Predictors and Outcomes of Ustekinumab Dose Intensification in Ulcerative Colitis: A Multicenter Cohort Study.

Ustekinumab has been shown to be effective for the treatment of ulcerative colitis (UC); however, >40% of patients have suboptimal clinical response after induction and maintenance dosing every 8 weeks.1,2 The best management approach for these patients is unclear. Many undergo empiric dose intensification to every 4 weeks or every 6 weeks, a nonstandardized decision because of limited data supporting therapeutic drug monitoring of ustekinumab.3 In Crohn's disease, approximately 50% of patients undergo ustekinumab dose intensification, which seems to be effective based on prior work from our group and others.4-8 However, similar data in UC are lacking. In this real-world multicenter cohort study, we sought to identify predictors and outcomes of ustekinumab dose intensification in UC.

1-Year Comparative Effectiveness of Tofacitinib vs Ustekinumab for Patients With Ulcerative Colitis and Prior Antitumor Necrosis Factor Failure.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Real-world data comparing the effectiveness of tofacitinib to ustekinumab are limited. We compared 52-week outcomes of tofacitinib vs ustekinumab for UC after antitumor necrosis factor (anti-TNF) failure. METHODS: In this retrospective cohort study, adults initiated tofacitinib or ustekinumab for UC after anti-TNF failure May 1, 2018 to April 1, 2021, at a US academic medical center. The primary outcome was steroid-free clinical remission (SFCR) at 12 and 52 weeks. The secondary outcome was drug survival (ie, time to drug discontinuation due to nonresponse). Adverse events (AEs) were also assessed. RESULTS: Sixty-nine patients initiated tofacitinib, and 97 patients initiated ustekinumab with median follow-up of 88.0 and 62.0 weeks, respectively. After inverse probability of treatment-weighted logistic and Cox regression, there was no association of tofacitinib vs ustekinumab with SFCR at 12 weeks (odds ratio, 1.65; 95% CI, 0.79-3.41), SFCR at 52 weeks (odds ratio, 1.14; 95% CI, 0.55-2.34), or drug survival (hazard ratio, 1.37; 95% CI, 0.78-2.37). Kaplan-Meier analysis demonstrated no separation in drug survival curves. Regression results were similar after excluding patients with prior tofacitinib or ustekinumab exposure. During available follow-up, 17 AEs were reported for tofacitinib (most commonly shingles, n = 4), and 10 AEs were reported for ustekinumab (most commonly arthralgia and rash, each n = 2). Two patients discontinued treatment due to AEs (1 tofacitinib for elevated liver enzymes, 1 ustekinumab for arthralgia). CONCLUSIONS: In a real-world UC cohort, tofacitinib and ustekinumab demonstrated similar effectiveness at 52 weeks. Adverse events were consistent with the known safety profiles of these agents.

In this real-world cohort of anti-TNF-exposed patients with ulcerative colitis, tofacitinib and ustekinumab demonstrated similar effectiveness in achieving steroid-free clinical remission at 12 and 52 weeks. Adverse events were consistent with the known safety profiles of these agents.

Clinical and Endoscopic Outcomes Through 78 Weeks of Tofacitinib Therapy for Ulcerative Colitis in a US Cohort.

BACKGROUND: Tofacitinib is an oral JAK inhibitor for the treatment of ulcerative colitis (UC). We assessed outcomes through 78 weeks of tofacitinib therapy for UC in a real-world setting. METHODS: This retrospective cohort study included adults initiating tofacitinib for UC from May 1, 2018, to April 1, 2021, at a large academic center in the United States. The primary outcome was steroid-free clinical remission at 78 (+/-4) weeks (SFCR 78; simple clinical colitis activity index ≤2 with no corticosteroid use within 30 days). The secondary outcome was tofacitinib discontinuation due to nonresponse (treatment persistence). Additional outcomes were endoscopic response/remission and adverse events (AEs). RESULTS: Seventy-three patients initiated tofacitinib, with a median follow-up of 88 weeks. Among patients with available data, 31 of 60 (51.7%) achieved SFCR 78, 21 of 47 (44.7%) achieved endoscopic remission during follow-up, and 25 of 73 (34.2%) discontinued tofacitinib during follow-up due to nonresponse (including 11 patients who required colectomy). Nineteen AEs were reported among 15 patients during follow-up: shingles (n = 4, all without documented vaccinations), deep venous thrombosis (n = 2), elevated liver enzymes (n = 2), skin abscess (n = 2), pneumonia (n = 2), possible miscarriage (n = 2), norovirus (n = 1), COVID-19 (n = 1), lymphopenia (n = 1), Clostridioides difficile infection (n = 1), and heart block (n = 1). One patient discontinued therapy due to an AE (elevated liver enzymes), and no deaths occurred. CONCLUSION: Tofacitinib treatment was effective in achieving SFCR for the majority of patients with UC through 78 weeks. Adverse events were consistent with the known safety profile of tofacitinib, and AEs requiring discontinuation were rare. Due to limitations regarding sample size, larger studies are needed to confirm these findings.

Tofacitinib treatment was effective in achieving steroid-free clinical remission for the majority of patients with UC through 78 weeks. Adverse events, which rarely required treatment discontinuation, were consistent with the known safety profile of tofacitinib.

Long-Term Outcomes After Ustekinumab Dose Intensification for Inflammatory Bowel Diseases.

In this retrospective cohort study, we demonstrated that dose intensification of ustekinumab to every 4 or every 6 weeks was effective in both achieving and maintaining clinical remission for >40% of inflammatory bowel disease patients for up to 24 months.