Smith C H, Jackson K, Bashir S J, Perez A, Chew A L, Powell A M, Wain M, Barker J N W N
Skin Therapy Research Unit, St John's Institute of Dermatology, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, UK.
Br J Dermatol. 2006 Jul;155(1):160-9. doi: 10.1111/j.1365-2133.2006.07316.x.
Infliximab, a mouse-human chimeric monoclonal antibody directed against tumour necrosis factor-alpha, has been shown to be effective for moderate to severe psoriasis, but there are few data published on its use in recalcitrant, treatment-resistant disease or in combination with other antipsoriatic therapies.
To report our experience with infliximab in the treatment of patients attending a tertiary referral service with severe recalcitrant disease.
All patients attending a tertiary referral service for severe psoriasis who were treated with infliximab between 2002 and July 2005 were entered into a prospective, open-label study. Details on disease phenotype, clinical course and adverse events were recorded together with measures of disease severity [Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index, clinical photography] at baseline, weeks 2 and 6, and then at 2-monthly intervals throughout the treatment period.
Twenty-three patients were treated with infliximab during the study; one patient had pustular psoriasis and was therefore excluded from statistical analysis. All had severe disease (baseline PASI 26.5+/-6.7, mean+/-SD, n=22) and had received at least two systemic therapies for psoriasis in the past; 16 were taking one or more concomitant therapies at the time of treatment initiation. At week 10, 95% had achieved a 50% or greater improvement in baseline PASI (PASI 50), and 77% had achieved a 75% or greater improvement (PASI 75). Efficacy was sustained in the longer term, with eight of 10 patients on treatment for more than 11 months maintaining at least a PASI 50. Only one patient had treatment withdrawn due to lack of efficacy, two suffered severe systemic infections including extrapulmonary tuberculosis (splenic abscess) and cellulitis, and six have discontinued due to adverse effects including infusion reactions (two), severe thrombocytopenia (one), hepatitis (one) and malignancy (two).
Data from this open-label study suggest that infliximab is a rapidly effective treatment for patients with severe, treatment-resistant disease, although approximately 25% of patients had to discontinue therapy due to the development of serious adverse effects. Long-term follow-up, continued pharmacovigilance, and further controlled comparative studies will be required to evaluate fully the risks associated with infliximab in the context of this already difficult to treat population.
英夫利昔单抗是一种针对肿瘤坏死因子-α的鼠-人嵌合单克隆抗体，已被证明对中度至重度银屑病有效，但关于其在顽固性、治疗抵抗性疾病中使用或与其他抗银屑病疗法联合使用的数据很少。
报告我们使用英夫利昔单抗治疗三级转诊服务中患有严重顽固性疾病患者的经验。
2002年至2005年7月期间，所有在三级转诊服务机构接受英夫利昔单抗治疗的重度银屑病患者均纳入一项前瞻性、开放标签研究。记录疾病表型、临床病程和不良事件的详细信息，以及在基线、第2周和第6周以及整个治疗期间每2个月一次的疾病严重程度测量指标[银屑病面积和严重程度指数（PASI）、皮肤病生活质量指数、临床照片]。
研究期间有23例患者接受了英夫利昔单抗治疗；1例患者患有脓疱型银屑病，因此被排除在统计分析之外。所有患者病情均严重（基线PASI 26.5±6.7，均值±标准差，n = 22），且过去至少接受过两种银屑病全身治疗；16例患者在开始治疗时正在接受一种或多种伴随治疗。在第10周时，95%的患者基线PASI改善了50%或更多（PASI 50），77%的患者改善了75%或更多（PASI 75）。长期疗效得以维持，10例治疗超过11个月的患者中有8例至少维持PASI 50。只有1例患者因疗效不佳而停药，2例发生严重全身感染，包括肺外结核（脾脓肿）和蜂窝织炎，6例因不良反应停药，包括输液反应（2例）、严重血小板减少症（1例）、肝炎（1例）和恶性肿瘤（2例）。
这项开放标签研究的数据表明，英夫利昔单抗对患有严重、治疗抵抗性疾病的患者是一种快速有效的治疗方法，尽管约25%的患者因出现严重不良反应而不得不停药。需要进行长期随访、持续的药物警戒以及进一步的对照比较研究，以全面评估在这个本就难以治疗的人群中与英夫利昔单抗相关的风险。
