Methotrexate combined and alone comparable for RA if disease activity remains low
medwireNews: Patients with rheumatoid arthritis (RA) who remain in low disease activity have similar 10-year outcomes regardless of whether their initial treatment is methotrexate alone or in combination with infliximab or prednisone and sulfasalazine (SSZ), suggests research.
“[W]e found that all long-term continuous good responders had similar clinical and radiological outcomes, but that initial [methotrexate] monotherapy responders achieved drug-free DAS [Disease Activity Score]-remission more often,” report Sytske Anne Bergstra (Leiden University Medical Center, the Netherlands) and colleagues.
This was contrary to what the researchers were expecting. They thought that through multipathway targeting with combination therapy, more patients with differing types of RA and characteristics would respond and that this type of therapy could stop or reverse some of the disease processes not targeted by methotrexate monotherapy.
They did find that more RA patients starting on combination treatment achieved a continuous good response. At 6 months, 59.4% of 261 patients receiving combination therapy achieved a DAS of 2.4 points or below, and this was maintained by 43.9% over the 10 years of follow-up. This DAS score was reached by 34.8% of 247 patients treated with methotrexate monotherapy, 32.9% of whom maintained it for 10 years.
However, the percentage of patients in remission remained higher in the methotrexate monotherapy group over follow-up, ranging from around 60 to 90% at any one visit, compared with around 50 to 80% in the combination therapy group. This was also true for the proportion of patients in drug-free remission, at about 50% versus 30%, respectively, but in both cases the differences failed to reach significance in linear and generalized linear mixed model analyses.
“It is left to speculation whether the differences in drug-free DAS remission could be due to discontinuation of prednisone or infliximab or indicates slight differences in efficacy between [methotrexate] monotherapy and SSZ monotherapy (after discontinuation of prednisone and [methotrexate] in one of the initial combination therapy arms),” the team comments in Rheumatology.
Regardless of initial treatment, outcomes improved for all patients over time. There was a “very small” significant treatment effect for DAS, erythrocyte sedimentation rate, and patient global health over time, with slightly worse outcomes among patients receiving combination treatment versus monotherapy, but the researchers say that this result seems “clinically negligible.”
No significant differences between the treatment groups were seen for the Health Assessment Questionnaire or the percentage of patients with Sharp/van der Heijde score progression of 5 or above.
The researchers conclude that “the main benefit from starting with combination therapy in all patients is that more patients achieve and maintain (after tapering to [methotrexate] monotherapy) low disease activity.”
Citing recent studies that have suggested that the initial prednisone dose could be lowered and SSZ may be omitted, the researchers say the findings make a case for low-dose corticosteroid bridging therapy combined with methotrexate as “optimal initial treatment.”
By Lucy Piper
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