Rheumatoid arthritis

Combined therapy gives patients a greater shot at remission in early RA


Early use of combination therapy in patients with rheumatoid arthritis offers more chance of remission – at least in patients with high levels of disease activity, a new review shows.

The systematic review and meta-analysis of 22 studies found that a combination of methotrexate (MTX) with a TNF or non-TNF biologic improved disease control, remission and functional capacity compared with monotherapy of either MTX or a biologic.

Researchers at the University of North Carolina-Chapel Hill looked at data from studies on early RA (first 12 months) from 2006-2017. The eligible studies included 9,934 participants in trials that assessed combinations of MTX and agents such as adalimumab, etanercept and infliximab, abatacept and tocilizumab.

Network meta-analyses found higher overall ACR50 response (50% improvement) for combination therapy of biologic plus MTX than for MTX monotherapy (relative risk range 1.20 [95% confidence interval (CI), 1.04 to 1.38] to 1.57 [95% CI, 1.30 to 1.88]).

There was no difference in trials between non-TNF biologic (abatacept, tocilizumab) and MTX combination therapy and non-TNF biologic monotherapy.

No significant differences were seen between combination therapy and monotherapy in treatment discontinuation rates due to adverse events.

Writing in the Journal of General Internal Medicine, the study authors said the systematic review was limited by the lack of head to head trials and because trials selectively recruited patients with high levels of disease activity in early RA.

Despite these limitations, they said the findings suggested that patients may benefit from combination therapy as first line treatment in early RA to induce remission.

“The 2015 ACR guideline conditionally recommends DMARD monotherapy first in patients with moderate to severe early disease and strongly recommends it for mild disease,” said Professor Katrina Donahue, vice chair of research in the department of family medicine  at UNC-Chapel Hill.

“Right now, biologics are generally prescribed after DMARD (usually MTX) failure. However, our systematic review of the research suggests that combined therapy may actually provide patients a greater shot at remission without any additional side effects.”

Co-author Professor Beth Jonas, chief of the division of rheumatology, allergy, and immunology in the department of medicine at the UNC School of Medicine said the study “lends support to the use of early combination therapy in patients with moderate to severe disease who do not have an early or robust response to DMARD monotherapy.”

“In some cases, such as in patients with the most aggressive disease, initial treatment with a combination of MTX and a biologic might be considered,” she said.

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