title: Apremilast (Otezla). No progress in plaque psoriasis or psoriatic arthritis.
abstract: When PUVA therapy and immunosuppressants such as methotrexate are ineffective, TNF alpha antagonists are an option for patients with severe plaque psoriasis, in the absence of a better alternative. This is also the case for patients with psoriatic arthritis after failure of a "disease-modifying" antirheumatic drug. Apremilast, an oral immunosuppressant that inhibits phosphodiesterase type 4, has been authorised in the European Union for use in these settings. In patients with plaque psoriasis, oral apremilast was compared with subcutaneous etanercept, aTNF alpha antagonist, in a randomised, doubleblind, placebo-controlled trial lasting 16 weeks and involving 250 patients in whom other treatments had failed or were inappropriate. This trial failed to show that apremilast was more effective than etanercept. And about one-quarter more patients experienced symptom relief compared with placebo. In patients with psoriatic arthritis, there are no clinical trials comparing apremilast with TNF alpha antagonists, and no interpretable trials of apremilast after failure of a TNF alpha antagonist. In three randomised, double-blind trials including a total of 1493 patients treated for 16 weeks, at least a modest improvement in joint status was reported in about 35% of patients treated with apremilast versus 19% with placebo. This would suggest that apremilast is less effective than a TNF alpha antagonist. In the trial versus etanercept, serious adverse events occurred in 3.6% of patients treated with apremilast versus 1.2% of those treated with the TNF alpha antagonist. The main adverse effects of apremilast are diarrhoea, nausea and vomiting, headache, sometimes marked weight loss, and infections. A risk of depression and cardiac arrhythmia must also be taken into account. A risk of cancer in the long-term is likely, given the immunosuppressive action of apremilast. Apremilast is a substrate of cytochrome P450 isoenzyme 3A4 and accumulates in patients with renal failure. This creates a risk of multiple pharmacokinetic interactions.
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D015535:Arthritis, Psoriatic / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D006801:Humans; D011565:Psoriasis / Q000188:drug therapy*; D013792:Thalidomide / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D013792:Thalidomide; C505730:apremilast