Vitiligo is an acquired depigmentation of the skin, which affects approximately 1% of the population worldwide. The condition can profoundly affect the wellbeing and the social, sexual, and professional lives of affected individuals and thus induces a strong therapeutic demand. 1 Ezzedine K Eleftheriadou V Whitton M van Geel N Vitiligo. Lancet. 2015; 386: 74-84 Summary Full Text Full Text PDF PubMed Scopus (440) Google Scholar Actual treatments rely on the use of topical steroids or topical calcineurin inhibitors, and are better combined with sun exposure or phototherapy. 1 Ezzedine K Eleftheriadou V Whitton M van Geel N Vitiligo. Lancet. 2015; 386: 74-84 Summary Full Text Full Text PDF PubMed Scopus (440) Google Scholar , 2 Passeron T Medical and maintenance treatments for vitiligo. Dermatol Clin. 2017; 35: 163-170 Summary Full Text Full Text PDF PubMed Scopus (30) Google Scholar The best results are achieved on the face, while some areas such as bony prominences and hands and feet show a very poor repigmentation rate. Although meta-analyses have confirmed the efficacy of these topical agents, primary studies have been done in relatively small populations and most of the treatments remain unapproved and thus used off-label. 3 Lee JH Kwon HS Jung HM et al. Treatment outcomes of topical calcineurin inhibitor therapy for patients with vitiligo: a systematic review and meta-analysis. JAMA Dermatol. 2019; (published online May 29.)https://doi.org/10.1001/jamadermatol.2019.0696 Crossref Scopus (33) Google Scholar Over the past decade substantial progress has been made in the understanding of vitiligo pathogenesis and the key role of the interferon γ pathway in the immune destruction of melanocytes. 4 Rashighi M Agarwal P Richmond JM et al. CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo. Sci Transl Med. 2014; 6223ra23 Crossref PubMed Scopus (268) Google Scholar Targeting this pathway using Janus kinase (JAK) inhibitors appears to be an appealing approach, and case reports and open-label studies have suggested the potential interest of topical or systemic use of JAK inhibitors for treating vitiligo. 5 Liu LY Strassner JP Refat MA Harris JE Kings BA Repigmentation in vitiligo using the Janus kinase inhibitor tofacitinib may require concomitant light exposure. J Am Acad Dermatol. 2017; 77: 675-682 Summary Full Text Full Text PDF PubMed Scopus (100) Google Scholar , 6 Kim SR Heaton H Liu LY King BA Rapid repigmentation of vitiligo using tofacitinib plus low-dose, narrowband UV-B phototherapy. JAMA Dermatol. 2018; 154: 370-371 Crossref PubMed Scopus (28) Google Scholar In The Lancet, David Rosmarin and colleagues 7 Rosmarin D Pandya AG Lebwohl M et al. Ruxolitinib cream for treatment of vitiligo: a randomised, controlled, phase 2 trial. Lancet. 2020; 396: 110-120 Summary Full Text Full Text PDF PubMed Scopus (75) Google Scholar report the largest, to my knowledge, prospective randomised trial done for vitiligo. 157 patients (mean age 48·3 years [SD 12·9]; 73 [46%] men and 84 [54%] women) were randomised, and after 24 weeks of treatment, those receiving ruxolitinib cream at 1·5% twice a day and 1·5% once daily showed a significantly higher rate of repigmentation than did patients in the placebo group. This was measured by a 50% or higher improvement from baseline in the facial Vitiligo Area Scoring Index, which was reached by 15 (45%) of 33 patients (odds ratio [OR] 24·7, 95% CI 3·3–1121·4; p=0·0001) in the 1·5% twice daily group, and 15 (50%) of 30 patients (OR 28·5, 95% CI 3·7–1305·2; p<0·0001) in the 1·5% once daily group, compared with vehicle (one [3%] of 32 patients). Repigmentation continued to increase right up to the end of the study period up to 52 weeks. Not surprisingly, the face was the most responsive area, with a third of all patients obtaining a repigmentation rate higher than 90% on this area. Although a third of patients could appear relatively low, we must take into consideration that the topical ruxolitinib was used as a monotherapy when we know that optimal repigmentation needs concomitant sun exposure or phototherapy. 2 Passeron T Medical and maintenance treatments for vitiligo. Dermatol Clin. 2017; 35: 163-170 Summary Full Text Full Text PDF PubMed Scopus (30) Google Scholar , 3 Lee JH Kwon HS Jung HM et al. Treatment outcomes of topical calcineurin inhibitor therapy for patients with vitiligo: a systematic review and meta-analysis. JAMA Dermatol. 2019; (published online May 29.)https://doi.org/10.1001/jamadermatol.2019.0696 Crossref Scopus (33) Google Scholar Further studies should answer crucial questions which remain, such as what is the rate of response in relation to the duration of the disease and the combined effects with phototherapy. Comparative trials against topical steroids and topical calcineurin inhibitors would also be of great value to help clinicians position topical ruxolitinib against the available therapeutic options. The overall tolerance of topical ruxolitinib appears good, even at the highest concentration of 1·5% twice a day. Acne appears to be the side-effect that will need close follow-up in phase 3 studies. It has a clear dose effect, with almost 20% prevalence at the highest concentration of 1·5% twice a day. However, all the cases reported in Rosmarin and colleagues' study were mild. Nevertheless, as topical ruxolitinib shows promising results for treating the face, such a side-effect might be a potential limitation for the use of this cream. With the high psychological burden of vitiligo, the effect on the quality of life of treated patients will be a key marker in the ongoing phase 3 studies. Ruxolitinib cream for treatment of vitiligo: a randomised, controlled, phase 2 trialTreatment with ruxolitinib cream was associated with substantial repigmentation of vitiligo lesions up to 52 weeks of treatment, and all doses were well tolerated. These data suggest that ruxolitinib cream might be an effective treatment option for patients with vitiligo. Full-Text PDF