Managing vitiligo has been a challenging journey. There have been limited options available for dermatologists to offer to help treat the chronic, inflammatory, autoimmune skin condition affecting approximately 2-3 million people1, including more than 1.5 million diagnosed, in the United States2. Vitiligo involves more than simply cosmetic issues, reinforcing the need for further research and management options for these patients and the dermatologists who care for them.
Progress in Research Around Vitiligo Management
In recent years, researchers have made important progress in understanding the underlying pathology of vitiligo. Based on preclinical data, the JAK/STAT pathway has been shown to mediate the production of IFNγ. IFNγ producing cytotoxic T lymphocytes have been shown to mediate melanocyte destruction in human vitiligo3. The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known.
As JAK inhibition is linked to reduced skin inflammation and T-cell-mediated melanocyte destruction, a logical approach is to diminish local inflammation and facilitate endogenous repigmentation in patients with vitiligo. Proof of concept of JAK inhibition was demonstrated in small studies4, leading to Phase 3 trials and the recent U.S. Food and Drug Administration (FDA) approval of the first topical JAK inhibitor for the topical treatment of nonsegmental vitiligo in patients 12 years of age and older.
“For patients who want to be repigmented, we had limited options to help,” explains David Rosmarin, M.D., Vice Chair of Research and Education, Department of Dermatology at Tufts Medical Center. “With the first approved pharmacologic treatment for nonsegmental vitiligo repigmentation now available, we now have a new option to offer our patients to help them manage their condition should they choose to treat their disease.”
Opzelura: The First and Only Topical JAK Inhibitor
In July 2022, the FDA approved Opzelura™ (ruxolitinib) cream 1.5% for the topical treatment of nonsegmental vitiligo in adult and pediatric patients 12 years of age and older. A nonsteroidal JAK inhibitor, Opzelura is applied topically on up to 10% body surface area (BSA) twice daily5.
The TRuE-V clinical trial program enrolled adults and adolescents 12 years of age and older with nonsegmental vitiligo affecting at least 0.5% facial BSA and 3% nonfacial BSA. Results from the Phase 3 TRuE-V clinical trial program demonstrated that the proportion of subjects achieving a 75% improvement in the facial Vitiligo Area Scoring Index (F-VASI75) was significantly greater at Week 24 (primary analysis) compared to vehicle, with further improvement in an open-label extension at Week 52.
- In the randomized Phase 3 TRuE-V1 and TRuE-V2 studies, the primary endpoint of F-VASI75 (the proportion of patients achieving a 75% improvement in the facial Vitiligo Area Scoring Index) at Week 24 was attained by significantly more patients who applied Opzelura versus vehicle in TRuE-V1/TRuE-V2, respectively (approximately 30% vs. approximately 8%/13%, P<0.0001)6. At Week 52, approximately 50% of Opzelura-treated patients achieved a 75% improvement in F-VASI75.
- Additionally, at Week 24, more than 15% of patients treated with Opzelura achieved ≥90% improvement from baseline in F-VASI (F-VASI90), compared to approximately 2% of patients treated with vehicle. At Week 52, the percentage of Opzelura-treated patients who achieved F-VASI90 doubled to approximately 30%.
In clinical trials, the most common adverse reactions (incidence ≥ 1%) are application site acne, application site pruritus, nasopharyngitis, headache, urinary tract infection, application site erythema, and pyrexia6. The labeling for Opzelura includes a Boxed Warning for serious infections, mortality, malignancy, major adverse cardiovascular events and thrombosis. See additional Important Safety Information below.
The Future of Vitiligo Management
While the management of vitiligo was often previously seen as cosmetic, new research and management approaches are increasingly focused on treating vitiligo as an immune-mediated disease.
“The approval of Opzelura for the treatment of nonsegmental vitiligo presents a new option and an opportunity to revisit discussions with appropriate patients who are seeking repigmentation,” adds Dr. Rosmarin. “By working closely with our patients to determine their treatment goals, we can help ensure those looking to treat their vitiligo are aware of what is now available.”
An individualized plan is important to help manage the disease, and novel approaches can offer new options to help some patients successfully achieve their desired goals.
Opzelura may work for some, but not all, patients. To learn more, visit www.Opzelurahcp.com.
OPZELURA is indicated for the topical treatment of nonsegmental vitiligo in adult and pediatric patients 12 years of age and older.
Limitations of Use: Use of OPZELURA in combination with therapeutic biologics, other JAK inhibitors, or potent immunosuppressants such as azathioprine or cyclosporine is not recommended.
IMPORTANT SAFETY INFORMATION
Patients treated with oral Janus kinase inhibitors for inflammatory conditions are at risk for developing serious infections that may lead to hospitalization or death. Reported infections include:
- Active tuberculosis, which may present with pulmonary or extrapulmonary disease.
- Invasive fungal infections, including cryptococcosis and pneumocystosis.
- Bacterial, viral, including herpes zoster, and other infections due to opportunistic pathogens.
Avoid use of OPZELURA in patients with an active, serious infection, including localized infections. If a serious infection develops, interrupt OPZELURA until the infection is controlled. Carefully consider the benefits and risks of treatment prior to initiating OPZELURA in patients with chronic or recurrent infection. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with OPZELURA.
Serious lower respiratory tract infections were reported in the clinical development program with topical ruxolitinib.
No cases of active tuberculosis (TB) were reported in clinical trials with OPZELURA. Cases of active TB were reported in clinical trials of oral Janus kinase inhibitors used to treat inflammatory conditions. Consider evaluating patients for latent and active TB infection prior to administration of OPZELURA. During OPZELURA use, monitor patients for the development of signs and symptoms of TB.
Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster), were reported in clinical trials with Janus kinase inhibitors used to treat inflammatory conditions including OPZELURA. If a patient develops herpes zoster, consider interrupting OPZELURA treatment until the episode resolves.
Hepatitis B viral load (HBV-DNA titer) increases, with or without associated elevations in alanine aminotransferase and aspartate aminotransferase, have been reported in patients with chronic HBV infections taking oral ruxolitinib. OPZELURA initiation is not recommended in patients with active hepatitis B or hepatitis C.
In a large, randomized, postmarketing safety study in rheumatoid arthritis (RA) patients 50 years of age and older with at least one cardiovascular risk factor comparing an oral JAK inhibitor to tumor necrosis factor (TNF) blocker treatment, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed with the JAK inhibitor. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with OPZELURA.
Malignancies were reported in patients treated with OPZELURA. Lymphoma and other malignancies have been observed in patients receiving JAK inhibitors used to treat inflammatory conditions. In RA patients treated with an oral JAK inhibitor, a higher rate of malignancies (excluding non-melanoma skin cancer (NMSC)) was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk.
Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with OPZELURA, particularly in patients with a known malignancy (other than successfully treated non-melanoma skin cancers), patients who develop a malignancy when on treatment, and patients who are current or past smokers.
Non-melanoma skin cancers, including basal cell and squamous cell carcinoma, have occurred in patients treated with OPZELURA. Perform periodic skin examinations during OPZELURA treatment and following treatment as appropriate. Exposure to sunlight and UV light should be limited by wearing protective clothing and using broad-spectrum sunscreen.
MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE)
In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with an oral JAK inhibitor, a higher rate of major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke), was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk. Discontinue OPZELURA in patients who have experienced a myocardial infarction or stroke.
Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with OPZELURA, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur. Discontinue OPZELURA in patients that have experienced a myocardial infarction or stroke.
Thromboembolic events were observed in trials with OPZELURA. Thrombosis, including pulmonary embolism (PE), deep venous thrombosis (DVT), and arterial thrombosis have been reported in patients receiving JAK inhibitors used to treat inflammatory conditions. Many of these adverse reactions were serious and some resulted in death. In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with an oral JAK inhibitor, a higher rate of thrombosis was observed when compared with TNF blockers. Avoid OPZELURA in patients at risk. If symptoms of thrombosis occur, discontinue OPZELURA and treat appropriately.
Thrombocytopenia, Anemia, and Neutropenia
Thrombocytopenia, anemia, and neutropenia were reported in the clinical trials with OPZELURA. Consider the benefits and risks for individual patients who have a known history of these events prior to initiating therapy with OPZELURA. Perform CBC monitoring as clinically indicated. If signs and/or symptoms of clinically significant thrombocytopenia, anemia, and neutropenia occur, patients should discontinue OPZELURA.
Treatment with oral ruxolitinib has been associated with increases in lipid parameters including total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides.
In nonsegmental vitiligo, the most common adverse reactions (incidence ≥1%) are application site acne (6%), application site pruritus (5%), nasopharyngitis (4%), headache (4%), urinary tract infection (2%), application site erythema (2%), and pyrexia (1%).
There is a pregnancy registry that monitors pregnancy outcomes in pregnant persons exposed to OPZELURA during pregnancy. Pregnant persons exposed to OPZELURA and healthcare providers should report OPZELURA exposure by calling 1-855-463-3463.
Advise women not to breastfeed during treatment with OPZELURA and for approximately four weeks after the last dose (approximately 5-6 elimination half-lives).
Photo Credit: Armin Rimoldi