Efficacy, tolerability, and predictors of response to infliximab therapy for Crohn's disease: A large single centre experience

Abstract

Background: Infliximab is licenced for use in Crohn's disease (CD). Trial data demonstrate that infliximab is effective for inducing remission of active CD, healing fistulising CD, and preventing relapse once in remission. However, long-term data regarding efficacy, safety, and predictors of response are still emerging. Aim: To examine these issues in a large cohort of patients who received infliximab for CD. Methods: A retrospective analysis of prospectively collected data was performed for 210 patients receiving infliximab for luminal or fistulising CD. Response to infliximab induction therapy, and sustained clinical benefit, were assessed by a decrease in Harvey-Bradshaw Index (HBI) of ≥2 points. Remission was defined as an HBI ≤ 4. Physician's global assessment was used where HBI could not be obtained. Demographic and disease factors that may predict response to therapy were analysed by Kaplan-Meier plots and univariate and multivariate analyses. Results: Overall, 173 (82.4%) patients responded to infliximab induction, with 114 (65.9%) achieving sustained clinical benefit. Almost 40% of the study cohort had an HBI ≤ 4, indicating remission, at last point of follow-up (median 24 months). Concomitant immunosuppression predicted sustained clinical benefit in the first 6 months of therapy (P = 0.03). An inflammatory disease phenotype (P = 0.04 univariate analysis, P = 0.03 Kaplan Meier analysis) and male gender (P = 0.03) also predicted sustained clinical benefit. Episodic therapy was associated with an increased likelihood of secondary non-response. Adverse events, including malignancies, were few. Conclusion: In this single centre study, infliximab was efficacious and well-tolerated in CD.

Understanding Infliximab in Crohn’s Disease: The Long-Term Outcomes

“…The medical records of 492 unselected patients (or 464 with outcome data, used here as the denominator to calculate rates) treated with infliximab at the Mayo Clinic (1998-2002) were systematically reviewed. The study showed an 86 % initial response rate (or 80 % calculated on an ITT basis), similar to the 82-89 % reported in most other publications such as the pediatric REACH trial [5], the Edmonton cohort [6], the large Leuven cohort [7], the Leeds cohort [8], and the Targan initial RCT [1] but higher than the short-term response rate achieved in the ACCENT trial (65 %) [2]. This figure (82-89 %) also includes those with partial response, variably defined in the different studies.…”

Medical Therapy for Crohn’s Disease: The Present

“…In a Canadian cohort of 130 patients, most on concurrent immunomodulators, 83 % maintained clinical response at 30 weeks and 64 % at 54 weeks [ 60 ]. Another study detailing a large single center experience with infl iximab showed an 82 % response to infl iximab induction, and a 66 % sustained clinical benefi t [ 61 ].…”

Review article: The pharmacokinetics and pharmacodynamics of drugs used in inflammatory bowel disease treatment

“…Smoking, long (>2 years) disease duration, small bowel extent of disease, complicated phenotype and prior failure of another anti-TNF agent are found in some, albeit not all, studies to confer an increased risk of primary nonresponse in CD [272][273][274][275]. Increased age, anti-neutrophil cytoplasmic antibody (ANCA)-positive status and anti-Saccharomyces cerevisiae antibody (ASCA)-negative status and prior anti-TNF exposure are risk factors for primary nonresponse in patients with UC [276,277].…”