Chatzidionysiou K, Lukina G, Gabay C, Hetland M L, Hauge E M, Pavelka K, Nordström D, Canhão H, Tomsic M, Rotar Z, Lie E, Kvien T K, van Vollenhoven R F, Saevarsdottir S
a Rheumatology Unit, Department of Medicine , Karolinska University Hospital and Karolinska Institutet , Stockholm , Sweden.
b ARBITER, Institute of Rheumatology , Moscow , Russia.
Scand J Rheumatol. 2019 Jan;48(1):17-23. doi: 10.1080/03009742.2018.1466363. Epub 2018 Sep 27.
To investigate whether smoking habits predict response to rituximab (RTX) in rheumatoid arthritis (RA).
We included patients from the CERERRA international cohort receiving the first treatment cycle with available smoking status (n = 2481, smokers n = 528, non-current smokers n = 1953) and at least one follow-up visit. Outcome measures were change in Disease Activity Score based on 28-joint count (ΔDAS28) and European League Against Rheumatism (EULAR) good response at 6 months, with non-current smokers as the referent group.
Compared with non-smokers at baseline, smokers were more often rheumatoid factor (RF)/anti-citrullinated protein antibody (ACPA) positive and males, had shorter disease duration, lower DAS28 and Health Assessment Questionnaire (HAQ) score, a higher number of prior biological disease-modifying anti-rheumatic drugs, and were more likely to receive concomitant conventional synthetic disease-modifying anti-rheumatic drug (csDMARDs). Disease activity had decreased less in smokers at 6 months (ΔDAS28 = 1.5 vs 1.7, p = 0.006), although the difference was no longer significant after correction for baseline DAS28 (p = 0.41). EULAR good response rates did not differ between smokers and non-smokers overall or stratified by RF/ACPA status, although smokers had lower good response rates among seronegative patients (ACPA-negative: 6% vs 14%, RF-negative: 11% vs 18%). Smoking did not predict good response [odds ratio (OR) = 1.04, 95% confidence interval (CI) = 0.76-1.41], while ACPA, DAS28, HAQ, and concomitant csDMARDs were significant predictors for good response. However, when stratified by country, smokers were less likely to achieve good response in Sweden (unadjusted OR = 0.24, 95% CI = 0.07-0.89), and a trend was seen in the Czech Republic (OR = 0.45, 95% CI = 0.16-1.02).
In this large, observational, multinational RA cohort, smokers starting RTX differed from non-smokers by having shorter disease duration and lower disease activity, but more previous treatments. The overall results do not support smoking as an important predictor for response to RTX in patients with RA.
探讨吸烟习惯是否可预测类风湿关节炎（RA）患者对利妥昔单抗（RTX）的反应。
我们纳入了CERERRA国际队列中接受首个治疗周期且有可用吸烟状态信息的患者（n = 2481，吸烟者n = 528，非当前吸烟者n = 1953），并且这些患者至少有一次随访。观察指标为基于28个关节计数的疾病活动评分变化（ΔDAS28）以及6个月时欧洲抗风湿病联盟（EULAR）的良好反应，以非当前吸烟者作为参照组。
与基线时的非吸烟者相比，吸烟者类风湿因子（RF）/抗瓜氨酸化蛋白抗体（ACPA）阳性更为常见且男性居多，病程较短，DAS28和健康评估问卷（HAQ）评分较低，既往使用过更多生物性改善病情抗风湿药物，并且更有可能同时接受传统合成改善病情抗风湿药物（csDMARDs）。6个月时吸烟者的疾病活动度下降较少（ΔDAS28 = 1.5 vs 1.7，p = 0.006），尽管在校正基线DAS28后差异不再显著（p = 0.41）。总体而言，吸烟者和非吸烟者的EULAR良好反应率无差异，按RF/ACPA状态分层后也无差异，尽管在血清阴性患者中吸烟者的良好反应率较低（ACPA阴性：6% vs 14%，RF阴性：11% vs 18%）。吸烟不能预测良好反应[比值比（OR） = 1.04，95%置信区间（CI） = 0.76 - 1.41]，而ACPA、DAS28、HAQ以及同时使用csDMARDs是良好反应的显著预测因素。然而，按国家分层时，在瑞典吸烟者实现良好反应的可能性较小（未调整OR = 0.24，95% CI = 0.07 - 0.89），在捷克共和国有这种趋势（OR = 0.45，95% CI = 0.16 - 1.02）。
在这个大型、观察性、多国RA队列中，开始使用RTX的吸烟者与非吸烟者相比，病程较短且疾病活动度较低，但既往治疗更多。总体结果不支持吸烟是RA患者对RTX反应的重要预测因素这一观点。
