From the Journals

Prior DMARD use in RA may limit adalimumab treatment response



A history of using multiple conventional synthetic disease-modifying antirheumatic drugs (DMARDs) is a key predictor for poorer response to adalimumab therapy in rheumatoid arthritis patients, according to data from a pair of studies with a total of 274 patients.

Although patients with RA who have failed methotrexate or tumor necrosis factor inhibitor therapy respond less than methotrexate-naive patients, “it remains unknown if response to the first biologic DMARD, in particular a [tumor necrosis factor inhibitor], depends on disease duration or prior numbers of failed [conventional synthetic] DMARDs,” wrote Daniel Aletaha, MD, of the Medical University of Vienna and colleagues.

In a study published in Annals of the Rheumatic Diseases, the researchers reviewed data from two randomized, controlled trials of patients with RA. In the larger trial of 207 adults (known as DE019), past use of two or more conventional synthetic DMARDs was associated with less improvement in 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) after 24 weeks of adalimumab (Humira), compared with use of one or no DMARDs (–1.8 vs. –2.2, respectively). Similarly, disease activity and disability scores improved significantly less in patients who had used two or more DMARDs, compared with those who used one or no DMARDs, according to the Simplified Disease Activity Index (SDAI; –22.1 vs. –26.9) and the Health Assessment Questionnaire Disability Index (HAQ-DI; –0.43 vs. –0.64).

The researchers also examined the role of disease duration on treatment response. Overall, patients with disease duration greater than 10 years showed more improvement at 24 weeks than did those with disease duration less than 1 year, based on HAQ-DI scores (1.1 vs. 0.7), but final scores on the SDAI and DAS28-CRP were not significantly different between those with disease duration greater than 10 years and those with duration of less than 1 year. These results suggest that the impact of DMARDs holds true regardless of disease duration, the researchers noted.

The findings were similar with regard to number of prior conventional synthetic DMARDs and the effects of disease duration in the second trial of 67 patients, known as the ARMADA study.

The study findings were limited by several factors, including the post hoc analysis design, use of only adalimumab data, and the small number of patients in several subgroups, the researchers noted. However, the results support the need for more standardized treatment guidelines and suggest that RA patients who fail to respond to methotrexate soon after RA diagnosis may benefit most from adding adalimumab, they said.

“Furthermore, these findings should be considered in future trials when defining inclusion criteria not only by duration of disease but also by number of prior DMARDs,” they concluded.

The study was sponsored by AbbVie, which markets adalimumab. Dr. Aletaha disclosed grants and consulting fees from AbbVie, as well as other pharmaceutical companies. Four of the authors were current or former employees of AbbVie, and some other authors also reported financial relationships with the company.

SOURCE: Aletaha D et al. Ann Rheum Dis. 2019 Aug 21. doi: 10.1136/annrheumdis-2018-214918.

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