Two year cost-effectiveness analysis of the carera trial in early RA: A piggy back study

Background: Rheumatoid arthritis (RA) causes high individual, medical and societal costs. EULAR guidelines suggest treating early, intensively and to target using disease modifying anti-rheumatic drugs (DMARDs), preferably with initial glucocorticoid (GC) bridging. COBRA slim, a combination of methotrexate (MTX) with a moderate dose prednisone step down bridge scheme showed a positive efficacy/tolerability balance in the Care in early RA (CareRA) trial. COBRA Slim in comparison to DMARD combination therapy with GC bridging, has the necessary intensity to induce remission, but with a lower risk of severe discomfort or adverse events, decreasing the early need for biologic (b)DMARDs. Objectives: Perform an economic evaluation on the 2 year pragmatic randomised CareRA trial. Methods: Patients with early RA (≤1 year) naïve to DMARDs were randomised to monotherapy or synthetic (cs)DMARD combination with or without GC bridging, after risk stratification based on classical prognostic markers. Clinical and patientreported data were collected at each visit (≥10 times in 2 years). Direct costs of visits and RA medication (systemic GCs, cs and bDMARDs) over 2 years were calculated for each patient from each of the 5 treatment arms (table 1). For cost-effectiveness analysis, benefits were expressed as the proportion of patients with DAS28CRP<2.6 at year 2. Missing data was imputed per item with expectation maximisation. For cost-utility analysis, utilities were calculated using a validated mapping algorithm reconstructing EQ-5D scores based on age, sex, HAQ and pain scores at relevant study visits. Quality-adjusted life years (QALYs) encapsulating the impact of treatment on a patient's length of life and health-related quality of life, were calculated as the time-weighted average of all available EQ-5D scores (area under the curve). Incremental cost-effectiveness ratios (ICERs) from each strategy were calculated. ICERs compare the additional costs a strategy imposes over another with the additional benefits it delivers. Means and medians based methods were calculated with confidence intervals via bootstrapping. Results: From the initial CareRA cohort (n=379), cost/benefit data of 326 patients was used for a 2 year economic analysis. The mayor driver of direct costs was bDMARDs (57%>87% of total costs). Number of consultations were comparable (±11) across all treatment strategies. The cost-effectiveness analysis in the high risk population showed a higher ICER for COBRA Avant Garde (mean € 198.65/1%, median € 78.41/1%) and a dominated ICER for COBRA Classic (mean € -181.40/1%, median € -35.01/1%) compared to the Slim. In the low risk arm, ICERs for COBRA Slim compared to Tight Step Up (TSU) were € 46.75/1% (mean) and € 43.64/1% (median). Cost-utility analysis in the high risk arm showed an incremental cost of € 1 469.36 for an increased utility of 0.012555 QALYS for COBRA Classic compared to COBRA Slim, resulting in an ICER of € 117 033.85/QALY. The ICER of COBRA Avant Garde vs COBRA Slim was € 69 329.19/QALY. In the low risk arm, the comparison of COBRA Slim to TSU yields an ICER of € 1 342.78 per QALY. Conclusions: COBRA Slim which consists of an initial combination of MTX and a moderate dosed GC remission induction scheme has a favourable cost-effective and cost-utility profile for patients with early RA independent of their prognostic factors. (Table Presented).