Bergsøe Christina Marisa, Sivapalan Pradeesh, Saeed Mohamad Isam, Eklöf Josefin, Saghir Zaigham, Sørensen Rikke, Biering-Sørensen Tor, Jensen Jens-Ulrik Stæhr
Department of Medicine, Section of Respiratory Medicine, Herlev and Gentofte Hospital, University of Copenhagen, 2900 Hellerup, Denmark.
Department of Internal Medicine, Zealand University Hospital, 4000 Roskilde, Denmark.
Biomedicines. 2021 May 26;9(6):604. doi: 10.3390/biomedicines9060604.
Patients with severe chronic obstructive pulmonary disease (COPD) experience frequent acute exacerbations and require repeated courses of corticosteroid therapy, which may lead to adverse effects. Methotrexate (MTX) has anti-inflammatory properties. The objective of this study was to describe the risk of COPD exacerbation in patients exposed to MTX. In this nationwide cohort study of 58,580 COPD outpatients, we compared the risk of hospitalization-requiring COPD exacerbation or death within 180 days in MTX vs. non-MTX users in a propensity-score matched study population as well as an unmatched cohort, in which we adjusted for confounders. The use of MTX was associated with a reduction in risk of COPD exacerbation in the propensity-score matched population at 180 days follow-up (HR 0.66, CI 0.66-0.66, < 0.001). Similar results were shown in our sensitivity analyses at 180-day follow-up on unmatched population and 365-day follow-up on matched and unmatched population (HR 0.76 CI 0.59-0.99, HR 0.81 CI 0.81-0.82 and HR 0.92 CI 0.76-1.11, respectively). MTX was associated with a lower risk of COPD exacerbation within the first six months after study entry. The finding seems biologically plausible and could potentially be a part of the management of COPD patients with many exacerbations.
重度慢性阻塞性肺疾病（COPD）患者经常急性加重，需要反复进行皮质类固醇治疗，这可能会导致不良反应。甲氨蝶呤（MTX）具有抗炎特性。本研究的目的是描述接触MTX的患者发生COPD加重的风险。在这项对58580名COPD门诊患者的全国性队列研究中，我们在倾向评分匹配研究人群以及未匹配队列中比较了MTX使用者与非MTX使用者在180天内需要住院治疗的COPD加重或死亡风险，在未匹配队列中我们对混杂因素进行了调整。在倾向评分匹配人群中，随访180天时使用MTX与COPD加重风险降低相关（风险比[HR]0.66，可信区间[CI]0.66 - 0.66，P < 0.001）。在未匹配人群180天随访以及匹配和未匹配人群365天随访的敏感性分析中也显示了类似结果（HR分别为0.76，CI 0.59 - 0.99；HR 0.81，CI 0.81 - 0.82；HR 0.92，CI 0.76 - 1.11）。MTX与研究入组后头六个月内较低的COPD加重风险相关。这一发现似乎在生物学上是合理的，并且可能成为频繁急性加重的COPD患者管理的一部分。
