A Cochrane review [Abstract] included 9 studies with a total of 2 842 subjects. At 6 to 36 months the American College of Rheumatology (ACR) 50 response rate was statistically significantly improved with etanercept plus disease-modifying anti-rheumatic drug (DMARD) treatment when compared with a DMARD in those people who had an inadequate response to any traditional DMARD (table T1) and in those people who were partial responders to MTX (RR 11.7, 95% CI 1.7 to 82.5). Similar results were observed when pooling data from all participants (responders or not) (ACR 50 response rates at 24 months: RR 1.9, 95% CI 1.3 to 2.8; 36 months: RR 1.6, 95% CI 1.3 to 1.9). Statistically significant improvement in physical function and a higher proportion of disease remission were observed in combination-treated participants compared with DMARDs alone in those people who had an inadequate response to any traditional DMARD (table T1). All changes in radiographic scores were statistically significantly less with combination treatment (etanercept plus DMARD) compared with MTX alone for all participants (responders or not).
| Outcome | Relative effect (95% CI) | Assumed risk - DMARD | Corresponding risk - ET 25 mg + DMARD (95% CI) | NNTB (95% CI) | Participants (studies) |
|---|---|---|---|---|---|
| ACR50 = American College of Rheumatology 50% improvement criteria; NNTB = number needed to treat for an additional beneficial outcome | |||||
| ACR50 | RR 1.96 (1.33 to 2.89) | 405 per 1000 | 793 per 1000(538 to 1000) | 3 (2 to 8) | 1 198(4 studies) |
| Remission(achievement of disease activity score < 2.6) | RR 1.92 (1.6 to 2.31) | 236 per 1000 | 454 per 1000(378 to 546) | 5 (4 to 8) | 987(2 studies) |
| Reduction in disability score (scale from 0 to 3) | The mean reduction in disability score ranged across control groups from-0.15 to -0.72 | The mean reduction in disability score in the intervention groups was0.36 lower(0.43 lower to 0.28 lower) | 1 227(4 studies) | ||
| Withdrawals due to adverse events | RR 0.75 (0.57 to 1.0) | 158 per 1000 | 118 per 1000(90 to 158) | 1 241(4 studies) | |
| Serious adverse events | RR 1.25 (0.74 to 2.11) | 141 per 1000 | 176 per 1000(104 to 297) | 1 241(4 studies) | |
| Serious infections | RR 0.91 (0.54 to 1.55) | 49 per 1000 | 45 per 1000(27 to 77) | 1 152(3 studies) | |
When etanercept monotherapy was compared with DMARD monotherapy, there was generally no evidence of a difference in ACR50 response rates when etanercept 10 mg or 25 mg was used; at 6 months etanercept 25 mg was significantly more likely to achieve ACR50 than DMARD monotherapy but this difference was not found at 12, 24 or 36 months.
There was no evidence of statistically significant differences in infections or serious infections between etanercept plus DMARD and DMARD alone at any point in time. Infection rates were higher in people receiving etanercept monotherapy compared with DMARD; however, there were no differences regarding serious infections. For those participants who had an inadequate response to DMARDs, the rate of total withdrawals was lower for the etanercept plus DMARD group compared with DMARD alone (RR 0.53, 95% CI 0.36 to 0.77). No other statistically significant differences were observed in any of the assessed comparisons.
Note: This review found no evidence of a difference in the rates of serious adverse events with either etanercept monotherapy or combined treatment with etanercept and DMARD in the short term. However, there are concerns with increased incidence of infections (particularly tuberculosis) and possibly increased malignancy risks, so the long-term benefit and safety need to be evaluated further.
Primary/Secondary Keywords