Study Shows Methotrexate and Prednisone Combination Therapy Achieves Remission for Most RA Patients

A majority (63%) of patients with rheumatoid arthritis and undifferentiated arthritis who take initial combination therapy consisting of methotrexate and low-dose prednisone achieved early remission. Of those, 32% achieved drug-free remission after one year, according to the results of a study presented in Washington, DC at the American College of Rheumatology’s annual meeting, which was co-sponsored by ACR and the Association of Rheumatology Health Professionals.

“After one year, more patients were in remission if they were treated with adalimumab compared to patients treated with DMARDS [disease-modifying antirheumatic drugs],” said lead investigator Lotte Heimans, MD, a researcher at the Department of Rheumatology, Leiden University Medical Center, Leiden, in The Netherlands, referring to those patients who tried treatments after the initial combination therapy failed.

The goal of the IMPROVED study was to assess if the induction of remission and drug-free remission is possible with initial combination therapy in early rheumatoid arthritis and undifferentiated arthritis. Another objective was to determine which treatment strategy yields more remission if the initial combination therapy fails.

The study involved 610 patients with early rheumatoid (RA) or undifferentiated arthritis (UA). UA was defined as an inflammatory arthritis in at least one joint, which in the opinion of rheumatologists, was likely to be an early stage of RA. The whole study was aimed at achieving remission, which was defined as DAS <1.6.

All patients were started with initial combination therapy that consisted of 25mg/wk methotrexate (MTX) and 60 mg/day of prednisone tapered to 7.5mg/day over seven weeks. If patients achieved remission after 4 months, they were considered to be in early remission and could taper prednisone down to zero.

If they were still in remission after eight months, they could also taper and ultimately stop taking methotrexate. If remission was lost after eight months, prednisone was restarted at a low dose of 7.5 mg/day.

If patients did not go into remission after four months, they were randomized either to a combination of multiple DMARDS and low-dose prednisone (arm 1) or to adalimumab (ADA) and methotrexate (arm 2). Arm 1 involved 25 mg/wk MTX, 400 mg/day hydroxychloroquine, 2000mg/day sulphasalazine, and 7.5 mg/day of prednisone. Arm 2 consisted of 40mg/2 weeks of ADA with 25 mg/wk of MTX

If not in remission after eight months, patients in arm 1 switched to ADA+MTX and patients in arm 2 increased ADA to 40 mg/week.

Of those in early remission, 96% tapered prednisone after four months and 53% tapered MTX after eight months. After 1 year, 69% of patient achieved remission and 32% were in drug free remission. After 8 months, patients in arm 1 and 2 of the study achieved similar levels of remission. But after 1 year, patients in arm 2, who at eight months tapered ADA+MTX combination to MTX monotherapy, more often achieved remission than those in arm 1 (41% vs. 25%, p=0.01), who tapered poly-DMARDS+prednisone to MTX therapy.

“There were no differences after one year between patients with RA and patients with UA,” Heimans said. “Overall we can say that remission steered treatment in the IMPROVED study leads to a very low disease activity and very good functional ability and there was virtually no damage progression in all patients.”