LEUVEN, Belgium—Step-down therapy for early rheumatoid arthritis (RA) including oral prednisolone is not just feasible in daily practice, it is also more effective than a step-up regimen, according to new research published online in Rheumatology.¹

"Our study advocates a more frequent use of step-down treatment strategy for early RA in daily practice because it is not only more efficacious, but also more effective than a step-up approach," report the researchers who were led by Patrick Verschueren, MD, of the University Hospitals Leuven in Belgium.

Study patients with severe RA and no contraindications were proposed step-down therapy, the others received step-up therapy. Step-down patients received a modified combination therapy in early RA (COBRA) regimen. This included 2 g of sulphasalazine daily, 15 mg of methotrexate (MTX) weekly, combined with step-down oral prednisolone starting at  60 mg daily and fast tapering to 7.5 mg over 6 weeks with discontinuation from week 28. At week 40, patients were randomized to maintenance therapy with either sulphasalazine or MTX if their disease activity score-28 (DAS28) was acceptably low. The step-up group began monotherapy with MTX, sulphasalazine, hydroxychloroquine, or azathioprine.

In both groups, treatment was adjusted at follow-up, based on DAS28 score. The researchers culled the DAS28, functionality Health Assessment Questionnaire (HAQ), adverse events, DMARD changes and steroid use every 4 months for 2 years.

A total of 19 patients received step-down therapy and 52 received the step-up. More patients in the step-down group completed the first year without unplanned DMARD changes and without dosage adjustment compared with their counterparts in the step-up group. Moreover, fewer RA patients who received step-down therapy made DMARD changes due to side effects or inefficacy compared with patients in the step-up group. The DAS response, proportion of patients in remission, HAQ response and proportion of patients without disability at 4 months was higher in the step-down group, the study showed.

The number of adverse events was comparable between the two groups. Overall, MTX was the most effective maintenance therapy after step-down.

Step-down not complex for most

There was concern that many patients would decline the COBRA step-down regimen due to its complexity, but that was not the case, "The number of patients declining to receive the COBRA regimen was surprisingly low," the study authors write. "As a matter of fact, the decision not to start a step-down treatment where it would strictly have been indicated was always made after a long discussion with the patient and in mutual agreement, taking into account medical and personal objections long as they were rational."

Steroid phobia prevails

The authors point out that steroid-phobia persists and, as a result, the step-down regimen is not likely to catch-on. "Given patients' preference for newer drugs and often irrational dislike of corticosteroids, stimulated by media and public opinion, step-down regimens using classical DMARDS and steroids will probably only become popular in daily practice with the more general support of the rheumatological community," they write.
 
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