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

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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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

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa361 ◽

2021 ◽

Author(s):

Jeongseok Kim ◽

Hyuk Yoon ◽

Nayoung Kim ◽

Kang-Moon Lee ◽

Sung-Ae Jung ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Clinical Response ◽

Induction Therapy ◽

Clinical Remission ◽

Tumor Necrosis ◽

Korean Patients ◽

Endoscopic Remission ◽

Remission Rates ◽

Factor Therapy ◽

Necrosis Factor

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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Predictors of Clinical Remission under Anti-tumor Necrosis Factor Treatment in Patients with Ankylosing Spondylitis: Pooled Analysis from Large Randomized Clinical Trials

The Journal of Rheumatology ◽

10.3899/jrheum.141278 ◽

2015 ◽

Vol 42 (8) ◽

pp. 1418-1426 ◽

Cited By ~ 14

Author(s):

Xenofon Baraliakos ◽

Andrew S. Koenig ◽

Heather Jones ◽

Annette Szumski ◽

David Collier ◽

...

Keyword(s):

Clinical Trials ◽

Ankylosing Spondylitis ◽

Tumor Necrosis Factor ◽

Disease Activity ◽

Clinical Remission ◽

Partial Remission ◽

Tumor Necrosis ◽

Disease Duration ◽

Hla B27 ◽

Necrosis Factor

Objective.Investigate the role and relation of disease duration of different factors for achieving clinical remission with anti-tumor necrosis factor (TNF) treatment in patients with active ankylosing spondylitis (AS).Methods.Data pooled from 4 large (n = 1281) clinical trials were used to compare disease duration subgroups for placebo or sulfasalazine (SSZ) versus etanercept (ETN), which, in turn, were analyzed by age of diagnosis ≤ 40 versus > 40 years, HLA-B27 status, and baseline C-reactive protein (CRP) ≤ upper limit of normal (ULN) versus > ULN using chi-square tests, and ANCOVA. The primary efficacy measure was Assessments of SpondyloArthritis international Society (ASAS) partial remission (PR) after 12 weeks of treatment. Also analyzed were Bath AS Disease Activity Index and Functional Index, AS Disease Activity Scores, and ASAS response rates.Results.Overall, a larger percentage of patients achieved ASAS-PR with ETN versus SSZ or placebo. More patients with ≤ 2-year disease duration treated with ETN experienced partial remission (34%) versus longer disease duration (30%, 27%, and 22% for > 2–5, > 5–10, and > 10 yrs, respectively; all p < 0.05). In the subgroup of patients with both disease duration ≤ 2 years and aged ≤ 40 years at diagnosis, the treatment response was even more pronounced. Similar results were seen in HLA-B27–positive patients in the disease duration ≤ 2-year subgroup. Overall, patients with high CRP at baseline had better treatment responses compared with patients with normal CRP.Conclusion.Treatment response under anti-TNF treatment with ETN at 12 weeks was greatest among patients with disease duration ≤ 2 years and even more pronounced in subgroups of patients ≤ 40 years old or HLA-B27–positive at diagnosis.

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The Use of Rheumatic Disease Comorbidity Index for Predicting Clinical Response and Retention Rate in a Cohort of Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Alpha Inhibitors

BioMed Research International ◽

10.1155/2019/6107217 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Martina Biggioggero ◽

Federica Mesina ◽

Ennio Giulio Favalli

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Response ◽

Tumor Necrosis ◽

Retention Rate ◽

First Line ◽

Necrosis Factor Alpha ◽

Comorbidity Index ◽

Factor Alpha ◽

Necrosis Factor ◽

Moderate Response

Introduction. To retrospectively evaluate the impact of comorbidities on treatment choice, 12-month clinical response, and 24-month retention rate in a cohort of patients with rheumatoid arthritis (RA) treated with a first-line tumor necrosis factor alpha inhibitor (TNFi), by using for the first time the Rheumatic Disease Comorbidity Index (RDCI). Methods. The study population was extracted from a local registry of RA patients receiving adalimumab or etanercept as first-line biologics between January 2001 and December 2013. The prevalence of comorbidities was computed, and patients were stratified according to RDCI for evaluating the role of comorbidities on TNFi choice, concomitant methotrexate, clinical response (1-year DAS28-ESR remission and low disease activity [LDA] and EULAR good-moderate response), and the 24-month retention rate. Results. 346 patients (172 adalimumab and 174 etanercept) were included. A significantly higher EULAR good/moderate response (P = 0.020) and DAS28-ESR remission (P = 0.003) were obtained according to RDCI (0, 1, 2, or ≥3). Lower RDCI (P = 0.022), male sex (P = 0.006), higher baseline DAS28-ESR (P = 0.001), ETN (P < 0.001), and concomitant methotrexate (P = 0.016) were predictors of EULAR good/moderate response. Elevated RDCI was a predictor of discontinuation of biologics (P = 0.036), whereas treatment with etanercept (P < 0.001) and methotrexate (P = 0.007) was associated with a lower risk of TNFi withdrawal. Conclusions. Multimorbidity, measured by RDCI, is a negative predictor of TNFi persistence on treatment and of achieving a good clinical response. The use of RDCI may be very useful for identifying patients with RA carrying those comorbid conditions associated with poor prognostic outcomes and for defining new treatment targets in multimorbid RA patients.

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