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(0x2f82cc8) 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.
| Outcome | Relative effect (95% CI) | Assumed risk - control | Corresponding 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 50 | RR 3.0 (1.5 to 6.0) | 8 per 100 | 23 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 units | The 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 component | RR 1.5 (1.0 to 2.1) | 27 per 100 | 39 per 100(27 to 57) | 9 (4 to 539) | 263(1 study) | |
| Improvement at least 20% on the SF-36 mental component | RR 1.3 (0.79 to 2.0) | 21 per 100 | 26 per 100(16 to 41) | - | 263(1 study) | |
| Radiographic progression rates* | RR 0.31 (0.11 to 0.86) | 12 per 100 | 4 per 100(1 to 10) | 13 (10 to 60) | 219(1 study) | |
| Discontinuation due to adverse events | RR 2.1 (1.3 to 3.3) | 8 per 100 | 16 per 100(10 to 25) | 13 (6 to 44) | 613(6 studies) | |
| Serious adverse events | RR 1.4 (0.36 to 5.7) | 2 per 100 | 3 per 100(1 to 14) | - | 330(2 studies) | |
Primary/Secondary Keywords