IMPORTANCE: Narrowband UV-B (NB-UV-B) phototherapy is used extensively to treat 
vitiligo. Afamelanotide, an analogue of α-melanocyte-stimulating hormone, is 
known to induce tanning of the skin.
OBJECTIVE: To evaluate the efficacy and safety of combination therapy for 
generalized vitiligo consisting of afamelanotide implant and NB-UV-B 
phototherapy.
DESIGN, SETTING, AND PARTICIPANTS: This study was performed in 2 academic 
outpatient dermatology centers and 1 private dermatology practice. We enrolled 
men and women 18 years or older with Fitzpatrick skin phototypes (SPTs) III to 
VI and a confirmed diagnosis of nonsegmental vitiligo that involved 15% to 50% 
of total body surface area. Vitiligo was stable or slowly progressive for 3 
months. Patients were randomized to combination therapy (n = 28) vs NB-UV-B 
monotherapy (n = 27). After 1 month of NB-UV-B phototherapy, 16 mg of 
afamelanotide was administered subcutaneously to the combination therapy group 
monthly for 4 months while NB-UV-B phototherapy continued; the other group 
continued to receive NB-UV-B monotherapy.
INTERVENTIONS: Narrowband UV-B monotherapy vs combined NB-UV-B phototherapy and 
afamelanotide.
MAIN OUTCOMES AND MEASURES: Response on the Vitiligo Area Scoring Index and 
Vitiligo European Task Force scoring system.
RESULTS: Response in the combination therapy group was superior to that in the 
NB-UV-B monotherapy group (P < .05) at day 56. For the face and upper 
extremities, a significantly higher percentage of patients in the combination 
therapy group achieved repigmentation, and at earlier times (face, 41.0 vs 61.0 
days [P = .001]; upper extremities, 46.0 vs 69.0 days [P = .003]). In the 
combination therapy group, repigmentation was 48.64% (95% CI, 39.49%-57.80%) at 
day 168 vs 33.26% (95% CI, 24.18%-42.33%) in the NB-UV-B monotherapy group. 
Notable adverse events included erythema in both groups and minor infections and 
nausea in the combination therapy group. Comparison between Fitzpatrick SPTs 
showed patients with SPTs IV to VI in the combination therapy group had 
improvement in the Vitiligo Area Scoring Index at days 56 and 84 (P < .05); no 
significant difference was noted in patients with SPT III.
CONCLUSIONS AND RELEVANCE: A combination of afamelanotide implant and NB-UV-B 
phototherapy resulted in clinically apparent, statistically significant superior 
and faster repigmentation compared with NB-UV-B monotherapy. The response was 
more noticeable in patients with SPTs IV to VI.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01430195.