Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Rheumatology Unit, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Ann Rheum Dis. 2018 May;77(5):650-657. doi: 10.1136/annrheumdis-2017-212395. Epub 2017 Dec 13.
With the wide range of biological disease-modifying anti-rheumatic drugs (bDMARDs) available for treating rheumatoid arthritis (RA), and limited evidence to guide the choice for individual patients, we wished to evaluate whether patient characteristics influence the choice of bDMARD in clinical practice, and to quantify the extent to which this would bias direct comparisons of treatment outcome.
Register-based study of all Swedish patients with RA initiating necrosis factor inhibitor (TNFi), rituximab, abatacept or tocilizumab in 2011-2015 as their first bDMARD (n=6481), or after switch from TNFi as first bDMARD (n=2829). Group differences in demographics, clinical characteristics and medical history were assessed in multivariable regression models. Predicted differences in safety and treatment outcomes were calculated as a function of patient characteristics, through regression modelling based on observed outcomes among patients with RA starting bDMARDs 2006-2010.
Patients starting non-TNFi were older than those starting TNFi, had lower socioeconomic status, higher disease activity and higher burden of diseases including malignancy, serious infections and diabetes. Differences were most pronounced at first bDMARD initiation. These factors were linked to treatment outcome independent of therapy, yielding worse apparent safety and effectiveness for non-TNFi biologics, most extreme for rituximab. Standardising to the age/sex distribution of the TNFi group reduced differences considerably.
There was significant channelling of older and less healthy patients with RA to non-TNFi bDMARDs, in particular as first bDMARD. Whether this channelling represents a maximised benefit/risk ratio is unclear. Unless differences in age, medical history and disease activity are accounted for, they will substantially confound non-randomised comparative studies of available bDMARDs' safety and effectiveness.
生物疾病修饰抗风湿药物（bDMARD）种类繁多，可用于治疗类风湿关节炎（RA），而针对个体患者的选择，仅有有限的证据可供指导，因此我们评估了患者特征是否会影响临床实践中 bDMARD 的选择，并量化了这种影响在多大程度上会对治疗结果的直接比较产生偏倚。
这是一项基于登记的研究，纳入了 2011 年至 2015 年期间首次使用肿瘤坏死因子抑制剂（TNFi）、利妥昔单抗、阿巴西普或托珠单抗作为其一线 bDMARD 的所有瑞典 RA 患者（n=6481），或在首次使用 TNFi 作为一线 bDMARD 后转换为其他 bDMARD 的患者（n=2829）。在多变量回归模型中评估了两组在人口统计学、临床特征和病史方面的差异。通过基于 2006 年至 2010 年开始使用 bDMARD 的 RA 患者的观察结果进行回归建模，计算了安全性和治疗结果的预测差异，作为患者特征的函数。
与使用 TNFi 的患者相比，起始非 TNFi 治疗的患者年龄更大、社会经济地位更低、疾病活动度更高、合并疾病负担更高，包括恶性肿瘤、严重感染和糖尿病。这些差异在首次 bDMARD 治疗时最为显著。这些因素与治疗结果独立于治疗有关，导致非 TNFi 生物制剂的表观安全性和有效性更差，其中利妥昔单抗的差异最为明显。根据 TNFi 组的年龄/性别分布进行标准化后，差异大大减少。
RA 患者中有大量年龄较大和健康状况较差的患者被转用非 TNFi bDMARD，尤其是作为一线 bDMARD。这种转用是否代表了最大化的获益/风险比尚不清楚。除非考虑到年龄、病史和疾病活动度的差异，否则它们将极大地混淆对现有 bDMARD 安全性和有效性的非随机对照研究。
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