Marozoff Shelby, Tan Jeremiah, Lu Na, Kirmani Ayesha, Loree Jonathan M, Xie Hui, Lacaille Diane, Kopec Jacek A, Esdaile John M, Corradetti Bonnie, Malone Peter, Koehn Cheryl L, Mennell Philippa, Hoens Alison M, Aviña-Zubieta J Antonio
Arthritis Research Canada, Vancouver, British Columbia, Canada.
Arthritis Research Canada and University of British Columbia, Vancouver, Canada.
ACR Open Rheumatol. 2023 Dec;5(12):685-693. doi: 10.1002/acr2.11620. Epub 2023 Oct 11.
We estimated the association between immunosuppressive and immunomodulatory agent (IIA) exposure and severe COVID-19 outcomes in a population-based cohort study.
Participants were 18 years or older, tested positive for SARS-CoV-2 between February 6, 2020, and August 15, 2021, and were from administrative health data for the entire province of British Columbia, Canada. IIA use within 3 months prior to positive SARS-CoV-2 test included conventional disease-modifying antirheumatic drugs (antimalarials, methotrexate, leflunomide, sulfasalazine, individually), immunosuppressants (azathioprine, mycophenolate mofetil/mycophenolate sodium [MMF], cyclophosphamide, cyclosporine, individually and collectively), tumor necrosis factor inhibitor (TNFi) biologics (adalimumab, certolizumab, etanercept, golimumab, infliximab, collectively), non-TNFi biologics or targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) (rituximab separately from abatacept, anakinra, secukinumab, tocilizumab, tofacitinib and ustekinumab collectively), and glucocorticoids. Severe COVID-19 outcomes were hospitalizations for COVID-19, ICU admissions, and deaths within 60 days of a positive test. Exposure score-overlap weighting was used to balance baseline characteristics of participants with IIA use compared with nonuse of that IIA. Logistic regression measured the association between IIA use and severe COVID-19 outcomes.
From 147,301 participants, we identified 515 antimalarial, 573 methotrexate, 72 leflunomide, 180 sulfasalazine, 468 immunosuppressant, 378 TNFi biologic, 49 rituximab, 144 other non-TNFi biologic or tsDMARD, and 1348 glucocorticoid prescriptions. Risk of hospitalizations for COVID-19 was significantly greater for MMF (odds ratio [95% CI]): 2.82 [1.81-4.40], all immunosuppressants: 2.08 [1.51-2.87], and glucocorticoids: 1.63 [1.36-1.96], relative to nonuse. Similar outcomes were seen for ICU admission and MMF: 2.52 [1.34-4.74], immunosuppressants: 2.88 [1.73-4.78], and glucocorticoids: 1.86 [1.37-2.54]. Only glucocorticoids use was associated with a significant increase in 60-day mortality: 1.58 [1.21-2.06]. No other IIAs displayed statistically significant associations with severe COVID-19 outcomes.
Current use of MMF and glucocorticoids were associated with an increased risk of severe COVID-19 outcomes compared with nonuse. These results emphasize the variety of circumstances of patients taking IIAs.
在一项基于人群的队列研究中，我们评估了免疫抑制和免疫调节药物（IIA）暴露与重症 COVID-19 结局之间的关联。
参与者年龄在 18 岁及以上，于 2020 年 2 月 6 日至 2021 年 8 月 15 日期间 SARS-CoV-2 检测呈阳性，数据来自加拿大不列颠哥伦比亚省全省的行政卫生数据。SARS-CoV-2 检测呈阳性前 3 个月内使用的 IIA 包括传统的改善病情抗风湿药物（抗疟药、甲氨蝶呤、来氟米特、柳氮磺胺吡啶，单独使用）、免疫抑制剂（硫唑嘌呤、霉酚酸酯/霉酚酸钠[MMF]、环磷酰胺、环孢素，单独及联合使用）、肿瘤坏死因子抑制剂（TNFi）生物制剂（阿达木单抗、赛妥珠单抗、依那西普、戈利木单抗、英夫利昔单抗，联合使用）、非 TNFi 生物制剂或靶向合成改善病情抗风湿药物（tsDMARDs）（利妥昔单抗与阿巴西普、阿那白滞素、司库奇尤单抗、托珠单抗、托法替布和乌司奴单抗联合使用分开），以及糖皮质激素。重症 COVID-19 结局为 COVID-19 住院治疗、入住重症监护病房（ICU）以及检测呈阳性后 60 天内死亡。使用暴露分数重叠加权法来平衡使用 IIA 与未使用该 IIA 的参与者的基线特征。逻辑回归分析评估了 IIA 使用与重症 COVID-19 结局之间的关联。
在 147301 名参与者中，我们确定了 515 份抗疟药、573 份甲氨蝶呤、72 份来氟米特、180 份柳氮磺胺吡啶、468 份免疫抑制剂、378 份 TNFi 生物制剂、49 份利妥昔单抗、144 份其他非 TNFi 生物制剂或 tsDMARDs 以及 1348 份糖皮质激素处方。与未使用相比，MMF（比值比[95%置信区间]）：2.82[1.81 - 4.40]、所有免疫抑制剂：2.08[1.51 - 2.87]以及糖皮质激素：1.63[1.36 - 1.96]使 COVID-19 住院风险显著增加。入住 ICU 及 MMF：2.52[1.34 - 4.74]、免疫抑制剂：2.88[1.73 - 4.78]以及糖皮质激素：1.86[1.37 - 2.54]也出现了类似结果。仅使用糖皮质激素与 60 天死亡率显著增加相关：1.58[1.21 - 2.06]。没有其他 IIA 与重症 COVID-19 结局显示出统计学上的显著关联。
与未使用相比，当前使用 MMF 和糖皮质激素与重症 COVID-19 结局风险增加相关。这些结果强调了服用 IIA 的患者情况的多样性。
