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Evidence summaries

Methotrexate for Rheumatoid Arthritis

Methotrexate has a substantial clinical benefit compared to placebo in the short term treatment (12 to 52 weeks) of people with rheumatoid arthritis. Level of evidence: "A"

A Cochrane review [Abstract] 1 included 7 studies with a total of 732 subjects with rheumatoid arthritis (RA) comparing methotrexate (weekly doses ranging between 5 mg and 25 mg) to placebo with a follow-up duration ranging from 12 to 52 weeks. All studies included patients who had failed prior treatment (for example, gold therapy, D-penicillamine, azathioprine or anti-malarials), and mean disease duration ranged between 1 and 14 years; 6 studies reporting more than 4 years.

Substantial clinically important and statistically significant differences between methotrexate and placebo were observed for measures of disease activity (table T1), in favour of methotrexate. One (n=189) study measured remission; no participants in either group met the remission criteria defined by at least 5 of (HASH(0x2fcfe80) 2 months): morning stiffness of < 15 minutes, no fatigue, no joint pain by history, no joint tenderness, no joint swelling, and ESR of < 20 mm/hr in men and < 30 mm/hr in women. Methotrexate participants were more likely to discontinue treatment because of adverse reactions, specifically liver enzyme abnormalities. Its use was associated with a 16% discontinuation rate due to adverse events.The most frequent side effects with methotrexate were infections, raised liver enzymes and stomatitis.

Methotrexate monotherapy compared with placebo

OutcomeRelative effect (95% CI)Assumed risk - controlCorresponding risk - MTX (95% CI)NNT (95% CI)Participants (studies)
NNT = number needed to treat; ACR = American College of Rheumatology improvement criteria; SF-36 = Short Form-36, health-related quality of life; *increase in erosion scores of > 3 units
Improvement in ACR 50RR 3.0 (1.5 to 6.0)8 per 10023 per 100(12 to 46)7 (4 to 22)300(1 study)
Improvement in physical function (Health Assessment Questionnaire Disability Index; scale from 0 to 3) The mean functional status ranged across control groups from0.53 to 1.34 unitsThe mean functional status in the intervention groups was0.27 lower(0.39 to 0.16 lower)4 (3 to 7)298(2 studies)
Improvement at least 20% on the SF-36 physical componentRR 1.5 (1.0 to 2.1)27 per 10039 per 100(27 to 57)9 (4 to 539)263(1 study)
Improvement at least 20% on the SF-36 mental componentRR 1.3 (0.79 to 2.0)21 per 10026 per 100(16 to 41)-263(1 study)
Radiographic progression rates*RR 0.31 (0.11 to 0.86)12 per 1004 per 100(1 to 10)13 (10 to 60)219(1 study)
Discontinuation due to adverse eventsRR 2.1 (1.3 to 3.3)8 per 10016 per 100(10 to 25)13 (6 to 44)613(6 studies)
Serious adverse eventsRR 1.4 (0.36 to 5.7)2 per 1003 per 100(1 to 14)-330(2 studies)

    References

    • Lopez-Olivo MA, Siddhanamatha HR, Shea B et al. Methotrexate for treating rheumatoid arthritis. Cochrane Database Syst Rev 2014;(6):CD000957. [PubMed]

Primary/Secondary Keywords