Prescrire Int. 2016 Jun;25(172):149-51.
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.
当补骨脂素紫外线A光化学疗法（PUVA疗法）和免疫抑制剂（如甲氨蝶呤）无效时，在没有更好替代方案的情况下，肿瘤坏死因子α拮抗剂是重度斑块状银屑病患者的一种选择。对于使用“改善病情的”抗风湿药物治疗失败的银屑病关节炎患者，情况也是如此。阿普斯特是一种口服免疫抑制剂，可抑制4型磷酸二酯酶，已在欧盟获批用于这些情况。在一项为期16周、涉及250名其他治疗失败或不适用的患者的随机、双盲、安慰剂对照试验中，对斑块状银屑病患者口服阿普斯特与皮下注射肿瘤坏死因子α拮抗剂依那西普进行了比较。该试验未能表明阿普斯特比依那西普更有效。与安慰剂相比，约多四分之一的患者症状得到缓解。在银屑病关节炎患者中，没有将阿普斯特与肿瘤坏死因子α拮抗剂进行比较的临床试验，也没有在肿瘤坏死因子α拮抗剂治疗失败后对阿普斯特进行的可解释试验。在三项共纳入1493名患者、治疗16周的随机、双盲试验中，报告称接受阿普斯特治疗的患者中约35%关节状况至少有适度改善，而接受安慰剂治疗的患者为19%。这表明阿普斯特的效果不如肿瘤坏死因子α拮抗剂。在与依那西普对比的试验中，接受阿普斯特治疗的患者中3.6%发生严重不良事件，而接受肿瘤坏死因子α拮抗剂治疗的患者为1.2%。阿普斯特的主要不良反应包括腹泻、恶心和呕吐、头痛，有时体重明显减轻以及感染。还必须考虑抑郁和心律失常的风险。鉴于阿普斯特的免疫抑制作用，长期存在患癌风险。阿普斯特是细胞色素P450同工酶3A4的底物，在肾衰竭患者中会蓄积。这会产生多种药代动力学相互作用的风险。
