P549 One-Year Comparison of Clinical and Endoscopic Outcomes of Tofacitinib Versus Vedolizumab for Ulcerative Colitis After Anti-Tumor Necrosis Factor Failure: A Real-World Cohort Study in the United States

Dalal, R.(1)*;Sharma, P.(2);Bains, K.(3);Pruce, J.(1);Allegretti, J.(1);

(1)Brigham and Women's Hospital- Harvard Medical School, Gastroenterology- Hepatology and Endoscopy, Boston, United States;(2)Pfizer, Gastroenterology, New York, United States;(3)Brigham and Women's Hospital, Nutrition, Boston, United States;

Background

Tofacitinib (tofa) is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We compared 52 week real-world outcomes of tofa vs vedolizumab (vedo) for UC after anti-TNF failure.

Methods

In this retrospective cohort study, adults initiated tofa or vedo after failure of >1 anti-TNF between 5/1/18 and 4/1/21 at a large U.S. medical center. Vedo patients were frequency matched to tofa patients 2:1 by age and sex. The primary outcome was steroid-free clinical remission at 12 and 52 (+/- 4) weeks (SFCR 12 and 52, simple clinical colitis activity index [SCCAI] <2 or provider assessment and no use of oral/IV steroids for >30 days). The secondary outcome was endoscopic response (ER) within 52 weeks (decrease in Mayo endoscopic subscore [MES] by >1 point). Other outcomes within 52 weeks: endoscopic remission (MES=0), biochemical response/remission (improvement by 25%/normalization of C-reactive protein), drug discontinuation for non-response (NR), improvement in arthralgia, UC hospitalization, and adverse events (AEs). Multivariable logistic regression was performed for primary/secondary outcomes adjusting for UC duration, number of prior anti-TNFs, steroid/immunomodulator use, albumin, Montreal disease extent >E1, MES = 3, and UC hospitalization within 12 months.

Results

136 vedo patients were matched to 68 tofa patients. Tofa patients had more anti-TNF exposures, higher CRP and SCCAI, and most had prior vedolizumab exposure (Table 1). 54% of tofa vs 46% of vedo patients achieved SFCR 12 and 59% vs 45% achieved SFCR 52. Within 52 weeks, 74% tofa vs 55% vedo had ER, 30% vs 27% had endoscopic remission, 55% vs 50% had improvement in arthralgia, 71% vs 59% had biochemical response, 46% vs 32% had biochemical remission, 5% vs 13% had UC hospitalization, 30% vs 29% discontinued treatment for NR, and 0% vs 2% discontinued treatment due to AEs (vedo group only: perforated diverticulitis, nausea, and oral pain) (Figure 1). During available follow-up (not limited to 52 weeks), the most common AEs (reported among >1% of total cohort) included rash (0% tofa vs 4% vedo), C. difficileinfection (1% vs 2%), shingles (2% vs 1%), COVID-19 (1% vs 2%), other infection (2% vs 4%), and elevated liver enzymes (1% vs 2%) (Figure 2). After multivariable logistic regression, tofa was associated with a non-significantly higher odds of SFCR 12 (OR 1.66, 95% CI 0.77-3.62) and significantly higher odds of SFCR 52 (OR 2.15, 95% CI 1.01-4.61) and ER within 52 weeks (aOR 3.42, 95% CI 1.08-10.80) vs vedo. 


Conclusion

Tofa was associated with higher odds of SFCR 52 and ER vs vedo for UC. AEs were consistent with known safety profiles. Due to limited sample sizes, larger cohort studies are needed.