Efficacy and safety of a novel methotrexate-containing emulgel in treatment of psoriasis vulgaris

Abstract - This study investigates the efficacy and safety of a novel 1% MTX topical emulgel in the treatment of psoriasis vulgaris in adult patients using placebo-controlled double-blind experimental design. INTRODUCTION Psoriasis is a chronic inflammatory disease that affects up to 5% of the world's population [1]. Methotrexate (MTX) is among the most widely used medication in treatment of this disease [2]. Due to the serious side effects associated with the systemically administered drug, topical therapy is highly preferred by patients. However, effective topical delivery is hindered by the skin barrier. Therefore, a novel topical formulation which can deliver the required drug amounts is needed. The objective of this study study was to formulate a novel topically applied 1% MTX-containing emulgel and evaluate its efficacy and safety in treatment of psoriasis vulgaris in adult patients in comparison with placebo. MATERIALS AND METHODS A 1% MTX-containing emulgel and identical MTX-free emulgel (placebo) were prepared and tested for its quality and stability. The study was conducted at the University of Aleppo Hospital over one year period. Ninety-six patients (60 males & 36 females), their age range between 18-30 yrs of age, with slight to moderate chronic plaque-type psoriasis affecting less than 10% of the body area were selected for this study. Patients were sequentially randomized into two parallel groups; Group 1 used active and Group 2 used placebo. Each patient was allocated a pre-coded 90 g (1% MTX emulgel or placebo) with instructions on how to self-administer the trial medication topically (without occlusion) to their lesions twice daily for 8 weeks. Lesions were scored at baseline and after 2, 4, 6, and 8 weeks of treatment for erythema, scale, and infiltration (score range: 0-5; with 5 being severe). Drug safety was evaluated by performing blood tests including complete blood count (CBC) and platelet count, kidney and hepatic function before initiating the treatment and after the 8th week of treatment. Follow up was carried out for 2-month. RESULTS AND DISCUSSION Only 83 patients completed the study (43 from Group 1 & 40 from Group 2). By the end of the treatment, breaking the code disclosed that 1% MTX emulgel was remarkably effective (p< 0.01) in managing the psoriasis vulgaris in comparing to the placebo, yet at very slow progress over 2- month. The overall improvement was 97% for patients treated with MTX vs. 3.33% for those treated with placebo. The lesion improvement score after 8-week treatment (Fig. 1), in terms of erythema, scale, and infiltration (score level 0 or 1 being considered excellent improvement) was 93%, 100%, 98% in Group 1 patients vs. 2.5%, 7.5%, and 0% in Group 2 patients, respectively. Laboratory evaluations, including CBC, platelet counts, renal and liver functions were within the normal limits suggesting the topical treatment was safe. The treatment was well-tolerated by all the patients, with no adverse drug-related symptoms apart from 1 out of 43 patients has developed ulcer at the application site after two weeks from drug application. The follow-up studies have revealed that no recurrence was observed among the treated group within the follow up period. a) before treatment b) after 4 weeks c) after 8 weeks Fig.1. Histopathologic changes of psoriatic lesion in 28 years old patient before and after treatment with 1% MTX emulgel twice daily for 8 weeks This study indicated that applying MTX topically could improve its safety and tolerability remarkably. MTX is widely used in treatment of other diseases such as arthritis in children and associated with severe side events. Thus, using this route to deliver MTX would be highly advantageous. However, the slow disease improvement progress suggest that the formulated emulgel was effective in delivering sufficient doses to treat psoriasis, but may be not enough for treating systemic diseases such as arthritis which require much higher doses. Therefore, further studies are required to evaluate the drug delivery rate from this novel emulgel formulation. Exploring more effective transdermal drug delivery systems such as microneedles to deliver MTX could be highly beneficial. CONCLUSIONS The findings of this study demonstrate that the novel 1% MTX-containing emulgel is safe, well tolerated and significantly more effective than placebo when topically applied to treat psoriasis vulgaris. REFERENCES [1] Naldi L. Epidemiology of psoriasis. Curr Drug Targets Inflamm Allergy 2004;3:121– 8. [2] Roenigk HH Jr, Auerbach R, Maibach HI et al. Methotrexate in psoriasis: consensus conference. J Am Acad Dermatol 1998; 38: