Long-term effectiveness of the cobra slim remission induction and treat to target strategy in patients with early rheumatoid arthritis lacking classical markers of poor prognosis: 2 year results of the carera trial

Background: EULAR guidelines recommend to treat all patients with early Rheumatoid Arthritis (eRA) with a combination of methotrexate (MTX) and a short-term course of Glucocorticoids (GC). The COBRA Slim strategy with MTX and a moderately dosed tapering down scheme of GC was effective, also in patients without classical markers of poor prognosis during the first year. Objectives: To compare the outcomes of MTX with or without initial step-down GC in Low-Risk patients during the second year of the CareRA trial, in terms of disease control, safety and DMARD use. Methods: CareRA is a two-year prospective investigator-initiated pragmatic multicentre RCT. DMARD naïve eRA patients were stratified into a High-or Low-Risk group based on classical prognostic markers (presence of erosions, RF, anti-CCP and DAS28-CRP). Low-Risk patients (n=90) were randomised to either Tight-Step Up (TSU) with MTX 15 mg weekly without GC or to COBRA Slim, a combination of MTX 15 mg weekly and prednisone tapering down scheme starting at 30 mg, tapered to 5 mg daily from w6 and stopped at w34. A treat-to-target approach was applied until year 1 and afterwards treatment was at the discretion of the rheumatologist. Proportions of DAS28-CRP remission at year 2 was a coprimary CareRA endpoint. Secondary outcomes were efficacy according to other remission criteria, EULAR/ACR response rates and functionality measured by HAQ (ITT analysis, last observation carried forward). Adverse events (AEs) and concomitant medication were registered. Results: At year 2, 67.4% of Slim and 70.2% of TSU patients were in remission according to DAS28CRP (p=0.777). Out of patients in DAS28CRP remission at year 1, 80.0% (24/30) in the Slim group, versus 69.0% (20/29) in the TSU group remained in remission at every three-monthly evaluation until year 2. Remission rates defined by Boolean criteria were higher in patients of the Slim (39.5%) versus TSU group (19.1%) (p=0.033). Functionality measured by mean area under the HAQ curve over 2 years was better in Slim patients (38.3±47.2) than in TSU patients (56.4±48.7) (p=0.025). Other secondary efficacy outcomes did not differ between the treatment arms. The total numbers of AEs reported as related to study therapy, were 69 in 34 TSU patients and 63 in 28 Slim patients. Biologicals were started in 14 Low-Risk patients (15.6%), more specifically in 8 Slim and 6 TSU patients during the CareRA trial. At the year 2 visit 62.5% of Slim patients were on MTX monotherapy and 12.5% on a combination of csDMARDs. In the TSU group 58.5% was taking MTX as only DMARD, and 19.5% took a combination of csDMARDs. Out of all Low-Risk patients 11.0% (8/73) was taking oral GC at the year 2 visit, 5 patients in the TSU group and 3 patients in Slim group, all at a low dosages. Conclusions: In eRA patients lacking classical markers of poor prognosis COBRA Slim showed persistently high remission rates and good disease control 2 years after initiating therapy in a treat to target setting. COBRA slim seems to be slightly more effective than TSU according to the year 2 Boolean remission criteria and the 2 year functionality AUC but the CareRA study was not powered for this analysis. (Table Presented).