Early disease activity may predict methotrexate response, radiographic progression in RA patients
medwireNews: Results of a post-hoc analysis suggest that high early disease activity is associated with poor response to methotrexate and the occurrence of radiographic progression among patients with rheumatoid arthritis (RA).
The researchers used pooled data from the PREMIER and OPTIMA trials to investigate predictors of an insufficient response to methotrexate, defined as not achieving stable low disease activity (Disease Activity Score at 28 joints based on C-reactive protein [DAS28-CRP]<3.2 points on two consecutive assessments) over 6 months of treatment.
As reported in the Annals of the Rheumatic Diseases, the 525 participants with an insufficient methotrexate response had significantly higher average DAS28-CRP scores at baseline than the 162 patients who responded to methotrexate, at 6.2 versus 5.6 points. Insuffient responders were also less likely to be male (24 vs 30%) and to have received previous treatment with systemic glucocorticoids (41 vs 49%).
In logistic regression analyses, DAS28-CRP scores at baseline and time-averaged over 4, 8 and 12 weeks were significant predictors of insufficient methotrexate response, at odds ratios (ORs) of 1.77, 3.28, 2.80 and 3.42, respectively, per unit increase in DAS28-CRP score.
Male sex (OR=0.49) and prior glucocorticoid use (OR=0.62) were identified as the strongest negative predictors of an insufficient methotrexate response at 6 months, say Josef Smolen (Medical University of Vienna, Austria) and colleagues.
Similarly, the researchers demonstrated that DAS28-CRP score, both at baseline and time-averaged over 4, 8 and 12 weeks, was positively associated with clinically relevant radiographic progression (CRRP) at 6 months – defined as an increase in modified total Sharp score of more than 1.5 points from baseline – whereas prior glucocorticoid use was a negative predictor of CRRP.
Together, these findings indicate “that changes in clinical disease activity as early as 4 weeks can predict response to methotrexate treatment” and radiographic progression at 6 months, write Smolen and colleagues.
The team also demonstrated that adding adalimumab to the treatment regimen was associated with better clinical outcomes for patients with an insufficient response to methotrexate after 6 months. For example, 64% of patients given rescue therapy with adalimumab in the OPTIMA study achieved low disease activity after 1 year of treatment with methotrexate plus adalimumab, compared with 41% of patients from PREMIER who continued to receive methotrexate monotherapy.
They emphasize, however, that these results are not based on head-to-head comparisons, and that the two trials “were done in different calendar years and had non-identical designs and baseline characteristics”.
Nonetheless, the researchers conclude that their findings “are in line with the treatment-to-target strategy and support timely adaptation of therapy with TNF [tumour necrosis factor] inhibitors in patients who have insufficient response to methotrexate”.
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