PMID- 32741143
OWN - NLM
STAT- MEDLINE
DCOM- 20210104
LR  - 20210104
IS  - 2326-5205 (Electronic)
IS  - 2326-5191 (Print)
IS  - 2326-5191 (Linking)
VI  - 72
IP  - 12
DP  - 2020 Dec
TI  - Pulmonary Adverse Events in Patients Receiving Low-Dose Methotrexate in the 
      Randomized, Double-Blind, Placebo-Controlled Cardiovascular Inflammation 
      Reduction Trial.
PG  - 2065-2071
LID - 10.1002/art.41452 [doi]
AB  - 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.
CI  - (c) 2020, American College of Rheumatology.
FAU - Sparks, Jeffrey A
AU  - Sparks JA
AUID- ORCID: 0000-0002-5556-4618
AD  - Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
FAU - Dellaripa, Paul F
AU  - Dellaripa PF
AD  - Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
FAU - Glynn, Robert J
AU  - Glynn RJ
AD  - Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
FAU - Paynter, Nina P
AU  - Paynter NP
AD  - Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
FAU - Xu, Chang
AU  - Xu C
AD  - Brigham and Women's Hospital, Boston, Massachusetts.
FAU - Ridker, Paul M
AU  - Ridker PM
AD  - Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
FAU - Solomon, Daniel H
AU  - Solomon DH
AUID- ORCID: 0000-0001-8202-5428
AD  - Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
LA  - eng
SI  - ClinicalTrials.gov/NCT01594333
GR  - P30 AR072577/AR/NIAMS NIH HHS/United States
GR  - P30 AR070253/AR/NIAMS NIH HHS/United States
GR  - U01 HL101422/HL/NHLBI NIH HHS/United States
GR  - K23 AR069688/AR/NIAMS NIH HHS/United States
GR  - L30 AR066953/AR/NIAMS NIH HHS/United States
GR  - U01 HL101389/HL/NHLBI NIH HHS/United States
GR  - R03 AR075886/AR/NIAMS NIH HHS/United States
GR  - R01 HL119718/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20201007
PL  - United States
TA  - Arthritis Rheumatol
JT  - Arthritis & rheumatology (Hoboken, N.J.)
JID - 101623795
RN  - 0 (Immunosuppressive Agents)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
CIN - Arthritis Rheumatol. 2020 Dec;72(12):1959-1962. PMID: 32720443
MH  - Adult
MH  - Age Factors
MH  - Cardiovascular Diseases/prevention & control
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Immunosuppressive Agents/*adverse effects/therapeutic use
MH  - Inflammation/prevention & control
MH  - Male
MH  - Methotrexate/*adverse effects/therapeutic use
MH  - Middle Aged
MH  - Pneumonia/*chemically induced
MH  - Risk Factors
MH  - Sex Factors
PMC - PMC7722048
MID - NIHMS1620299
EDAT- 2020/08/03 06:00
MHDA- 2021/01/05 06:00
PMCR- 2020/12/08
CRDT- 2020/08/03 06:00
PHST- 2020/04/16 00:00 [received]
PHST- 2020/06/12 00:00 [accepted]
PHST- 2020/08/03 06:00 [pubmed]
PHST- 2021/01/05 06:00 [medline]
PHST- 2020/08/03 06:00 [entrez]
PHST- 2020/12/08 00:00 [pmc-release]
AID - 10.1002/art.41452 [doi]
PST - ppublish
SO  - Arthritis Rheumatol. 2020 Dec;72(12):2065-2071. doi: 10.1002/art.41452. Epub 2020 
      Oct 7.