VML 295 (LY-293111), a novel LTB4 antagonist, is not effective in the prevention of relapse in psoriasis

Leukotriene Bq (LTB4) receptor antagonists have been the subject of several studies in the treatment of inflammatory diseases, including psoriasis, A novel oral LTB4 antagonist, VML 295 (LY-293111) has recently been developed and has a pronounced effect on epidermal inflammatory parameters. However. oral treatment of psoriasis for 4 weeks did not result in a decrease in di sease severity. The present study was performed in order to investigate whe ther prolonged treatment with VML 295 up to 8 weeks has a beneficial effect on the overall severity of psoriasis, Moreover, we studied to what extent VML 295 is able to prevent relapse in psoriasis, In the present study, 35 p atients with stable chronic plaque psoriasis were included, A representativ e plaque of at least 16 cm(2) was initially treated with clobetasol-17-prop ionate lotion under hydrocolloid occlusion in all patients, Clearance was a chieved within 6 weeks in 31 patients. After clearance, the patients were r andomized to treatment and received oral VML 295 capsules 200 mg twice dail y or placebo for S weeks. Twenty-five patients completed the study. The pso riasis area and severity index (PASI) was assessed before treatment, at: cl earance, and on days 15, 29, 43 and 57 of the treatment period. Biopsies we re taken from the treated lesion before treatment, after clearance and at r elapse, and cells were analysed by flow cytometry with markers for differen tiation (keratin 10), inflammation (vimentin), and proliferation (DNA conte nt). After 8 weeks of treatment, 14 of 15 VML, 295-treated patients had rel apsed and 11 of 16 placebo-treated patients had relapsed. A total of six pa tients were withdrawn. The time to relapse and the number of relapsed patie nts was not significantly different comparing the treatment groups, There w as no significant difference in PASI scores between VML 295-treated patient s and placebo-treated patients after 8 weeks of treatment. Flow cytometric parameters for differentiation, inflammation and proliferation did not show significant differences between VML 295- and placebo-treated patients. We conclude that oral VML 295 (LY-293111) is not effective in preventing relap se in psoriasis, either clinically or at the cellular level, and that in ou r group of patients VML 295 had no beneficial effect on overall psoriasis s everity. Moreover, we conclude that further development of LTB4 modulating drugs for the treatment of psoriasis is not indicated.