Studies included in this systematic review.
| Study | No. of Participants | Duration | Interventions | Outcomes | Methodological Quality* | Notes |
|---|---|---|---|---|---|---|
| Bresnihan 199833 | 472 | 24 wks | Placebo (n = 119), 30 mg anakinra (n = 119), 75 mg anakinra (n = 115), 150 mg anakinra (n = 115) | ACR 20, HAQ, VAS (pain), ESR, CRP, Larsen scores, withdrawals, injection site reactions | Silver; no intention-to-treat analysis; method of randomization was not reported; 26.7% withdrawal rate | Excluded patient data from analysis if outcome data was missing |
| Cohen 200235 | 317 | 24 wks | Placebo (n = 48), 0.04 mg/kg (n = 63), 0.1 mg/kg (n = 46), 0.4 mg/kg (n = 55), 1.0 mg/kg (n = 59), 2.0 mg/kg (n = 46) daily. Methotrexate was required for inclusion in this study | ACR20/50/70, withdrawals, injection site reactions (continuous data not included as no SD/SE data provided) | Silver; method of randomization was not reported; blinding was only described for the patients; 21% withdrawal rate at 24 weeks | Originally designed as a 12 wk trial, expanded to 24 wks; only 3 patients reconsented to the 24 wk study |
| Cohen 200436 | 506 | 24 wks | Placebo (n = 251), anakinra 100 mg daily (n = 250) | ACR20/50/70, HAQ, ESR, injection site reactions, adverse events (total, serious), infections (total, serious), | Silver; no intention-to-treat analysis; method of randomization was not reported | Number of total withdrawals was not reported in this study |
| Fleischman 200334 | 1414 | 6 mo | Placebo (n = 283), anakinra 100 mg daily (n = 1116) | withdrawals, injection site reactions, deaths, adverse events (total, serious), infections (total, serious) | Silver; no intention-to-treat analysis; method of randomization was not reported; 21.9% withdrawal rate | |
| Genovese 200437 | 244 | 24 wks | Placebo + etanercept 25 mg biweekly (n = 80) anakinra 100 mg daily + etanercept 25 mg weekly (n = 81), anakinra 100 mg daily + etanercept 25 mg biweekly (n = 81). Methotrexate was required for inclusion in this study | ACR20/50/70, withdrawals, injection site reactions, adverse events (total, serious), infections (total, serious) | Silver; though full blinding was only reported for the patients; no intention-to-treat analysis; method of randomization was not reported; 17.4% withdrawal rate | The anakinra+ etanercept 25 mg weekly group did not have a placebo-controlled comparison |
↵* Methodological quality was defined using the system described by Tugwell, et al30 as follows: Platinum: A published systematic review that has at least 2 individual controlled trials each satisfying the following: Sample size of at least 50 per group — if these do not find a statistically significant difference, they are adequately powered for a 20% relative difference in the relevant outcome. Blinding of patients and assessors for outcomes. Handling of withdrawals > 80% followup [imputations based on methods such as last observation carried forward (LOCF) are acceptable]. Concealment of treatment allocation. Gold: At least 1 randomized clinical trial meeting all the following criteria for the major outcome(s) as reported: Sample sizes of at least 50 per group — if these do not find a statistically significant difference, they are adequately powered for a 20% relative difference in the relevant outcome. Blinding of patients and assessors for outcomes. Handling of withdrawls > 80% followup (imputations based on methods such as LOCF are acceptable). Concealment of treatment allocation. Silver: A randomized trial that does not meet the above criteria. Silver ranking would also include evidence from at least 1 study of non-randomized cohorts that did and did not receive the therapy, or evidence from at least one high quality case-control study. A randomized trial with a “head-to-head” comparison of agents would be considered silver level ranking unless a reference were provided to a comparison of one of the agents to placebo showing at least a 20% relative difference. Bronze: The bronze ranking is given to evidence if a least 1 high quality case series without controls (including simple before/after studies in which patients act as their own control) or if the conclusion is derived from expert opinion based on clinical experience without reference to any of the foregoing (for example, argument from physiology, bench research, or first principles). ACR: American College of Rheumatology; HAQ: Health Assessment Questionnaire; VAS: visual analog scale; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; SD/SE: standard deviation/error.