Cost-effective Tapering Algorithm in Patients with Rheumatoid Arthritis: Combination of Multibiomarker Disease Activity Score and Autoantibody Status

Abstract

Objective.To analyze the effect of a risk-stratified disease-modifying antirheumatic drug (DMARD)–tapering algorithm based on multibiomarker disease activity (MBDA) score and anticitrullinated protein antibodies (ACPA) on direct treatment costs for patients with rheumatoid arthritis (RA) in sustained remission.Methods.The study was a posthoc retrospective analysis of direct treatment costs for 146 patients with RA in sustained remission tapering and stopping DMARD treatment, in the prospective randomized RETRO study. MBDA scores and ACPA status were determined in baseline samples of patients continuing DMARD (arm 1), tapering their dose by 50% (arm 2), or stopping after tapering (arm 3). Patients were followed over 1 year, and direct treatment costs were evaluated every 3 months. MBDA and ACPA status were used as predictors creating a risk-stratified tapering algorithm based on relapse rates.Results.RA patients with a low MBDA score (< 30 units) and negative ACPA showed the lowest relapse risk (19%), while double-positive patients showed high relapse risk (61%). In ACPA-negative and MBDA-negative (< 30 units), and ACPA or MBDA single-positive (> 30 units) groups, DMARD tapering appears feasible. Considering only patients without flare, direct costs for synthetic and biologic DMARD in the ACPA/MBDA-negative and single positive groups (n = 41) would have been €372,245.16 for full-dose treatment over 1 year. Tapering and stopping DMARD in this low-risk relapse group allowed a reduction of €219,712.03 of DMARD costs. Average reduction of DMARD costs per patient was €5358.83.Conclusion.Combining MBDA score and ACPA status at baseline may allow risk stratification for successful DMARD tapering and cost-effective use of biologic DMARD in patients in deep remission as defined by the 28-joint count Disease Activity Score using erythrocyte sedimentation rate.

Value of the Multibiomarker Disease Activity Score to Predict Remission in RA: What Does the Evidence Show?

“…An article in this issue of The Journal by Hagen, et al, addresses the cost-effectiveness of being able to discontinue DMARD, particularly biological DMARD 14 . If a patient is in medication-free remission with complete control of their RA, their cost of treatment will be dramatically lower than that of a patient who does require medication to control their disease.…”

Clinical predictors of response to methotrexate in patients with rheumatoid arthritis: a machine learning approach using clinical trial data

“…It has been suggested that the presence of multiple autoantibodies at baseline may reflect a more active autoimmune response which is more susceptible to suppression by MTX in the initial stages, but not in later stages [32]. Indeed, ACPA positivity has been associated with lower rates of drug-free remission in RA in several large studies [33][34][35][36], potentially indicating the persistence of a population of ACPA IgG-producing autoreactive B-cells that is resistant to therapy and accounts for the inability to achieve drug-free remission in RA in the long run [32]. Given that ACPA and RF seropositivity can be helpful in informing response to treatment with other antirheumatic medications in RA (e.g., abatacept and rituximab), confirming the value of differential prediction of early response to MTX treatment in RA by serostatus in future studies may help to further refine the approach to the management of early RA [37,38].…”

Prevention and cure: The major unmet needs in the management of rheumatoid arthritis

“…After a follow-up period of 12 months, about 2/3 of patients remained in remission whereas 1/3 experienced a disease flare. The rate of flares was low in the continuation arm (16%) and significantly higher in the tapering (38.9%) and stopping arms (52%)(101).…”

“…With respect to serum biomarkers, the best-studied predictor of relapse is ACPA positivity. In the BEST study, as well as in the RETRO and HIT-HARD studies, ACPA positivity was associated with higher relapse risk and failure of b-DMARDs discontinuation (73,101,105). In a very recent study, serum calprotectin resulted as an independent predictor of relapse in a cohort of patients with RA and psoriatic arthritis (106).…”