TY - JOUR

T1 - Risk of chronic obstructive pulmonary disease exacerbation in patients who use methotrexate—a nationwide study of 58,580 outpatients

AU - Bergsøe, Christina Marisa

AU - Sivapalan, Pradeesh

AU - Saeed, Mohamad Isam

AU - Eklöf, Josefin

AU - Saghir, Zaigham

AU - Sørensen, Rikke

AU - Biering-Sørensen, Tor

AU - Jensen, Jens Ulrik Stæhr

N1 - Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021

Y1 - 2021

N2 - 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, p < 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.

AB - 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, p < 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.

KW - Airway inflammation

KW - Anti-inflammatory

KW - Chronic obstructive pulmonary disease

KW - Exacerbation of chronic obstructive pulmonary disease

KW - Immunosuppression

U2 - 10.3390/biomedicines9060604

DO - 10.3390/biomedicines9060604

M3 - Journal article

C2 - 34073252

AN - SCOPUS:85107745822

VL - 9

JO - Biomedicines

JF - Biomedicines

SN - 2227-9059

IS - 6

M1 - 604

ER -