Treatment of vitiligo with the topical Janus kinase inhibitor ruxolitinib: A 32-week open-label extension study with optional narrow-band ultraviolet B

To the Editor: Janus kinase inhibitors have shown promise in the treatment of vitiligo.1Craiglow B.G. King B.A. Tofacitinib citrate for the treatment of vitiligo: a pathogenesis-directed therapy.JAMA Dermatol. 2015; 151: 1110-1112Crossref PubMed Scopus (164) Google Scholar, 2Harris J.E. Rashighi M. Nguyen N. et al.Rapid skin repigmentation on oral ruxolitinib in a patient with coexistent vitiligo and alopecia areata (AA).J Am Acad Dermatol. 2016; 74: 370-371Abstract Full Text Full Text PDF PubMed Scopus (135) Google Scholar, 3Rothstein B. Joshipura D. Saraiya A. et al.Treatment of vitiligo with the topical Janus kinase inhibitor ruxolitinib.J Am Acad Dermatol. 2017; 76: 1054-1060.e1Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar In our original trial of topical ruxolitinib cream, the response was predominantly seen in facial vitiligo.3Rothstein B. Joshipura D. Saraiya A. et al.Treatment of vitiligo with the topical Janus kinase inhibitor ruxolitinib.J Am Acad Dermatol. 2017; 76: 1054-1060.e1Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar We carried out a 32-week extension with an objective to determine if continued use of topical ruxolitinib would cause repigmentation in locations that previously did not respond. The primary end-point was an improvement in Vitiligo Area Scoring Index (VASI) at 52 weeks. The study was approved by the Tufts institutional review board and was conducted with the same methodology as the original trial.3Rothstein B. Joshipura D. Saraiya A. et al.Treatment of vitiligo with the topical Janus kinase inhibitor ruxolitinib.J Am Acad Dermatol. 2017; 76: 1054-1060.e1Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar Patients continued to be treated with twice-daily application of topical ruxolitinib 1.5% cream on areas predetermined at baseline. Application of the cream was limited to 10% of the body surface area or 3.75 g/application. On the basis of previous evidence for synergism of Janus kinase inhibitors and ultraviolet light,4Joshipura D. Plotnikova N. Goldminz A. et al.Importance of light in the treatment of vitiligo with JAK-inhibitors.J Dermatolog Treat. 2018; 29: 98-99Crossref PubMed Scopus (20) Google Scholar, 5Liu L.Y. Strassner J.P. Refat M.A. Harris J.E. King B.A. Repigmentation in vitiligo using the Janus kinase inhibitor tofacitinib may require concomitant light exposure.J Am Acad Dermatol. 2017; 77: 675-682.e1Abstract Full Text Full Text PDF PubMed Scopus (107) Google Scholar concomitant narrow band ultraviolet B (NB-UVB) treatment was permitted. Eight of 9 patients continued in the extension study. Five patients completed the trial, while 3 dropped out due to lack of response. Three patients opted for optional NB-UVB (Supplemental Table I; available at http://www.jaad.org). A statistically significant mean improvement in overall VASI of 37.6% ± 31.2% (P = .011) was observed for enrolled patients (n = 8) at week 52 from baseline (Fig 1). Five of 8 patients had a treatment response. In patients with >0.5% facial surface area affected (n = 4), a statistically significant mean improvement of 92% ± 7.1%, (P = .0001) in facial VASI was seen at week 52, with 1 patient being completely repigmented. Three of 6 patients had a response on their nonacral upper extremities, with a VASI improvement of 12.6% ± 19.5%; 2 of these 3 had been treated with combination phototherapy. Slight acral repigmentation was seen in a patient at week 38. Two of 3 patients (both of whom had opted for combination phototherapy) responded on the trunk with a mean VASI improvement of 16.7% ± 16.7%. These 2 patients had failed prior phototherapy and topical ruxolitinib monotherapy on truncal lesions (Fig 2). Two patients developed new lesions on areas not being treated, while none of the treated areas got worse. A mean improvement of 16.7% ± 35.6% was seen in Physician Global Vitiligo Assessment, a mean improvement of 1.5 was seen in Dermatology Life Quality Index, and the change in body surface area was 20.78% ± 35.35% at week 52; however, none of these data were statistically significant. Five patients who completed the trial were followed up at 6 months after treatment discontinuation, and all of them maintained response, with maximum duration of >40 weeks. Interestingly, relapse has been seen in a patient after the use of oral ruxolitinib.2Harris J.E. Rashighi M. Nguyen N. et al.Rapid skin repigmentation on oral ruxolitinib in a patient with coexistent vitiligo and alopecia areata (AA).J Am Acad Dermatol. 2016; 74: 370-371Abstract Full Text Full Text PDF PubMed Scopus (135) Google Scholar Minor adverse events, including erythema in 3 of 8 patients and transient acne in 2 patients, were observed. Limitations include open-label design, a small sample size, and inability to monitor natural sun exposure. A limited response was seen after an additional 32 weeks, but improvement was seen with NB-UVB and topical ruxolitinib combination. In conclusion, patients with vitiligo who used topical ruxolitinib 1.5% cream twice daily with optional NB-UVB saw a statistically significant mean improvement in overall VASI score at week 52, and this effect was most pronounced for those treating facial vitiligo. Supplemental Table IBaseline patient demographic and clinical characteristics in the extension phase, including details about NB-UVB in selected patients (n = 8)CharacteristicValueSex, N (%) Male4 (50) Female4 (50)Age, y, mean (range)50 (33-62)Patients opting for combination phototherapy, N (%)3 (37.5)Patients with vitiligo affecting >0.5% BSA of face, N (%)4 (36.4)Acral vitiligo, N (%)6 (75)Patients with acral vitiligo opting for combination phototherapy, N (%)3 (50)Patients with vitiligo on nonacral extremities, N (%)6 (75)Patients with vitiligo on nonacral extremities opting for combination phototherapy, N (%)3 (50)Patients with truncal vitiligo, N (%)3 (37.5)Patients with truncal vitiligo opting for combination phototherapy, N (%)2 (66.6)NB-UVB protocol: patient 001 FrequencyTwice weekly Starting doseUnknown Maximum dose reached2000 mJ/cm2, genitalia shielded Total phototherapy sessions56 sessions over 31 weeksNB-UVB protocol: patient 002 FrequencyTwice weekly Starting dose100 mJ/cm2 Maximum dose reached4227 mJ/cm2, genitalia and face shielded Total phototherapy sessions61 sessions over 26 weeksNB-UVB protocol: patient 006 FrequencyThrice weekly Starting dose200 mJ/cm2 Maximum dose reached1489 mJ/cm2, genitalia shielded Total phototherapy sessions34 sessions over 14 weeksBSA, Body surface area; NB-UVB, narrow band ultraviolet B. Open table in a new tab BSA, Body surface area; NB-UVB, narrow band ultraviolet B.