Upadacitinib was efficacious for inducing and maintaining response and remission in moderately to severely active CD, irrespective of previous biologic failure.
The efficacy and safety of the oral JAK1 inhibitor upadacitinib in patients with CD has been shown in the induction studies U-EXCEED and U-EXCEL. Responders at 12 or 24 weeks were eligible for re-randomization and included in the maintenance study U-ENDURE. In these studies, the superiority of upadacitinib compared with placebo was demonstrated across clinical, endoscopic, steroid-free, and QOL measures.
The aim of the sub-analysis presented by Brian Gordon Feagan, MD, MSc, of the University of Western Ontario, was to assess endoscopic outcomes in patients with or without a history of biologic failure, defined as inadequate response or intolerance, among those who received upadacitinib treatment in the study program. Therefore, pooled data from U-EXCEL, U-EXCEED, or U-Endure were analyzed. “In general, a lower inflammatory burden was seen in patients without biologic failure compared with those who failed a biologic,” Dr. Feagan explained. In the biologic-failure group, 60% had at least failed two, and many patients even three prior biologics, in most cases TNF-blockers.
In the induction studies, higher rates of endoscopic response (defined as a decrease in Simple Endoscopic Score for CD [SES-CD] >50% from baseline or, for patients with an SES-CD of 4 at baseline, at least a 2-point reduction from baseline) and endoscopic remission (defined as SES-CD <4 and at least a 2-point reduction from baseline and no subscore >1 in any individual variable) were seen in upadacitinib-treated patients compared with placebo. Of the patients treated with upadacitinib without biologic failure, 52% achieved an endoscopic response compared with 16.2% with placebo. The same was true for 35.7% of upadacitinib-treated patients with prior failure compared with 5.3% with placebo.
“In patients with prior biologic failure, there was a lesser effect but still with a delta of 30,” Dr. Feagan said.
At week 12, 36% of upadacitinib-treated patients without biologic failure achieved endoscopic remission (vs 10.1% with placebo). The corresponding results for patients with biologic failure were 19.6% versus 2.8% in the placebo group.
The most difficult endpoint was sustained remission, defined as the percentage of patients who achieved endoscopic remission at both time points. Specifically, 57.1% of patients treated with high-dose upadacitinib and 35.5% treated with the low dose achieved endoscopic remission compared with 6.3% in the placebo group.
Upadacitinib induction and maintenance treatment doses were well tolerated with no new safety signals.
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