Upadacitinib in Moderate-to-Severe Crohn's Disease (CD): A Systematic Review of Remission Outcomes in Adults With Inadequate Response or Intolerance to Biologic Drugs

OBJECTIVES: To assess the efficacy of oral upadacitinib in adults with moderate-to-severe Crohn’s Disease (CD) who had inadequate response or intolerance to one or more biologics.

METHODS: Electronic searches were conducted in OVID MEDLINE, OVID Embase, google scholar, and ClinicalTrials.Gov. Citations were screened in duplicate by two authors. Data was extracted from eligible articles and risk of bias (ROB) was assessed using the Cochrane ROB tool. Primary outcome was corticosteroids (Cs)-free remission among patients receiving glucocorticoids at baseline. Secondary outcomes were remission based on CD Activity Index (CDAI) remission (CDAI score <150), stool frequency (SF)- abdominal pain score (APS) clinical remission (average daily very soft/liquid SF≤2.8 and APS≤1, with neither worsening from baseline), and endoscopic remission (Simplified Endoscopic Score for CD [SES-CD] ≤4 and ≥2-point reduction from baseline, with no subscore >1).

RESULTS: Four RCTs were included, with sample sizes ranging from 36 to 502. All the trials were placebo controlled. Three trials reported Cs-free remission with upadacitinib (U) (13.3% at week 16 to 39.7% at week 52) compared with placebo (PB) (11.7% at week 12 to 4.9% at week 52). Similarly, secondary outcomes favored upadacitinib compared with placebo in terms of CDAI remission (U vs PB: 31% to 47.6% vs 15% to 21% reported in four trials), SF–APS clinical remission (U vs PB: 33% to 47% vs 9% to 14.4% reported in four trials), and endoscopic remission (U vs PB: 28.6% to 34.6% vs 0% to 5.5% reported in three trials) over a follow up period ranging from 12 to 52 weeks. ROB was assessed as 'low' risk to 'some' concerns for the included studies.

CONCLUSIONS: While upadacitinib demonstrated superior efficacy in achieving remission compared with placebo, additional trials with current standard of care as comparators are necessary to establish its effectiveness in such individuals.