Background In clinical practice, dimethylfumarate is considered an alternative at the level of conventional systemic drugs in the first line (cyclosporine, methotrexate, acitretin) for moderate-to-severe plaque psoriasis (PP).
Purpose To establish whether dimethylfumarate, methotrexate, cyclosporine and acitretin can be considered equivalent therapeutic alternatives (ATE) in efficacy in PP.
Material and methods We conducted a search of clinical trials of these drugs, phase III, double-blind, controlled with methotrexate or placebo, efficacy evaluated at 12 weeks or next, adults diagnosed with PP and uncontrolled disease with topical treatments and/or phototherapy. The 75% reduction in the Psoriasis Area and Severity index was used as the main variable (PASI75). An indirect comparison (IC) of cyclosporin versus fumarates and dimethylfumarate versus methotrexate was performed using the Bucher method, using the Indirect Treatment Comparisons calculator from the Canadian Agency for Health Technology Assessment. For cyclosporine with more than one published study, a previous meta-analysis was performed (Der Simonian–Laird method), using the Joaquin Primo calculator. Considering that the failure can be recovered with an effective second line, it was taken as delta value, for PASI75 the value in previous published studies of IC of biological in PP, 15%. The results were analysed graphically and the relative position of the 95% CI and the equivalence margin were observed. To establish the positioning, the ATE Guide was followed.
Results Included four clinical trials, two of ciclosporin, one of dimethylfumarate and one of fumarates. The acitretin studies were excluded because they did not meet the inclusion criteria. The difference in PASI75 expressed as RAR (IC95%) of methotrexate versus dimethylfumarate, and ciclosporin versus fumarates, was: 2.2% (-22,2;26,6) y 17 (-14,83;48,83). Applying the ATE Guide, methotrexate and dimethylfumarate can be declared ATE, being the probability of clinically relevant difference <50% (most of the 95% CI is in the equivalence range) and the failure does not involve serious/irreversible damage. Cyclosporine and fumarates could not be considered ATE (the RAR exceeded the delta with more than 50% probability so that the difference was clinically relevant).
Conclusion Dimethylfumarate and methotrexate could be considered ATE. Ciclosporin and fumarates could not be considered ATE. For a definitive statement of ATE, the criteria of safety and adequacy should be considered.
References and/or acknowledgements No conflict of interest.
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