Effectiveness of different combinations of DMARDs and glucocorticoid bridging in early rheumatoid arthritis: two-year results of CareRA

Rheumatology (Oxford). 2019 Dec 1;58(12):2284-2294. doi: 10.1093/rheumatology/kez213.

Abstract

Objectives: To investigate whether MTX should be combined with an additional DMARD and bridging glucocorticoids as initial treatment for patients with early RA to induce an effective long-term response.

Methods: The Care in early RA study is a two-year investigator-initiated pragmatic multicentre randomized trial. Early RA patients, naïve to DMARDs and glucocorticoids, were stratified based on prognostic factors. High-risk patients were randomized to COBRA-Classic (n = 98): MTX, sulfasalazine, prednisone step-down from 60 mg; COBRA-Slim (n = 98): MTX, prednisone step-down from 30 mg; or COBRA-Avant-Garde (n = 93): MTX, leflunomide, prednisone step-down from 30 mg. Low-risk patients were randomized to COBRA-Slim (n = 43); or Tight Step Up (TSU) (n = 47): MTX without prednisone. Clinical/radiological outcomes at year 2, sustainability of response, safety and treatment adaptations were assessed.

Results: In the high-risk group 71/98 (72%) patients achieved a DAS28-CRP < 2.6 with COBRA-Slim compared with 64/98 (65%) with COBRA-Classic and 69/93 (74%) with COBRA-Avant-Garde (P = 1.00). Other clinical/radiological outcomes and sustainability of response were similar. COBRA-Slim treatment resulted in less therapy-related adverse events compared with COBRA-Classic (P = 0.02) or COBRA-Avant-Garde (P = 0.005). In the low-risk group, 29/43 (67%) patients on COBRA-Slim and 34/47 (72%) on TSU achieved a DAS28-CRP < 2.6 (P = 1.00). On COBRA-Slim, low-risk patients had lower longitudinal DAS28-CRP scores over 2 years, a lower need for glucocorticoid injections and a comparable safety profile compared with TSU.

Conclusion: All regimens combining DMARDs with glucocorticoids were effective for patients with early RA up to 2 years. The COBRA-Slim regimen, MTX monotherapy with glucocorticoid bridging, provided the best balance between efficacy and safety, irrespective of patients' prognosis.

Trial registration: ClinicalTrials.gov, http://www.clinicaltrials.gov, NCT01172639.

Keywords: DMARDs (synthetic); early rheumatoid arthritis; effectiveness; glucocorticoids; methotrexate; treatment.

Publication types

  • Multicenter Study
  • Pragmatic Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antirheumatic Agents / administration & dosage
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / drug therapy*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Glucocorticoids / administration & dosage
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Joints / diagnostic imaging*
  • Leflunomide / administration & dosage*
  • Male
  • Middle Aged
  • Prednisone / administration & dosage*
  • Prognosis
  • Prospective Studies
  • Radiography
  • Severity of Illness Index
  • Sulfasalazine / administration & dosage*
  • Time Factors
  • Treatment Outcome

Substances

  • Antirheumatic Agents
  • Glucocorticoids
  • Immunosuppressive Agents
  • Sulfasalazine
  • Leflunomide
  • Prednisone

Associated data

  • ClinicalTrials.gov/NCT01172639