Number of Prior DMARDs Could Negatively Impact Response to Anti-TNFs in RA

It is already understood that a longer disease duration and delays in using disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA) is associated with worse disease control, but a new study, published just last month, has shown that the number of conventional DMARDs used before starting anti—tumor necrosis factor (anti-TNF) therapy could reduce the magnitude of a patient’s response to anti-TNFs like adalimumab.

The study, appearing in Annals of the Rheumatic Diseases, is a post-hoc analysis of data from 2 trials: DE019 and ARMADA. Both were randomized, placebo-controlled, double-blind clinical trials that evaluated adalimumab versus placebo as an add-on therapy to methotrexate in patients with active RA. The analysis included 207 and 67 patients with RA from the 2 studies, respectively, all of whom received 40 mg of adalimumab every 2 weeks with concomitant methotrexate.

Of the patients in the DE019 study, 36.2% had received methotrexate or another DMARD previously, 30.0% had received 2 DMARDs, and 33.8% had received more than 2 DMARDs. In the patients in the ARMADA study, 76% had received prior DMARDs. As duration of disease increased, the number of DMARD treatments patients had received also increased in both trials.

The researchers found that, in the DE019 study, the proportion of patients who achieved American College of Rheumatology (ACR) criteria for 20%, 50%, and 70% improvement with adalimumab therapy at week 24 decreased as the number of prior DMARDs increased. Improvement from baseline was highest among patients who had received methotrexate or 1 prior DMARD.

Notably, baseline disease activity among patients in this trial did not differ among groups, and disease duration did not impact improvement from baseline to week 24 in terms of Disease Activity Score in a count of 28 joints with C-reactive protein or Simplified Disease Activity Index.

The smaller ARMADA trial found generally similar results; lower ACR20, ACR50, and ACR70 response rates were observed at week 24 of adalimumab therapy among patients with more than 2 prior DMARDs plus methotrexate versus patients with 2 or fewer prior DMARDs plus methotrexate.

While the analysis was limited because it only evaluated studies in which patients had been treated with prior DMARDs for long periods of time, the authors write that lengthy delays in starting therapy or the use of multiple DMARDs before starting an anti-TNF agent may reduce the potential response of a patient to these biologic agents. These findings demonstrate the benefits of early intervention, and underscore a need for more standardized treatment guidelines for RA, they add.

Reference

Aletaha D, Maa JF, Chen S, et al. Effect of disease duration and prior disease-modifying antirheumatic drug use on treatment outcomes in patients with rheumatoid arthritis [published online August 21, 2019]. Ann Rheum Dis. doi: 10.1136/annrheumdis-2018-214918.