Topical vs Oral JAK Inhibitors in Vitiligo, With Iltefat Hamzavi, MD

Janus kinase (JAK) inhibitors have reshaped the treatment of vitiligo, with topical and oral agents now filling distinct roles, according to Iltefat Hamzavi, MD, of Henry Ford Health.

During an interview with HCPLive during the 2026 Fall Clinical Dermatology Conference in Las Vegas, Hamzavi spoke about key takeaways from his session, “Seminar-In-Depth: Is This the JAK We’re Looking For? The Evolving Role of JAK Inhibitors in Vitiligo.”

Where Do JAK Inhibitors Fit in Vitiligo Treatment?

Hamzavi explained topical JAK inhibitors, led by US Food and Drug Administration (FDA)-approved ruxolitinib cream, have become the preferred agent largely because of their strong safety profile. Before their approval, clinicians relied on off-label topical calcineurin inhibitors and steroids without long-term safety data, a significant gap given vitiligo often requires years of treatment. Long-term trials, data on combining topical JAK inhibitors with phototherapy, and exposure in hundreds of thousands of patients have since clarified what to expect and how to manage adverse effects.

Oral JAK inhibitors, including upadacitinib, ritlecitinib, and povorcitinib, have completed large phase 3 trials involving nearly 3000 patients, with few systemic adverse effects observed, Hamzavi said. He advised caution in patients with active cardiovascular risk, high body mass index, smoking history, a strong family history of cardiovascular disease, or very high cholesterol. For most patients, particularly younger individuals, he said oral agents may stabilize vitiligo more effectively than prior options for rapidly progressive disease, such as oral steroids or methotrexate.

Which Patients Are Candidates for Oral vs Topical JAK Therapy?

According to Hamzavi, topical ruxolitinib suits localized disease affecting less than 10% of body surface area without markers of instability. Clinicians should look for 3 physical findings signaling unstable, progressive disease: trichrome lesions, confetti-like depigmentation, and koebnerization.

Once disease exceeds 10% of body surface area, the volume of cream required raises the risk of adverse effects, making oral therapy the better choice, he said. Oral agents are also favored for unstable disease. Because melanocytes turn over slowly and repigmentation can take a year, Hamzavi emphasized preventing further depigmentation and its psychosocial impact.

Editor’s note: This summary has been edited for grammar and clarity using artificial intelligence tools. Hamzavi has disclosed serving as a consultant for AbbVie, Pfizer, Incyte, UCB, Boehringer Ingelheim, Sonoma, Merck, Takeda,Teva, Novartis, Jansen, Avita, Galderma, Vimela, and Almirall; an investigator for Pfizer, Incyte, Avita, L'Oréal/La Roche-Posay, ITN, and AbbVie; and a board member and past president of the Hidradenitis Suppurativa and Global Vitiligo foundations.

References

1. Hamzavi I. Seminar-in-depth: is this the JAK we’re looking for? The evolving role of JAK inhibitors in vitiligo. Presented at: 2026 Fall Clinical Dermatology Conference; October 8-11, 2026; Las Vegas, NV.

2. 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(16):1445-1455. doi:10.1056/NEJMoa2118828

3. HCPLive. Ritlecitinib improves repigmentation in nonsegmental vitiligo phase 3 data. https://www.hcplive.com/view/ritlecitinib-improves-repigmentation-nonsegmental-vitiligo-phase-3-data. Published July 30, 2026. Accessed October 9, 2026.