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CE1 METHODOLOGICAL CHALLENGES WITH CONDUCTING NETWORK META-ANALYSES ASSESSING LONG-TERM COMPARATIVE EFFICACY IN PSORIASIS: A CRITIQUE OF ASSUMPTIONS UNDERPINNING RECENT INDIRECT TREATMENT COMPARISONS

      Objectives

      In network meta-analysis (NMA) of psoriasis trials, cross-over after an initial placebo-controlled period limits the connectivity of long-term evidence networks. We illustrate the challenges with conducting NMAs assessing efficacy beyond cross-over in psoriasis by critically appraising the assumptions underpinning recent long-term NMAs.

      Methods

      We compared three recent NMA studies (Armstrong et al. 2019, Sawyer et al. 2018, and Diels et al. 2017) assessing long-term (beyond 16 to 24 weeks) comparative efficacy in psoriasis and investigated how the three studies derived comparative efficacy estimates in the absence of a connected network. While each of the review methods address a slightly different research question, we assumed the underlying goal was to approximate the results from a standard connected network. The purpose of the study was therefore to assess the assumptions required for each approach that would provide unbiased estimates of the comparative effectiveness of included agents.

      Results

      Armstrong et al. did not analyze comparative RCT data but instead removed placebo arms with cross-over, pooled individual active arms from 23 RCTs, and conducted naïve indirect comparisons between pooled arms (which assumes that all trials are equivalent in terms of prognostic factors, an unlikely assumption). Sawyer et al. analyzed a largely disconnected network with four comparative RCTs, as well as a larger network that was connected through 17 comparisons that assumed placebo response rates observed during induction period were maintained to week 52. Diels et al. only included comparative RCTs in their NMA and constructed a network of 11 RCTs by assuming a class-effect among TNFα inhibitors (i.e., all TNFα inhibitors have similar efficacy).

      Conclusions

      Recent analyses assessing long-term comparative efficacy in psoriasis have methodological limitations and should be interpreted with caution. Future studies should consider the assumptions underpinning NMAs and assess how alternative NMA methods can be leveraged to yield more rigorous long-term indirect treatment comparisons.