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Number of Prior DMARDs, Disease Duration Linked to Diminished Drug Response in RA
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Longer disease duration and a greater number of previous DMARDs in a patient’s history is associated with decreased response rates to adalimumab plus methotrexate among patients with rheumatoid arthritis, according to data published in Annals of the Rheumatic Diseases.
“A delay in initiating disease-modifying antirheumatic drugs (DMARDs) can negatively affect long-term outcomes and be associated with greater disease activity, more extensive joint damage and worsened physical disability in patients with rheumatoid arthritis,” Daniel Aletaha, MD, MSc, MBA, of the Medical University of Vienna, and colleagues wrote. “Conversely, rapid implementation of conventional synthetic DMARDs or tumor necrosis factor inhibitors results in better disease control than delaying start of therapy.”
“However, longer disease duration is not necessarily associated with reduced clinical responsiveness based on observations that patients with different disease durations achieve similar outcomes in clinical trials,” they added. “In contrast, patients with RA who have failed methotrexate or TNF [inhibitor] therapy have much lower response rates than methotrexate naive patients, although it is not clear if these differences are primarily related to having failed an increasing number of prior DMARD therapies or increasing disease duration.”
To determine whether disease duration and the number of previous DMARDs used impact response to treatment among patients with RA, Aletaha and colleagues conducted a post hoc analysis of data from two studies — DE019 and ARMADA. According to the researchers, both studies were randomized, placebo-controlled, double-blind clinical trials of the safety and efficacy of adalimumab (Humira, AbbVie) as an add-on therapy to methotrexate for RA. DE019 included 207 participants, while ARMADA had 67 participants and was used to confirm the results of the larger study.
The researchers assessed treatment response at week 24 using the DAS28-CRP, the Simplified Disease Activity Index (SDAI) and the Health Assessment Questionnaire Disability Index (HAQ-DI). Other outcomes included the proportions of patients with ACR 20/50/70 improvement responses.
According to the researchers, among participants in DE019, more previous DMARDs — in particular, more than two, compared with none or one — was associated with smaller improvements in DAS28-CRP, SDAI and HAQ-DI from baseline to week 24. In addition, although a disease duration of more than 10 years, compared with less than 1year, was associated with higher HAQ-DI scores at week 24, DAS28-CRP and SDAI results were mixed. According to the researchers, data from the ARMADA trial confirmed these findings.
“The number of prior DMARDs and disease duration affect response to therapy in patients with established RA, although the effect of the number of prior DMARDs on improvement in disease activity appears to be relevant regardless of disease duration,” Aletaha and colleagues wrote. “These results support recommendations that combination therapy with a biologic agent and methotrexate be initiated without delay in patients who do not have a satisfactory response to treatment with methotrexate alone.” – by Jason Laday
Disclosure: Aletaha reports grants and consulting fees from AbbVie, Janssen, Pfizer and Roche, as well as consulting fees from Amgen, Celgene, Eli Lilly, Merck, Novartis, Sandoz, Sanofi/Genzyme and UCB. Please see the full study for additional authors’ disclosures.
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