Ruxolitinib: The first and only US FDA–approved topical repigmentation treatment for vitiligo

Vitiligo, a chronic autoimmune condition characterized by skin depigmentation, significantly impacts patients’ quality of life (QoL) and psychosocial well-being. At a symposium held during the Advances in Medicine (AIM) 2025 conference, Dr Chau-Yee Ng of the Vitiligo Clinic and Pigment Research Center, Chang Gung Memorial Hospital, Taipei, Taiwan, shared latest advances in vitiligo research, highlighting US FDA’s approval of ruxolitinib cream (Lumirix^®, Rxilient Medical), the first topical Janus kinase (JAK) inhibitor designed to target repigmentation in vitiligo.

A challenging disease
Vitiligo is an autoimmune disorder affecting approximately 1–2 percent of the global population. The typi­cal white patches caused by loss of skin pigmentation can lead to sig­nificant emotional distress. [Cureus 2023;15:e45030]

Vitiligo is often associated with other autoimmune conditions, com­monly Hashimoto’s thyroiditis, with a higher risk in individuals with larger affected body surface area (BSA) and longer disease duration. [Br J Derma­tol 2013;168:756-761]

“The condition is characterized by subtle disease activity and a pro­longed, unpredictable clinical course,” noted Ng. “Recovery with treatment can be prolonged. Thus, photograph­ic documentation with polarized and wood’s light source is crucial for monitoring treatment effectiveness, tracking disease activity and potential repigmentation.”

Pathogenesis of vitiligo
The development of vitiligo is linked to a combination of genetic predispo­sition and environmental triggers, such as skin friction and trauma, chemical exposure, ultraviolet (UV) irradiation, and infections. Damage to melano­cytes due to oxidative stress triggers an autoimmune response. This leads to destruction of melanocytes by CD8+ T-cells, which causes depigmentation and appearance of white patches. Interferon (IFN)-γ released in the pro­cess further attracts more autoreactive T-cells, exacerbating the condition. In addition, interleukin (IL)-15 is an im­portant cytokine that sustains resident memory T-cells, which contribute to progression and maintenance of vitiligo. [Dermatol Sin 2023;41:133-144; Annu Rev Immunol 2020;38:621-648]

“IFN-γ plays a critical role in the pathogenesis of vitiligo, and it signals through the JAK1/JAK2/STAT path­way,” explained Ng. “In addition to recruitment of autoreactive T-cells, IFN-γ also exerts direct cytotoxic ef­fects on melanocytes. Hence, it is an important therapeutic target for vit­iligo treatment. JAK inhibitors have emerged as a unique class of drugs as they target both IFN-γ and IL- 15.” [Dermatol Sin 2023;41:133-144; Annu Rev Immunol 2020;38:621-648]

Ruxolitinib: A significant breakthrough in vitiligo treatment
Ruxolitinib, a topical inhibitor of JAK 1 and 2, is indicated for treatment of nonsegmental vitiligo with facial involve­ment in patients ≥12 years of age. It is the first and only US FDA—approved treatment for skin repigmentation in vitiligo. [Lumirix Hong Kong Prescrib­ing Information; https://www.fda.gov/ drugs/news-events-human-drugs/ fda-approves-topical-treatment-ad­dressing-repigmentation-vitiligo-pa­tients-aged-12-and-older] Of note, monobenzone, the other US FDA– approved topical treatment for vitili­go, permanently depigments normal skin surrounding vitiliginous lesions. [https:/www.accessdata.fda.gov\/drugsatfda_docs/label/2003/08173slr015_benoquin_lbl.pdf]

In a randomized, double-blind, phase II study, ruxolitinib monotherapy demonstrated effective and sustained repigmentation in adults (n=157) with vitiligo. A significantly higher propor­tion of patients who applied 1.5 per­cent ruxolitinib cream QD or BID had a ≥50 percent improvement from base­line in facial Vitiligo Area Scoring Index (F-VASI) score at week 24 vs vehicle (QD: 50 vs 3 percent; odds ratio [OR], 28.5; 95 percent confidence interval [CI], 3.7–1,305.2; p<0.0001) (BID: 45 vs 3 percent; OR, 24.7; 95 percent CI, 3.3–1,121.4; p=0.0001). Contin­uous improvement was seen through 52 weeks of therapy. (Figure) [Lancet 2020;396:110-120]

Two phase III, randomized con­trolled trials of ruxolitinib cream (TRuE-V1 [n=330] and TRuE-V2 [n=334]) in patients ≥12 years of age with nonsegmental vitiligo confirmed the results of the phase II study. In TRuE-V1, a significantly higher pro­portion of patients in the ruxolitinib monotherapy vs vehicle cream group achieved ≥75 percent improvement from baseline in F-VASI at week 24 (29.8 vs 7.4 percent; relative risk [RR], 4.0; 95 percent CI, 1.9–8.4; p<0.001) vs the vehicle cream group. Similar findings were reported in TRuE-V2 (30.9 vs 11.4 percent; RR, 2.7; 95 per­cent CI, 1.5–4.9; p<0.001). (Table) [N Engl J Med 2022;387:1445-1455]

Ruxolitinib cream was well tolerat­ed, and application site reactions were mild or moderate, with acne and pru­ritus at the application site being the most common adverse events. [N Engl J Med 2022;387:1445-1455]

“I have personally witnessed such impressive results in my practice,” said Ng. (Case report)

“Epidermal concentration of rux­olitinib after topical application is considerably higher [approximately 2,000-fold] than after oral adminis­tration, while plasma concentration remains much lower [approximately one-thirtieth]. This localized deliv­ery provides targeted treatment of skin with a reduced risk of systemic side effects,” added Ng. [Int J Pharm 2020;590:119889]

Treatment recommendations
Depending on the subtype (segmen­tal vs nonsegmental), disease activity, and extent of melanocyte destruction, various topical and systemic treatments, pho­totherapy, and surgical interventions are used to halt disease progression and facil­itate repigmentation in patients with vitiligo.