Multiple DMARD use may attenuate adalimumab response in RA
medwireNews: Previous exposure to multiple conventional DMARDs is associated with a blunted response to treatment with adalimumab plus methotrexate among patients with rheumatoid arthritis (RA), indicate findings from a post-hoc analysis.
“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,” say the study authors.
Daniel Aletaha (Medical University of Vienna, Austria) and colleagues analyzed data from 207 patients treated with adalimumab 40 mg every 2 weeks plus methotrexate in the phase III DE019 trial. In all, 33.8% of participants had received prior treatment with methotrexate plus more than two other conventional DMARDs, while 30.0% had received methotrexate plus two DMARDs, and the remaining 36.2% had been given methotrexate plus up to one other DMARD.
As reported in the Annals of the Rheumatic Diseases, the proportion of patients who achieved an ACR20, 50, or 70 response over 24 weeks decreased in a linear fashion as the number of prior DMARDs used increased.
ACR20 response rates were 72.0%, 61.3%, and 57.1% for patients receiving up to one, two, or more than two DMARDs plus methotrexate, while ACR50 response rates were 45.3%, 35.5%, and 34.3%, respectively, and the corresponding ACR70 response rates were 26.7%, 17.7%, and 10.0%.
Aletaha et al say that the improvement in disease activity from baseline to week 24 was greatest among patients given methotrexate alone or with one DMARD, and lowest among those given methotrexate plus two or more DMARDs. For example, average improvements in DAS28-CRP in these two groups were 2.2 versus 1.8 points.
The study authors also observed a similar association between disease duration and adalimumab response, with greater ACR50 and 70 responses seen for patients with disease duration of up to 5 versus more than 5 years.
However, they note that these associations were “more variable” than those between prior DMARD use and adalimumab response, “suggesting that number of prior DMARDs may have an independent effect on disease outcomes.”
In a multivariate regression analysis adjusting for factors including disease activity and physical function, greater number of prior DMARDs and longer disease duration were both associated with a significantly lower likelihood of achieving an ACR70 response.
Aletaha et al also investigated the same associations using data from the ARMADA trial of 67 patients, finding “generally similar” results, but they note that the small patient numbers (n=67) in ARMADA “did not provide sufficient power to confirm all analyses.”
They also caution that their analysis only included patients who had been treated with conventional DMARDs for “prolonged periods,” with study participants having an average disease duration of 11 years.
And they say that “the impact of the prior number of [conventional] DMARDs may be different in studies that switched [conventional] DMARDs rapidly before introduction of biologic DMARDs.”
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