A cost-effectiveness analysis of different intensive combination therapies for early rheumatoid arthritis: 1 year results of the carera trial

Background: The (Care in Early RA) CareRA trial compared different treatment strategies in patients with early Rheumatoid Arthritis (ERA) with or without markers of poor prognosis. No significant differences were shown between the treatment arms in terms of remission rate and functionality at 16 and 52 weeks. The differential cost-effectiveness of these therapeutic strategies could aid in determining the optimal approach for ERA. Objectives: To compare the cost-effectiveness of different therapeutic strategies used in the CareRA trial during the first treatment year in patients with early Rheumatoid Arthritis. Methods: The CareRA trial is a 2-year investigator-initiated randomized pragmatic superiority trial comparing remission induction regimens in a treat-to-target approach. DMARD naïve ERA patients were stratified into a high- or low-risk group based on prognostic markers. High-risk patients were randomized to a COBRA Classic (Methotrexate (MTX) + Sulphasalazine + prednisone step-down from 60mg), COBRA Slim (MTX + prednisone step-down from 30mg) or COBRA Avant-Garde (MTX + Leflunomide + prednisone step-down from 30mg) scheme. Low-risk patients were randomized to MTX tight step-up (MTX-TSU) or COBRASlim. The direct costs for each patient in the trial were calculated by summing the cost of a rheumatology consultation, per protocol CareRA study medication and RA-related medication such as biologicals and extra glucocorticoids not stipulated in the protocol. The incremental cost-effectiveness ratio (ICER) was calculated using these costs and the treatment efficacy as observed in CareRA. Efficacy parameters investigated were the proportion of patients in remission (DAS28(CRP) <2.6) and the proportion with a clinically meaningful improvement of Health Assessment Questionnaire (HAQ change >0.22) at week 52. Results: 349 out of 379 patients had sufficient cost information to be evaluated at week 52. Remission was achieved in 65,6% Classic, 61.7% Slim (high-risk) and 64.1% Avant-Garde patients; and in 56.8% MTX-TSU and 70.0% Slim (low-risk) patients. A clinically meaningful HAQ response was reached in 66.7% Classic, 70.2% Slim (high-risk) and 75.6% Avant-Garde patients; and in 58.3% MTX-TSU and 60.0% Slim (low-risk) patients. Mean ±SD total costs during year one were Δ1044.3 ± Δ871.0 Δ859.7 ±Δ431.3 and Δ1267.7 ±Δ632.7 for the Classic, Slim (high-risk) and Avant-Garde respectively; and Δ880.6 ±Δ917.4 and Δ867.5 ±Δ364.0 for MTX-TSU and Slim (low-risk) patients. In MTX-TSU patients, the high average cost ±SD of Δ268.6 ±Δ876.5 was remarkable. Cost-effectiveness analysis in the high-risk arm showed a higher ICER for Classic (Δ47.3/1% remission) and Avant-Garde (Δ170.0/1% remission) compared to Slim (highrisk); In the low-risk arm, the cost-effectiveness of MTX-TSU was shown to be comparable to Slim (low-risk), with an ICER of Δ-0.99/1% remission. Conclusions: Cobra Slim, a combination of MTX with a moderately dosed glucocorticoid remission induction showed favorable cost-effectiveness in both ERA patients with or without poor prognosis.