OBJECTIVE: We previously reported that low-dose methotrexate (MTX) was associated with an increased risk of pulmonary adverse events (AEs) in a large randomized, placebo-controlled trial. Herein, we report details on the predictors and severity of pulmonary AEs. METHODS: We conducted a prespecified analysis of pulmonary AEs in the Cardiovascular Inflammation Reduction Trial. Adults with known cardiovascular disease and diabetes/metabolic syndrome were randomly allocated to receive low-dose MTX (target dose 15-20 mg/week) or placebo after a 6-8-week open-label run-in phase in which all patients received low-dose MTX. Individuals with systemic inflammatory diseases were excluded. Pulmonary AEs were adjudicated in a blinded manner. We described severe pulmonary AEs and examined associations of baseline characteristics with pulmonary AEs in patients receiving low-dose MTX. RESULTS: A total of 2,391 subjects were randomized to receive low-dose MTX and 2,395 to receive placebo. There were 13 severe pulmonary AEs (0.5%) and 7 cases of possible pneumonitis (0.3%) in the low-dose MTX group, compared to 8 (0.3%) and 1 (<0.1%), respectively, in the placebo group. Among those randomized to receive low-dose MTX, risk factors for any pulmonary AE included female sex (hazard ratio [HR] 1.69 versus male sex [95% confidence interval (95% CI) 1.16-2.45]), white race (HR 2.35 versus other race [95% CI 1.03-5.36]), and insulin use (HR 1.60 versus non-use [95% CI 1.11-2.30]). The only risk factor for severe pulmonary AEs was older age at baseline (HR 1.09 per year increase [95% CI 1.02-1.16]). CONCLUSION: In this large placebo-controlled trial, pulmonary AEs, including possible pneumonitis, were uncommon but were more likely to occur in those randomized to receive low-dose MTX. White race, older age, male sex, and insulin use were associated with an increased risk of pulmonary AEs in those receiving low-dose MTX.
RCT Entities:
OBJECTIVE: We previously reported that low-dose methotrexate (MTX) was associated with an increased risk of pulmonary adverse events (AEs) in a large randomized, placebo-controlled trial. Herein, we report details on the predictors and severity of pulmonary AEs. METHODS: We conducted a prespecified analysis of pulmonary AEs in the Cardiovascular Inflammation Reduction Trial. Adults with known cardiovascular disease and diabetes/metabolic syndrome were randomly allocated to receive low-dose MTX (target dose 15-20 mg/week) or placebo after a 6-8-week open-label run-in phase in which all patients received low-dose MTX. Individuals with systemic inflammatory diseases were excluded. Pulmonary AEs were adjudicated in a blinded manner. We described severe pulmonary AEs and examined associations of baseline characteristics with pulmonary AEs in patients receiving low-dose MTX. RESULTS: A total of 2,391 subjects were randomized to receive low-dose MTX and 2,395 to receive placebo. There were 13 severe pulmonary AEs (0.5%) and 7 cases of possible pneumonitis (0.3%) in the low-dose MTX group, compared to 8 (0.3%) and 1 (<0.1%), respectively, in the placebo group. Among those randomized to receive low-dose MTX, risk factors for any pulmonary AE included female sex (hazard ratio [HR] 1.69 versus male sex [95% confidence interval (95% CI) 1.16-2.45]), white race (HR 2.35 versus other race [95% CI 1.03-5.36]), and insulin use (HR 1.60 versus non-use [95% CI 1.11-2.30]). The only risk factor for severe pulmonary AEs was older age at baseline (HR 1.09 per year increase [95% CI 1.02-1.16]). CONCLUSION: In this large placebo-controlled trial, pulmonary AEs, including possible pneumonitis, were uncommon but were more likely to occur in those randomized to receive low-dose MTX. White race, older age, male sex, and insulin use were associated with an increased risk of pulmonary AEs in those receiving low-dose MTX.
Authors: G S Alarcón; J M Kremer; M Macaluso; M E Weinblatt; G W Cannon; W R Palmer; E W St Clair; J S Sundy; R W Alexander; G J Smith; C A Axiotis Journal: Ann Intern Med Date: 1997-09-01 Impact factor: 25.391
Authors: Paul M Ridker; Brendan M Everett; Aruna Pradhan; Jean G MacFadyen; Daniel H Solomon; Elaine Zaharris; Virak Mam; Ahmed Hasan; Yves Rosenberg; Erin Iturriaga; Milan Gupta; Michelle Tsigoulis; Subodh Verma; Michael Clearfield; Peter Libby; Samuel Z Goldhaber; Roger Seagle; Cyril Ofori; Mohammad Saklayen; Samuel Butman; Narendra Singh; Michel Le May; Olivier Bertrand; James Johnston; Nina P Paynter; Robert J Glynn Journal: N Engl J Med Date: 2018-11-10 Impact factor: 91.245
Authors: Daniel H Solomon; Robert J Glynn; Elizabeth W Karlson; Fengxin Lu; Cassandra Corrigan; Josh Colls; Chang Xu; Jean MacFadyen; Medha Barbhaiya; Nancy Berliner; Paul F Dellaripa; Brendan M Everett; Aruna D Pradhan; Sarah P Hammond; Meredith Murray; Deepak A Rao; Susan Y Ritter; Anna Rutherford; Jeffrey A Sparks; Jackie Stratton; Dong H Suh; Sara K Tedeschi; Kathleen M M Vanni; Nina P Paynter; Paul M Ridker Journal: Ann Intern Med Date: 2020-02-18 Impact factor: 25.391
Authors: Jeffrey A Sparks; Medha Barbhaiya; Elizabeth W Karlson; Susan Y Ritter; Soumya Raychaudhuri; Cassandra C Corrigan; Fengxin Lu; Jacob Selhub; Daniel I Chasman; Nina P Paynter; Paul M Ridker; Daniel H Solomon Journal: Semin Arthritis Rheum Date: 2017-02-10 Impact factor: 5.532
Authors: Jeffrey A Sparks; Kathleen M M Vanni; Matthew A Sparks; Chang Xu; Leah M Santacroce; Robert J Glynn; Paul M Ridker; Daniel H Solomon Journal: J Am Soc Nephrol Date: 2021-09-22 Impact factor: 10.121