JAK Inhibition, Durable Repigmentation Strategies Among Vitiligo Advances

Vitiligo has entered a new era of treatment innovation, according to Seemal Desai, MD, FAAD, who presented “Vitiligo Spotlight: A Closer Look at JAK Inhibitors” at the 2025 Fall Clinical Dermatology Conference.

Dr. Desai characterized the current moment as a “Renaissance period” in vitiligo management, driven by mechanistic insights into interferon-gamma pathways and expanding clinical data on topical and oral JAK inhibitors. He offered a strategic overview of vitiligo management tiers, clinical pearls on topical application, and emerging evidence from long-term extension trials. He also underscored the ongoing challenges patients face in obtaining access to evidence-based therapies.

Dr. Desai opened his remarks with a call for consistent nomenclature: “Vitiligo is a disease. It is a chronic, autoimmune, CD8+ T-cell and interferon-gamma–driven inflammatory disease—not a cosmetic condition.” This distinction is critical, especially as some insurers have recently denied coverage for vitiligo therapies on cosmetic grounds, including phototherapy and topical ruxolitinib. Such reclassification is both scientifically inaccurate and detrimental to patient care, Dr. Desai said, emphasizing the need for the dermatology community to reinforce the inflammatory and autoimmune nature of vitiligo.

Dr. Desai presented a structured treatment approach that categorizes patients by disease extent and refractoriness:

• Localized/limited disease: Single patch or <10% BSA
• Moderate disease: Wider surface area, some BSA reduction
• Recalcitrant disease: Slow or no response despite appropriate treatment
• Recalcitrant severe disease: Rapid progression due to unregulated inflammation

He shared that approximately 9% to 10% of patients in his tertiary referral center fall into the most severe category, often with ongoing CD8+ T-cell activity that is difficult to suppress.

TOPICAL JAK INHIBITION

Dr. Desai highlighted ruxolitinib 1.5% cream as his first-line topical therapy for patients 12 and older, citing its mechanism of action in blocking JAK1/2-mediated interferon-gamma signaling. Twice-daily application is essential, he said, as once-daily dosing does not reflect studied efficacy. Application should be limited to ≤10% BSA to remain within approved labeling and manage cost, and it should be focused on the most psychologically or cosmetically impactful lesions (eg, face, hands, genitalia). Nonresponders should continue therapy beyond 6 months if tolerated, as repigmentation may occur as late as 18 to 24 months. Dr. Desai emphasized that even in patients with confetti-like or trichrome lesions, indicative of disease instability, ruxolitinib can yield pigmentation gains.

For patients unable to access branded topical ruxolitinib, Dr. Desai said he sometimes prescribes compounded 2% tofacitinib. However, he stressed that it provides less effective inhibition of the JAK1/2 pathway. Still, new 104-week data show that ruxolitinib continues to drive repigmentation even in late starters or early nonresponders. Facial Vitiligo Area and Severity Index (VASI) 75 and VASI 90 scores improve gradually over time, reinforcing the need for sustained treatment and patient counseling.

“Vitiligo responds more slowly than atopic dermatitis,” he said. “Patients need encouragement; this is a marathon, not a sprint.”

ORAL JAK INHIBITORS IN THE PIPELINE

Dr. Desai also provided an overview of investigational oral JAK inhibitors for vitiligo. One JAK1/2 inhibitor has completed phase 3 trials and is under review for approval for vitiligo (as well as for hidradenitis suppurativa. Early trials of JAK1-selective and JAK3/TEC-selective agents have shown promising facial repigmentation rates.

Several other candidates are in phase 3 development, with more targeted inhibition strategies emerging.

Dr. Desai closed by reiterating that patients with vitiligo deserve treatment access, empathy, and long-term support.

“There is research on the horizon,” he said. “And our responsibility is to keep advocating for these patients every step of the way.”