Simplified Combination Tx for Early Rheumatoid Arthritis Is Safe, Effective

man holding his hand in pain
man holding his hand in pain
COBRA is a combination therapy regimen for RA that has been shown to be safe and effective in the early stages of RA for improving short- and long-term outcomes.

A simplified version of COBRA (Combinatietherapie Bij Reumatoide Artritis) therapy for early rheumatoid arthritis (RA) has similar long-term efficacy and safety as the original COBRA regimen, according to a study published in Rheumatology.1

COBRA is a combination therapy regimen (high-dose prednisolone, methotrexate, and sulfasalazine) for RA that has been shown to be safe and effective in the early stages of RA for improving short- and long-term outcomes. However, rheumatologists are reluctant to use COBRA therapy because of the large pill burden, complex treatment schedule, and potential adverse effects of high-dose steroids.2

Simplified COBRA therapy, or COBRA-light, attempts to address these issues by using a lower initial dose of prednisolone, a higher dose of methotrexate, and no sulfasalazine.2 The COBRA-light trial demonstrated that COBRA-light was noninferior to COBRA in early RA at 6 and 12 months.2,3

In this long-term follow-up study of COBRA-light, researchers evaluated the safety and efficacy of COBRA-light compared with COBRA therapy over the course of 4 years of follow-up.1

Of 149 patients from the COBRA-light study who participated in the long-term extension trial, 72 and 77 of them were treated for 1 year with COBRA-light and COBRA, respectively.1

At 4 years, both regimens resulted in similar disease activity scores, as well as similar rates of Boolean clinical remission.1

Patient reports of physical functioning, as measured by the Dutch Health Assessment Questionnaire, and radiologic outcomes according to the Sharp-van der Heijde score, were also similar for both treatments.1

No differences in rates of survival, major comorbidities, or use of other disease-modifying antirheumatic drugs were found between the groups.1

Summary & Clinical Applicability

Combination therapy with COBRA has been shown to be effective in early RA, but this regimen is seldom prescribed because its use is complex and unwieldy for the patient. Researchers found that simplified COBRA therapy for early RA had similar long-term safety and efficacy outcomes compared with the standard COBRA therapy.

“Practical implications of our findings include a free choice for both physicians and patients to either start their treatment with COBRA-light or COBRA therapy; and assuming that barriers towards the use of COBRA therapy continue to exist, COBRA-light is an equally effective and safe therapy to use in early active RA,” the investigators wrote.1


This study was underpowered to detect differences in survival and major comorbidities between the treatment groups.

This study was funded by Pfizer.

Related Articles


  1.  Konijn NPC, van Tuyl LHD, Boers M, et al. Similar efficacy and safety of initial COBRA-light and COBRA therapy in rheumatoid arthritis: 4-year results from the COBRA-light trial [published online June 25, 2017]. Rheumatology. doi: 10.1093/rheumatology/kex223.
  2.   den Uyl D, ter Wee M, Boers M, et al. A non-inferiority trial of an attenuated combination strategy (‘COBRA-light’) compared to the original COBRA strategy: clinical results after 26 weeks. Ann Rheum Dis. 2014;73(6):1071-1078. doi: 10.1136/annrheumdis-2012-202818 
  3. ter Wee MM, den Uyl D, Boers M, et al. Intensive combination treatment regimens, including prednisolone, are effective in treating patients with early rheumatoid arthritis regardless of additional etanercept: 1-year results of the COBRA-light open-label, randomised, non-inferiority trial. Ann Rheum Dis. 2015;74(6):1233-1240. doi: 10.1136/annrheumdis-2013-205143