Does methotrexate improve response in patients with rheumatoid arthritis with previous biologic therapy?

This study investigated the effect of adding methotrexate (Otrexup) after adalimumab (Humira) treatment In patients with rheumatoid arthritis (RA).

They found that methotrexate added to adalimumab improves disease activity (DA) in patients without previous biologic treatment.

Rheumatoid arthritis (RA) is a chronic condition. It is caused by painful inflammation in the joints. RA is treated with disease-modifying anti-rheumatic drugs (DMARDs). There are many types of DMARDs. Biological DMARDs (bDMARDs) are antibodies that target specific chemicals or receptors. This reduces inflammation and slows degeneration in the joints. Adalimumab is a bDMARD. It targets a chemical called tumor necrosis factor (TNF). 

BDMARDs are often combined with methotrexate. This is a drug that targets several inflammatory pathways. Methotrexate was most commonly prescribed for early RA. More patients are now treated with a bDMARD as a first-line treatment (FLT). It is unclear if adding methotrexate improves disease activity (DA) in patients already treated with bDMARDs. 

This study included 2654 patients with RA. Patients were assigned to treatment with adalimumab only or adalimumab + methotrexate. Disease activity (DA) was measured using the DAS28 score. DA was compared between patients with previous bDMARD and no bDMARD (naïve) treatment. DA was measured at 3, 6, and 12 months. 

Adalimumab treatment was associated with reduced DA in both groups. Naïve patients had a greater DA reduction with adalimumab + methotrexate. There was no improvement in DA with methotrexate in patients with previous bDMARD treatment.

Pain scores were also improved in naïve patients treated with adalimumab + methotrexate. Stopping methotrexate had a negative impact on DA in naïve patients. There was no effect of stopping methotrexate in patients with previous bDMARDs. 

The authors concluded that methotrexate added to adalimumab treatment improves DA in patients without previous biologic treatment.

This was not a randomized study. The decision to add methotrexate depended on DA. The dose of methotrexate also varied. This makes it difficult to determine the effect of adding methotrexate treatment in these patients. More controlled studies are needed.