Increased early disease activity predicts methotrexate failure in RA
medwireNews: The chances of patients with early rheumatoid arthritis (RA) not responding to methotrexate treatment at 6 months increase significantly with increasing disease activity during the first 12 weeks, study findings indicate.
Furthermore, among patients who do not achieve stable low disease activity (LDA) at 6 months, defined as a Disease Activity Score at 28 joints based on C-reactive protein (DAS28-CRP) below 3.2 at two consecutive assessments, those who receive additional adalimumab have better outcomes than patients who continue with methotrexate alone for an additional 12 months, report Josef Smolen (Medical University of Vienna, Austria) and colleagues.
The findings are based on a post-hoc analysis of nearly 700 patients enrolled in two randomized trials (OPTIMA and PREMIER) that examined the efficacy of methotrexate and adalimumab in methotrexate-naïve patients.
The researchers observed that each unit increase in baseline DAS28-CRP was associated with a 1.8-fold increased likelihood for insufficient response to methotrexate, defined as not achieving stable LDA at 6 months, and a 1.5-fold increased likelihood for clinically relevant radiographic progression (CRRP), defined as an increase in modified total Sharp score of more than 1.5 from baseline to 6 months.
At 4 weeks, the risk increased to 3.3- and 3.2-fold, respectively, with each unit increase in time-averaged DAS28-CRP, and similar results were observed at 8 weeks (odds ratios [ORs]=2.8 and 3.3) and 12 weeks (ORs=3.4 and 3.6) from treatment initiation.
Men were less likely than women to have an insufficient response to methotrexate, and previous glucocorticoid use was associated with a lower likelihood of insufficient methotrexate response and CRRP.
Smolen and team also analyzed longer term data for 348 OPTIMA participants who had an insufficient response to methotrexate at 6 months and advanced to adalimumab plus methotrexate rescue therapy, and for 177 PREMIER participants who continued with methotrexate following an initial insufficient response.
After 1 year of additional treatment, the proportion of patients who achieved LDA was significantly higher in the group that received adalimumab rescue therapy compared with the group that continued to receive methotrexate monotherapy, at 64% versus 41%, while the mean DAS28-CRP score was significantly lower (2.9 vs 3.6).
After adjustment for potential confounders, switching to adalimumab rescue therapy was associated with a 3.3-fold greater likelihood for achieving LDA compared with continuing on methotrexate.
Writing in the Annals of the Rheumatic Diseases, Smolen and co-authors point out that although methotrexate was the initial treatment used in their analysis, “prior research suggests that the predictive value of early disease activity on later outcomes is independent of the particular regimen, as correlations in a previous report were observed whether patients received methotrexate monotherapy or methotrexate plus a tumour necrosis factor (TNF) inhibitor.”
They conclude that their findings “support, and indirectly confirm, treatment-to-target strategies and timely adaptation of therapy with TNF inhibitors in patients with early RA and identify risk factors of patients who are not responding sufficiently to methotrexate.”
By Laura Cowen
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