Topical pentoxifylline can be an effective and safe adjunctive therapy to NBUVB therapy in treating vitiligo: A split-side clinical trial.

Abstract

Vitiligo is the most common depigmenting disease and involves 0.5–4% of the population, without any age or gender predominance. The disease is characterized by the autoimmune destruction of melanocytes, manifesting as spots, macules, and white patches on mucocutaneous membranes.1 Various treatments and strategies have been introduced into practice with mixed or limited evidence.2, 3 Tacrolimus, a calcineurin inhibitor, is a relatively safe immunomodulatory agent for long-term use and as efficient as topical corticosteroids, with its combination with Narrow Band Ultraviolet B (NBUVB) being linked to a better repigmentation rate compared with NBUVB monotherapy.4, 5 Pentoxifylline is a methyl-xanthine derivative compound trialled for a variety of dermatological conditions as monotherapy or adjuvant therapy. It has several physiological effects at the cellular level, including activity against tumour necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1, IL-2, IL-6, IL-8 and IL-12, together with hemorheological and antifibrinolytic effects.s1,s2 Hence, one can hypothesize that pentoxifylline could be a potential treatment for TNF-α-mediated skin diseases, as it might be involved in the depigmentation process in vitiligo. In our split-side, triple-blinded clinical trial (code:IRCT20120909010795N3), we enrolled thirty-five pairs of bilateral symmetric vitiligo lesions of various anatomical sites in 18 patients aged ≥18 years receiving NBUVB phototherapy. Each patient served as her/his control, randomized to apply 10% pentoxifylline cream either on the right or left side and 0.1% tacrolimus ointment on the remaining side twice daily for three months. At the same time, NBUVB therapy was continued for all patients. The melanin, erythema and Vitiligo Area Scoring Index (VASI) were evaluated at the baseline, end of the first month and end of the third month of therapy for each side. Both pentoxifylline and tacrolimus in combination with NBUVB significantly promoted repigmentation. No meaningful difference was observed between the two groups for decrease in melanin value (p = 0.286), decrease in VASI (p = 0.233) and change in erythema value (p = 0.263) (Table 1). Adverse events were not reported during the study. Furthermore, the groups were similar in terms of the repigmentation rate (change in VASI score) during the course of the study (χ2 = 2.428, degree of freedom (df) = 4, p = 0.658). Supplementary figure depicts the series of photographs for five patients. Reference groupa a Reference group: NBUVB + Tacrolimus. β [95% CI], pb b Slope of NBUVB + Tacrolimus (reference) group = β coefficient [95% confidence interval (CI)], p. Interaction β [95% CI], pc c Difference between slope of two groups = β coefficient [95% CI], p. Two recent meta-analyses have been assessed the efficacy of tacrolimus and NBUVB combination therapy in vitiligo. Arora et al.5 showed that tacrolimus/NBUVB combination therapy was superior to NBUVB monotherapy in achieving an excellent response. Besides, such a combination can avert the early-phase phototherapy-induced erythematous reaction.s3 Dong et al.s4 added that tacrolimus/NBUVB combination therapy could significantly decrease the poor response rate (<25% repigmentation) compared with NBUVB monotherapy. In our study, tacrolimus/NBUVB therapy led to a significant improvement in vitiligo lesions over three months based on VASI scores and melanin values, with no skin or systemic complications being observed. Sisti et al.s5 stated that 50% repigmentation of vitiligo lesions cannot be obtained in less than two months of tacrolimus treatment and a 0–14% non-response rate is expected. Correspondingly, we found a maximum of 40% repigmentation and 11.43% non-response in the tacrolimus group. Although the efficacy of pentoxifylline has been studied for a variety of skin conditions, to our knowledge, the present study is the first to investigate the effect of pentoxifylline on vitiligo, yielding noticeable results. Measurements were almost similar to that of tacrolimus, with no side effects being observed. Interestingly, only one patient did not respond to the therapy. Given this similar efficacy and lower cost of pentoxifylline, it appears that pentoxifylline might be a good choice for treating vitiligo. However, a 3-month period might not be enough to investigate if the topical pentoxifylline is effective or not; hence, more large-scale and well-designed clinical trials with longer follow-up periods are warranted. Data S1 Methodological details. Figure S1 (A–E) Photography series of five patients at the baseline (X1) and end of the study (X2), [P] pentoxifylline + NBUVB, [T] tacrolimus + NBUVB. Note that while B and D photos are showing a visible change at the end of the study, A, C and E photos are showing areas of treated skin that did not visibly respond with repigmentating treatments. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.