Home > Rheumatology > Starting methotrexate, bridging glucocorticoids effective in early, high-risk RA

Starting methotrexate, bridging glucocorticoids effective in early, high-risk RA

Annals of Rheumatic Diseases
Reuters Health - 27/04/2021 - In high-risk early rheumatoid arthritis (RA) patients, initiating methotrexate with glucocorticoid bridging showed "excellent" five-year outcomes, researchers say.

The approach, known as COBRA-Slim, was also more effective than methotrexate monotherapy in low-risk patients, according to an analysis of the CareRA trial.

"As long as treatment is adapted to target during follow-up, there is no need for upfront use of conventional synthetic disease-modifying antirheumatic drug (csDMARD) combination therapy or biologicals," Dr. Patrick Verschueren of KU Leuven in Belgium told Reuters Health by email.

"Contrary to what is still believed, this does not lead to overconsumption of glucocorticoids long term," he said. "COBRA-Slim should not be considered as symptomatic treatment but as an essential intervention to achieve maximal benefit from the bio-psycho-social window of opportunity for the global management of patients with RA."

As reported in Annals of Rheumatic Diseases, Dr. Verschueren and colleagues analyzed five-year outcomes of different treatment schedules in CareRA. Patients completing the two-year randomized controlled trial were eligible for the three-year observational CareRA-plus study. Patients were, on average, in their early 50s, and most were women.

COBRA-Slim outcomes were compared with methotrexate step-up without glucocorticoids or csDMARD combinations with glucocorticoid bridging.

Specifically, the researchers compared disease activity (Disease Activity Score based on 28 joints calculated with C reactive protein; DAS28-CRP) and functionality (Health Assessment Questionnaire; HAQ).

Among 322 eligible patients, 252 (78%) entered CareRA-plus and 203 (81%) completed the study. At five years, DAS28-CRP and HAQ scores were comparable among the treatment groups.

Low-risk patients starting COBRA-Slim had lower scores on both measures than those starting on methotrexate only.

Further, at study completion, 56% of patients never had their original csDMARD therapy intensified, with similar rates among all treatments.

In high-risk patients, safety was comparable among treatments.

In low-risk patients, 18 adverse events occurred in 10 COBRA-Slim patients and 36 in 17 patients treated with initial methotrexate monotherapy.

Over the course of the study, 22% of patients initiated biologics, 25% took glucocorticoids for more than three months and 17%, for more than six months outside the bridging period.

Dr. Verschueren said, "There are still barriers to the implementation of this approach, many of which are related to negative perceptions about the risk profile of glucocorticoids. However, the long-term CareRA study results are reassuring, and in clinical practice I see no firm contraindications to the COBRA-Slim regimen except in patients with severe comorbidities that might deteriorate with moderately dosed glucocorticoids, even if only used short-term - e.g., uncontrolled diabetes, heart failure."

"For such patients," he said, "I would still consider starting glucocorticoid bridging, but at a lower dose."

Dr. Stuart Kaplan, chief of rheumatology at South Nassau Communities Hospital in Oceanside, New York, commented by email to Reuters Health, "This is a somewhat revolutionary idea in that most clinicians are generally afraid of the side effects of steroids and therefore try to avoid them as much as possible."

"In fact," he said, "as pointed out in the article, the American College of Rheumatology recommendations advise to minimize the use of bridging glucocorticoids. This study suggests that bridging steroids early on in the treatment of RA may actually be your 'friend,' providing excellent long-term outcomes without chronic glucocorticoid use."

"This is an intriguing approach that is worthy of further study to validate the finding," Dr. Kaplan concluded.

SOURCE: https://bit.ly/3gCFCDU Annals of Rheumatic Diseases, online April 2, 2021.

By Marilynn Larkin

Posted on