Medscape InDiscussion: Crohn's Disease

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

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 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/