Using methotrexate in the treatment of advanced vitiligo

Vitiligo is a chronic disease with a genetic predisposition resulting from destruction of skin melanocytes and characterized by depigmentation foci.1 Vitiligo is a polygenic disease, but the autoimmune theory is considered being the most relevant.2, 3 The gold standard treatment for vitiligo is Narrow-band ultraviolet B (NB-UVB) therapy. However, systemic immunosuppressive drugs should be administered if the disease is widespread and progressive. First-line systemic immunosuppressants include systemic glucocorticosteroids, but their effectiveness is not always sufficient. Because of the known contraindications of corticosteroids, the search is ongoing for safe and effective alternative. Methotrexate use is described in the treatment of vitiligo, but the efficacy evaluation sample was small.4, 5 Therefore, we compared the clinical efficacy of mid-wave narrow-band NB-UVB 311 nm as monotherapy and in combination with methotrexate and developed an effective regimen of methotrexate administration to stabilize the process. We conducted a prospective controlled study of 77 patients diagnosed with advanced vitiligo, all subtypes of vitiligo, including acrofacial, were studied. The 1st group received low-dose methotrexate, 10 mg once a week for 4 months in combination with 311 nm NB-UVB, and the 2nd group received the course of 311 nm NB-UVB monotherapy. The starting treatment was 0.1 J/cm2 NB-UVB, with a gradual increase in 0.1 J/cm2 for each subsequent session. No significant differences were found between the groups in terms of sex, age, and duration of the disease. Vitiligo extent score (VES) on a vitiligo calculator showed the area of the lesion relative to the body surface area (BSA).6 Before the treatment, the maximum lesion area was 36.72% in group 1 and 35.92% in group 2. After the treatment, the maximum lesion area was reduced to 18.31% in group 1 and to 26.71% in group 2. The Dermatology Life Quality Index (DLQI) showed the impact of the disease on quality of life. The mean DLQI score in both groups before treatment was 15. At week 7 of the therapy, group 1 had an average DLQI score of 10, and group 2 had an average DLQI score of 13. After therapy, the DLQI averaged 7 points in group 1 and 9 points in group 2. We assessed weekly the clinical efficacy of therapy during the first month and once every 4 weeks thereafter. Immediate treatment results were analyzed 4 months after the study. The clinical effect was assessed: 0—no response, 1—stabilization, 2—moderate effect, and 3—pronounced effect. Table 1 presents the therapy outcomes in groups based on Fisher–Freeman-Holton's exact test and Student's paired t-test. A pair-wise comparison of the frequencies of different treatment outcomes using Fisher's exact test shows a greater difference between subgroups “No response” (less in group 1) and “Expressed effect” (more in group 1) at a significance level of 0.05. A correlation was revealed between VES and DLQI. From Figure 1, we can conclude that the greater the absolute change in VES, the greater the absolute change in DLQI. This study showed the positive clinical potential of methotrexate, as well as its safety and good tolerability. The efficacy of both treatments was confirmed, but the complex therapy with methotrexate prevents the progression and allowed better and faster repigmentation of vitiligo foci than mono phototherapy. Weak dynamics was observed in patients with acrofacial vitiligo on the extremities, while group 1st patients showed stabilization, and group 2nd did not give a positive response. Patients of both groups showed a decrease in VES values, mostly in group 1 patients. Low-dose methotrexate has a positive effect on the stabilization of vitiligo and favors the drug tolerance and prevented the development of side effects, allowing a long-term effect on pathogenetic mechanisms and stabilizing the process in the skin. The authors declare no conflict of interest. (The Department of Skin and Venereal Diseases named after V.A. Rakhmanov of Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia). The Medical Ethical Committee of the Sechenov University, Moscow, Russia (protocol No. 04–20, March 11, 2020). All patients who took part in the study signed a voluntary informed consent approved by the ethics committee. Patients were given ample time before signing consent to review information about screening techniques and upcoming therapies.