Article Text

PDF
OP0226 Sustained effectiveness of methotrexate with step-down glucocorticoid remission induction (cobra slim) for early rheumatoid arthritis in a treat-to- target setting: 2-year results of the carera trial
  1. V Stouten1,
  2. J Joly2,
  3. D De Cock1,
  4. S Pazmino1,
  5. K Van der Elst2,3,
  6. R Westhovens1,2,
  7. P Verschueren1,2,
  8. on behalf of CareRA study group
  1. 1Skeletal Biology and Engineering Research Center, KU Leuven Department of Development and Regeneration
  2. 2Rheumatology, University Hospitals Leuven
  3. 3Skeletal Biology and Engineering Research Center, KU Leuven Department of Public Health and Primary Care, Leuven, Belgium

Abstract

Background The CareRA trial showed that remission induction with MTX and a moderate-dose of Glucocorticoids (GC) (COBRA Slim) in a treat-to-target setting is effective and safe in early Rheumatoid Arthritis (eRA) patients. This strategy showed equally high remission rates at 52 weeks (W), a favourable safety profile compared to DMARD combinations and GC and very few patients had to start biologicals.

Objectives To compare the outcome of different intensive combination treatment strategies in high-risk patients of the CareRA trial at W104, focussing on persistent disease control.

Methods CareRA is a two-year prospective investigator-initiated pragmatic multicentre RCT; csDMARD 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). High-risk patients (n=289) were randomized to 1/3 arms: 1) COBRA Classic (n=98): Methotrexate (MTX)+Sulphasalazine+60mg prednisone tapered weekly to 7.5mg daily from W7; 2) COBRA Slim (n=98): MTX+30mg prednisone tapered to 5 mg daily from W6; 3) COBRA Avant-Garde (n=93): MTX+Leflunomide+30mg prednisone tapered to 5 mg daily from W6. From W28, GCs were tapered in all patients and stopped at W34. A predefined treat-to-target approach was applied until W52 and afterwards treatment was at the discretion of the rheumatologist. From W40, DMARD monotherapy was aimed for. From W28 onwards patients were evaluated every 3 months till W104. Efficacy measures were proportions of DAS28-CRP remission, good EULAR response, clinically meaningful HAQ response, HAQ=0 (ITT analysis). Adverse events related to therapy (AEs) were registered. Missing data were imputed by last observation carried forward.

Results Remission rates at W104 in high-risk patients were 65.3%, 73.5% and 73.1% in the Classic, Slim and Avant-Garde group respectively (p=0.369). Also, other efficacy outcomes did not differ between groups (see table). From the high-risk patients that were in remission at year 1, 54.7%, 67.8% and 70.2% in the Classic, Slim and Avant-Garde group respectively, stayed in remission at every three-monthly evaluation until w104. Also DAS28-CRP scores remained relatively stable during the second year in these groups. In high-risk patients, the total numbers of AEs reported as related to study therapy, were 209 in 72 Classic patients, 164 in 69 Slim patients and 208 in 74 Avant-Garde patients (p=0.029). Serious AEs were reported in 3 Classic, 4 Slim and 3 Avant-Garde patients. Biologicals were started in 44 high-risk patients (15.2%), of which 7 receiving 2 different biologicals and 2 receiving 3 different ones. Biologicals were administered in 18 Classic, 11 Slim and 15 Avant-Garde patients.

Conclusions All groups showed persistently high remission rates 2 years after remission induction with csDMARDs and GCs in a treat to target setting. COBRA Slim showed comparable efficacy with less adverse events compared to DMARD combinations with moderate or high GC induction dosages. In almost 70% of COBRA Slim patients achieving remission at year 1, this was maintained throughout the second year.

Disclosure of Interest None declared

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.