JAMA：抗风湿生物制剂或不增加恶性肿瘤风险

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9月5日，《美国医学会杂志》(<em>JAMA</em>)发表的一项Meta分析显示，与安慰剂或其他缓解疾病抗风湿药(DMAD)相比，使用生物制剂治疗类风湿性关节炎(RA)并不会增加患者发生恶性肿瘤的风险。

这项Meta分析由德克萨斯大学M.D. Anderson癌症中心的Maria A. Lopez-Olivo博士及其同事进行，共纳入63项为期至少24周的随机临床试验，涉及29，423例RA成人患者，目的是评价使用以下9种生物制剂是否会增加发生恶性肿瘤的风险：阿巴西普、阿达木单抗、阿那白滞素、塞妥珠单抗、依那西普、戈利木单抗、英夫利昔单抗、利妥昔单抗和托珠单抗。

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在该Meta分析纳入的随机临床试验中，样本量从20例至1，399例不等。大部分(79%)受试者为白人，76%为女性。RA平均病程为1年以下至13年。63项试验中的56项由药企资助，3项未披露资金来源，其余4项由国家机构资助，但所用的药物均由药企免费提供。证据显示，药企资助的试验可能会高估疗效及安全性。共有15，989例受试者接受生物制剂+甲氨蝶呤和(或)其他DMAD联合治疗，3，615例受试者接受生物制剂单药治疗，9，819例使用安慰剂的受试者作为对照。

在这些试验期间，共观察到211例恶性肿瘤，联合治疗组、单药治疗组和对照组的恶性肿瘤发生率分别为0.77%、0.64%和0.66%，差异不显著。48例恶性肿瘤为皮肤癌(包括4例黑色素瘤)，14例为淋巴瘤，26例未指明，5例为非淋巴瘤血液性肿瘤。其余118例恶性肿瘤为累及以下器官的实体瘤：肾上腺、膀胱、乳腺、胃肠道系统、肝、肺、卵巢、胰腺、前列腺、肾、睾丸、甲状腺、舌和子宫。可见并无涉及某种特定类型癌症的模式。

同样，也无涉及某种特定生物制剂的模式。恶性肿瘤风险增加的情况仅见于52周时接受TNF抑制剂+甲氨蝶呤治疗的RA患者。这种效应在研究者进行的3项独立分析中并无一致性，并且未见于接受TNF抑制剂单药治疗的患者，也未见于另外3个时间点。

该Meta分析结果表明，从短期恶性肿瘤风险来看，生物制剂的安全性一般较好，但这些药物在合并癌症或癌症危险因素的RA患者中的安全性尚不清楚。未来尚需对观察性研究做进一步系统评价，以明确这些药物的远期风险。
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<a title="" href="http://dx.doi.org/10.1016/j.cell.2011.10.017" target="_blank">doi:10.1016/j.cell.2011.10.017</a>
PMC:
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<br/><strong>Risk of Malignancies in Patients With Rheumatoid Arthritis Treated With Biologic Therapy:A Meta-analysis</strong><br/>


Maria A. Lopez-Olivo, MD, PhD; Jean H. Tayar, MD; Juan A. Martinez-Lopez, MD; Eduardo N. Pollono, MD; Jose Polo Cueto, MD; M. Rosa Gonzales-Crespo, MD; Stephanie Fulton, MSIS; Maria E. Suarez-Almazor, MD, PhD

Context  Concerns exist regarding the potential development of malignancies in patients with rheumatoid arthritis (RA) who are receiving biologic response modifiers (BRMs).

Objective  To assess the risk of malignancy in patients with RA enrolled in randomized controlled trials (RCTs) of BRMs.

Data Sources  Electronic databases, conference proceedings, and websites of regulatory agencies were searched for RCTs evaluating abatacept, adalimumab, anakinra, certolizumab, etanercept, golimumab, infliximab, rituximab, and tocilizumab in RA from inception through July 9, 2012.

Study Selection  Independent selection of studies included RCTs that compared the safety of any BRMs used in RA patients with placebo and/or any traditional disease-modifying antirheumatic drugs with a minimum of 24 weeks of follow-up.

Data Extraction  Independent reviewers selected studies and extracted data on quality and outcomes. Pooled estimates and 95% confidence intervals were calculated for each BRM.

Results  Sixty-three RCTs with 29 423 patients were analyzed. No statistically significant increased risk of developing malignancy was observed. Of the 29 423 patients, 211 developed a malignancy during the trial (118 solid tumors, 48 skin cancers, 14 lymphomas, 5 hematologic nonlymphomas, and 26 not specified). The incidence rate for any malignancy during the first year of therapy was very low in the BRM plus methotrexate group (0.77%; 95% CI, 0.65%-0.92%), the BRM monotherapy group (0.64%; 95% CI, 0.42%-0.95%), and the controls (0.66%; 95% CI, 0.52%-0.84%). Anakinra plus methotrexate showed lower odds compared with methotrexate alone (Peto odds ratio, 0.11; 95% CI, 0.03-0.45). No statistically significant risk was observed for specific cancer sites, although the Peto odds ratio for lymphoma was 2.1 (95% CI, 0.55-8.4) in patients receiving tumor necrosis factor inhibitors compared with controls.

Conclusion  The use of BRMs among patients with RA included in RCTs of at least 6 months' duration was not significantly associated with an increased risk of malignancy compared with other disease-modifying antirheumatic drugs or with placebo.

<br/>来源：EGMN

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