Medscape InDiscussion: Crohn's Disease

Drs Peter Higgins and Michael Chiorean discuss risk stratification, monitoring, and treatment of Crohn's disease after surgery. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/967627). The topics and discussions are planned, produced, and reviewed independently of advertiser. This podcast is intended only for US healthcare professionals. Resources Laparoscopic Ileocaecal Resection Versus Infliximab for Terminal Ileitis in Crohn's Disease: Retrospective Long-term Follow-up of the LIR!C Trial https://www.thelancet.com/journals/langas/article/PIIS2468-1253(20)30117-5/fulltext Infliximab Reduces Endoscopic, but Not Clinical, Recurrence of Crohn's Disease After Ileocolonic Resection https://www.gastrojournal.org/article/S0016-5085(16)00293-6/fulltext?referrer=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F Crohn's Disease Management After Intestinal Resection: A Randomised Trial https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(14)61908-5.pdf Controlled Trial of Metronidazole Treatment for Prevention of Crohn's Recurrence After Ileal Resection https://www.gastrojournal.org/article/0016-5085(95)90121-3/pdf?referrer=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F Metronidazole https://reference.medscape.com/drug/flagyl-metronidazole-342566 Nitroimidazoles https://reference.medscape.com/drugs/nitroimidazoles Ciprofloxacin for the Prevention of Postoperative Recurrence in Patients With Crohn's Disease: A Randomized, Double-blind, Placebo-Controlled Pilot Study https://academic.oup.com/ibdjournal/article/19/5/1073/4603177?login=true Postoperative Therapy With Infliximab Prevents Long-term Crohn's Disease Recurrence https://www.cghjournal.org/article/S1542-3565(14)00053-6/fulltext Mesalamine https://reference.medscape.com/drug/asacol-hd-pentasa-mesalamine-342074 Infliximab https://reference.medscape.com/drug/remicade-inflectra-infliximab-343202 Infliximab, Azathioprine, or Combination Therapy for Crohn's Disease https://www.nejm.org/doi/full/10.1056/nejmoa0904492 Adalimumab https://reference.medscape.com/drug/amjevita-humira-adalimumab-343187 What Is the Role of Fecal Calprotectin Levels in the Diagnosis of Inflammatory Bowel Disease (IBD)? https://www.medscape.com/answers/179037-54913/what-is-the-role-of-fecal-calprotectin-levels-in-the-diagnosis-of-inflammatory-bowel-disease-ibd P115 Monitoring Faecal Calprotectin at 3 Months Post-Surgery Is Useful to Predict Further Postoperative Endoscopic Recurrence in Crohn's Disease https://academic.oup.com/ecco-jcc/article/13/Supplement_1/S145/5300800 Ustekinumab https://reference.medscape.com/drug/stelara-ustekinumab-345050

Drs Peter Higgins and Bram Verstockt discuss breaking the therapeutic ceiling in Crohn's disease and the differential effectiveness of therapies and phenotypes in identifying responses to treatment. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/967626). The topics and discussions are planned, produced, and reviewed independently of advertiser. This podcast is intended only for US healthcare professionals. Resources Crohn's Disease https://emedicine.medscape.com/article/172940-overview A Blood-Based Prognostic Biomarker in IBD https://gut.bmj.com/content/68/8/1386 Role of the IL23/IL17 Pathway in Crohn's Disease https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042267/ A Study of Efficacy and Safety of Combination Therapy With Guselkumab and Golimumab in Participants With Moderately to Severely Active Ulcerative Colitis (VEGA) https://clinicaltrials.gov/ct2/show/NCT03662542 Results of Novel Clinical Study Show Adults With Moderately to Severely Active Ulcerative Colitis Achieved Higher Rates of Clinical Response, Clinical Remission, and Endoscopic Improvement at 12 Weeks With Guselkumab and Golimumab Combination Therapy Versus Either Monotherapy Alone https://www.prnewswire.com/news-releases/results-of-novel-clinical-study-show-adults-with-moderately-to-severely-active-ulcerative-colitis-achieved-higher-rates-of-clinical-response-clinical-remission-and-endoscopic-improvement-at-12-weeks-with-guselkumab-and-golimumab-301486054.html Digestive Disease Week 2022 https://ddw.org/ Triple Combination Therapy in High Risk Crohn's Disease (CD) https://clinicaltrials.gov/ct2/show/NCT02764762 Anti-TNF and Crohn's Disease: When Should We Stop? http://www.eurekaselect.com/article/15866

Drs Peter Higgins and Raja Atreya discuss the phenomenon of durable drug free remission in a subset of patients with Crohn's disease and the future of intermittent induction and sequencing of therapies. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/967625). The topics and discussions are planned, produced, and reviewed independently of advertiser. This podcast is intended only for US healthcare professionals. Resources Efficacy and Safety of Mirikizumab in a Randomized Phase 2 Study of Patients With Crohn's Disease https://linkinghub.elsevier.com/retrieve/pii/S0016-5085(21)03725-2 Long-Term Safety and Efficacy of Risankizumab Treatment in Patients with Crohn's Disease: Results from the Phase 2 Open-Label Extension Study https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8684487/ Five-Year Efficacy and Safety of Ustekinumab Treatment in Crohn's Disease: The IM-UNITI Trial https://linkinghub.elsevier.com/retrieve/pii/S1542-3565(21)00203-2 Ustekinumab as Induction and Maintenance Therapy for Crohn's Disease https://www.nejm.org/doi/full/10.1056/NEJMoa1602773 Risankizumab as Induction Therapy for Crohn's Disease: Results from the Phase 3 ADVANCE and MOTIVATE Induction Trials https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00467-6/fulltext Risankizumab as Maintenance Therapy for Moderately to Severely Active Crohn's Disease: Results from the Multicentre, Randomised, Double-Blind, Placebo-Controlled, Withdrawal Phase 3 FORTIFY Maintenance Trial https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00466-4/fulltext A37 Efficacy and Safety of Risankizumab as Maintenance Therapy in Patients With Crohn's Disease: 52 Week Results From the Phase 3 Fortify Study https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8859234/ Th17 Cells in Inflammatory Bowel Disease: Cytokines, Plasticity, and Therapies https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846404 Expansion of IL-23 Receptor Bearing TNFR2+ T Cells Is Associated With Molecular Resistance to Anti-TNF Therapy in Crohn's Disease https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580782/ Comparative Efficacy and Safety of Biologic Therapies for Moderate-to-Severe Crohn's Disease: A Systematic Review and Network Meta-analysis https://linkinghub.elsevier.com/retrieve/pii/S2468-1253(21)00312-5 European Crohn's and Colitis Organisation https://www.ecco-ibd.eu/ Mercaptopurine Therapy and TPMT and NUDT15 Genotype https://www.ncbi.nlm.nih.gov/books/NBK100660/

Drs Peter Higgins and Frank Scott discuss the challenges of delays in care for patients with Crohn's disease, how insurance denials and delays harm patients, and what doctors can do to help. Relevant disclosures can be found with the episode show notes on Medscape.com (https://www.medscape.com/viewarticle/967624). The topics and discussions are planned, produced, and reviewed independently of advertiser. This podcast is intended only for US healthcare professionals. Resources Specialty Drug Coverage Varies Across Commercial Health Plans in the US https://www.healthaffairs.org/doi/full/10.1377/hlthaff.2017.1553 2021 AMA Prior Authorization (PA) Physician Survey https://www.ama-assn.org/system/files/prior-authorization-survey.pdf Corticosteroid Use and Complications in a US Inflammatory Bowel Disease Cohort https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4918923/ Increased Risk of Venous Thromboembolic Events With Corticosteroid vs Biologic Therapy for Inflammatory Bowel Disease https://www.cghjournal.org/article/S1542-3565(14)01045-3/fulltext Impact of Prior Authorization of Antiepileptic Drugs in Children With Epilepsy https://www.pedneur.com/article/S0887-8994(18)30151-6/fulltext Prior Authorization Delays Biologic Initiation and Is Associated With a Risk of Asthma Exacerbations https://pubmed.ncbi.nlm.nih.gov/33404389/ Treatment Delays Associated With Prior Authorization for Infusible Medications: A Cohort Study https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062557/ Delays Related to Prior Authorization in Inflammatory Bowel Disease https://publications.aap.org/pediatrics/article/149/3/e2021052501/184867/Delays-Related-to-Prior-Authorization-in What Is the Role of Fecal Calprotectin Levels in the Diagnosis of Inflammatory Bowel Disease (IBD)? https://www.medscape.com/answers/179037-54913/what-is-the-role-of-fecal-calprotectin-levels-in-the-diagnosis-of-inflammatory-bowel-disease-ibd Variation In Use and Content of Prescription Drug Step Therapy Protocols, Within and Across Health Plans https://www.healthaffairs.org/doi/10.1377/hlthaff.2021.00822?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed What Is Step Therapy/Fail First? https://www.crohnscolitisfoundation.org/get-involved/be-an-advocate/steptherapy H.R. 2163 – Safe Step Act https://www.congress.gov/bill/117th-congress/house-bill/2163 Step Therapy's Balancing Act — Protecting Patients While Addressing High Drug Prices https://www.nejm.org/doi/10.1056/NEJMp2117582?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed Battle Heats up Over Bill on "Step Therapy," Drug Rebates https://www.coloradopolitics.com/legislature/battle-heats-up-over-bill-on-step-therapy-drug-rebates/article_0f6e56c4-c0b8-11ec-9ead-47fa6f99ac6e.html Crohn Disease Pathology https://emedicine.medscape.com/article/1986158-overview#a6

Drs Peter Higgins and Judy Cho discuss recent success in sickle cell anemia and whether we're any closer to using intestinal gene therapy in Crohn's disease. Relevant disclosures can be found with the episode show notes on Medscape.com (https://www.medscape.com/viewarticle/967621). The topics and discussions are planned, produced, and reviewed independently of advertiser. This podcast is intended only for US healthcare professionals. Resources Sickle Cell Anemia https://emedicine.medscape.com/article/205926-overview Crohn's Disease https://emedicine.medscape.com/article/172940-overview Inflammatory Bowel Disease https://emedicine.medscape.com/article/179037-overview CRISPR-Cas systems: Overview, Innovations and Applications in Human Disease Research and Gene Therapy https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508700/ CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia https://www.nejm.org/doi/full/10.1056/NEJMoa2031054 Biologic and Clinical Efficacy of LentiGlobin for Sickle Cell Disease https://www.nejm.org/doi/10.1056/NEJMoa2117175 Causes of Crohn's disease https://medlineplus.gov/genetics/condition/crohn-disease/#causes IL-10R Polymorphisms Are Associated With Very-Early-Onset Ulcerative Colitis https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744177/ Characterization of Crohn Disease In X-Linked Inhibitor of Apoptosis-Deficient Male Patients and Female Symptomatic Carriers https://pubmed.ncbi.nlm.nih.gov/24942515/ A Frameshift Mutation in NOD2 Associated With Susceptibility to Crohn's Disease https://www.nature.com/articles/35079114 Extended Haplotype Association Study in Crohn's Disease Identifies a Novel, Ashkenazi Jewish-Specific Missense Mutation in the NF-κB Pathway Gene, HEATR3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3785105/ Autologous Stem Cell Transplant for Crohn's Disease https://www.mountsinai.org/clinical-trials/autologous-stem-cell-transplant-for-crohns-disease Stem-Cell Transplantation for Crohn's Disease: Same Authors, Different Conclusions? https://www.thelancet.com/journals/langas/article/PIIS2468-1253(17)30076-6/fulltext#%20 A Myeloid-Stromal Niche and gp130 Rescue in NOD2-Driven Crohn's Disease https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284870/ Expression of NOD2 in Paneth Cells: A Possible Link to Crohn's Ileitis https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1773866/ Role of ATG16L, NOD2 and IL23R in Crohn's Disease Pathogenesis https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3270503/

Drs Peter Higgins and Jean-Frederic Colombel discuss exciting new evidence in Crohn's disease research that may help in identifying those at risk before disease starts and pave the way for a vaccine. Relevant disclosures can be found with the episode show notes on Medscape.com (https://www.medscape.com/viewarticle/967620). The topics and discussions are planned, produced, and reviewed independently of advertiser. This podcast is intended only for US healthcare professionals. Resources Inflammatory Bowel Disease https://emedicine.medscape.com/article/179037-overview Crohn Disease https://emedicine.medscape.com/article/172940-overview Ulcerative Colitis https://emedicine.medscape.com/article/183084-overview Standardising the Lactulose Mannitol Test of Gut Permeability to Minimise Error and Promote Comparability https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047110/ Cohort Profile of the PRoteomic Evaluation and Discovery in an IBD Cohort of Tri-service Subjects (PREDICTS) Study: Rationale, Organization, Design, and Baseline Characteristics https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446072/ Combined Serological, Genetic, and Inflammatory Markers Differentiate Non-IBD, Crohn's Disease, and Ulcerative Colitis Patients https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3792797/ The GEM PROJECT https://crohnsandcolitis.ca/Research/Funded-research/The-gem-project Serum Zonulin Measured by Commercial Kit Fails to Correlate With Physiologic Measures of Altered Gut Permeability in First Degree Relatives of Crohn's Disease Patients https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027468/ Tofacitinib and Newer JAK Inhibitors in Inflammatory Bowel Disease — Where We Are and Where We Are Going https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9007061/ Effects of B-Cell Directed Therapy on the Preclinical Stage of Rheumatoid Arthritis: The PRAIRI Study https://ard.bmj.com/content/annrheumdis/78/2/179.full.pdf Longitudinal Analysis Reveals High Prevalence of Epstein-Barr Virus Associated With Multiple Sclerosis https://www.science.org/doi/10.1126/science.abj8222 Digestive Disease Week abstracts https://ddw.org/education/abstracts/ Serious Infections in Pediatric Inflammatory Bowel Disease 2002-2017 — A Nationwide Cohort Study https://www.jpeds.com/article/S0022-3476(21)00658-2/fulltext#%20 GM-CSF Autoantibodies: Predictors of Crohn's Disease Development and a Novel Therapeutic Approach https://academic.oup.com/jcag/article/4/Supplement_1/5/6158591