Intensive Treatment Strategies With Bridging Steroids Demonstrate Excellent 5-Year Outcomes in Rheumatoid Arthritis

Researchers compared the outcomes of different treatment schedules from the care in early rheumatoid arthritis (CareRA) trial over 5 years.

In patients with rheumatoid arthritis (RA), all intensive treatment strategies using bridging steroids demonstrate excellent long-term clinical outcomes, without the need for chronic glucocorticoid use in the majority of this population, according to study results published in Annals of the Rheumatic Diseases.

Researchers sought to compare the outcomes of different treatment schedules used in the CareRA trial.

The 3-year, observational CareRA-plus trial, a follow-up study to the investigator-initiated, multicenter, pragmatic, 2-year CareRA randomized controlled trial was used in the current analysis.  In CareRA, a total of 379 patients with early RA (<1 year) who were naive to and had no contraindications to treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or glucocorticoids were enrolled in the current study. In CareRA-plus, the 5-year outcomes of participants who received treatment with initial methotrexate (MTX) monotherapy with glucocorticoid bridging (COBRA-Slim) were compared with outcomes among those who received treatment with MTX step-up therapy without glucocorticoids or csDMARD combinations with steroid bridging, per prognostic patient group.

Longitudinal models were used to compare disease activity (Disease Activity Score based on 28 joints calculated with C-reactive protein [DAS28-CRP]) and functionality (Health Assessment Questionnaire [HAQ]) between the treatment groups. Safety and drug use were described for all participants.

Of a total of 322 individuals who completed the 2-year CareRA study, 252 (78%) re-consented to enrollment in CareRA-plus. Overall, 203 patients (81%) completed the study. Participants were compared based on their originally allocated treatment in the high-risk or low-risk group – high-risk arm: COBRA-Slim (n=75) vs COBRA Classic (n=69) or COBRA Avant-Garde (n=59); and low-risk arm: COBRA Slim (n=23) vs tight step-up (n=26). The 2 risk groups were well balanced in regard to demographics and clinical characteristics, registered at baseline CareRA.

Results of the current study showed that low-risk participants who were initiated on the COBRA-Slim had significantly lower DAS28-CRP and HAQ scores compared with those who were initiated on MTX only (P <.001 and P =.041, respectively). Upon completion of the study, 56% (n=114) of the participants never had their original DMARD therapy intensified, with comparable rates reported between all treatments.

Further, among participants in the high-risk arm, safety was comparable between the treatments. In contrast, among participants in the low-risk arm, a total of 18 adverse events (AEs) were reported in 10 individuals in COBRA-Slim and 36 AEs were reported in 17 individuals who received treatment with initial MTX monotherapy (P =.048). During the 5-year study, 22% of participants were initiated on biologic therapy; 25% of patients received glucocorticoids for greater than 3 months; and 17% received glucocorticoids for greater than 6 months outside the bridging period.

Researchers noted, “The results of the additional 3-year follow-up on CareRA-plus confirm and extend on the conclusions after 2 years in the CareRA trial.” Regarding the possible impact of this study on clinical practice or future developments, it appears that “the COBRA-Slim scheme can serve as an effective initial treatment option for all types of patients with early RA, avoiding chronic glucocorticoid use in a large majority and reserving more intensive treatment combinations for insufficient responders only,” they concluded.


Stouten V, Westhovens R, Pazmino S, et al.  Five-year treat-to-target outcomes after methotrexate induction therapy with or without other csDMARDs and temporary glucocorticoids for rheumatoid arthritis in the CareRA trialAnn Rheum Dis. Published online April 2, 2021. doi:10.1136/annrheumdis-2020-219825