Eficácia e segurança do Apremilast no tratamento da psoríase moderada a grave: uma revisão sistemática e metanálise

Abstract

Psoriasis is a chronic inflammatory disease of unknown etiology, which genetic and environmental factors interact, determining the emergence of erythematous, scaly patches on the skin. For more extensive cases, several therapeutic modalities are available, however, most of them have their use limited by the unfavorable profile of adverse effects. Therapy with biological agents brings positive results in the short and long term, but the medications are costly, and the subcutaneous route of administration can reduce their acceptance by some patients. There is an unmet demand for oral medications that have good tolerability. The aim of this study was to evaluate, through a systematic review, the efficacy and safety of apremilast, a new oral agent, approved for the treatment of patients with moderate to severe psoriasis. The search strategy included the terms psoriasis, apremilast and phosphodiesterase 4 inhibitor, in the electronic databases MEDLINE via PubMed, Cochrane Library, Embase, Web of Science e Lilacs. Records of studies and protocols, gray literature, annals of scientific events and a database of theses and dissertations (CAPES) were also searched, as well as a manual search by checking the reference list of the included articles. There was no restriction on the year or language of the publication. Randomized clinical trials that compared apremilast with placebo, with any conventional systemic medication or with biologicals were included. Two independent researchers participated in the selection of the studies, data extraction, assessment of the risk of bias and the certainty of the evidence. One thousand four hundred forty-two studies were initially selected by title and abstract, and after applying the eligibility criteria, 43 were included for the full text. Of these, thirty-three studies were excluded and ten included in the review, nine comparing apremilast to placebo, and only one comparing it directly to methotrexate. Eight studies were included in the meta-analysis for the main efficacy outcomes. A total of 3034 patients were included, 64.6% men and 35.4% women, with a mean age of 47.1 years. For the primary efficacy endpoint, which was obtaining the PASI 75 (Psoriasis Area Severity Index) in 16 weeks, apremilast was more effective than placebo (RR = 4.60; 95% CI: 3.43-6.18), with a moderate certainty of the evidence. For the other efficacy outcomes, apremilast also showed superiority, with the certainty of the evidence ranging from very low to moderate. Adverse effects (AE) were reported as mild or moderate by most participants and the rates of discontinuation due to AE was low (placebo = 4.3%; apremilast = 5.8%). The present review concluded that apremilast can be an effective and safe alternative for the treatment of patients with moderate to severe psoriasis, however, studies that compare apremilast directly with other medications and that evaluate its cost-effectiveness are necessary and may contribute to better decision-making in clinical practice