medwireNews: Background therapy with methotrexate may partly explain placebo responses observed in rheumatoid arthritis (RA) clinical trials, study findings indicate.
Daniel Aletaha (Medical University of Vienna, Austria) and co-authors report in the Annals of the Rheumatic Diseases that clinical trial participants who received placebo but continued background therapy with methotrexate had “consistently higher” response rates than those treated with placebo only.
The findings arose from a post-hoc, pooled analysis of 398 placebo-treated participants from the GO-AFTER and SIRROUND-T randomized controlled trials, which both included people with and without ongoing background methotrexate therapy following an insufficient response to the conventional DMARD.
The researchers found that, at week 16, the ACR20 response rate was 25.3% in the 285 participants who received placebo and continued methotrexate compared with 12.4% in the 113 participants who received placebo only, a significant difference.
In addition, a significantly higher proportion of patients who continued methotrexate achieved CDAI low disease activity (≤10 points) at week 16 relative to those who did not receive background methotrexate, at 8.8% versus 1.8%.
Of note, the differences between the groups were apparent by 8 weeks for all of the outcomes and occurred as early as 4 weeks for ACR20 and ACR50 responses.
There were also significantly greater improvements from baseline in swollen and tender joint counts and patient and evaluator global assessments among the people on placebo plus background methotrexate versus those given placebo only.
In addition, C-reactive protein levels were unchanged over time in the methotrexate group but worsened in the no methotrexate group, resulting in a significant difference at week 16.
The investigators say they hypothesized “that a suspected limited patient adherence to [methotrexate] in real life would potentially be improved after patients enrol into a tightly monitored trial setting,” which could increase placebo responses in those continuing background therapy.
They believe their findings support this hypothesis and show that “[b]ackground therapies are a potentially important confounder in RA clinical trials and should be effectively aligned before recruitment of patients into a clinical trial, possibly also through introducing ‘run-in’ phases in future clinical trials.”
The team concludes: “This may lead to lower numbers of patients necessary to be recruited into a clinical trial and re-emphasises the importance of adequate [methotrexate] treatment and improving compliance in patients diagnosed with RA.”
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