A Promising New Treatment for Vitiligo?

Graeme M. Lipper, MD


July 12, 2017

Vitiligo: A Treatment Challenge in Dermatology

Vitiligo is an autoimmune disease characterized by CD8(+) T lymphocyte–mediated destruction of melanocytes, resulting in patches of skin depigmentation. This chronic condition is notoriously difficult to treat and can cause significant cosmetic disfigurement with profound social and emotional consequences. Treatment with topical corticosteroids or calcineurin inhibitors, often combined with phototherapy, may yield partial repigmentation in patches of facial and truncal vitiligo, but acral sites are refractory to all available treatments.[1,2]

Janus kinase (JAK) inhibitors, such as ruxolitinib and tofacitinib, suppress cytotoxic T lymphocytes and have been studied for the treatment of rheumatoid arthritis, psoriasis vulgaris, and psoriatic arthritis. To date, tofacitinib has been approved for the treatment of rheumatoid arthritis. In a murine model, JAK inhibition reversed CD8(+) T lymphocyte–mediated alopecia areata,[3] an inflammatory skin disorder that shares a pathophysiology with vitiligo. Intriguingly, a patient with both alopecia areata and vitiligo showed rapid repigmentation after starting oral ruxolitinib,[4] and after 5 months of therapy, oral tofacitinib citrate yielded significant repigmentation of both facial and acral vitiligo.[5]

Oral JAK inhibitors carry potentially serious adverse reactions, including pancytopenia, malignancy, and infections. In contrast, these risks are not associated with topical JAK inhibitors, prompting interest in the development of topical formulations of tofacitinib and ruxolitinib to treat alopecia areata and vitiligo.

Could Topical Ruxolitinib Be Safe and Effective?

Encouraged by promising case reports, Rothstein and colleagues[6] recently designed a proof-of-concept study using twice-daily topical ruxolitinib 1.5% cream to treat vitiligo in a small group of patients (n = 12 screened patients, 11 patients enrolled; 54% male; mean age = 52 years). The primary outcome measure of the study was percent improvement in the Vitiligo Area Scoring Index (VASI) from baseline to week 20.

Nine patients completed the full 20-week treatment period, with the following results:

  • A 23% overall improvement in VASI score was seen in all enrolled patients at week 20, with the earliest signs of repigmentation seen at week 4.

  • VASI scores improved most dramatically for facial vitiligo (76% improvement in 4/4 patients with significant facial vitiligo).

  • 3/7 patients with nonacral upper extremity vitiligo showed improvement.

  • 1/8 patients with acral vitiligo showed improvement.

  • No patients showed truncal or lower extremity repigmentation.

Side effects were mild and included erythema, mild acneiform or papular eruptions, and transient perilesional hyperpigmentation. This latter finding seemed to predict a better repigmentation response. Because follow-up data were not available, the investigators couldn't comment about the durability of repigmentation in those who showed clinical improvement.

The Potential of JAK Inhibitors for Inflammatory Skin Conditions

In this small, noncontrolled pilot study, the JAK 1/2 inhibitor ruxolitinib showed some promise as a topical treatment for facial vitiligo. As Rothstein and colleagues note, theirs was only a proof-of-concept trial, lacking placebo control and clinical follow-up. Investigators could not control for such confounding variables as seasonal variations in sun exposure, and the small sample size lacked the statistical power required to tease out statistically significant responses in all but facial vitiligo. Nevertheless, JAK inhibitors have a plausible mechanism for improving vitiligo and other cytotoxic T-cell-mediated inflammatory skin diseases such as alopecia areata, and show some promise, both as stand-alone treatments and as part of a combination regimen.

The next step will be to conduct a randomized, placebo-controlled clinical trial with adequate statistical power to clarify the efficacy and safety of topical JAK inhibitors for the treatment of vitiligo. Such studies will need to control for sun exposure and take into consideration potential ethnic or gender-related differences in clinical response. Perhaps most important, future studies must include long-term clinical follow-up to determine how long JAK inhibitor–induced repigmentation lasts.


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