk said. “I do check vitamin D levels in my vitiligo patients, and if they are deficient, I recommend replacing their vitamin D so that they are within the normal range. And there is some data to support that repigmentation in vitiligo does correlate with serum levels of vitamin D.”

Dr. Grimes agreed with the importance of checking vitamin D levels in people with vitiligo. “We should really be certain that our patients have healthy vitamin D levels. And if you don’t want to check it, if you empirically have a patient take 2,000 international units of vitamin D, that’s better than not addressing it at all.”

Medically reviewed by Amit G. Pandya, M.D., President of the Global Vitiligo Foundation — Written by Torrey Kim

Source

Unveiling the Unseen Struggles: A Comprehensive Review of Vitiligo’s Psychological, Social, and Quality of Life Impacts

Abstract

This review explores the psychosocial impact of vitiligo on patients, its consequences for their quality of life, and the need for holistic support.

Vitiligo’s psychosocial burden, driven by the need to conceal lesions and societal beauty ideals, leads to stress, sadness, and low self-esteem. Social stigma affects self-esteem, especially in cultural contexts, exacerbating the need for culturally sensitive support. Anxiety and depression are common due to visible differences and societal pressures.

Vitiligo significantly reduces the quality of life, especially in younger patients, impacting daily activities, careers, and relationships. Disease severity worsens these effects, particularly in visible areas and among individuals with darker skin tones. Long-term disease activity may improve acceptance and quality of life.

Psychological support and counseling are crucial, as many patients don’t seek medical help. Education plays a key role, improving understanding and reducing anxiety. Raising awareness about the impact of vitiligo can challenge perceptions and contribute to enhancing patients’ well-being.

In conclusion, this review highlights the interplay between psychosocial factors, quality of life, and the importance of addressing social stigma, providing psychological support, and advancing education and awareness for those with vitiligo.

Introduction & Background

Vitiligo, an acquired disorder resulting in the loss of skin pigmentation, is a chronic condition of depigmentation with global significance. Its estimated prevalence ranges around 1-2% worldwide, though precise figures can be challenging to ascertain (Table 1[1]. Recent advancements have significantly enhanced our comprehension of vitiligo’s origin, now definitively categorized as an autoimmune disorder [2]. This disorder involves a targeted reduction in melanocytes, subsequently leading to the depigmentation of specific skin areas. It’s important to note that vitiligo presents as well-defined, fully depigmented, chalky-white patches [3]. Despite its wide occurrence, a conclusive cure for vitiligo remains elusive, and the efficacy of available treatments varies individually, frequently yielding unsatisfactory outcomes [1].

Prevalence type Description Range/Percentage Notes Ref.
1 Global Prevalence Estimated worldwide prevalence 0.5–1% It is difficult to estimate precisely. [15]
2 Bornholm Study Prevalence on the island of Bornholm in Denmark 0.38% A most extensive epidemiological study in 1977 and One of the earliest surveys in 1977. [16]
3 French West Indies Prevalence in the black population of the French West Indies Similar to or slightly less than the white population. [17]
4 Regional Prevalence The highest incidence: India, followed by Mexico and Japan India: up to 8.8%, Mexico: 2.6–4%, Japan: 1.68% Disparity between prevalence and incidence data. [18]
5 Gender Differences Equal prevalence in males and females Gender-related seeking of consultation. [14,19]
6 Meta-Analysis Pooled prevalence from various studies Community-based: 0.2%, Hospital-based: 1.8% from 82 population- or community-based studies and 22 hospital-based studies. [20]
7 Age-Related Prevalence Vitiligo prevalence and age distribution Non-segmental vitiligo occurs across ages; segmental vitiligo tends to appear young. [21]
8 Age-Related Increase Vitiligo prevalence increases with age Varies with different age groups. Supported by multiple studies. [22,23]
9 Multinational Study (Europe, USA, and Japan) vitiligo prevalence among 35,694 survey participants (Europe, n = 18 785; USA, n = 8517; Japan, n = 8392) 1.3% The overall prevalence is 1.3%, with 0.6% diagnosed cases, 0.4% undiagnosed cases, and 0.3% displaying signs of vitiligo. [24]
10 Korean Study Three-year period, comprehensive review using Korean population data 0.12–0.13% Vitiligo in the Korean population is associated with various autoimmune/non-autoimmune diseases, including thyroiditis, atopic dermatitis, and psoriasis. [25]

Upadacitinib Meets Primary End Point of Phase 2 Trial for Vitiligo and Advances to Phase 3

AbbVie recently announced that its phase 2b study investigating upadacitinib (Rinvoq) for the treatment of adults with nonsegmental vitiligo met the primary end point of percent change from baseline in the Facial Vitiligo Area Scoring Index (F-VASI) at week 24 with the 11 mg and 22 mg doses versus placebo. Overall, the percent reduction from baseline in F-VASI at week 52 was numerically greater than results at week 24 for all upadacitinib doses, and no new safety signals were found.AbbVie announced at the European Academy of Dermatology and Venerology (EADV) Congress in Berlin, Germany, that based on this data, it will be advancing its clinical trial program of upadacitinib for vitiligo to phase 3.1

Key findings from the data include:

  • At week 24, upadacitinib achieved the primary end point of percent change from baseline in F-VASI with 11 mg and 22 mg doses versus placebo
  • Higher response rates were observed with upadacitinib versus placebo in secondary end points, including F-VASI 75 at week 24 with the 11 mg and 22 mg doses and Total Vitiligo Area Scoring Index (T-VASI) 50 at week 24 with the 22 mg dose
  • The mean percent reduction from baseline in F-VASI was numerically greater at week 52 than results at week 24 for all upadacitinib dose groups
  • Response rates observed for F-VASI 75 and T-VASI 50 at week 52 were numerically greater than those at week 24 for all upadacitinib dose groups

“There is a high unmet need in vitiligo, with no systemic treatment options approved, leaving patients frustrated in seeking options for re-pigmentation of the skin,” said Roopal Thakkar, MD, senior vice president of development and regulatory affairs and chief medical officer at AbbVie, in the news release. “We will continue to apply our significant experience in advancing research and driving innovation in treatments for immune-mediated diseases, including underserved diseases with high burden on patients, such as vitiligo.”

Treatment-emergent adverse event (TEAE) rates were similar with upadacitinib and placebo in period 1. The most common TEAEs included COVID-19, acne, headache, and nasopharyngitis. Numerically higher rates of serious TEAEs and TEAEs leading to study drug discontinuation were observed in the upadacitinib 22 mg group versus the other groups.

According to the news release, “One death adjudicated as undetermined/unknown cause and deemed by the investigator to have no reasonable possibility of being related to study drug occurred in the upadacitinib 22 mg group (period 1). One adjudicated event of nonfatal ischemic stroke occurred with upadacitinib 11 mg (period 2) in a patient with known cardiovascular risk factors. One event of malignancy (breast cancer) occurred with upadacitinib 11 mg (period 2) in a patient with positive family history of breast cancer.”

During the study, one event of a serious infection, COVID-19 pneumonia, was reported in the upadacitinib 22 mg group. There were no adjudicated events of venous thromboembolism, gastrointestinal perforation, or active tuberculosis.

“Vitiligo impacts millions of people globally, and there is no cure. The disease can have a great impact on patients’ physical and mental health, as depigmentation of the skin can be severe,” said Thierry Passeron, MD, PhD, professor and chair of the department of dermatology at the Université Côte d’Azur, in the news release. “In vitiligo, it can take time to see optimal skin re-pigmentation during treatment, which makes long-term studies critical to providing valuable insights on a treatment’s meaningful impact for patients.”

Source: 

Image Credit: Envato Elements

Worldwide expert recommendations for the diagnosis and management of vitiligo Part 2

Abstract

Background

The treatment of vitiligo can be challenging. Up-to-date agreed consensus recommendations on the use of topical and systemic therapies to facilitate the clinical management of vitiligo are currently lacking.

Objectives

To develop internationally agreed-upon expert-based recommendations for the treatment of vitiligo.

Methods

In this consensus statement, a consortium of 42 international vitiligo experts and four patient representatives participated in different online and live meetings to develop a consensus management strategy for vitiligo. At least two vitiligo experts summarized the evidence for different topics included in the algorithms. A survey was then given to a core group of eight experts to resolve the remaining issues. Subsequently, the recommendations were finalized and validated based on further input from the entire group during two live meetings.

Results

The recommendations provided summarize the latest evidence regarding the use of topical therapies (steroids, calcineurin inhibitors and Jak-inhibitors) and systemic therapies, including steroids and other systemic immunomodulating or antioxidant agents. The different modalities of phototherapies (NB-UVB, photochemotherapy, excimer devices and home phototherapy), which are often combined with other therapies, are also summarized. Interventional approaches as well as depigmentation strategies are presented for specific indications. Finally, the status of innovative and targeted therapies under development is discussed.

Conclusions

This international consensus statement culminated in expert-based clinical practice recommendations for the treatment of vitiligo. The development of new therapies is ongoing in vitiligo, and this will likely improve the future management of vitiligo, a disease that still has many unmet needs.

INTRODUCTION

The treatment of vitiligo can be particularly challenging. Clear guidelines for choosing among the therapeutic options available are important given the variable response rates. Long-term treatment is usually necessary due to the high relapse rate and chronic disease course.1 In recent years, systemic treatments (including the emerging use of JAK inhibitors) have gained increased attention.2 However, while disease stabilization is a likely outcome for most patients, repigmentation rates remain variable. In part 2 of this international consensus statement, recommendations for the use of topical and systemic treatments are outlined in more detail. It should be noted that many vitiligo therapies are not licensed and can only be prescribed ‘off-label.’

MATERIALS AND METHODS

In order to reach a broad international consensus, a consortium of 42 international experts and four patient representatives participated in this consensus effort. To summarize the up-to-date evidence on vitiligo, each topic was assigned to a writing group (ranging from 3 to 8 members) represented by at least two vitiligo experts who searched the literature and provided the essential data (narrative review) on which recommendations could be made for this consensus statement. The results and remaining issues were discussed during three online VTF meetings (30 September, 28 October and 9 December 2021). To get preliminary approval on the remaining issues, a digital survey was sent out to a core review group of eight vitiligo experts. Additionally, two meetings were carried out with this core review group to reach a final consensus based on the answers to the survey. Each statement received unanimous agreement, unless specified otherwise. These results were further discussed in detail with patient representatives and vitiligo experts at the Vitiligo International Patient Organizations Committee (VIPOC) meeting (Amsterdam April 2022) and the Vitiligo Task Force meeting (Milan, September 2022) until full agreement was reached. In total, 18 patient representatives (15 present live and 3 participating online) participated in this VIPOC meeting.

RESULTS

Topical steroids/topical immunomodulators (TIMS: topical calcineurin inhibitors/topical Jak-inhibitors)

Topical corticosteroids

Topical corticosteroids (TCS) are recommended for vitiligo, particularly for extrafacial locations and more limited treatment areas; however, they can also serve as an alternative to TIMS for treatment of the face. TCS are often considered to be more effective for stabilization of vitiligo than for repigmentation, although clear evidence is lacking.3 The best results of TCS in terms of repigmentation can be expected in the face and neck. In adults and children, once-daily application of potent TCS is recommended for patients with limited involvement. Like all other treatments, acral lesions and lesions with poliosis usually respond poorly. Most studies used potent to very potent corticosteroids once daily, applied topically for 3–6 months. Based on expert opinion, the risk of local side effects (skin atrophy, telangiectasia, hypertrichosis, acneiform eruptions and striae) can be reduced by using an intermittent/alternating treatment scheme (e.g. 2 weeks on 2 weeks off) and will enable longer treatment periods. These considerations apply particularly to prolonged treatment and facial lesions, where topical calcineurin inhibitor (TCI) have a better safety profile. Based on expert consensus, TCS should be used with caution on the eyelids (risk of cataract and glaucoma) or other sensitive areas (e.g. axillar and inguinal regions). For children, TCS are considered safe if they are continuously used for no more than 2–4 months. For prolonged use, the same intermittent scheme and precautions are strongly preferred. Systemic absorption is a concern when large areas of skin or regions with thin skin are treated with ultra-potent TCS for a prolonged period of time without intervals. Long-term maintenance treatment may be necessary to maintain repigmentation (see part 1).

Topical immunomodulators

Topical calcineurin inhibitors

TCIs are first-line treatment in adults and children with limited involvement, especially for lesions in the face, neck and body folds with thin skin (e.g. inguinal, axillary regions). No differences in efficacy were found between TCI and TCS although TCI might be less effective for extrafacial lesions.45 The topical safety profile of TCI is better when compared to potent TCS, especially the risk of skin atrophy. TCI are particularly useful in areas where prolonged use of potent TCS is contraindicated. A twice-daily application of TCI can be recommended (Radakovic-Fijan et al., 2009).6 The treatment should be prescribed initially for 6 months. When effective, prolonged treatment (e.g. up to 12 months or more) can be proposed. TCI are also useful for younger patients. The efficacy of TCI may be comparable to that of highly potent steroids in both facial and non-facial paediatric vitiligo.7 As with all treatments, physicians will need to consider the pros and cons of the use of TCS, tacrolimus ointment and pimecrolimus cream in paediatric patients.

For optimal repigmentation, the combination of TCI with UV light can be considered, taking safety aspects into account. TCI monotherapy can induce ≥25% repigmentation in 55.0% of patients and ≥75% repigmentation in 18.1% after 3 months.8 More favourable results were observed in the head and neck region of children (≥75% repigmentation in 35.4%). The most commonly reported early side-effects of TCI are local reactions (burning sensation, pruritus and erythema). To date, the use of TCI has not been associated with significant systemic immunosuppression, skin infections or increased risk for skin cancer and other malignancies (including lymphoma) in clinical vitiligo trials.9 A higher risk of non-Hodgkin lymphoma has been observed with the use of TCI in dermatology. However, most of the data came from patients with atopic dermatitis treated with TCI.10 The severity of atopic dermatitis was associated with a greater risk of lymphoma.11 In addition, studies have also suggested the possibility that some early cases of lymphoma, including cutaneous T-cell lymphoma, may be misdiagnosed as atopic dermatitis and treated with TCI, leading to overestimation of the effect of this treatment. It should be noted that TCI still constitute an off-label prescription for vitiligo in all countries, and costs are often not reimbursed. Patients should be informed about all these aspects as part of the shared decision-making process.

Topical JAK-inhibitors

The topical JAK-inhibitor ruxolitinib is now the first treatment approved for the repigmentation of vitiligo. Two randomized, double-blind, phase III studies were conducted in 674 patients. Response rates were much better than placebo, with 50.3% and 74.6% of patients achieving a Facial-VASI (F-VASI) 75 and 50, respectively, at week 52. Moreover, 51.1% of patients achieved a total VASI (T-VASI) of 50 at week 52. Treatment-related adverse events (AEs) occurred in 13.7% of patients who applied ruxolitinib cream over the course of the study, with the most common AEs being application site acne (4.4%) or pruritus (3.5%).12

Phototherapies

Phototherapy remains an essential tool in the treatment of vitiligo (Table 1). Treatment results can be optimized with careful patient selection, focusing on patient awareness and compliance. Decisions between localized and total body phototherapy are based on extent, feasibility and lesion distribution.13 Moderate natural UV exposure has also been proposed, taking into account the UV index, skin phototype and safety aspects.

TABLE 1. Phototherapy pearls in vitiligo (Modified table from Mohammad et al. 201716).

Types NB-UVB (peak 311 nm)

Total body

  • Early localized or with signs of rapid progression
  • Active or stable vitiligo (non-segmental)
Targeted

  • NB-UVB
  • Excimer lamps or laser: Deliver targeted UVB (peak 308 nm)
  • Segmental vitiligo
  • Stable localized non-segmental
  • Vitiligo (non-segmental) in light skin (time consuming if extensive vitiligo)
Photochemotherapy
PUVA exposes patients to UVA (320–400 nm) after treatment with psoralen

Oral PUVA is no longer recommended for vitiligo and contraindicated in children and pregnancy, has ocular and systemic toxicity, and increases the risk of both melanoma and non-melanoma skin cancer; commonly causes nausea and headache

TOPICAL PUVA

Fewer treatments, smaller cumulative dose of UVA is safe for children; causes blistering and perilesional hyperpigmentation, is less effective at arresting disease activity

KUVA uses khellin as the photosensitizer

PUVASOL: Uses sun light as a source of UVA: Cost effective when machines are not available

Pretreatment monitoring Routine antinuclear antibody screening is not mandatory but may be recommended for non-photoadaptors61
NBUVB starting dose
  • For light skin populations: 200 mJ/cm2 for all skin types to avoid phototoxic reactions
  • For darker skin populations: higher starting doses 400–500 mJ/cm2 are considered
Dose escalation Each dose is increased by 10%–20% or held depending on the severity of erythema, up to a maximum dose of 1500 mJ/cm2 for the face and 3000 mJ/cm2 for the body
Response predictors Before starting treatment: Favourable response predictors include paediatric age, location on face and neck, recent disease onset. In contrast, areas with white hair and large, longstanding-lesions and acral areas are not expected to repigment readily

During treatment: The presence of perifollicular pigmentation on dermoscopy is predictive of a positive response to NB-UVB62

Number of sessions
  • Consider non-responders after 30–48 sessions, some late responders may require 72 sessions63
  • No consensus about the maximum allowed number of sessions
  • Ideal frequency is three sessions per week, but twice weekly treatment is also reasonable for convenience
Excimer light Dosing may start at 100 mJ/cm2 and is gradually increased weekly by 10%–25%19

Three session/week causes faster repigmentation than two sessions/week, but the final response depends on the total number of treatments and not frequency25

Related medications
  • No topicals are allowed before the session except for mineral oil to help UV penetration of xerotic skin.
  • NSAIDs helps achieving therapeutic doses for non-photoadaptors by minimizing burns and session interruption70
  • Sun protection is recommended between the sessions to prevent phototoxicity from additional exposure to the sun
Dose adjustment Mandatory if the patient misses more than a week of sessions
Stopping treatment UVB can be stopped abruptly but a maintenance scheme is recommended with topical treatments after stop of UVB. Tapering has also been suggested after complete repigmentation by the phototherapy Vitiligo Working Group: twice a week for a month, then once a week for 1 month, then once every other week for 2 months, then stop12

NB-UVB

NB-UVB is the preferred first-line therapy for widespread or rapidly progressive disease. NB-UVB is the modality of choice to administer total body UV treatment, while excimer lamp or laser 308 nm UV sources are preferred for limited vitiligo. Early initiation of NB-UVB is encouraged, because of its ability to halt disease activity and induce repigmentation.14 This is especially important in segmental and acral vitiligo, where repigmentation is notoriously difficult in later stages. Limitations include resistant anatomical sites (e.g. fingers, toes, bony prominences) and areas lacking a melanocyte reservoir (e.g. lesions with leukotrichia).15

Rather than performing minimal erythema dose testing, experts propose to start at a fixed dose and use a recommended dosing schedule (Table 1).16 Starting dose and dose increments need to be adjusted according to the patient’s phototype and response. For children, the use of phototherapy has been reported for patient as young as 3 years of age, when assisted by a parent or nurse.17 Specific eligibility considerations for NB-UVB use in children include the child’s ability to comprehend basic instructions, ability to remain still for focal and whole body phototherapy and absence of known phobias for enclosed spaces. Precautions should be taken to limit risk of phototoxicity. To limit cumulative exposure risks, in children and adults, experts recommend that phototherapy should be stopped if there is no improvement after 3 months or unsatisfactory results after to 6 months.18

The most common acute adverse effects of NB-UVB therapy are erythema and xerosis. There has been no significant association between NB-UVB therapy and basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and/or melanoma in vitiligo trials to date, while there is a small increased risk of in BCCs among those also treated with PUVA therapy.19 A recent study from Korea reported that among 60,321 cases, more than 200 sessions of NB-UVB increased the risk of actinic keratosis, while up to 500 sessions did not increase the risks of melanoma or non-melanoma skin cancer.20 Lichenoid papules in vitiligo lesions develop in about 4% of patients, especially in individuals undergoing more than 300 treatment sessions.21

Photochemotherapy

Oral PUVA is no longer recommended.22 Topical PUVA or topical PUVA SOL therapy is useful for localized lesions without systemic complications associated with oral psoralen (e.g. gastralgia and/or nausea, risk of severe generalized phototoxicity that could be increased in case of kidney and/or liver insufficiency).1322 The most common side effect of topical PUVA or topical PUVA SOL therapy is erythema and the risk of skin phototoxicity. However, the possible association of topical PUVA and/or topical PUVAsol with an increased risk of skin cancer still needs more investigation.

Excimer devices

Excimer laser and lamp treatment are equally effective or even superior compared to NB-UVB.2326 The required treatment duration is shorter, which improves patient compliance.2728 Excimer devices can be considered for localized disease.29 The targeted nature of these devices may prevent the darkening of non-lesional skin at a distance. Excimer treatment is also excessively time-consuming for both the patient and the health care professional when treating large areas.13

Reports are variable regarding the superiority of excimer laser for segmental vitiligo.1330 The presence of melanocyte reservoir in the form of pigmented hairs improves the likelihood of success. Safety and tolerability of excimer laser therapy are comparable to NB-UVB,25 but the cost of therapy is often higher and will need to be considered during the shared decision-making process. Acute adverse effects include erythema and blistering, while long-term adverse effects are not well established.26 The risk of acute adverse effects is most likely operator-dependent and may be reduced by proper training. One study using excimer treatment for children with vitiligo found it to be effective, although transient side effects were observed in 9 of 30 included patients.31

Home phototherapy

Home phototherapy saves patients the enormous burden of multiple visits to phototherapy centres. The shortage of home phototherapy units, high initial cost, low energy output of the device over time, lack of mechanical servicing and unfamiliarity of patients with the modality are important limitations to the use of these units. Available units include handheld devices for the treatment of focal lesions, medium-sized panels for small areas of the body and multi-panelled full-body devices for extensive BSA involvement. An initial period of in-office phototherapy may be helpful to evaluate treatment responsiveness prior to prescribing a home unit.1516

Compared to in-office treatment, home phototherapy demonstrated better compliance, similar repigmentation outcomes, similar frequency of adverse effects and lower time investment, but significantly less patient satisfaction.3235 Newer devices are designed to be user-friendly with higher safety standards and easier dose adjustment, which may improve patient satisfaction. Thorough patient education regarding shielding of sensitive sites, recognizing adverse effects and regular follow-up are essential to treatment success.36

Systemic treatments for vitiligo

Oral steroids and immunosuppressants (including biologics)

Oral steroid minipulse (OMP) therapy

The experts recommend oral mini-pulses of moderate doses of betamethasone (5 mg) or dexamethasone (2.5–5 mg depending on body weight) twice weekly on 2 consecutive days per week for the treatment of rapidly progressive vitiligo to stop disease progression, after careful consideration of the risks and benefits. The recommended duration is up to 3 months, with a maximum of 6 months due to the risk of adverse effects. While treatment can usually be stopped abruptly, tapering of the dose can also be performed 1–3 months after initiation. Instead of dexamethasone, methylprednisolone (equivalent to dexamethasone at fivefold higher dose), prednisone and prednisolone (both equivalent to dexamethasone at 6.25-fold higher dose) were suggested by some experts. OMP therapy in patients with extensive and rapidly spreading disease was reported to arrest the activity of the disease in more than 80% of patients.63738 Repigmentation seems difficult to achieve with OMP monotherapy. Combined with UV exposure, OMP therapy may achieve a higher degree of repigmentation, but safety aspects of long-term treatment with steroids need to be considered and discussed.39 As relapse of vitiligo is common after discontinuation of treatment, topical maintenance therapy can be considered (see Part 1). Adverse effects associated with short- and long-term use of OMP therapy have to be taken into consideration and should be discussed with the patient. The possible development of weight gain, insomnia, agitation, acne, menstrual disturbances, hypertrichosis, growth retardation in children and immunosuppression are potential side effects, although they can be minimized with intermittent, low-dose use.

The use of systemic steroids (prednisolone 20 mg/day or 0.3 mg per kg body weight/day in children) for 3 weeks in combination with excimer laser and TCI has also been reported to be beneficial in early SV.30

Other immunomodulating agents

Methotrexate, cyclosporine, azathioprine and minocycline can be used in patients with progressive vitiligo, although strong evidence for efficiency and safety is lacking.4042 Immunosuppressants such as methotrexate, cyclosporine and azathioprine have not been studied in combination with phototherapy. No biologics can currently be recommended for vitiligo (e.g. anti-TNF-ɑ and anti-IL-17).4344 Systemic JAK inhibitors are promising, and their use can be considered when available and approved by regulatory agencies.

Other systemic interventions

Vitamin E, vitamin C, resveratrol, ubiquinone, alpha lipoic acid, panthotenic acid, catalase/superoxide dismutase combination and Ginkgo biloba are antioxidants that have been used alone or in combination with phototherapy with the aim of achieving stabilization and repigmentation of vitiligo lesions.4548 Due to differences in patient selection, protocols, mixture of compounds used in trials, poor methodology in some studies using these different combinations of antioxidants and a lack of corroborating reports, there is little or no consensus on their use for vitiligo. There is, however, some evidence for improvement with the combination of phototherapy with oral antioxidants like Polypodium leucotomos and gliadin-protected superoxide dismutase (SOD).464849 RCTs with good methodology and reproducible results are needed to fully consider the use of antioxidants and vitamins in vitiligo.

Surgical interventions

Surgery should be reserved for patients with SV and other localized and stabilized forms of vitiligo (non-segmental) after the documented failure of medical interventions. For vitiligo (non-segmental), patients with a stable form of the disease and a negative history of Koebner phenomenon are eligible, but the risk of relapse must be explained thoroughly to the patient.50 Disease activity can be assessed using objective clinical follow-up based on photographs comparing two time points (e.g. using Vitiligo Disease Activity Score (VDAS)). The Vitiligo Disease Activity Index (VIDA) score, mini-punch test grafting, dermoscopy and in vivo reflectance confocal microscopy have also been used within this context, but their exact value remains uncertain.5153 Several techniques exist, including punch grafting, suction blister grafting, non-cultured epidermal cellular grafting and cultured epidermal cellular grafting. Each method has its pros and cons. Surgical interventions are often performed differently depending on the location and size of the treated lesions (Table 2).26

TABLE 2. Different options for surgery.

1. Mini Punch grafting
  • A method of directly transferring 1–2 mm punch grafts from donor to recipient sites
  • The simplest and least expensive method6465
  • Often limited for large area due to time restrictions
  • Can lead to a cobblestone appearance
  • Micropunch grafting using a motorized 0.8-mm punch can be used to reduce the time to perform the procedure6667
2. Suction blister grafting
  • Excellent cosmetic results
  • Practically no scarring of the donor site
  • Raising suction blisters can be painful and time-consuming (ameliorated by local anaesthesia and heat induction, respectively)
  • Cumbersome when treating large lesions
  • Associated with adverse events, such as colour mismatch and perilesional halo68
3. Split thickness grafting Ultrathin epidermal sheet grafting can treat larger areas (up to 200 cm2), but requires skill and experience to harvest an extremely thin split-skin graft from the donor site to avoid scarring
4. Cellular grafting using non-cultured suspensions of epidermal cells  

  • Large recipient sites with small amounts of donor tissue are possible69
  • Can be completed in 3–4 h in an outpatient setting, and given areas can be treated with donor to recipient ratio of between 1:5 and 1:10

 

5. Cellular grafting using pure cultured melanocytes
  • Best for large lesions
  • Expensive, time-consuming and requires a GMP-certified laboratory, making it impractical for routine clinical use68

Depigmentation

The potential sociocultural issues linked to depigmentation therapies, especially in patients with darker skin types, should be thoroughly explored before initiating therapy.54 In case of depigmentation failure, it was recommended to postpone the treatment until the disease flares.55 Topical depigmenting agents include monobenzyl ether of hydroquinone (MBEH), 4-methoxyphenol (4MP, mequinol or p-hydroxyanisole) and phenol. MBEH (p-benzyloxy-phenol, monobenzone) is the only topical depigmenting agent that is currently approved for vitiligo by the Food and Drug Administration. The drug may induce depigmentation at sites distal to the drug application. The expected results (61%–92% depigmentation) with 20% MBEH are usually achieved at treated sites after 10 months.56 However, in successfully depigmented areas, 78% of patients can experience repigmentation after the end of MBEH therapy, which should be explained to the patient. Nearly half of the subjects can experience dose-dependent skin irritation, which may be resolved with a reduction in MBEH concentration. MBEH is better suited for treating larger remaining areas of pigmentation compared to laser and cryotherapy; however, MBEH is not currently available in all countries.

Cryotherapy and pigment lasers are the two options for physical depigmentation therapies.57 Cryotherapy can achieve rapid depigmentation via irreversible tissue damage, in particular in patients sensitive to Koebner’s phenomenon. The advantages of cryotherapy remain its low cost and excellent safety profile, but it requires an experienced physician for optimal results and to minimize the risk of scarring.

Several types of lasers involving wavelengths between 532 and 755 nm targeting pigmentation are also used for depigmentation. The Q-switched ruby laser (QSR) exhibits high absorption by melanin and is therefore more suited for lighter skin types. Meanwhile, the Q-switched alexandrite laser (QSA) has a faster pulse frequency than the QSR that permits more rapid therapy and emits light of a greater wavelength (755 vs. 694 nm), which may provide better tissue penetration. The Nd:YAG laser has been used at a wavelength of 532 nm to target only epidermal pigment and to induce koebnerization of vitiliginous lesions.58

Innovative and emergent therapies

Vitiligo patients can be strongly encouraged to participate in the latest clinical trials to promote the development of new and more efficient therapies. Topical JAK inhibitor (e.g. ruxolitinib cream) has shown clinical efficacy and is now FDA and EMA approved for vitiligo. Oral JAK inhibitors upadacitinib and povorcitinib (JAK1 inh), Baracitinib (JAK1/2 inh) are currently being tested in phase II ongoing trials. Ritlecitinib (JAK3/TEC inh) has been evaluated with different doses in a phase II trial including 364 patients. After 24 weeks, the proportion of change from baseline was significantly different compared to placebo in F-VASI for the ritlecitinib 50 mg groups with (−21.2 vs. 2.1, p < 0.001).59 Strategies to target IL-15 or its receptor CD122 to inhibit the generation and the maintenance of skin resident memory T cells demonstrated durable treatment responses in a preclinical mouse model of vitiligo, and clinical trials using this strategy are under way.60

Blocking the initiation of the disease could also be an important step for future therapies for vitiligo. Older and more recent data shed light on the role of innate immunity in vitiligo that connects cellular stress pathways [through PAMPs and DAMPs (pathogen- and danger-associated molecular patterns: ROS or heat shock protein 70i)] to adaptative autoimmunity against melanocytes.61 HP70i seems to be a critical DAMP in the initiation of the disease. Blocking HSP70i activity might offer a good strategy, as shown in preclinical animal models. Preventing melanocyte detachment, by using anti-matrix metalloproteinase-9 antibodies could also be effective.62 Recent data suggest dysbiosis in the skin and gut of vitiligo patients.6364 Modulating the vitiligo microbiome offers appealing strategies, but no therapeutic intervention using this strategy has yet been reported.

In contrast to other chronic skin inflammatory diseases, targeting the immune response in vitiligo will likely not be sufficient to obtain maximal repigmentation in all patients.2 Promoting the differentiation and proliferation of melanocyte stem cells in vitiligo lesions located on acral areas or in areas with poliosis is more challenging due to the limited availability of melanocyte stem cells. WNT signalling, which is repressed in the depigmented skin of vitiligo patients, may be an important pathway to target to induce melanocyte differentiation.65

DISCUSSION/CONCLUSION

Current therapeutic options for vitiligo are backed by substantial evidence. Although strategies that provide complete clearance will warrant further research, this should not discourage dermatologists and patients from treating vitiligo, as disease stabilization is within reach in most cases. To date, the odds of repigmentation remain primarily dependent on the involved body areas and grade of disease activity; therefore, early treatment is recommended. Options such as JAK inhibitors and research into other drugs that affect adaptive and innate immunity are exciting developments that continue to pave a promising way forwards.

ACKNOWLEDGEMENTS

We are grateful to all the participating patient representatives and vitiligo experts who attended the VTF meetings, VIPOC meetings and final VTF conclusive consensus meeting in Milan (EADV 2022). We express our deep gratitude to all patient representatives who played a significant role in the development of this work through their dedicated involvement in the process (JMM, NM, PM and GP).

CONFLICT OF INTEREST STATEMENT

Nanja van Geel MD, PhD received grants, is consultant and/or investigator for AbbVie, Incyte, Merck/MSD, Pfizer and Sun Pharma; and is chair of the Vitiligo Task Force for the European Academy of Dermatology and Venereology (EADV). She was involved in the development of several measurement instruments for vitiligo. Khaled Ezzedine MD, PhD has served as a consultant for AbbVie, Incyte Corporation, Pfizer, Pierre Fabre Pharmaceuticals, Merck/MSD and Almirall. Amit G. Pandya MD, has served as an investigator for Incyte. He is a consultant for AbbVie, Avita Medical, Immune Tolerance Network, Incyte, Pfizer, Thalocan, Trifecta, TWi, Viela Bio, Vyne and Villaris and holds stock options for Tara Medical and Zerigo Health. Thierry Passeron MD, PhD received consutancies fees from Abbvie, Incyte, Pfizer, Vyne therapeutics and Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, Incyte, Pfizer, Vyne therapeutics. Albert Wolkerstorfer MD, PhD, is consultant for InCyte, Novartis, AvitaMedical, Candela and Lumenis. Jung Min Bae MD, PhD has served as a consultant for Pfizer, AbbVie, LaserOptek, Ilooda and Cutech Korea. Viktoria Eleftheriadou MD, PhD VE is a consultant for Incyte, Abbvie, Pfizer and Almirall. Samia Esmat MD, is consultant for Pfizer. Pearl Grimes MD, conducts clinical trials, for which the Vitiligo & Pigmentation Institute of Southern California receives financial support for purposes of conducting these trials, from Procter & Gamble, Clinuvel, L’Oreal, Johnson & Johnson, LaserOptek, Mother Science, Incyte, Pfizer, AbbVie/Allergan and SkinBetterScience. Dr. Grimes receives no direct compensation for this work. Somesh Gupta MD, is conducting a clinical trial sponsored by Pfizer on Abrocitinib and Ritlecitinib. Iltefat H. Hamzavi MD is Consultant to Abbvie, Pfizer, Incyte, UCB, Boerhinger Ingelheim, Sonoma, Union therapeutics, Novartis, Jansen, Avita, Galderma and is Investigator for Lenicura, Pfizer, Incyte, Avita, L’oreal/La Roche Posay. He is also Board member and Past-president of the HS foundation and Global Vitiligo foundation. John E. Harris MD, PhD, 3rd Rock Venture—Consultant (Fees); AbbVie, Inc—Consultant (Fees); Aclaris Therapeutics, Inc—Consultant (Fees), Investigator (Grants/Research Funding); Admirx—Consultant (Fees); Aldena—Consultant (Fees), Founder (Stock); Almiral—Consultant (Fees); AnaptysBio—Consultant (Fees); Avita—Consultant (Fees); BiologicsMD—Consultant (Fees); Boston Pharma—Consultant (Fees); BridgeBio—Consultant (Fees); Celgene—Investigator (Grants/Research Funding); Cogen Therapeutics—Consultant (Fees); Dermavant—Consultant (Fees), Investigator (Grants/Research Funding); Dermira—Consultant (Fees); EMD Serono—Consultant (Fees), Investigator (Grants/Research Funding); Frazier Management—Consultant (Fees); Genzyme/Sanofi—Consultant (Fees), Investigator (Grants/Research Funding); Granular Therapeutics, Inc—Consultant (Fees); Incyte—Consulting (Fees), Investigator (Grants/Research Funding), Equity; Janssen—Consultant (Fees); LEO Pharma—Consultant (Fees), Investigator (Grants/Research Funding); Matchpoint Therapeutics—Consultant (Fees); Merck—Consultant (Fees); NIRA Biosciences—Consultant (Fees), Founder (Stock); Pandion—Consultant (Fees); Pfizer—Consultant (Fees), Investigator (Grants/Research Funding); Platelet Biogenesis—Consultant (Fees); Rheos Medicines—Consultant (Fees), Investigator (Grants/Research Funding), Equity (Stock); Sonoma Biotherapeutics—Consultant (Fees); Steifel/GSK—Investigator (Grants/Research Funding); Sun Pharmaceuticals—Consultant (Fees), Investigator (Grants/Research Funding); Temprian Therapeutics—Consultant (Fees); TeVido BioDevices—Consultant (Fees), Investigator (Grants/Research Funding), Equity (Stock); Twi Biotech—Consultant (Fees); Villaris Therapeutics—Consulting (Fees), Investigator (Grants/Research Funding), Founder (Stock); Vimela Therapeutics—Consultant (Fees), Founder (Stock); Villaris Therapeutics was recently acquired by Incyte. Sang Ho Oh MD, PhD has served as a consultant for Merck/MSD. Richard H. Huggins MD, has served as an investigator for Arcutis, Avita, CLinuvel, Incyte, Pfizer and The Immune Tolerance Network; and is Treasurer of the Global Vitiligo Foundation. Eric Lan MD, PhD, has served for Pfizer, Dermira (Eli Lilly), Abbvie, Teva Pharmaceutical, Cerner Enviza clinical trials. None of the trials focus on vitiligo. Caroline Le Poole PhD, is the CSO of Temprian Therapeutics, promoting the clinical translation of HSP70iQ435A for the treatment of vitiligo. Harvey Lui MD, is a consultant (fees to professional medical corporation) for Incyte, and has been a clinical investigator (fees to institition) for Pfizer in vitiligo. Jung Min Bae MD, PhD has surved as a consultant for Pfizer, AbbVie, LaserOptek, Ilooda and Cutech Korea. Noufal Raboobee MD, has received honoraria from AbbVie, Pfizer, Novartis, Lilly, Janssen and Sanofi, is the President of the Dermatology Society of South Africa and President of the Vitiligo Society of South Africa. David Rosmarin MD, received honoraria as a consultant for AbbVie, Abcuro, AltruBio, Arena, Boehringer-Ingelheim, Bristol Meyers Squibb, Celgene, Concert, CSL Behring, Dermavant, Dermira, Incyte, Janssen, Kyowa Kirin, Lilly, Novartis, Pfizer, Regeneron, Recludix, Revolo Biotherapeutics, Sanofi, Sun Pharmaceuticals, UCB, VielaBio; has received research support from AbbVie, Amgen, Bristol Meyers Squibb, Celgene, Dermira, Galderma, Incyte, Janssen, Lilly, Merck, Novartis, Pfizer and Regeneron Pharmaceuticals Inc; and has served as a paid speaker for AbbVie, Amgen, Bristol Meyers Squibb, Celgene, Dermavant, Incyte, Janssen, Lilly, Novartis, Pfizer, Regeneron Pharmaceuticals Inc. and Sanofi. Tamio Suzuki MD, PhD has served as a consultant for AbbVie, Pfizer, J-TEC and Pola; and is the secretary general of the Japanese Society of Vitiligo. Mauro Picardo MD, received grants or honoraria from PPM, Naos, Incyte, Pfizer and has a patent on Pioglidazone in Vitiligo. Julien Seneschal MD, PhD: received grants and/or honoraria from AbbVie, Bristol Myers Squibb, Calypso Biotech, Eli Lilly, Incyte, LEO Pharma, Novartis, Pfizer, Pierre Fabre, Sanofi, Sun Pharmaceuticals and Viela Bio; and has a patent on MMP9 inhibitors and uses thereof in the prevention or treatment of a depigmenting disorder and three-dimensional model of depigmenting disorder. All other co-authors have no disclosures to declare.

FUNDING INFORMATION

None declared.

ETHICS STATEMENT

None declared.

DISCLAIMER

This recommendation was proposed based on expert opinions, feedback from patient representatives and published evidence. Future updates of these recommendations are inevitable as new treatments may override current management recommendations as well as in response to potential adverse responses. The Vitiligo Task Force does not represent or warrant a legislative or all-encompassing consensus based on the contents of this documentation. Medical professionals may treat vitiligo following procedures and treatment plans which substantially differ from those mentioned or described in this recommendation. The Vitiligo Task Force expressly disclaims any responsibility or liability for any damages, loss, injury, or liability whatsoever experienced as a result of reliance on the information contained in this publication. The contents of this manuscript can in no way be regarded as advice in legal matters (including use for claims). Inquiring about allergies and intolerance reactions, as well as detecting probable contraindications and risks, should be considered to be part of a physician’s general responsibilities when prescribing medications. It is assumed that all patients should be informed of the specific risks associated with a given treatment.

Source

Image Credit: Envato Elements

Worldwide expert recommendations for the diagnosis and management of vitiligo Part 1

Abstract

Background

The treatment of vitiligo can be challenging and depends on several factors such as the subtype, disease activity, vitiligo extent, and treatment goals. Vitiligo usually requires a long-term approach. To improve the management of vitiligo worldwide, a clear and up-to-date guide based on international consensus with uniform stepwise recommendations is needed.

Objectives

To reach an international consensus on the nomenclature and to develop a management algorithm for the diagnosis, assessment, and treatment of vitiligo.

Methods

In this consensus statement, a consortium of 42 international vitiligo experts and four patient representatives participated in online and live meetings to develop a consensus management strategy for vitiligo. At least two vitiligo experts summarized the evidence of topics included in the algorithms. A survey was utilized to resolve remaining issues among a core group of eight experts. Subsequently, the unanimous recommendations were finalized and validated based on further input from the entire group during two live meetings.

Results

The algorithms highlight the importance of shared decision-making. Dermatologists are encouraged to provide patients with detailed explanations of the prognosis and expected therapeutic outcomes based on clinical examination. The treatment goal should be discussed and clearly emphasized to patients given the different approaches for disease stabilization and repigmentation. The evaluation of disease activity remains a cornerstone in the tailor-made approach to vitiligo patients.

Conclusions

These new treatment algorithms are intended to guide clinical decision-making in clinical practice. Promising novel therapies for vitiligo are on the horizon, further highlighting the need for reliable outcome measurement instruments and greater emphasis on shared decision-making.

CONFLICT OF INTEREST STATEMENT

Nanja van Geel MD, PhD received grants, is consultant and/or investigator for AbbVie, Incyte, Merck/MSD, Pfizer and Sun Pharma; and is chair of the Vitiligo Task Force for the European Academy of Dermatology and Venereology (EADV). She was involved in the development of several measurement instruments for vitiligo. Khaled Ezzedine MD, PhD has served as a consultant for AbbVie, Incyte Corporation, Pfizer, Pierre Fabre Pharmaceuticals, Merck/MSD and Almirall. Amit G. Pandya MD has served as an investigator for Incyte. He is a consultant for AbbVie, Avita Medical, Immune Tolerance Network, Incyte, Pfizer, Thalocan, Trifecta, TWi, Viela Bio, Vyne, and Villaris and holds stock options for Tara Medical and Zerigo Health. Thierry Passeron MD, PhD received consultancies fees from Abbvie, Incyte, Pfizer, Vyne therapeutics and Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from from Abbvie, Incyte, Pfizer, Vyne therapeutics. Albert Wolkerstorfer MD, PhD, is consultant for InCyte, Novartis, AvitaMedical, Candela and Lumenis. Jung Min Bae MD, PhD has served as a consultant for Pfizer, AbbVie, LaserOptek, Ilooda and Cutech Korea. Viktoria Eleftheriadou MD, PhD VE is a consultant for Incyte, Abbvie, Pfizer and Almirall. Samia Esmat MD is consultant for Pfizer. Pearl Grimes MD conducts clinical trials, for which the Vitiligo & Pigmentation Institute of Southern California receives financial support for purposes of conducting these trials, from Procter & Gamble, Clinuvel, L’Oreal, Johnson & Johnson, LaserOptek, Mother Science, Incyte, Pfizer, AbbVie/Allergan and SkinBetterScience. Dr. Grimes receives no direct compensation for this work. Somesh Gupta MD is conducting a clinical trial sponsored by Pfizer on Abrocitinib and Ritlecitinib. Iltefat H. Hamzavi MD is Consultant to Abbvie, Pfizer, Incyte, UCB, Boerhinger Ingelheim, Sonoma, Union therapeutics, Novartis, Jansen, Avita, Galderma and is Investigator for Lenicura, Pfizer, Incyte, Avita, L’oreal/La Roche Posay. He is also Board member and Past-president of the HS foundation and Global Vitiligo foundation. John E. Harris MD, PhD, 3rd Rock Venture – Consultant (Fees); AbbVie, Inc – Consultant (Fees); Aclaris Therapeutics, Inc – Consultant (Fees), Investigator (Grants/Research Funding); Admirx—Consultant (Fees); Aldena—Consultant (Fees), Founder (Stock); Almiral—Consultant (Fees); AnaptysBio—Consultant (Fees); Avita—Consultant (Fees); BiologicsMD—Consultant (Fees); Boston Pharma—Consultant (Fees); BridgeBio—Consultant (Fees); Celgene—Investigator (Grants/Research Funding); Cogen Therapeutics—Consultant (Fees); Dermavant—Consultant (Fees), Investigator (Grants/Research Funding); Dermira—Consultant (Fees); EMD Serono—Consultant (Fees), Investigator (Grants/Research Funding); Frazier Management—Consultant (Fees); Genzyme/Sanofi—Consultant (Fees), Investigator (Grants/Research Funding); Granular Therapeutics, Inc—Consultant (Fees); Incyte—Consulting (Fees), Investigator (Grants/Research Funding), Equity; Janssen—Consultant (Fees); LEO Pharma—Consultant (Fees), Investigator (Grants/Research Funding); Matchpoint Therapeutics—Consultant (Fees); Merck—Consultant (Fees); NIRA Biosciences—Consultant (Fees), Founder (Stock); Pandion—Consultant (Fees); Pfizer—Consultant (Fees), Investigator (Grants/Research Funding); Platelet Biogenesis—Consultant (Fees); Rheos Medicines—Consultant (Fees), Investigator (Grants/Research Funding), Equity (Stock); Sonoma Biotherapeutics—Consultant (Fees); Steifel/GSK—Investigator (Grants/Research Funding); Sun Pharmaceuticals—Consultant (Fees), Investigator (Grants/Research Funding); Temprian Therapeutics—Consultant (Fees); TeVido BioDevices—Consultant (Fees), Investigator (Grants/Research Funding), Equity (Stock); Twi Biotech—Consultant (Fees); Villaris Therapeutics—Consulting (Fees), Investigator (Grants/Research Funding), Founder (Stock); Vimela Therapeutics—Consultant (Fees), Founder (Stock); Villaris Therapeutics was recently acquired by Incyte. Sang Ho Oh MD, PhD has served as a consultant for Merck/MSD. Richard H. Huggins MD has served as an investigator for Arcutis, Avita, Clinuvel, Incyte, Pfizer and The Immune Tolerance Network; and is Treasurer of The Global Vitiligo Foundation. Eric Lan MD, PhD, has served for Pfizer, Dermira (Eli Lilly), Abbvie, Teva Pharmaceutical, Cerner Enviza clinical trials. None of the trials focus on vitiligo. Caroline Le Poole PhD is the CSO of Temprian Therapeutics, promoting the clinical translation of HSP70iQ435A for the treatment of vitiligo. Harvey Lui MD is a consultant (fees to professional medical corporation) for Incyte and has been a clinical investigator (fees to institution) for Pfizer in vitiligo. Jung Min Bae MD, PhD has served as a consultant for Pfizer, AbbVie, LaserOptek, Ilooda and Cutech Korea. Noufal Raboobee MD has received honoraria from AbbVie, Pfizer, Novartis, Lilly, Janssen and Sanofi, is the President of the Dermatology Society of South Africa and President of the Vitiligo Society of South Africa. David Rosmarin MD received honoraria as a consultant for AbbVie, Abcuro, AltruBio, Arena, Boehringer-Ingelheim, Bristol Meyers Squibb, Celgene, Concert, CSL Behring, Dermavant, Dermira, Incyte, Janssen, Kyowa Kirin, Lilly, Novartis, Pfizer, Regeneron, Recludix, Revolo Biotherapeutics, Sanofi, Sun Pharmaceuticals, UCB, VielaBio; has received research support from AbbVie, Amgen, Bristol Meyers Squibb, Celgene, Dermira, Galderma, Incyte, Janssen, Lilly, Merck, Novartis, Pfizer, and Regeneron Pharmaceuticals Inc; and has served as a paid speaker for AbbVie, Amgen, Bristol Meyers Squibb, Celgene, Dermavant, Incyte, Janssen, Lilly, Novartis, Pfizer, Regeneron Pharmaceuticals Inc. and Sanofi. Tamio Suzuki MD, PhD has served as a consultant for AbbVie, Pfizer, J-TEC and Pola; and is the secretary general of the Japanese Society of Vitiligo. Mauro Picardo MD, received grants or honoraria from PPM, Naos, Incyte and Pfizer and has a patent on Pioglidazone in Vitiligo. Julien Seneschal MD, PhD received grants and/or honoraria from AbbVie, Bristol Myers Squibb, Calypso Biotech, Eli Lilly, Incyte, LEO Pharma, Novartis, Pfizer, Pierre Fabre, Sanofi, Sun Pharmaceuticals and Viela Bio; and has a patent on MMP9 inhibitors and uses thereof in the prevention or treatment of a depigmenting disorder and three-dimensional model of depigmenting disorder. All other co-author have no disclosure to declare.

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Image Credit: Envato Elements

Disease Burden and Management of Vitiligo

Vitiligo is a skin disease characterized by selective loss of melanocytes followed by depigmentation in the affected areas of the skin.1 The disease, which has a complex pathogenesis, can have a serious psychosocial impact on patients.1 Although management of vitiligo is complex, there are safe, effective treatments available and promising emerging therapies.1,2 In a recent AJMC® Peer Exchange™, experts who specialize in treating patients with vitiligo were joined by professionals from the insurance industry to explore the clinical and economic burden of vitiligo, review treatment paradigms and standard-of-care therapies, and discuss unmet needs and future directions in treatment. The session was moderated by Jeffrey D. Dunn, PharmD, MBA, chief clinical officer at Cooperative Benefits Group in Salt Lake City, Utah.

Disease Burden

Vitiligo is a chronic, acquired disease of the skin and mucous membranes that is characterized by sharply demarcated, milky white, depigmented macules and patches, with neat borders and variable dimensions and distribution.3,4 There are 2 forms of the disease: segmental and nonsegmental.1,5 Segmental vitiligo is characterized by unilateral, localized distribution of lesions. It is more common in younger children, and often has rapid onset and stabilization with early hair follicle involvement. Nonsegmental vitiligo is characterized by bilateral distribution of lesions on the body, with progressive onset and multiple flare-ups, later hair follicle involvement, and an unpredictable course.6

Vitiligo has been dismissed as a cosmetic disease.7 However, patients may experience a severe impact on quality of life because the disorder can be psychologically devastating.3,7-9 Vitiligo lesions, which typically occur in exposed areas of the skin such as the hands and face, are often mistaken for an infectious disease, which contributes to the stigma experienced by patients.1,3,7-9 Furthermore, the lesions may have a strong negative impact on patients’ self-esteem and perception of self,3 and patients may experience psychological problems such as depression, anxiety, and shame, which can result in social isolation.1,7 In fact, recent systematic reviews of the available evidence for the psychosocial burden in vitiligo found that depression and anxiety were the most commonly reported psychological disorders; feelings of stigmatization, adjustment disorders, sleep disturbance, relationship difficulties such as sexual dysfunction, and avoidance or restriction behavior were the most prevalent psychosocial comorbidities; female sex, visible or genital lesions, age younger than 30 years (particularly adolescents), and greater body surface area involvement were factors associated with a significantly higher psychosocial burden; and lesion concealment was the most common coping strategy.9,10 Importantly, most interventions significantly improved quality of life for patients.10 Therefore, it is important to assess quality of life during consultations and refer patients to psychological help, if needed.1,3,9

Finally, vitiligo carries a significant economic burden as management of the disease is associated with high direct and indirect costs.7 Costs include those for prescription and OTC medications, medical office visits, phototherapy, lost workdays, public avoidance, and impaired quality of life.11 Because patients with insurance are more likely to receive treatment, it is important that payers understand that early treatment of vitiligo lesions has better results, as well as benefits via early detection of associated autoimmune diseases.7,12

Epidemiology and Pathogenesis

The average age of onset follows a bimodal pattern, with early onset at a mean of 7.3 years and late onset at a mean of 40.5 years; the overall mean (SD) age of onset is 31.8 (20.2) years.13,14 Although vitiligo can occur in individuals of all genetic backgrounds, the prevalence varies widely across geographic areas, ranging from a low of 0.06% to a high of 2.28%.1,15 In the United States, the prevalence of vitiligo varies between 0.76% based on clinician adjudication and 1.38% based on self-report.16 The incidence and prevalence of segmental vitiligo is not well established1; however, it is less common than nonsegmental vitiligo and affects between 5% and 16% of patients.17,18

Vitiligo has a complex multifactorial pathogenesis.4 However, the exact mechanisms that integrate the genetic susceptibility of each individual with melanocyte auto-aggression and failure of immune tolerance mechanisms are not fully elucidated.19 The most common theory for the pathogenesis of vitiligo is that a convergence of immunological and nonimmunological factors ultimately leads to the development of the disease. Patients with a background of genetic susceptibility and intrinsic skin abnormalities are more susceptible to oxidative stress damage, which triggers the release of various factors that activate the immune system and lead to melanocyte loss.4

There is strong evidence for the importance of genetic factors in the development of vitiligo; however, these influences are complex and the genetic risk is not absolute.1 The disease tends to aggregate in families, as approximately 20% of patients have at least 1 first-degree relative with vitiligo, and the relative risk of vitiligo for first-degree relatives is increased.20 However, monozygotic twins have only a 23% concordance rate, highlighting the importance of additional stochastic or environmental factors in the development of the disease.21 There are nearly 50 different genetic loci that confer a vitiligo risk, with relevant genes involved in the innate and adaptive immune system, melanogenesis, and apoptosis. Furthermore, several of these genes are associated with other pigmentary and autoinflammatory disorders, as well as autoimmune disorders such as thyroid disease, type 1 diabetes, and rheumatoid arthritis.22

Intrinsic alterations in the skin of patients with vitiligo include a thicker epidermis with a reduced number of basal melanocytes and the presence of degenerated keratinocytes with swollen mitochondria, increased levels of reactive oxygen species (ROS), and reduced E-cadherin expression. The melanocytes have a senescent phenotype with high intracellular ROS levels, reduced antioxidant activity, abnormalities in mitochondrial function, and release of senescence-associated proteins. The fibroblasts have a myofibroblast phenotype, increased intracellular ROS, and mediators that contribute to the downregulation of E-cadherin. Finally, there is a decrease in microbial diversity, possibly due to the altered microenvironment of the skin.4

In this background of intrinsic skin alterations together with genetic susceptibility, additional environmental stress causes widespread alterations in the antioxidant system.1 Oxidative stress leads to the secretion of interferon-γ (IFN-γ) by natural killer (NK) cells and innate lymphoid cells (ILCs).4 The increase in IFN-γ levels has several effects, starting with the release of CXCL9 and CXCL10, which recruit CD8+ T cells, and MMP9, which contributes to the detachment of melanocytes from the basal layer, from damaged keratinocytes. Damaged melanocytes release damage-associated molecular patterns, heat shock protein 70, and HMGB1, which further activates NK cells and ILCs, acting as a positive feedback loop, and activates dendritic cells, further potentiating the development of a specific immune response through the activation of autoreactive CD8+ T cells. Following this autoimmune reaction, a portion of T cells remains in the skin as resident memory T cells (TRM), which may be responsible for the recurrence of vitiligo following repigmentation.1,4

Diagnosis and Assessment

The diagnosis of vitiligo is generally straightforward and made clinically based on appearance of the characteristic lesions. It usually does not require confirmatory laboratory tests, and a skin biopsy is only used to exclude other disorders. The diagnosis may be facilitated by use of a handheld UV irradiation device that emits UVA, commonly referred to as a Wood lamp. Under the Wood lamp, the vitiligo lesions emit a bright blue-white fluorescence and appear sharply demarcated, which helps identify focal melanocyte loss and detect areas of depigmentation that may not be visible to the eye.3,6,23

Physicians should reserve enough time for a careful initial assessment of a patient with vitiligo. The evaluation entails a detailed history and complete skin examination to assess disease severity and individual prognostic factors. An assessment form created by the Vitiligo European Task Force summarizes the personal and family history elements of the clinical examination items and may be useful for evaluation. It is important to routinely ask patients about family history of vitiligo and premature hair graying and about personal and family history of thyroid disease or other autoimmune diseases. Aspects that should be assessed include the skin phototype, disease duration, extent, activity, rate of progression or spread of lesions, presence of the Koebner phenomenon, presence of halo nevi, previous treatments (including their type, duration, and effectiveness), previous episodes of repigmentation, and occupational history/exposure to chemicals.6

Finally, the quality of life of patients with vitiligo should be assessed regularly. Assessment tools used in the research setting include the Short Form-12, the Dermatology Life Quality Index, the Vitiligo Impact Scale, the Vitiligo-Specific Health-Related Quality of Life Instrument, and the Vitiligo Impact Patient Scale.1 All patients with vitiligo should be offered psychological support and counseling.23

Stakeholder Insights

More than 1 million individuals in the United States have vitiligo. However, “it is very hard to know the exact incidence and prevalence of vitiligo in the population,” said David Rosmarin, MD, vice chair of education and research at Tufts Medical Center in Boston, Massachusetts. This is because many patients do not seek care for their disease. They may not be aware of it or may have received a misdiagnosis. Therefore, some patients may be missed when the incidence and prevalence are calculated. The reason for the reported differences in incidence is not well understood, as vitiligo can affect any individual. However, “how it affects somebody in terms of their quality of life may vary greatly depending on the culture and some of the subgroups,” Rosmarin said. He underscored that it is the burden on mental health that clinicians are particularly concerned about when it comes to vitiligo. Although some individuals adapt to their disease, perhaps because it is less noticeable on fair skin or because they are older, others find that it has a significant impact on their quality of life.

Brett King, MD, PhD, associate professor of dermatology at Yale School of Medicine in New Haven, Connecticut, emphasized the social impact of the disease. “Imagine having white spots all over [your] face or having white spots just surrounding your eyes, having big raccoon eyes, having white spots all over your arms and your hands,” he said. Other individuals may react negatively to these lesions, thinking they are infectious, and avoid touching them. In other words, vitiligo is associated with stigma. Therefore, patients can find day-to-day life challenging. There are data showing the impact that the disease has on work productivity, life decisions, and quality of life.

In terms of the economic burden of vitiligo, David Epstein, MD, MBA, an independent consultant, shared that from the payer perspective, this is not being tracked because most medications are not expensive. Dunn agreed and said that the challenge, from the payer perspective, will be how to manage the direct costs once new treatments are approved. But from the perspective of the patient, there certainly is an economic impact associated with the treatment, Rosmarin said, especially with phototherapy sessions, which may require patients to miss work.

The fact that vitiligo is an autoimmune disease was emphasized by Rosmarin and King. A further clinical clue about the autoimmune nature of vitiligo is the fact that it is sometimes associated with autoimmune thyroid disease, King said. The autoimmune nature of vitiligo also points to the other causative aspect of the disease, which is the genetic predisposition that is probably present in all patients. This genetic predisposition is likely what explains the well-documented association between autoimmune thyroid disease and vitiligo, which is also seen in patients with other autoimmune skin diseases. Finally, although emerging data suggest there is systemic inflammation in vitiligo, it is not clear whether patients are predisposed to any other internal organ disease, King said.

Although several tools are used in the research setting to assess quality of life of patients with vitiligo, there are no standardized tools used in clinical practice, Rosmarin said. Clinicians typically ask questions, such as whether patients have switched to different clothing or changed their going-out habits or whether they feel people are staring at them, to determine how the disease is affecting patients. Furthermore, Rosmarin wished there were better tools to assess quality of life of patients with vitiligo in the research setting as well.

Management of Vitiligo

Several guidelines have been published for the treatment of patients with vitiligo.23-26 As most of the therapeutic options are time-consuming and require long-term follow-up, management of vitiligo requires a personalized treatment approach that considers the preferences of the patient. The choice of treatment depends on factors including the subtype of vitiligo, as well as the extent, distribution, and activity of the disease. The patient’s age, phototype, effect on quality of life, and motivation for treatment also play a role in the decision-making process.1

The areas that have the best response to treatment are the face, neck, trunk, and midextremities, whereas the lips and distal extremities are more resistant. The repigmentation starts at the periphery of the lesions in a perifollicular pattern, and at least 2 to 3 months of continued treatment is necessary to determine efficacy for the individual patient.1

Commonly used treatments for vitiligo are topical corticosteroids (TCSs) and topical calcineurin inhibitors (TCIs). TCSs can be used for patients with limited lesions that are not on the face. The first choice should be a less potent TCS, and treatment should be no longer than 3 months if administered daily, or 6 months if following a discontinuous scheme. TCIs are as effective as TCSs on facial lesions and have less severe adverse effects.24

UV light–based therapy is associated with an improved outcome when combined with an additional therapy. Phototherapy treatments include narrowband UV-B (NBUVB) and psoralen and UVA (PUVA). NBUVB is indicated for generalized nonsegmental vitiligo, with total body treatments being suggested for lesions involving more than 15% to 20% of the body area, whereas targeted phototherapies are indicated for localized and small lesions.24

The combination of phototherapy and TCS and TCI treatments appears safe and leads to better results. Additionally, phototherapy should be used for 3 to 4 weeks following surgical procedures to enhance repigmentation. There is less evidence for combining phototherapy with antioxidant therapy; however, it might be beneficial. The only therapy for which combination with phototherapy is not recommended is therapy with vitamin D analogues.24

Systemic steroid treatment may also be used in some cases. Patients experiencing rapid disease progression may be treated with systemic oral minipulse steroids, a treatment that consists of twice-a-week corticosteroid administration.24 For patients with more resistant vitiligo, options include surgical grafting as a third-line therapy and depigmenting treatments as a fourth-line therapy.1

Additionally, patients should be offered advice on cosmetic camouflage by a cosmetician or a specialized nurse, as this can be beneficial for patients with vitiligo lesions in exposed areas. Cosmetic camouflage includes foundation-based cosmetics and self-tanning products containing dihydroxyacetone. Patients may also opt to have cosmetic tattoos, especially on the lips and nipples.1,24

Stakeholder Insights

Although there are other agents available, the main 3 therapies used in the front line are TCSs, TCIs, and phototherapy, which can be used alone or in combination, Rosmarin said. Corticosteroids are inexpensive but can be difficult to use for prolonged periods, which are typically needed for repigmentation. Calcineurin inhibitors generally work well for repigmentation of the face. However, as it is a large molecule, it does not work as well on other parts of the body. Phototherapy is also very effective, as it stimulates the melanocytes to migrate back to the lesion and calms the immune system. However, it can be inconvenient for patients to go to the clinic 3 times a week for treatments, especially if they live far away and must miss work.

Treatment goals vary by patient, Rosmarin said. Some patients just want to get a diagnosis and they do not want any treatment. Others experience severe anxiety about spread of the lesions and want to stop progression, which is easier to do than repigmenting. For some patients, the goal is to repigment at least some areas. Finally, the goal can also be repigmentation maintenance, which may be helped by twice-a-week application of a TCI. Vitiligo is a chronic disease with no permanent cure, and new spots may appear at any time. Existing and emerging therapies manage the underlying cause of an overactive immune system but do not cure the disease.

On the other hand, it is possible to achieve remission without continued treatment, King noted, which is not the case for other autoimmune diseases such as psoriasis. Furthermore, once repigmentation has been achieved, it is also likely that patients will be less motivated to continue treatment as diligently, which ends up also being a cost-saving mechanism. King emphasized that it is important for patients, providers, and payers to understand that vitiligo treatment is a monthslong process. There are data indicating that a significant proportion of patients achieves success in 6 months, but others need up to a year.

In terms of insurance coverage, some payers will not cover even the diagnosis of vitiligo, although this is rare. As for treatment, corticosteroids are generally covered and do not require prior authorization, Rosmarin said. However, both Rosmarin and King expressed that coverage for calcineurin inhibitors and phototherapy varies depending on the payer and the plan and is frequently denied.

From the payer perspective, vitiligo is acknowledged as a disease and assessed in a way similar to other diseases, with a focus on the standard of care, Epstein said. Coverage for the management of vitiligo is based on the opinions from experts and key opinion leaders. The main concern of payers at this moment is the potential manipulation of information from the manufacturer side. Dunn concurred with the idea that payers view vitiligo as a disease and not merely a cosmetic problem. Part of the problem, in his view, is that right now most of the therapies used to treat vitiligo are relatively inexpensive, as there are a lot of generic medications available; however, as more expensive options become available, there will be a need to work with providers to determine the best use for these medications. Together, they must determine who are the appropriate patients for the new medications and how to assess whether the new medications are working. Both agreed that there will probably be a need to use payer tools to control costs, such as initial authorization followed by reauthorization after a period, with physician attestation as to progress.

King agreed that it is important to have documentation that patients are getting better with treatment. This is also important from the physician and patient point of view, as neither would normally want to continue a treatment that is not working. He further said that payers and formulary managers will need to be thoughtful about which patients are likely to get better and which are not, and to develop decision trees around those parameters. A key question will be the appropriate amount of time to determine whether a patient is having a meaningful clinical response to treatment; that is, what percentage of skin repigmentation in a set period would be the cutoff for continuing treatment.

Emerging Therapies and Unmet Needs in Vitiligo

There are various agents being tested for the treatment of patients with vitiligo, including calcineurin inhibitors, MC1R agonists, antioxidants, metabolism inhibitors, cytokine inhibitors, and kinase inhibitors.27 The most promising new therapies are the Janus kinase (JAK) inhibitors tofacitinib and ruxolitinib.

Tofacitinib

Oral tofacitinib, a JAK 1/3 inhibitor, demonstrated promising repigmentation results in case studies and a retrospective observational study. The addition of NBUVB therapy seems to improve its efficacy. It is well tolerated in most patients, and adverse events include respiratory tract infections, diarrhea, arthralgia, weight gain, and mild lipid and liver enzyme elevation. In rare cases it can lead to malignancies.2

Ruxolitinib

Ruxolitinib is a JAK 1/2 inhibitor that has been tested in 2 phase 2 clinical trials (NCT02809976 and NCT03099304) and is being evaluated in 3 phase 3 trials (NCT04052425, NCT04057573, and NCT04530344).28 The phase 2 trials’ results showed that ruxolitinib may be a good option for vitiligo management as patients had substantial repigmentation and good dose tolerance.28 Furthermore, results from the phase 3 trials presented at the 2022 American Academy of Dermatology Annual Meeting showed that approximately half the patients treated with ruxolitinib cream achieved at least 75% improvement in the facial lesions at 52 weeks, leading to FDA approval of ruxolitinib cream (Opzelura) in July 2022.29,30

Stakeholder Insights

Dunn explained that, in a setting where there are various options that work, from the payers’ perspective there is a fiduciary responsibility to encourage the use of the most cost-effective therapy first. Therefore, there may be a need for payers to influence the first therapy choice without overstepping their bounds in determining whether a drug works. On the other hand, King said the fact that vitiligo is an autoimmune disease that responds to JAK inhibitors, as do other autoimmune diseases, may also be a factor in the decision algorithm; using the more expensive treatment might lead to less expenditure over the lifetime of the patient. Epstein stressed that payers would be looking at specialists, key opinion leaders, and specialty societies to make these determinations and indicate when these drugs would best be used in the front line. There will need to be collaboration between specialists to determine the best treatment for each patient and minimize burden, King said. On the other hand, Epstein noted that the safety profiles of some of the new agents will also have to be considered.

In terms of managing costs, payers used to focus on disease states. However, that focus has switched dramatically to the drugs, Epstein explained. So, for JAK inhibitors, the focus of payers will not be on the use of this agent in vitiligo but on how to manage the use of JAK inhibitors more broadly. This change is putting pressure on insurance purchasers, which eventually gets passed down to patients through deductibles, coinsurance, and premiums. This is a challenge because patient affordability is likely to become an issue, Dunn said.

Rosmarin and King suggested that the fact that none of these therapies are specifically approved for the treatment of vitiligo is influencing their coverage and that approval of a new agent would change this scenario because they would be significantly less expensive than the new agent. Dunn suggested that a step approach, where patients must try a generic medication before getting approval for a biologic agent, may be a solution. However, Rosmarin cautioned that although a step approach may be reasonable for treatment of facial lesions, which respond well to calcineurin inhibitors, it would not be advisable for other areas such as the hands, which are notoriously challenging to treat. Therefore, the newer agents might be more adequate as first-line therapies for the extremities, genitals, and trunk.

Considering this, it is possible that payers may restrict coverage for the treatment of sensitive areas such as the head, neck, and hands, Epstein said. King agreed that this might make sense; however, he cautioned that these decisions should be driven by data. Physicians will always advocate for the patient to get the treatment, because having vitiligo in any part of the body can be debilitating. However, if the data say a certain treatment works well in one location but not so well in another, then it is reasonable that it should be covered for the locations where it works. Physicians would then have to make the argument if they want to use it for the location where it does not typically work as well.

On the other hand, this approach may be challenging to implement with the introduction of new agents such as ruxolitinib. Ruxolitinib has shown a significant effect in all areas of the body, with a greater effect on the face. This is not surprising, as all therapies work better on the face. If payers cover ruxolitinib treatment only for facial lesions, because that is where it is more effective, then patients would lose access to the best medication available for repigmentation of other areas, Rosmarin explained. However, he agrees that starting with a generic medication before introducing a JAK inhibitor may be the way forward, with the key being that these requirements are data driven.

The greatest unmet need for patients was the lack of an FDA-approved treatment for vitiligo, Rosmarin said. Vitiligo is a difficult disease to treat. Whereas all it takes for the disease to develop is an overactive immune system that destroys the melanocytes, treatment is a 2-step process. The immune system must be regulated so that there is a more hospitable environment for the melanocytes, which then must be coaxed to migrate back to the lesions. Treatment can often facilitate both processes.

JAK inhibitors, especially ruxolitinib, have shown the greatest promise for patients with vitiligo, Rosmarin said. Results from 2 phase 3 trials have shown that after 1 year of treatment with ruxolitinib cream, patients regain 75% or more of pigmentation on the face and 50% or more on the whole body. Furthermore, its safety profile is also promising, and it was approved for the treatment of atopic dermatitis in September 2021. The choice of JAK inhibitors for vitiligo was deliberate, King explained. JAK inhibitors disrupt the signaling pathway that induces the T cells to attack and destroy the melanocytes. Therefore, there are ample data to support the use of JAK inhibitors in vitiligo.

King mentioned the concept behind the REVEAL trial (NCT04338581) that is testing an antibody of IL-15, which is necessary for the survival of TRMs. Targeting IL-15 would dampen or even abolish the survival signal, which could lead to a durable disease remission without ongoing treatment. Although this provocative concept is not ready to be used in practice, it could revolutionize the field if it is safe and effective. Rosmarin added that depending on what the data show, there is a possibility that a combination of therapies including the IL-15 antibody at the end might be the best option for some patients.

In the next 5 years, it is expected that there will be several new agents approved for vitiligo, which will change how the disease is managed and will have implications for all stakeholders. This has already started with the approval of ruxolitinib cream and will probably be followed by oral JAK inhibitors and then other novel agents. Rosmarin concluded by saying, “There is going to be some work to do to decide how these different treatments fit into the paradigm, and we just don’t know that yet, but it’s important to be data driven and follow that pathway so we can make those best decisions for patients.”

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