Dataset Information

Adverse Effects of Low-Dose Methotrexate: A Randomized Trial.

ABSTRACT:

Background

Low-dose methotrexate (LD-MTX) is the most commonly used drug for systemic rheumatic diseases worldwide and is the recommended first-line agent for rheumatoid arthritis. Despite extensive clinical use for more than 30 years, few data on adverse event (AE) rates derive from randomized, placebo-controlled trials, where both causality and magnitude of risk can be inferred.

Objective

To investigate AE rates, risk, and risk differences comparing LD-MTX versus placebo.

Design

Prespecified secondary analyses of a double-blind, placebo-controlled, randomized trial. (ClinicalTrials.gov: NCT01594333).

Setting

North America.

Participants

Adults with known cardiovascular disease and diabetes or metabolic syndrome.

Intervention

Random allocation to LD-MTX (≤20 mg/wk) or placebo. All participants received folic acid, 1 mg/d, 6 days per week.

Measurements

Risks for specific AEs of interest, as well as for all AEs, were compared across treatment groups after blinded adjudication.

Results

After an active run-in period, 6158 patients were enrolled and 4786 randomly assigned to a group; median follow-up was 23 months and median dosage 15 mg/wk. Among the randomly assigned participants, 81.2% were male, median age was 65.7 years, and median body mass index was 31.5 kg/m2. Of 2391 participants assigned to LD-MTX, 2080 (87.0%) had an AE of interest, compared with 1951 of 2395 (81.5%) assigned to placebo (hazard ratio [HR], 1.17 [95% CI, 1.10 to 1.25]). The relative hazards of gastrointestinal (HR, 1.91 [CI, 1.75 to 2.10]), pulmonary (HR, 1.52 [CI, 1.16 to 1.98]), infectious (HR, 1.15 [CI, 1.01 to 1.30]), and hematologic (HR, 1.15 [CI, 1.07 to 1.23]) AEs were elevated for LD-MTX versus placebo. With the exception of increased risk for skin cancer (HR, 2.05 [CI, 1.28 to 3.28]), the treatment groups did not differ in risk for other cancer or mucocutaneous, neuropsychiatric, or musculoskeletal AEs. Renal AEs were reduced in the LD-MTX group (HR, 0.85 [CI, 0.78 to 0.93]).

Limitation

The trial was done in patients without rheumatic disease who tolerated LD-MTX during an active run-in period.

Conclusion

Use of LD-MTX was associated with small to moderate elevations in risks for skin cancer and gastrointestinal, infectious, pulmonary, and hematologic AEs, whereas renal AEs were decreased.

Primary funding source

National Institutes of Health.

SUBMITTER: Solomon DH

PROVIDER: S-EPMC7229518 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Adverse Effects of Low-Dose Methotrexate: A Randomized Trial.

Solomon Daniel H DH Glynn Robert J RJ Karlson Elizabeth W EW Lu Fengxin F Corrigan Cassandra C Colls Josh J Xu Chang C MacFadyen Jean J Barbhaiya Medha M Berliner Nancy N Dellaripa Paul F PF Everett Brendan M BM Pradhan Aruna D AD Hammond Sarah P SP Murray Meredith M Rao Deepak A DA Ritter Susan Y SY Rutherford Anna A Sparks Jeffrey A JA Stratton Jackie J Suh Dong H DH Tedeschi Sara K SK Vanni Kathleen M M KMM Paynter Nina P NP Ridker Paul M PM

Annals of internal medicine 20200218 6

<h4>Background</h4>Low-dose methotrexate (LD-MTX) is the most commonly used drug for systemic rheumatic diseases worldwide and is the recommended first-line agent for rheumatoid arthritis. Despite extensive clinical use for more than 30 years, few data on adverse event (AE) rates derive from randomized, placebo-controlled trials, where both causality and magnitude of risk can be inferred.<h4>Objective</h4>To investigate AE rates, risk, and risk differences comparing LD-MTX versus placebo.<h4>Des ...[more]

PMID: 32066146

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Dataset Information

Adverse Effects of Low-Dose Methotrexate: A Randomized Trial.

Background

Objective

Design

Setting

Participants

Intervention

Measurements

Results

Limitation

Conclusion

Primary funding source

Publications

Adverse Effects of Low-Dose Methotrexate: A Randomized Trial.

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