Maradit-Kremers H et al. (2006) Patient, disease, and therapy-related factors that influence discontinuation of disease-modifying antirheumatic drugs: a population-based incidence cohort of patients with rheumatoid arthritis. J Rheumatol 33: 248–255

A large number of patients fail to respond to disease-modifying antirheumatic drugs (DMARDs), which are a major component of the treatment of rheumatoid arthritis. Failure to respond to these agents is an important clinical issue and is almost impossible to predict at the present time. A team of researchers from the Mayo Clinic conducted a long-term, retrospective, observational study of patients with rheumatoid arthritis, in an attempt to identify which factors predict discontinuation of DMARDs.

The study included 345 patients (72.8% female) first diagnosed with rheumatoid arthritis between 1955 and 1995, who were followed for a mean of 15.4 years from diagnosis. Of all the disease characteristics assessed, only high disease activity was associated with an increased risk of discontinuation. Contrary to common assumption, disease duration and the number of previous DMARD treatments were not. Interestingly, the type of DMARD mattered: durations of treatment with either hydroxychloroquine or methotrexate were substantially longer than with any other kind of DMARD. Methotrexate-treatment duration was extended with the addition of folate supplementation. In addition, methotrexate failure was associated with almost twice the likelihood of discontinuing another DMARD.

The authors suggest that it might be possible to identify patients who will later discontinue DMARD treatment, using these predictors. Patients who do not respond to methotrexate are a particularly high-risk group, and could be considered for new therapies. They also recommend that folate supplementation be included in all future methotrexate regimens.