News from the AGA

Four new and noteworthy IBD drug studies


Inflammatory bowel disease (IBD) is a vibrant area of clinical research. Many of the 250+ abstracts presented at the inaugural Crohn’s & Colitis Congress — a partnership of the Crohn’s & Colitis Foundation and AGA — looked at the efficacy and safety of IBD therapies. Below is a summary of four noteworthy drug studies from the Congress, as determined by the Congress organizing committee. You can review all abstracts presented at the Crohn’s & Colitis Congress in Gastroenterology.

Double-blind, randomized, placebo-controlled, crossover trial to evaluate induction of clinical response in patients with moderate-severe Crohn’s disease treated with rifaximin

By Scott D. Lee, University of Washington Medicine, et al.

Significance: It is now known that the intestinal microbiome is integral to the pathogenesis of IBD. However, antibiotic treatments for IBD have previously shown limited effectiveness. In this 8-week clinical trial, there was a fourfold greater response to the antibiotic rifaximin in Crohn’s disease treatment, compared with placebo. The positive impact on clinical disease activity was seen even in patients with a significant disease burden and prior exposure to one or more biologic therapies. Quality of life and laboratory measurements were numerically improved. No new safety concerns were identified. These results offer renewed hope for the use of antibiotics in treating Crohn’s disease.

Post-hoc analysis of tofacitinib Crohn’s disease phase 2 induction efficacy in subgroups with baseline endoscopic or biomarker evidence of inflammation

By Bruce E. Sands, Icahn School of Medicine at Mount Sinai, et al.

Significance: Tofacitinib, a Janus kinase (JAK) inhibitor, is under investigation for treatment of ulcerative colitis and Crohn’s disease. To date, response rates in ulcerative colitis have been higher than for Crohn’s disease. In this report, investigators performed post-hoc analysis studies using objective baseline criteria of disease activity. Their findings showed a greater proportion of patients with moderate to severe Crohn’s disease were in remission with tofacitinib compared to placebo. These results provide evidence of JAK inhibition for the treatment of Crohn’s disease and support further investigation.

Refined population pharmacokinetic model for infliximab precision dosing in pediatric inflammatory bowel disease

By Laura E. Bauman, Cincinnati Children’s Hospital Medical Center, et al.

Significance: Long-term clinical remission from IBD with anti-TNF therapies has generally been limited to less than half of the treated patients. Improved outcomes are seen with optimal pre-infusion trough drug levels, a measurement of the level of drugs in the patient’s bloodstream. However, standard weight-based dosing for pediatric patients has provided widely varying trough drug levels. The investigators report the development of a multifactorial pharmacokinetic model for predicting infliximab trough levels during maintenance therapy for IBD. Such dynamic approaches to treatment address a specific gap in pediatric IBD therapeutic strategies.

Primary nonresponse to tumor necrosis factor antagonists is associated with inferior response to second-line biologics in patients with inflammatory bowel diseases: A systematic review and meta-analysis

By Siddharth Singh, University of California San Diego Health, et al.

Significance: Primary nonresponse to anti-TNF therapy is seen in 35%-65% of IBD patients and another 40%-60% lose responsiveness during the first year of treatment. Physicians struggle with what treatments to recommend for these patients. The investigators in this study performed a literature search and identified eight randomized controlled trials of biologics in patients with prior exposure to anti-TNF and compared outcomes based on their prior responses to anti-TNF. The analysis reveals a 24% decrease in likelihood to achieve remission in patients who changed medications because of immediate nonresponse compared to loss of responsiveness or intolerance during the treatment. These findings raise important questions about the biology of IBD, including the pharmacology of anti-TNF in a subset of patients.

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