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Donahue KE, Gartlehner G, Schulman ER, et al. Drug Therapy for Early Rheumatoid Arthritis: A Systematic Review Update [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2018 Jul. (Comparative Effectiveness Review, No. 211.)

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Drug Therapy for Early Rheumatoid Arthritis: A Systematic Review Update [Internet].

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Appendix GTests of Consistency for Main Network Meta-Analyses

Main Network Meta-Analyses

We identified a total of 14 studies with a low or medium risk of bias for use in our main network meta-analyses (NWMA) comparing the efficacy of drug therapies for early rheumatoid arthritis. Those findings are presented in our main report.

Below, we present findings for our tests of consistency for specific drug comparisons.

Tests of Consistency: Models Excluding High Risk of Bias Studies

To test for consistency, we compared consistency and inconsistency models. In addition, where there were closed loops in the network diagram with both direct and indirect evidence available, we examined differences in results between direct and indirect evidence using network sidesplits. Of the closed loops in the networks, network sideplits could not be computed for the loop consisting of Tocilizumab, Tocilizumab+MTX, and MTX because all three treatments were included in the same two trials and therefore, only direct evidence was available.

ACR50 Response

For the ACR50 outcome (see Appendix Table G-1), there was no significant difference in the consistency and inconsistency models (χ2(1)=0.28, p=0.868). Results did not differ significantly between direct and indirect evidence for Abatacept versus Abatacept plus MTX (coefficient [95% CI]=−0.09 [−0.69 to 0.52], p=0.777) or for Infliximab plus MTX versus Methylprednisolone plus MTX (coefficient [95% CI]= −0.37 [−1.99 to 1.25], p=0.653).

Remission According to Disease Activity Score

For the DAS outcome (see Appendix Table G-2), there was no significant difference in the consistency and inconsistency models (χ2(1)=0.52, p=0.772). Results did not differ significantly between direct and indirect evidence for Abatacept versus Abatacept plus MTX (coefficient (95% CI)=−0.60 (−2.31 to 1.11], p=0.491) or for Infliximab plus MTX versus Methylprednisolone plus MTX (coefficient [95% CI]= −0.44 [−2.72 to 1.84], p=0.705).

All Withdrawals

For all withdrawals (see Appendix Table G-3), there was no significant difference in the consistency and inconsistency models (χ2(1)=0.43, p=0.808). Results did not differ significantly between direct and indirect evidence for Abatacept versus Abatacept plus MTX (coefficient [95% CI]=−0.31 [−2.01 to 1.38], p=0.716) or for Infliximab plus MTX versus Methylprednisolone plus MTX (coefficient [95% CI]= 1.29 [−3.33 to 5.90], p=0.585).

Withdrawals Due to Adverse Events

For the DAS outcome (see Appendix Table G-4), there was no significant difference in the consistency and inconsistency models (χ2(1)=2.86, p=0.239). Results did not differ significantly between direct and indirect evidence for Abatacept versus Abatacept plus MTX (coefficient [95% CI]= −1.92 [−4.15 to 0.31], p=0.091) or for Infliximab plus MTX versus Methylprednisolone plus MTX (coefficient [95% CI]= 0.16 [−6.23 to 6.55], p=0.962).

Appendix Table G-1Table with network sidesplits: ACR50 response

Drug ADrug BDirect Coefficient95% CIpIndirect Coefficient95% CIpCoefficient Difference95% CIp
AbataceptAbatacept+MTX0.16−0.07, 0.380.1780.24−0.33, 0.820.406−0.09−0.69, 0.520.777
Infliximab+MTXMethylprednisolone+ MTX0.00−0.51, 0.511.0000.37−1.17, 1.910.636−0.37−1.99, 1.250.653

ACR50 = American College of Rheumatology 50% response; CI = confidence interval; MTX = methotrexate

Appendix Table G-2Table with network sidesplits: Remission according to Disease Activity Score

Drug ADrug BDirect Coefficient95% CIpIndirect Coefficient95% CIpCoefficient Difference95% CIp
AbataceptAbatacept+MTX0.35−0.26, 0.960.2570.95−0.66, 2.570.247−0.60−2.31, 1.110.491
Infliximab+ MTXMethylprednisolone+ MTX0.10−0.62, 0.810.7950.53−1.61, 2.680.625−0.44−2.72, 1.840.705

CI = confidence interval; MTX = methotrexate

Appendix Table G-3Table with network sidesplits: All withdrawals

Drug ADrug BDirect Coefficient95% CIpIndirect Coefficient95% CIpCoefficient Difference95% CIp
AbataceptAbatacept+MTX−0.47−1.08, 0.130.126−0.16−1.68, 1.370.839−0.31−2.01, 1.380.716
Infliximab+ MTXMethylprednisolone+ MTX0.00−2.68, 2.681.000−1.29−5.04, 2.470.5021.29−3.33, 5.900.585

CI = confidence interval; MTX = methotrexate

Appendix Table G-4Table with network sidesplits: Withdrawals due to adverse events

Drug ADrug BDirect Coefficient95% CIpIndirect Coefficient95% CIpCoefficient Difference95% CIp
AbataceptAbatacept+MTX−1.48−2.26, −0.70<0.0010.44−1.43, 2.320.644−1.92−4.15, 0.310.091
Infliximab+ MTXMethylprednisolone+ MTX−1.10−4.22, 2.030.491−1.26−7.68, 5.170.7020.16−6.23, 6.550.962

CI = confidence interval; MTX = methotrexate

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