Article type
Year
Abstract
Introduction/Objective: Two previous meta-analyses have examined the efficacy of DMARD for the treatment of rheumatoid arthritis. Both of them included drug-placebo and head-to-head drug comparisons. Because of the methodological limitations of 'lumping' together trials with different comparison groups, the purpose of this study was to conduct a systematic review and meta-analysis of placebo-controlled DMARDS.
Methods: An electronic literature search was conducted using MEDLINE and EMBASE, followed by hand searches. All controlled clinical trials (CCTs) comparing the most commonly used DMARDS against placebo in patients with RA were included if they reported the outcome measures of interest The methodological quality of the trials was assessed using Jadad's score. Rheumatoid arthritis outcome measures were extracted from the publications for the 6-month endpoint. The pooled analysis was performed using standardized mean differences (SMDs) for joint counts, pain and global assessments. Weighted mean differences (WMDs) were used for ESR. Toxicity was evaluated with pooled odds ratios for withdrawals. A chi-square test was used to assess heterogeneity among trials. Random effects models were used in the presence of statistically significant heterogeneity.
Results: The outcome measures most frequently reported included joint counts and ESR. All DMARDS included in the analysis showed a statistically significant benefit Antimalarials had the lowest withdrawals due to toxicity.
#CCT #pts Swollen jts Tender jts ESR Toxicity
Methotrexate 5 313 -0.6 [-0.9, -0.4] -0.8 [-1.1,-0.6] -8.9 [-18.2,0.3] 3.5 [1.8, 6.6]
Cyclosporine 3 318 -0.6 [-0.9, -0.4] -0.6 [-0.9, -0.3] -0.2 [-5.2, 4.9] 7.6 [3.3, 17.4]
IM Gold 4 415 -0.5 [-0.7, -0.3] -13.2 [-18.1, -8.2] 3.9 [2.1, 7.2]
Antimalarials 4 591 -0.5 [-0.7, -0.4] -0.3 [-0.5, -0.2] -6.4 [-8.5, -4.3] 0.83 [0.4, 1.7]
Sulfasalazine 6 468 -0.5 [-0.8, -0.2] -0.5 [-0.7, -0.2] -17.6 [-22.0, -13.2] 3.0 [1.8, 5.0]
Cyclophosphamide 2 88 -0.6 [-1.1, -0.1] -0.5 [-1.0, -0.05] -11.7 [-25.6, 2.3] 2.3 [0.5, 10.0]
Conclusions: No major differences were observed in the efficacy of the various drugs, but differences were found in their toxicity. This data suggests that initial treatment in rheumatoid arthritis can commence with low toxicity drugs without a major compromise in efficacy.
Methods: An electronic literature search was conducted using MEDLINE and EMBASE, followed by hand searches. All controlled clinical trials (CCTs) comparing the most commonly used DMARDS against placebo in patients with RA were included if they reported the outcome measures of interest The methodological quality of the trials was assessed using Jadad's score. Rheumatoid arthritis outcome measures were extracted from the publications for the 6-month endpoint. The pooled analysis was performed using standardized mean differences (SMDs) for joint counts, pain and global assessments. Weighted mean differences (WMDs) were used for ESR. Toxicity was evaluated with pooled odds ratios for withdrawals. A chi-square test was used to assess heterogeneity among trials. Random effects models were used in the presence of statistically significant heterogeneity.
Results: The outcome measures most frequently reported included joint counts and ESR. All DMARDS included in the analysis showed a statistically significant benefit Antimalarials had the lowest withdrawals due to toxicity.
#CCT #pts Swollen jts Tender jts ESR Toxicity
Methotrexate 5 313 -0.6 [-0.9, -0.4] -0.8 [-1.1,-0.6] -8.9 [-18.2,0.3] 3.5 [1.8, 6.6]
Cyclosporine 3 318 -0.6 [-0.9, -0.4] -0.6 [-0.9, -0.3] -0.2 [-5.2, 4.9] 7.6 [3.3, 17.4]
IM Gold 4 415 -0.5 [-0.7, -0.3] -13.2 [-18.1, -8.2] 3.9 [2.1, 7.2]
Antimalarials 4 591 -0.5 [-0.7, -0.4] -0.3 [-0.5, -0.2] -6.4 [-8.5, -4.3] 0.83 [0.4, 1.7]
Sulfasalazine 6 468 -0.5 [-0.8, -0.2] -0.5 [-0.7, -0.2] -17.6 [-22.0, -13.2] 3.0 [1.8, 5.0]
Cyclophosphamide 2 88 -0.6 [-1.1, -0.1] -0.5 [-1.0, -0.05] -11.7 [-25.6, 2.3] 2.3 [0.5, 10.0]
Conclusions: No major differences were observed in the efficacy of the various drugs, but differences were found in their toxicity. This data suggests that initial treatment in rheumatoid arthritis can commence with low toxicity drugs without a major compromise in efficacy.