A large real-world administrative claims study published in Clinical Gastroenterology and Hepatology reveals that the advanced therapy upadacitinib is associated with a lower risk of treatment failure in ulcerative colitis patients compared to five other advanced therapies.
Upadacitinib Effectiveness Tracked via Real-World Claims Data
- Upadacitinib is a JAK1 inhibitor.
- Treatment failure in this study means a patient required a UC-related hospital admission, a UC-related surgery, or a new systemic corticosteroid course lasting longer than two weeks.
- Real-world claims data tracks what happens to patients in everyday clinical practice, offering a broad look at effectiveness outside tightly controlled clinical trials.
Real-World Data Trumps Indirect Comparisons in Ulcerative Colitis Care
More than a dozen advanced therapies are approved for moderate-to-severe ulcerative colitis. Yet, clinicians have long had to rely on indirect comparisons because only one head-to-head randomized trial—pitting vedolizumab against adalimumab—has been completed. To close this clinical knowledge gap, researchers led by Marianne Hupé at Western University in London, Ontario, analyzed de-identified health insurance claims from a large US database covering commercially insured and Medicare Advantage enrollees.
The study evaluated 7,283 patients with a mean age of 47 years, nearly half of whom were women, who initiated 9,078 advanced therapy treatment episodes between 2016 and 2023. Every patient maintained continuous health plan enrollment and had not used the same advanced therapy during the prior 12 months. The median follow-up duration across the treatment groups ranged from 63 to 92 weeks.
Huge shoutout to Dr. Yash Shaw, GI fellow, for an outstanding oral presentation at #DDW2026:“Real-world outcomes of upadacitinib vs ustekinumab, risankizumab, mirikizumab & guselkumab as 2nd-line therapy in UC after infliximab exposure.” Great presentation, big crowd! 👏 pic.twitter.com/gfxcDRaSan
The analysis tracked six distinct advanced therapies: adalimumab (2,315 episodes), infliximab (1,624 episodes), vedolizumab (3,164 episodes), ustekinumab (1,274 episodes), tofacitinib (547 episodes), and upadacitinib (154 episodes). Following statistical correction, upadacitinib showed a reduced likelihood of therapeutic failure relative to infliximab (hazard ratio [HR], 0.61), adalimumab (HR, 0.59), vedolizumab (HR, 0.69), ustekinumab (HR, 0.65), and tofacitinib (HR, 0.59).
| Advanced Therapy Comparison vs. Upadacitinib | Hazard Ratio (HR) for Treatment Failure |
|---|---|
| Adalimumab | 0.59 |
| Infliximab | 0.61 |
| Vedolizumab | 0.69 |
| Ustekinumab | 0.65 |
| Tofacitinib | 0.59 |
Prior Treatment History Alters Therapeutic Advantage
The clinical advantage of upadacitinib shifted depending on whether patients had previously tried other advanced medications. For individuals who had received an advanced therapy within the preceding 12 months, upadacitinib demonstrated a decreased likelihood of therapeutic failure compared with infliximab (HR, 0.41), vedolizumab (HR, 0.60), ustekinumab (HR, 0.59), and tofacitinib (HR, 0.51). However, among patients with no prior advanced therapy exposure in the past year, the advantage of upadacitinib reached statistical significance relative to only adalimumab and tofacitinib.
Patients prescribed upadacitinib spent the largest proportion of their follow-up period in corticosteroid-free disease stability, achieving an adjusted mean proportion of quarters of 0.70 (95% CI, 0.63-0.77). Patients on the other evaluated therapies achieved adjusted mean proportions ranging from 0.60 to 0.63. Vedolizumab also showed a lower risk of treatment failure compared to infliximab (HR, 0.88) and adalimumab (HR, 0.86).
The study was supported by an award from the Crohn’s and Colitis Foundation. Four study authors disclosed financial relationships with multiple companies, including research grants, consulting or advisory board fees, and lecture fees.
JAK Inhibitors Carry Cardiovascular Safety Warnings
JAK inhibitors carry specific safety warnings, particularly regarding older populations at high cardiovascular risk derived from past rheumatoid arthritis trials.
Administrative Claims Data Lacks Objective Disease Measures
The study authors acknowledged notable limitations in their methodology. The reliance on administrative claims data meant the investigation lacked objective disease measures, such as endoscopic scores or biomarker levels, precluding a direct evaluation of mucosal healing and biological responses. Unmeasured clinical confounders could have influenced outcomes despite rigorous statistical adjustment, and claims databases cannot capture the exact clinical reasoning behind why a patient stops or transitions between therapies.
Disclaimer: This article is for informational purposes only and does not constitute medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition.
