RA-PRO PRAGMATIC TRIAL

Summary

Participation Requirements

Description

Treatment of RA with a biologic or tsDMARD was associated with improved function, quality of life, and productivity. Similar to another review of biologic vs. placebo, in our Cochrane systematic review of MTX-IR RA patients (48 studies; 16,355 patients),the addition of a TNFi-biologic to MTX was ass...

Treatment of RA with a biologic or tsDMARD was associated with improved function, quality of life, and productivity. Similar to another review of biologic vs. placebo, in our Cochrane systematic review of MTX-IR RA patients (48 studies; 16,355 patients),the addition of a TNFi-biologic to MTX was associated with clinically meaningfully and statistically significantly improved HAQ vs. MTX/DMARD or placebo, with a mean difference of -0.25 (95% CI, -0.28 to -0.22), greater than the minimal clinically important difference (MCID) of 0.22. TsDMARDs were similarly effective. No meaningful differences were noted in TNFi-biologic vs. tsDMARD, but head-to-head studies of biologics are lacking. HAQ is a sensitive outcome for RA trials. A PCORI systematic review for early RA treatment concluded that "Evidence was insufficient to evaluate any differences between biologics for their impact on either functional capacity or HRQOL", a key knowledge gap our study will fill. The 2015 ACR RA treatment guideline, based on widely acknowledged low to moderate quality evidence, recommends adding TNFi-biologic, non-TNFi biologic or a tsDMARD to MTX in MTX-IR patients with active RA. In practice, most patients receive a TNFi-biologic first. This is not based on solid evidence, but on arbitrary algorithms often proposed by health insurance plans, physician experience (first TNFi launched 22 yrs ago vs. first tsDMARD 8 yrs ago). This study will fill a critical knowledge gap by generating CER data for important PROs between these treatment options. This will facilitate informed decision-making, since PROs may be more sensitive to different mechanisms of action, and are highly relevant to patients. The proposed study will also provide needed evidence for real-world treatment decisions made by public and private payers. This head-to-head pragmatic trial will be the first to provide CER data for improvement in key PROs with recommended strategies in MTX-IR RA, and addresses PCORI and IOM priority areas by comparing the two most commonly used RA treatment strategies for MTX-IR. This research is patient-centered, as study outcomes were identified by patients and payers. Currently, treatment choices are based on physician experience and insurance payer limitations. Investigators will generate evidence to help patients make decisions for themselves based on outcomes they care most about based on the relative efficacy for outcomes. Investigators will: (1) compare improvements in PROs with RA treatment strategies to each other using a state-of-the-art real-world pragmatic effectiveness study design, which will for the first time include most RA patients with comorbidities;(2) compare their toxicity in a real-world population for TNFi-biologic vs. tsDMARD. To our knowledge, no previous RCT comparing these drugs has examined a PRO as a primary outcome in RA, which our study will pioneer by using HAQ. HAQ is sensitive to change with effective treatments.

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