Standard versus biological combination therapy for rheumatoid arthritis

This study reported the 2-year outcomes of a previous trial of conventional (addition of sulfasalazine and hydroxychloroquine) versus biological (addition of infliximab) treatment in patients who failed initial methotrexate treatment.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that typically affects the small joints in the hands and feet. It is an autoimmune disorder, meaning that the immune system attacks the body’s own cells.

Disease-modifying anti-rheumatic drugs (DMARDs) are a group of medications commonly used in patients with RA. DMARDs partly turn off the immune response against self, thereby slow the progression of RA and delay joint damage. There are 2 main types of DMARDs: standard and biologic. Common standard DMARDs include methotrexate (Trexall, Rheumatrex), hydroxychloroquine (Plaquenil) and sulfasalazine (Azulfidine). Infliximab (Remicade) is a biologic DMARD that belongs to a class of drugs called tumor necrosis factor (TNF) inhibitors.

DMARD therapy usually starts with Methotrexate. While 20-40% of patients have an excellent response to this therapy alone, others may require additional drugs. Sulfasalazine and hydroxychloroquine are often added when methotrexate alone fails. Infliximab (Remicade) is an alternative add-on drug when methotrexate alone fails.

This study reported on the 2-year outcome of a previous trial comparing methotrexate plus sulfasalazine and hydroxychloroquine (standard therapy) to methotrexate plus infliximab. 

487 patients aged above 18 years were enrolled in this study. All patients had symptom duration of less than 1 year (‘early RA’) and were started on methotrexate. After 3-4 months, those with a poor response to methotrexate were randomly assigned to either group A (conventional treatment: addition of sulfasalazine and hydroxychloroquine) or group B (biological treatment: addition of infliximab).

At the end of year 1, more patients in group B achieved a good response (defined clinically based on joint inflammation, lab tests and general well-being) than group A. This trend continued at the end of year 2 with 38% of group B achieving a good response versus 31% of group A, but these results were not statistically significant.

After 2 years, joint damage from inflammation (based on imaging studies) was significantly greater in patients who received the conventional therapy.

107 adverse events were recorded, evenly distributed between the two groups. Blood-related and nervous-system events were more common in group A. Liver-related, skin and allergic reactions were more common in group B. 

Addition of a TNF inhibitor to methotrexate in patients with early RA who failed monotherapy leads to significantly better radiological outcomes (reduced joint damage in imaging), but  it is not superior to the standard therapy (addition of 2 DMARDs) in terms of clinical response at 2 years. 

TNF inhibitors are substantially more expensive than standard DMARDs, and make patients prone to infections. Therefore, these drawbacks should be weighed against their limited benefits.