Early, Intensive Therapy Linked to Long-Term Mortality Benefits in RA

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Researchers in The Netherlands found data from a study period of 23 years that showed combination therapy with sulfasalazine and methotrexate was effective for disease control and fewer adverse events, when compared with monotherapy with sulfasalazine.

A long-term study has revealed that early and intensive therapy in patients with rheumatoid arthritis (RA) results in long-term benefits on mortality, according to study results published in the Annals of the Rheumatic Diseases.

Researchers followed a group of 155 patients with early RA who were originally a part of the COBRA trial (Combinatietherapie bij Reumatoide Artritis) for a total of 23 years. The COBRA study randomly assigned patients to receive either sulfasalazine (n=79) or concomitant sulfasalazine, methotrexate, and tapered prednisolone (n=76) for a total study duration of 56 weeks. Prednisolone and methotrexate were both discontinued at 28 and 40 weeks, respectively, and sulfasalazine (2 g daily) was continued. Mortality among study participants was compared within a reference sample that consisted of individuals from the general population.

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After analysis, the researchers found that a total of 44 patients had died after 23 years of follow-up (standard mortality ratio, 0.80; 95% CI, 0.59-1.06), which included 20 and 24 patients from the combination therapy (standard mortality ratio, 0.75; 95% CI, 0.47-1.14) and sulfasalazine monotherapy (standard mortality ratio, 0.85; 95% CI, 0.56-1.25) groups, respectively. In the reference sample, a total of 55 individuals had died during the same period.

One key limitation of the study was the small sample size.

“The study confirms that early and intensive treatment of RA has long-term benefits and suggests that treating to target is especially important for patients with poor prognosis,” the researchers wrote.


Poppelaars PB, van Tuyl LHD, Boers M. Normal mortality of the COBRA early rheumatoid arthritis trial cohort after 23 years of follow-up. Ann Rheum Dis. 2019;78(5):586-589.