Achieving stable low disease activity with adalimumab plus methotrexate

This trial compared the efficacy of 2 treatment regimens: methotrexate (MTX) monotherapy versus dual therapy of MTX plus biological drug in patients with early rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease that occurs when the immune system mistakenly attacks the body’s own tissues, in this case the joints. Disease-modifying anti-rheumatic drugs (DMARDs) are a group of medications commonly used in patients with RA. DMARDs suppress the immune response and slow disease progression. There are 2 main types of DMARDs: standard and biologic. MTX (Trexall, Rheumatrex) is the most common standard DMARD in use. Adalimumab (Humira) is a biologic DMARD that belongs to a class of drugs called tumor necrosis factor (TNF) inhibitors.

MTX is often the initial treatment of choice for RA. MTX may be given alone or combined with biologics to achieve better control of the disease.

Clinicians assess the response to therapy based on disease activity scores, such as the DAS28. This is a measurement of disease activity based on the number of swollen or tender joints and blood markers indicating ongoing inflammation. The goal is a low disease activity, meaning that the signs and symptoms have reduced or stopped for as long as possible.

This trial investigated the effects of a combined regimen (MTX plus adalimumab) versus MTX alone on long term disease activity. 

1032 patients with early RA (less than a year duration) were randomly assigned to receive adalimumab plus MTX or MTX plus a placebo for 26 weeks (period 1). 207/466 (44%) patients in the dual therapy group achieved stable low disease activity according to DAS28 scores and imaging scans (joint damage remained static). In comparison, 112/460 (24%) patients in the monotherapy group achieved the same target.

Following period 1, patients in the dual therapy group who achieved low disease activity were randomized once more to adalimumab continuation or withdrawal (continuing methotrexate alone) for an additional 52 weeks (period 2). Participants in the monotherapy group responding to treatment continued methotrexate alone.

73 of 105 (70%) patients in the adalimumab-continuation group and 61 of the 112 (54%) patients in the methotrexate monotherapy group achieved stable low-activity disease after 78 weeks of treatment. The majority of patients randomized to adalimumab withdrawal maintained their good response until week 78 of the trial. The rate of side effects did not differ substantially between groups, although it was high in both. 

Both regimens tested in this trial resulted in a stable low disease activity. A higher proportion of patients in the dual therapy group achieved this target, but the difference was not statistically significant. Results were much the same whether adalimumab was continued or withdrawn in patients who initially responded to dual therapy.

These results thus do not support unequivocally either therapy.