Week 12 Reduction in Modified Multiplier of the Simple Endoscopic Score for Crohn's Disease Is Predictive of Delayed Response to Upadacitinib in Crohn's Disease.
Emily C L Wong, Parambir S Dulai, John K Marshall et al.
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In 30 seconds
This post-hoc analysis of patient-level data from the U-EXCEED and U-EXCEL randomised trials examined early markers of delayed clinical response to upadacitinib in moderate-to-severe Crohn’s disease. Among 122 week-12 nonresponders with week-24 data, 64 (52.5%) achieved a delayed response after further open-label treatment. Failure to achieve at least a 20% reduction in the Modified Multiplier of the Simple Endoscopic Score for Crohn's Disease (MM-SES-CD) by week 12 was associated with lower odds of delayed response (adjusted odds ratio, 0.22; 95% confidence interval, 0.09-0.53; P = .001).
Key findings
- Of 122 week-12 nonresponders with week-24 data, 64 (52.5%) achieved delayed clinical response.
- Delayed response occurred in 13/39 [33.3%] without at least a 20% week-12 MM-SES-CD reduction versus 51/83 [61.5%] with that reduction.
- Failure to achieve at least a 20% MM-SES-CD reduction was associated with lower odds of delayed response (adjusted odds ratio, 0.22; 95% confidence interval, 0.09-0.53; P = .001).
- Week-12 SES-CD improvement and reductions in C-reactive protein or fecal calprotectin did not predict delayed response.
Why it matters
Clinical symptoms at week 12 may not capture all later responses to upadacitinib. In this analysis, an early change in MM-SES-CD distinguished groups with different likelihoods of response by week 24, while the assessed biomarker changes did not. This provides a potential endoscopic marker for interpreting early nonresponse, while recognising that the finding is an association from a post-hoc analysis.
What to keep in mind
This was a post-hoc analysis, and week-24 data were available for only 122 of 194 week-12 nonresponders. The delayed-response assessment followed an additional open-label treatment period.