Ruxolitinib Cream (Opzelura)
By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
Ruxolitinib cream has gained a new indication for nonsegmental vitiligo. Vitiligo is an autoimmune skin disease mediated through the Janus kinase (JAK) signaling pathway, leading to the death of melanocytes. Ruxolitinib is a JAK1, JAK2 inhibitor that targets the JAK-signal transducer and activator of transcription (JAK-STAT) pathway. The FDA gave ruxolitinib cream a priority review. It is distributed as Opzelura.
Ruxolitinib cream can be prescribed to treat nonsegmental (bilateral) vitiligo in adult and pediatric patients age 12 years and older.1
Apply a thin layer twice daily to affected areas (up to 10% of body surface area).1 Ruxolitinib cream is available in 60 g tubes at 1.5% concentration.
Ruxolitinib cream is the first FDA-approved home treatment for vitiligo. Standard care has been topical corticosteroids or a topical calcineurin inhibitor (e.g., tacrolimus, pimecrolimus) off label for body surface involvement (≤ 10%). Another traditional solution is using phototherapy, including narrowband ultraviolet B (NBUVB) and psoralen ultraviolet A treatment (PUVA).2,3 Ruxolitinib cream provides topical administration of a JAK inhibitor, reducing the risks of potential serious adverse reactions associated with systemic administration (e.g., infections, cardiovascular risks, malignancies, and thrombosis).
The most common adverse reactions are application site reactions (acne, pruritus, erythema), along with nasopharyngitis, headache, urinary tract infection, and pyrexia.1
JAK inhibition targets interferon gamma-mediated melanocyte damage. The efficacy was demonstrated in two double-blind, 24-week, vehicle-controlled trials: Topical Ruxolitinib Evaluation in Vitiligo Study 1 and 2 (TRuE-V1 and TRuE-V2).1,4 The authors included subjects with mainly stable nonsegmental vitiligo on ≤ 10% of total body surface; mainly white (80.2%); and predominately Fitzpatrick skin types II, III, and IV. Researchers randomized subjects 2:1 to ruxolitinib cream (n = 221 in study 1 and n = 228 in study 2) or placebo (n = 109 and n = 115, respectively). About two-thirds of subjects had undergone some other therapy before participating in TRuE-V1 or V2 (about one-third of these participants had undergone topical calcineurin inhibitors, topical corticosteroids, or phototherapy). The primary endpoint was decrease of a least 75% from baseline in the facial Vitiligo Area Scoring Index (F-VASI75). A reduction of 90% (F-VASI90) was a secondary endpoint.
The authors reported VASI75 successes were 30% for ruxolitinib for both studies vs. 7.5% in study 1 and 12.9% in study 2 for placebo. F-VASI90 successes were 15.5% in study 1 and 15.4% in study 2 vs. 2.2% and 1.9%, respectively. After completion of week 24, all patients could apply ruxolitinib for an additional 28 weeks as an open-label treatment extension period. F-VASI75 successes were 52.6% in study 1 and 48% in study 2 for subjects who applied ruxolitinib for 52 weeks and 27% and 30%, respectively, for those who crossed over from placebo. The results of a subgroup analysis of a Phase II trial suggested younger patients (≤ age 50 years; 59% in study 1 vs. 31% in study 2) and a larger percent of women (60% in study 1 vs. 33.3% in study 2) responded (F-VASI50).5 Subjects’ head/neck regions also responded better to treatment (60%) than feet (29%) or hands (15%).
Vitiligo is a chronic autoimmune depigmentation disorder of the skin, with a prevalence between 0.5% and 2%.2 Nonsegmental vitiligo is the most common form of the disease. Standard therapy is phototherapy, with NBUVB emerging as first-line treatment (67% showing repigmentation after four months), and PUVA treatment (46% success).6 Topical corticosteroids and calcineurin inhibitors also are treatment options, with success ranging from 40% to 60% achieving > 75% facial repigmentation.2 Ruxolitinib is another therapeutic option.
There are no published comparative studies among these treatment options. Limited data suggest phototherapy may improve the effectiveness of JAK inhibitors.7 A clinical trial comparing ruxolitinib cream and NBUVB is in progress (NCT05247489). Initially, participants will apply ruxolitinib as monotherapy. At week 12, those who show only < 25% improvement in total body Vitiligo Area Scoring Index will undergo NBUVB phototherapy to go with their ruxolitinib cream regimen. NBUVB will be given three times per week for 36 weeks (week 12 through week 48).8 The estimated study completion is January 2024. The cost for ruxolitinib cream is $1,950 for 60 g.
1. Incyte. Opzelura prescribing information. September 2022.
2. Karagaiah P, Valle Y, Sigova J, et al. Emerging drugs for the treatment of vitiligo. Expert Opin Emerg Drugs 2020;25:7-24.
3. National Institute of Arthritis and Musculoskeletal and Skin Diseases. Vitiligo: Diagnosis, treatment, and steps to take. Last reviewed October 2022.
4. Rosmarin D, Passeron T, Pandya AG, et al. Two phase 3, randomized, controlled trials of ruxolitinib cream for vitiligo. N Engl J Med 2022;387:1445-1455.
5. Hamzavi I, Rosmarin D, Harris JE, et al. Efficacy of ruxolitinib cream in vitiligo by patient characteristics and affected body areas: Descriptive subgroup analyses from a phase 2, randomized, double-blind trial. J Am Acad Dermatol 2022;86:1398-1401.
6. Zubair R, Hamzavi IH. Phototherapy for vitiligo. Dermatol Clin 2020;38:55-62.
7. Phan K, Phan S, Shumack S, Gupta M. Repigmentation in vitiligo using Janus kinase (JAK) inhibitors with phototherapy: Systematic review and meta-analysis. J Dermatol Treat 2022;33:173-177.
Ruxolitinib cream can be prescribed to treat nonsegmental (bilateral) vitiligo in adult and pediatric patients age 12 years and older.
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