Trial Suggests Reserved Approach May be Best in Patients with Early RA

Methotrexate alone superior in efficacy to combination treatment with DMARDs.

Methotrexate alone superior in efficacy to combination treatment with DMARDs.

In a surprising result of the CareRA trial, researchers found that methotrexate alone was superior in efficacy to combination treatment with methotrexate and other disease-modifying antirheumatic drugs (DMARDs) in the management of early rheumatoid arthritis (RA).

Previously, early and intensive treatment was considered by many to be an appropriate strategy for managing early inflammation, thereby potentially minimizing long-term joint degeneration and other hazards of the long-term low-level inflammatory activation associated with the disease.

Over the course of the 400-patient, 16-week trial, patients with a less-than 1-year history of rheumatoid arthritis were randomized equally to receive 1 of 3 treatments: 1) treatment with methotrexate, sulfasalazine, a prednisone taper (starting at 60 mg daily), 2) treatment with methotrexate, sulfasalazine, a prednisone taper (starting at 30 mg daily), and 3) treatment with methotrexate, leflunomide, and a prednisone taper (starting at 30 mg daily).

Consistent with methods in other efficacy trials, researchers determined the percentage of patients developing remission based on C-reactive protein levels and disease activity scores based on a 28-joint survey. In secondary analyses, investigators evaluated responses based on the European League Against Rheumatism health assessment questionnaire with a response consisting of a score of zero (no disability) on the instrument.

After 16 weeks of treatment, 70.4% of patients receiving classic therapy (treatment 1) experienced a response versus 73.6% of patients receiving therapy with a lower initial steroid taper dose (treatment 2), and 68.1% of patients receiving the combination integrating leflunomide. However, these responses rates may have been different by chance, as no significant difference in response rates were detected (P = .713).

Similarly, on secondary end points, response rates were not different between treatment options. The only significant finding was a higher rate of treatment-related adverse events in patients receiving high-dose glucocorticoid therapy (regimen 1) and treatment of methotrexate with leflunomide (treatment 3) than patients receiving traditional methotrexate and sulfasalazine therapy with a lower initiation dose of glucocorticoid (treatment 2).

Specifically, with regard to the adverse event profiles of the 3 regimens, just under half (46.9%) of patients receiving the attenuated dose of glucocorticoid (treatment 2) experienced an adverse event related to treatment, as compared with more than half (61.2%) of patients receiving treatment 1, and more than two-thirds (69.1%) of patients receiving treatment 3.

Results of this trial show that, in patients with early RA, less treatment may lead to equivalent outcomes with a lower risk of treatment-related adverse events—at least in early therapy (limited to the initial 16 weeks of treatment). This trial provides some basis for reserving advanced therapies for patients in later stages of RA.

Reference

Verschueren P, De Cock D, Corluy L, et al. Methotrexate in combination with other DMARDs is not superior to methotrexate alone for remission induction with moderate-to-high-dose glucocorticoid bridging in early rheumatoid arthritis after 16 weeks of treatment: the CareRA trial. Ann Rheum Dis. 2015;74(1):27-34.