Clinical Outcomes and Response Predictors of Vedolizumab Induction Treatment for Korean Patients With Inflammatory Bowel Diseases Who Failed Anti-TNF Therapy: A KASID Prospective Multicenter Cohort Study

Abstract Background We investigated the real-life effectiveness and safety of vedolizumab (VDZ) induction therapy among Korean patients with Crohn disease (CD) or ulcerative colitis (UC) for whom anti-tumor necrosis factor therapy previously failed. Methods Adult patients who started VDZ induction therapy at 16 centers were prospectively enrolled in the Korean VDZ nationwide registry. The coprimary outcomes were clinical remission, defined as a Crohn’s Disease Activity Index score <150 points and a partial Mayo score ≤2 points with a combined rectal bleeding and stool frequency subscore ≤1 point at week 14 and endoscopic remission defined as a Mayo endoscopic subscore ≤1 point. We also analyzed predictors of clinical remission. Results Between August 2017 and November 2019, a total of 158 patients (80 with CD and 78 with UC) received VDZ induction therapy. Clinical remission rates among patients with CD and patients with UC were 44.1% and 44.0%, respectively. Among patients with UC, the endoscopic remission rate was 32.4%. Clinical response and remission rates showed increasing trends during induction therapy. Multivariable analysis revealed that clinical response at week 6 was the only predictor of clinical remission at week 14 for both patients with CD and patients with UC. Among patients who experienced 1 or more adverse events (n = 71; 44.9%), disease exacerbation (n = 28; 17.7%) was the most common adverse event. Conclusions Among Korean patients with CD or UC for whom anti-tumor necrosis factor therapy failed, VDZ induction therapy was effective and safe. The early clinical response was associated with clinical remission after VDZ induction therapy.

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DOP58 Non-white race is associated with decreased efficacy of tumor necrosis factor antagonist therapy in Ulcerative Colitis: A post-hoc analysis of individual level data from golimumab clinical trials

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab073.097 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S093-S094

Author(s):

R Greywoode ◽

F Petralia ◽

T Ullman ◽

J F Colombel ◽

R Ungaro

Keyword(s):

Clinical Trials ◽

Clinical Response ◽

Clinical Remission ◽

Tumor Necrosis ◽

Lower Odds ◽

Individual Level ◽

Level Data ◽

Tnf Antagonist ◽

Endoscopic Remission ◽

Necrosis Factor

Abstract Background Observational studies suggest non-white patients with inflammatory bowel disease (IBD) have worse clinical outcomes.1 There are limited data on whether race impacts response to biologic therapy. We therefore aimed to evaluate the efficacy of the tumor necrosis factor (TNF) antagonist golimumab comparing white to non-white participants, using individual participant level data from phase 2/3 randomized clinical trials of TNF antagonist therapy in ulcerative colitis (UC). Methods We conducted a pooled analysis of individual-level data from the induction and maintenance trials of golimumab in UC accessible through Yale University Open Data Access Project (YODA). There were insufficient non-white participants in infliximab studies accessible through YODA, precluding meaningful analysis. We analyzed patients in the placebo and treatment arms separately. Our primary outcome was clinical response and secondary outcomes were clinical remission and endoscopic healing according to clinical trial definitions. We compared white and non-white (defined as Black, Asian, or Other race) participants using multivariable logistic regression a priori adjusting for age, sex, treatment group, baseline Mayo score, immunomodulator and corticosteroid use. Effect estimates were expressed as adjusted odds ratios (aOR) and 95% confidence intervals (95% CI). Results A total of 1,006 participants were included in the induction trial (PURSUIT-SC; 18% non-white) and 783 participants in the maintenance trial (PURSUIT-M; 17% non-white). Non-white participants had significantly lower odds of week 6 clinical response (aOR 0.43, 95%CI 0.28–0.66), clinical remission (aOR 0.41, 95%CI 0.22–0.77) and endoscopic remission (aOR 0.48, 95%CI 0.30–0.74) compared to white participants (Figure). Non-white participants also had a lower adjusted odds of week 30 clinical response (aOR 0.64, 95%CI 0.40–1.01), clinical remission (aOR 0.45, 95%CI 0.28–0.74), and endoscopic remission (aOR 0.62, 95%CI 0.41–0.96). By week 54, the lower odds of these outcomes among non-whites were no longer statistically significant (Figure). Conclusion Non-white UC patients were less likely to achieve clinical response, clinical remission, and endoscopic healing with golimumab compared to white patients in these clinical trials. Further studies are needed to understand these differences and whether they are observed with other drugs or outside the context of clinical trials. Reference

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P348 Clinical outcomes and response predictors of vedolizumab treatment for anti-TNF-failed patients with IBD in Korea: A prospective multicenter cohort study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.477 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S333-S334

Author(s):

J Kim ◽

H Yoon ◽

K M Lee ◽

S A Jung ◽

D I Park ◽

...

Keyword(s):

Ulcerative Colitis ◽

Clinical Response ◽

Clinical Outcomes ◽

Induction Therapy ◽

Clinical Remission ◽

Response Rates ◽

Faecal Calprotectin ◽

Korean Patients ◽

Response Predictors ◽

Endoscopic Remission

Abstract Background Vedolizumab (VDZ) inhibits gut lymphocyte trafficking by binding to α4β7 integrin, which can be effective for patients with Crohn’s disease (CD) or ulcerative colitis (UC). We aimed to investigate the clinical outcomes and response predictors of VDZ treatment for Korean patients with CD or UC, who were previously failed to anti-tumour necrosis factor (TNF) therapy. Methods Between August 2017 and November 2019, a total of 159 patients with CD (n = 81) or UC (n = 78) received a VDZ induction therapy from 16 centres and were prospectively enrolled. Of those, patients who were evaluated at week 14 after three induction doses of VDZ (week 0, 2, and 6) were analysed. The co-primary endpoints were corticosteroid-free clinical remission and endoscopic remission/response (for UC) at week 14. We also analysed predictors of corticosteroid-free clinical remission, persistence of vedolizumab and safety. Results A total of 153 patients were analysed (CD, 77 [50.3%]; male, 94 [61.4%]; median age, 40 years [range, 17–80]; median disease duration, 8.0 years [range, 0.1–38.0]). All patients had previously experienced failures to at least one anti-TNF agent (one, 105 [68.6%]; two, 44 [28.8%]; three, 4 [2.6%]). Corticosteroid-free clinical remission/response rates in CD and UC patients were 44.6%/51.8% and 39.4%/62.0%, respectively. In patients with UC, endoscopic remission and response rates defined by Mayo endoscopic subscore/ulcerative colitis endoscopic index of severity were 33.8%/14.1% and 55.4%/39.1%, respectively. Multivariate analysis revealed that a clinical response at week 6 were associated with a corticosteroid-free clinical remission at week 14 in both CD (Odds ratio [OR] 33.84, 95% confidence interval [CI] 6.25–183.31, p < 0.001) and UC (OR 12.22, 95% CI 1.30–115.28, p = 0.029). In addition, UC patients with higher baseline levels of C-reactive protein (CRP) and faecal calprotectin were less likely to be in corticosteroid-free clinical remission (CRP > 0.31 mg/dl: OR 0.05, 95% CI 0.00–0.60, p = 0.019; faecal calprotectin > 2,000 μg/g: OR 0.04, 95% CI 0.00–0.93, p = 0.045). The cumulative probabilities of continuing VDZ after one year were 48.7% for CD and 65.7% for UC, respectively. During median 10 months of follow-up periods (range, 3–26 months), disease exacerbation was the most common adverse event (n = 73, 47.7%), followed by nasopharyngitis (n = 23, 15.0%) and arthralgia (n = 19, 12.4%). Conclusion In anti-TNF-failed Korean patients with CD and UC, VDZ induction therapy was effective with an acceptable safety profile. Early clinical response and higher inflammatory burden at baseline were associated with corticosteroid-free clinical remission after VDZ induction therapy.

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