Clinical outcomes of patients with corticosteroid refractory immune checkpoint inhibitor-induced enterocolitis treated with infliximab.

INTRODUCTION: Immune checkpoint inhibitors (CPIs) have changed the treatment landscape for many cancers, but also cause severe inflammatory side effects including enterocolitis. CPI-induced enterocolitis is treated empirically with corticosteroids, and infliximab (IFX) is used in corticosteroid-refractory cases. However, robust outcome data for these patients are scarce. METHODS: We conducted a multicenter (six cancer centers), cohort study of outcomes in patients treated with IFX for corticosteroid-refractory CPI-induced enterocolitis between 2007 and 2020. The primary outcome was corticosteroid-free clinical remission (CFCR) with Common Terminology Criteria for Adverse Events (CTCAE) grade 0 for diarrhea at 12 weeks after IFX initiation. We also assessed cancer outcomes at 1 year using RECIST V1.1 criteria. RESULTS: 127 patients (73 male; median age 59 years) were treated with IFX for corticosteroid-refractory CPI-induced enterocolitis. Ninety-six (75.6%) patients had diarrhea CTCAE grade >2 and 115 (90.6%) required hospitalization for colitis. CFCR was 41.2% at 12 weeks and 50.9% at 26 weeks. In multivariable logistic regression, IFX-resistant enterocolitis was associated with rectal bleeding (OR 0.19; 95% CI 0.04 to 0.80; p=0.03) and absence of colonic crypt abscesses (OR 2.16; 95% CI 1.13 to 8.05; p=0.03). Cancer non-progression was significantly more common in patients with IFX-resistant enterocolitis (64.4%) as compared with patients with IFX-responsive enterocolitis (37.5%; p=0.013). CONCLUSION: This is the largest study to date reporting outcomes of IFX therapy in patients with corticosteroid-refractory CPI-induced enterocolitis. Using predefined robust endpoints, we have demonstrated that fewer than half of patients achieved CFCR. Our data also indicate that cancer outcomes may be better in patients developing prolonged and severe inflammatory side effects of CPI therapy.

Randomized controlled trial: a pilot study of a psychoeducational intervention for fatigue in patients with quiescent inflammatory bowel disease.

INTRODUCTION: Fatigue is a frequent, debilitating symptom of inflammatory bowel disease (IBD). Despite this, studies report dissatisfaction among IBD patients regarding how little attention is given to fatigue-related issues during consultations. We performed a pilot randomized controlled trial (RCT) to assess whether a brief, structured, multidisciplinary psychological support program improved fatigue, mood and quality of life indices in patients with quiescent IBD. METHODS: The intervention consisted of three small-group psychoeducational sessions over 6 months. Primary outcomes were effect on fatigue severity and impact scores. Secondary outcomes included effect on depression, anxiety, somatization scores, generic and disease-specific quality of life. RESULTS: Twenty-three patients were enrolled, 10 in the intervention arm and 13 controls. Mean fatigue severity and impact scores improved for patients in the intervention group (by 14.5-13.1 and 49.7-45.8, respectively), and worsened in controls (by 11.5-12.6 and 33.5-35 respectively). Mean Short Form 36 (SF-36) scores for role limitations due to physical health decreased from 44.4 to 38.9 in the intervention group, but increased from 44.2 to 51.9 among controls. Energy scores in the intervention group improved from 17.8 to 26.6, but only from 31.4 to 31.7 among controls. Short IBD questionnaire scores improved in both groups, from 46.2 to 45.2 in controls compared with 44.4-40 in the intervention group. DISCUSSION: In this small pilot RCT, positive effects were demonstrated on fatigue, energy levels and other quality of life outcomes. Larger, adequately powered studies with longer follow up are required.ClincialTrials.gov identifier: NCT02709434.

Efficacy and tolerability of initiating, or switching to, infliximab biosimilar CT-P13 in inflammatory bowel disease (IBD): a large single-centre experience.

OBJECTIVES: Recently, the infliximab biosimilar (CT-P13) received market authorisation for inflammatory bowel disease (IBD), allowing cost benefits when switching to CT-P13. We aim to assess the efficacy and safety of switching from originator infliximab to CT-P13 for new and existing patients. MATERIAL AND METHODS: Treatment response, remission, primary and secondary loss of response rates, and adverse events in patients who initiated infliximab originator in the 12 months pre-switch (n = 53) were compared with the patients who initiated CT-P13 in the 12 months post-switch (n = 69). Sustained responses were compared for existing infliximab originator patients who switched to CT-P13 (n = 191) and those who continued with the originator (n = 19). RESULTS: There was no difference in remission (58.1% vs. 47.4%, p = .37), response (12.6% vs. 10.5%, p = .80), secondary loss of response (24.6% vs. 42.1%, p = .10), or adverse events (4.7% vs. 0% p = 1.0) between those who switched to CT-P13 and those who continued infliximab originator. There was no difference in remission (42.0% vs. 26.4%, p = .074), response (21.7% vs. 22.6%, p = .91), primary non-response (5.8% vs. 15.1%, p = .09), secondary loss of response (21.7% vs. 22.6%, p = .91), or adverse events (8.7% vs. 11.3%, p = .63) in those who initiated CT-P13 compared with infliximab originator. CONCLUSIONS: There was no difference in the efficacy and safety of infliximab originator and CT-P13 during the first 12 months after switching.

Global prevalence of, and risk factors for, gastro-oesophageal reflux symptoms: a meta-analysis.

OBJECTIVES: Gastro-oesophageal reflux symptoms are common in the community, but there has been no definitive systematic review and meta-analysis of data from all studies to estimate their global prevalence, or potential risk factors for them. DESIGN: Medline, Embase and Embase Classic were searched (until September 2016) to identify population-based studies that reported the prevalence of gastro-oesophageal reflux symptoms in adults (≥15 years); gastro-oesophageal reflux was defined using symptom-based criteria or questionnaires. The prevalence was extracted for all studies, and according to the criteria used to define it. Pooled prevalence, according to study location and certain other characteristics, OR and 95% CIs were calculated. RESULTS: Of the 14 132 citations evaluated, 102 reported the prevalence of gastro-oesophageal reflux symptoms in 108 separate study populations, containing 460 984 subjects. Prevalence varied according to country (from 2.5% in China to 51.2% in Greece) and criteria used to define gastro-oesophageal reflux symptoms. When only studies using a weekly frequency of heart burn or regurgitation to define presence were considered, pooled prevalence was 13.3% (95% CI 12.0% to 14.6%). Prevalence was higher in subjects ≥50 years (OR 1.32; 95% CI 1.12 to 1.54), smokers (OR 1.26; 95% CI 1.04 to 1.52), non-steroidal anti-inflammatory drug (NSAID)/aspirin users (OR 1.44; 95% CI 1.10 to 1.88) and obese individuals (OR 1.73; 95% CI 1.46 to 2.06). CONCLUSIONS: The prevalence of gastro-oesophageal reflux symptoms varied strikingly among countries, even when similar definitions were used to define their presence. Prevalence was significantly higher in subjects ≥50 years, smokers, NSAID users and obese individuals, although these associations were modest.

Prevalence of Dyspepsia in Individuals With Gastroesophageal Reflux-Type Symptoms in the Community: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Dyspepsia and gastroesophageal reflux are highly prevalent in the general population, but they are believed to be separate entities. We conducted a systematic review and meta-analysis to estimate the prevalence of dyspepsia in individuals with gastroesophageal reflux symptoms (GERS), and to quantify overlap between the disorders. METHODS: We searched MEDLINE, EMBASE, and EMBASE Classic databases to identify population-based studies reporting the prevalence of dyspepsia and GERS in adults, defined using specific symptom-based criteria or based on answers to questionnaires. We calculated pooled prevalence values, according to study location and criteria used to define weekly GERS or dyspepsia, as well as odds ratios (ORs) with 95% CIs. The degree of overlap between dyspepsia and GERS was examined. RESULTS: Of 14,132 papers evaluated, 79 reported prevalence of weekly GERS. Nineteen of these study populations, comprising 111,459 participants, also reported the proportion of individuals with dyspepsia. The prevalence of dyspepsia in individuals with weekly GERS was 43.9% (95% CI, 35.1%-52.9%). The pooled OR for dyspepsia in individuals with weekly GERS, compared with those without, was 6.94 (95% CI, 4.33%-11.1%). The OR for dyspepsia in individuals with weekly GERS was significantly higher in all geographical regions studied and for all diagnostic criteria. The pooled degree of overlap between dyspepsia and GERS was 25.9% (95% CI, 19.9%-32.4%). CONCLUSIONS: The odds of dyspepsia in individuals with weekly GERS is almost 7-fold that of individuals without GERS; dyspepsia and GERS overlap in more than 25% of individuals. Reasons for this remain speculative, but might include shared pathophysiological mechanisms or residual confounding factors. However, patients with GERS should be questioned about coexistent dyspepsia, to optimize treatment approaches.