Methotrexate Combination Helps Prolong Anti-TNF Use

Patients who received methotrexate in combination with other disease-modifying antirheumatic drugs were significantly more likely to remain on anti–tumor necrosis factor therapy than were patients who received methotrexate monotherapy or other DMARDs without methotrexate, based on data from more than 10,000 patients in the British Society for Rheumatology Biologics Register. The findings were published online Feb. 17 in the Annals of the Rheumatic Diseases.

Previous studies have examined the impact of DMARDs on the continuation of anti-TNF therapy, but most of these did not compare the effects of specific DMARDs, said Dr. Moetaza M. Soliman of the University of Manchester (England) and colleagues (Ann. Rheum. Dis. 2011 Feb. 17 [doi:10.1136/ard.2010.139774]).

After 5 years of follow-up, patients who received methotrexate (MTX) in combination with either sulfasalazine or hydroxychloroquine or a combination of the two agents were significantly less likely to discontinue anti-TNF therapy, compared with those who received MTX alone. The adjusted hazard ratios were 0.76, 0.81, and 0.80, respectively, compared with methotrexate alone.

Patients who received no DMARDs were 40% more likely to discontinue anti-TNF, compared with those who received MTX. Patients who received leflunomide or sulfasalazine were 41% and 23% more likely, respectively, to discontinue anti-TNF therapy, compared with those who received MTX.

The study population included 3,339 patients receiving no DMARDs, 4,418 on MTX, 610 taking leflunomide, 308 receiving sulfasalazine, 902 on MTX plus sulfasalazine, 401 taking MTX plus hydroxychloroquine, and 418 on MTX plus a sulfasalazine and hydroxychloroquine combination. The average age of the patients was 56 years, and the average disease duration was 13 years.

The results were similar when the researchers controlled for reasons for discontinuation, including adverse events and lack of efficacy.

The study was limited by the smaller size of certain treatment groups, but it is the largest of its type to date. The results support the use of MTX alone or in combination with other DMARDs as a way to extend compliance with anti-TNF therapy, the researchers noted.

"Further study is required to understand if longer-term anti-TNF treatment persistence would be improved by simply stopping these DMARDs or whether they should be substituted, where possible, with other DMARDs such as MTX, if tolerated," they said.

The study was funded by the British Society for Rheumatology, which receives some income from pharmaceutical companies including Abbott Laboratories, Amgen, Roche, Schering-Plough, and Wyeth Pharmaceuticals.