BOOK
Crohn's Disease, An Issue of Gastroenterology Clinics of North America, E-Book
(2017)
Additional Information
Book Details
Abstract
Dr. Loftus is a widely recognized expert in the diagnosis and treatment of Crohn's disease. He has created an issue devoted the current state-of-the-art on Crohn's disease; authors have written comprehensive reviews on the latest research to inform clinical diagnosis and treatment. Articles are devoted to the following topics: Genetics; Epidemiology, natural history, and risk stratification of Crohn’s disease; The microbiome in Crohn’s disease: Role in pathogenesis and role of microbiome replacement therapies; Endoscopic and radiographic assessment of Crohn’s disease; Intestinal and non-intestinal cancer risk in Crohn’s disease; Sexuality, fertility, and pregnancy in Crohn’s disease; Interdisciplinary management of perianal Crohn’s disease; Targeting specific immunologic pathways in human inflammatory bowel disease; Evolution of treatment paradigms in Crohn’s disease; Preventing and managing postoperative recurrence of Crohn’s disease; Where and how to use anti-TNF agents and anti-integrins in Crohn’s disease; Ustekinumab and anti-interleukin-23 agents in Crohn’s disease; Update on therapeutic drug monitoring in Crohn’s disease; and Janus kinase antagonists and other novel small molecules for the treatment of Crohn’s disease. Readers will come away from this issue armed with the information they need to improve management of this disease as well as patient outcomes.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | Cover | ||
| Crohn’s Disease\r | i | ||
| Copyright\r | ii | ||
| Contributors | iii | ||
| EDITOR | iii | ||
| AUTHORS | iii | ||
| Dedication | vi | ||
| Contents | vii | ||
| Preface: Crohn’s Disease: Etiology, Complications, Assessment, Therapy, and Management | vii | ||
| Crohn’s Disease: Genetics Update | vii | ||
| Epidemiology, Natural History, and Risk Stratification of Crohn's Disease | vii | ||
| The Microbiome in Crohn’s Disease: Role in Pathogenesis and Role of Microbiome Replacement Therapies | vii | ||
| Endoscopic and Radiographic Assessment of Crohn’s Disease | viii | ||
| Intestinal and Nonintestinal Cancer Risks for Patients with Crohn’s Disease | viii | ||
| Sexuality, Fertility, and Pregnancy in Crohn’s Disease | viii | ||
| Interdisciplinary Management of Perianal Crohn’s Disease | viii | ||
| Management of Crohn’s Disease After Surgical Resection | ix | ||
| Targeting Specific Immunologic Pathways in Crohn’s Disease | ix | ||
| Use of Anti–Tumor Necrosis Factors and Anti-Integrins in the Treatment of Crohn’s Disease | ix | ||
| Ustekinumab and Anti-Interleukin-23 Agents in Crohn’s Disease | ix | ||
| Janus Kinase Antagonists and Other Novel Small Molecules for the Treatment of Crohn’s Disease | x | ||
| Update on Therapeutic Drug Monitoring in Crohn’s Disease | x | ||
| The Evolution of Treatment Paradigms in Crohn’s Disease: Beyond Better Drugs | x | ||
| GASTROENTEROLOGY\rCLINICS OF NORTH AMERICA\r | xi | ||
| FORTHCOMING ISSUES | xi | ||
| December 2017 | xi | ||
| March 2018 | xi | ||
| June 2018 | xi | ||
| RECENT ISSUES | xi | ||
| June 2017 | xi | ||
| March 2017 | xi | ||
| December 2016 | xi | ||
| Preface:\rCrohn's Disease: Etiology, Complications, Assessment, Therapy, and Management | xiii | ||
| Crohn's Disease | 449 | ||
| Key points | 449 | ||
| INTRODUCTION | 449 | ||
| THE TOP INFLUENTIAL CROHN'S DISEASE RISK GENES | 450 | ||
| NOD2 | 450 | ||
| IL-23 | 451 | ||
| HLA | 451 | ||
| ATG16L1, IRGM, and LRRK2/MUC19 | 451 | ||
| SLC22/OCTN on 5q31 | 454 | ||
| TNF | 454 | ||
| GENES ASSOCIATED WITH PEDIATRIC OR EARLY ONSET OF CROHN'S DISEASE | 454 | ||
| CLINICAL IMPLICATIONS OF GENETIC VARIANTS FOUND IN CROHN'S DISEASE | 454 | ||
| Genes Related to the Clinical Behavior of Crohn's Disease, Disease Location, and Need for Surgery | 454 | ||
| Genes Related to Extraintestinal Manifestations of Crohn's Disease | 455 | ||
| Genes Related to Anti-Tumor Necrosis Factor Response in Crohn's Disease | 456 | ||
| CROHN'S DISEASE GENETICS IN NON-WHITE POPULATIONS | 456 | ||
| REMAINING CHALLENGES IN CROHN'S DISEASE GENETICS | 456 | ||
| Unexplored Regions: Chromosome X, Mitochondrial DNA, and Rare Variants | 456 | ||
| Complex Gene–Gene and Gene–Environmental Interactions | 457 | ||
| SUMMARY AND FUTURE DIRECTIONS | 457 | ||
| REFERENCES | 457 | ||
| Epidemiology, Natural History, and Risk Stratification of Crohn's Disease | 463 | ||
| Key points | 463 | ||
| INTRODUCTION | 463 | ||
| INCIDENCE AND PREVALENCE OF CROHN'S DISEASE | 464 | ||
| IMPORTANT ENVIRONMENTAL RISK FACTORS | 466 | ||
| NATURAL HISTORY OF CROHN'S DISEASE | 468 | ||
| Natural Course of Disease Location and Behavior | 468 | ||
| Natural Course of Perianal Disease | 471 | ||
| Natural Course of Disease Outcomes | 472 | ||
| Disease activity and relapse | 472 | ||
| Hospitalization | 474 | ||
| Surgery | 475 | ||
| RISK STRATIFICATION OF CROHN'S DISEASE | 475 | ||
| Clinical Risk Factors | 475 | ||
| Endoscopic Risk Factors | 475 | ||
| Risk Stratification | 476 | ||
| SUMMARY | 476 | ||
| REFERENCES | 477 | ||
| The Microbiome in Crohn's Disease | 481 | ||
| Key points | 481 | ||
| INTRODUCTION | 481 | ||
| CROHN'S DISEASE AND ALTERED MICROBIOME | 482 | ||
| HOST MICROBIOME INTERACTIONS IN CROHN'S DISEASE | 482 | ||
| Evolution of Microbiome | 482 | ||
| Heredibility of the Microbial Community | 483 | ||
| Mucosal Immunity | 483 | ||
| MICROBIAL RESTORATION THERAPIES IN CROHN'S DISEASE | 484 | ||
| Mouse Models | 485 | ||
| Human Studies | 485 | ||
| PREBIOTICS, PROBIOTICS, AND POSTBIOTICS IN CROHN'S DISEASE | 486 | ||
| Prebiotics | 486 | ||
| Probiotics | 486 | ||
| Postbiotics | 487 | ||
| MICROBIAL RESTORATION THERAPIES IN CROHN'S DISEASE: MORE QUESTIONS THAN ANSWERS | 487 | ||
| MICROBIAL RESTORATION THERAPIES IN CROHN'S DISEASE: A CLOSER LOOK AT 2050 | 489 | ||
| SUMMARY | 490 | ||
| REFERENCES | 490 | ||
| Endoscopic and Radiographic Assessment of Crohn's Disease | 493 | ||
| Key points | 493 | ||
| BACKGROUND | 493 | ||
| ENDOSCOPY | 494 | ||
| ENDOSCOPIC SCORING SYSTEMS | 495 | ||
| Crohn's Disease Endoscopic Index of Severity | 495 | ||
| Simple Endoscopic Score for Crohn's Disease | 496 | ||
| Rutgeerts Score | 497 | ||
| Capsule Endoscopy Scoring Systems | 498 | ||
| RADIOLOGIC IMAGING MODALITIES | 499 | ||
| MAGNETIC RESONANCE SCORING SYSTEMS | 501 | ||
| Magnetic Resonance Index of Activity Score | 501 | ||
| Crohn's Disease MRI Index Score (London) | 502 | ||
| Magnetic Resonance Enterography Global Score | 503 | ||
| Nancy Score | 506 | ||
| Clermont-Ferrand Index (Clermont Score) | 506 | ||
| MRI Perianal Fistula Scoring System | 507 | ||
| CROHN'S DISEASE ULTRASOUND SCORING SYSTEMS | 509 | ||
| LÉMANN INDEX | 509 | ||
| LIMITATIONS AND FUTURE DIRECTIONS | 509 | ||
| SUMMARY | 510 | ||
| REFERENCES | 510 | ||
| Intestinal and Nonintestinal Cancer Risks for Patients with Crohn's Disease | 515 | ||
| Key points | 515 | ||
| INTRODUCTION | 515 | ||
| COLORECTAL CANCER IN CROHN'S DISEASE | 516 | ||
| Epidemiology | 516 | ||
| Pathogenesis of Colorectal Cancer in Crohn's Disease | 516 | ||
| Surveillance of Colorectal Cancer in Patients with Crohn's Disease | 518 | ||
| SMALL BOWEL ADENOCARCINOMA | 518 | ||
| Epidemiology | 518 | ||
| Risk Factors | 519 | ||
| Pathogenesis | 520 | ||
| Prevention and Treatment | 520 | ||
| LYMPHOPROLIFERATIVE DISORDERS | 520 | ||
| Epidemiology | 520 | ||
| Diagnosis of Lymphoproliferative Disorders | 520 | ||
| NONMELANOMA SKIN CANCER | 521 | ||
| Epidemiology | 521 | ||
| Risk Factors, Pathogenesis, and Prevention of Nonmelanoma Skin Cancer in Crohn's Disease | 522 | ||
| MELANOMA | 522 | ||
| Epidemiology | 522 | ||
| Pathogenesis, Risk Factors, and Prevention of Melanoma in Crohn's Disease | 523 | ||
| CERVICAL CANCER AND CERVICAL DYSPLASIA IN CROHN'S DISEASE | 523 | ||
| Epidemiology | 523 | ||
| Risk Factors, Surveillance, and Prevention of Cervical Neoplasia in Crohn's Disease | 524 | ||
| FISTULA-ASSOCIATED PERIANAL CANCER | 524 | ||
| SUMMARY | 524 | ||
| ACKNOWLEDGMENTS | 525 | ||
| REFERENCES | 525 | ||
| Sexuality, Fertility, and Pregnancy in Crohn's Disease | 531 | ||
| Key points | 531 | ||
| INTRODUCTION | 531 | ||
| SEXUALITY | 532 | ||
| FERTILITY | 533 | ||
| In Men | 533 | ||
| In Women | 535 | ||
| PREGNANCY | 535 | ||
| Effect of Pregnancy on Inflammatory Bowel Disease | 535 | ||
| Effect of inflammatory bowel disease on pregnancy | 536 | ||
| Medication use in pregnancy | 537 | ||
| Aminosalicylates | 537 | ||
| Corticosteroids | 537 | ||
| Antibiotics | 538 | ||
| Immunomodulators | 539 | ||
| Anti–tumor necrosis factor agents | 539 | ||
| Anti-integrins | 540 | ||
| Anti–interleukin-12/interleukin-23 | 541 | ||
| Tofacitinib | 541 | ||
| SUMMARY | 541 | ||
| REFERENCES | 541 | ||
| Interdisciplinary Management of Perianal Crohn's Disease | 547 | ||
| Key points | 547 | ||
| INTRODUCTION | 547 | ||
| DIAGNOSIS | 548 | ||
| Treatment Goals and Classification of Healing | 548 | ||
| Classification of Perianal Fistula from Crohn's Disease (Expansion of the Parks Classification) | 549 | ||
| Simple and complex fistula | 551 | ||
| Medical management | 551 | ||
| Surgical options | 551 | ||
| Incision and drainage of abscesses | 552 | ||
| Seton placement | 552 | ||
| Fistulotomy | 553 | ||
| Fibrin glue and fistula plug | 553 | ||
| Endorectal advancement flap | 555 | ||
| Ligation of intersphincteric tract procedure | 556 | ||
| Fecal diversion | 557 | ||
| Proctectomy | 557 | ||
| Emerging therapies | 557 | ||
| PREDICTORS OF RECURRENCE | 558 | ||
| SUMMARY | 558 | ||
| REFERENCES | 558 | ||
| Management of Crohn's Disease After Surgical Resection | 563 | ||
| Key points | 563 | ||
| INTRODUCTION | 563 | ||
| RISK STRATIFICATION OF POSTOPERATIVE RECURRENCE | 564 | ||
| ASSESSING FOR ENDOSCOPIC RECURRENCE | 564 | ||
| TIMING OF INITIATION OF PROPHYLACTIC THERAPY | 565 | ||
| PHARMACOLOGIC AGENTS FOR PREVENTION OF RECURRENCE OF CROHN'S DISEASE | 566 | ||
| COLONOSCOPIC SURVEILLANCE AFTER SURGICAL RESECTION | 569 | ||
| TREATMENT OF ESTABLISHED ENDOSCOPIC RECURRENCE | 570 | ||
| PROPOSED MANAGEMENT ALGORITHM | 571 | ||
| GASTROINTESTINAL SYMPTOMS IN ABSENCE OF ENDOSCOPIC RECURRENCE | 572 | ||
| KNOWLEDGE GAPS AND FUTURE DIRECTIONS | 572 | ||
| REFERENCES | 573 | ||
| Targeting Specific Immunologic Pathways in Crohn's Disease | 577 | ||
| Key points | 577 | ||
| INTRODUCTION | 577 | ||
| EXTRACELLULAR TARGETS: LEUKOCYTE MIGRATION | 578 | ||
| EXTRACELLULAR TARGETS: BEYOND TUMOR NECROSIS FACTOR ALPHA INHIBITORS | 580 | ||
| INTRACELLULAR AND INTRANUCLEAR TARGETS: JANUS KINASE/SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION FACTORS PATHWAYS | 582 | ||
| NEW PERSPECTIVES | 583 | ||
| REFERENCES | 584 | ||
| Use of Anti–Tumor Necrosis Factors and Anti-Integrins in the Treatment of Crohn's Disease | 589 | ||
| Key points | 589 | ||
| INTRODUCTION | 589 | ||
| ANTI–TUMOR NECROSIS FACTORS | 590 | ||
| Clinical Remission | 590 | ||
| Treatment of Fistulae | 590 | ||
| Mucosal Healing | 591 | ||
| Long-Term Outcomes | 591 | ||
| Safety | 592 | ||
| Quality of Life | 592 | ||
| Comparative effectiveness | 593 | ||
| ANTI-INTEGRINS | 593 | ||
| Clinical Remission | 594 | ||
| Treatment of Fistulae | 595 | ||
| Mucosal Healing | 595 | ||
| Long-Term Outcomes | 596 | ||
| Safety | 596 | ||
| Quality of Life | 597 | ||
| Comparative effectiveness | 597 | ||
| INDIRECT COMPARISON OF ANTI–TUMOR NECROSIS FACTORS AND ANTI-INTEGRINS | 597 | ||
| SUMMARY | 598 | ||
| REFERENCES | 598 | ||
| Ustekinumab and Anti-Interleukin-23 Agents in Crohn's Disease | 603 | ||
| Key points | 603 | ||
| INTRODUCTION | 603 | ||
| IMMUNOLOGY OF THE INTERLEUKIN-12/23 PATHWAY | 604 | ||
| USTEKINUMAB | 604 | ||
| Mechanism of Action | 604 | ||
| Pharmacokinetics | 605 | ||
| Efficacy | 606 | ||
| Psoriasis | 606 | ||
| Psoriatic arthritis | 606 | ||
| Data from Crohn's disease | 606 | ||
| Open-label studies | 610 | ||
| Endoscopic response as treatment endpoint | 611 | ||
| Immunogenicity and role of therapeutic drug monitoring | 615 | ||
| Comparative efficacy | 615 | ||
| Safety Data | 616 | ||
| Data from psoriasis | 616 | ||
| Data from Crohn's disease | 616 | ||
| Data in pregnancy | 617 | ||
| POTENTIAL PLACE OF USTEKINUMAB IN THE THERAPY OF CROHN'S DISEASE | 617 | ||
| SPECIFIC INTERLEUKIN-23 INHIBITION | 618 | ||
| Brazikumab (MEDI2070) | 618 | ||
| Risankizumab | 619 | ||
| FUTURE DIRECTIONS | 620 | ||
| DISCLOSURE STATEMENT | 620 | ||
| REFERENCES | 621 | ||
| Janus Kinase Antagonists and Other Novel Small Molecules for the Treatment of Crohn's Disease | 627 | ||
| Key points | 627 | ||
| INTRODUCTION | 627 | ||
| SMALL MOLECULE THERAPIES: ADVANTAGE OVER BIOLOGICS | 628 | ||
| Oral Administration | 628 | ||
| Shorter Half-Life | 628 | ||
| Less Immunogenicity | 628 | ||
| PATHOPHYSIOLOGY OF JANUS KINASE INHIBITION | 629 | ||
| The Janus Kinase Family | 629 | ||
| Type I and II cytokines | 629 | ||
| Mechanisms of Janus Kinase Signaling | 629 | ||
| Janus Kinase Signaling and the Pathogenesis of Inflammatory Bowel Disease | 629 | ||
| TOFACITINIB: A PAN JANUS KINASE INHIBITOR | 631 | ||
| Tofacitinib in Ulcerative Colitis | 631 | ||
| Tofacitinib in Crohn's Disease | 632 | ||
| Safety and Tolerability of Tofacitinib | 633 | ||
| Herpes Zoster Risk with Janus Kinase Inhibitors | 633 | ||
| Risk of Malignancy with Janus Kinase Inhibitors | 633 | ||
| Filgotinib: novel selective Janus kinase 1 inhibitor | 634 | ||
| FITZROY: Phase II Filgotinib Study in Crohn's Disease | 634 | ||
| Filgotinib in Anti-tumor Necrosis Factor–Exposed Patients with Crohn's Disease | 634 | ||
| Safety and Tolerability of Filgotinib | 635 | ||
| Janus Kinase Inhibitors: An Evolving Pipeline | 635 | ||
| TARGETING NOVEL INFLAMMATORY PATHWAYS | 635 | ||
| Transforming Growth Factor-β1 and Inflammation | 635 | ||
| Transforming Growth Factor-β1 and Smad7 in Crohn's Disease | 636 | ||
| Mongersen: Smad7 antisense oligonucleotide | 636 | ||
| Effect of Smad7 Inhibition on Fibrosis | 637 | ||
| Safety and Tolerability of Mongersen | 638 | ||
| TARGETING LYMPHOCYTE TRAFFICKING: OTHER SMALL MOLECULES FOR CROHN'S DISEASE | 638 | ||
| Sphingosine-1-Phosphate Receptors | 638 | ||
| Fingolimod: Sphingosine-1-Phosphate Modulator for Multiple Sclerosis | 639 | ||
| Ozanimod: Sphingosine-1-phosphate 1 receptor modulator | 639 | ||
| Ozanimod in Ulcerative Colitis: Phase II Study Results | 639 | ||
| Safety and Tolerability of Ozanimod in Ulcerative Colitis | 640 | ||
| Ozanimod: Effect on Lymphocyte Count | 640 | ||
| Ozanimod in Crohn's Disease | 640 | ||
| SUMMARY | 640 | ||
| REFERENCES | 641 | ||
| Update on Therapeutic Drug Monitoring in Crohn's Disease | 645 | ||
| Key points | 645 | ||
| INTRODUCTION | 645 | ||
| MEASURING BIOLOGIC CONCENTRATIONS AND ANTI–DRUG ANTIBODIES | 646 | ||
| ASSOCIATION BETWEEN THERAPEUTIC DRUG MONITORING AND CLINICAL AND ENDOSCOPIC OUTCOMES | 647 | ||
| THERAPEUTIC DRUG MONITORING IN COMBINATION THERAPY | 648 | ||
| LOSS OF RESPONSE | 648 | ||
| Anti–tumor Necrosis Factor Concentrations | 649 | ||
| Anti–drug Antibodies | 649 | ||
| THERAPEUTIC DRUG MONITORING AFTER INDUCTION | 650 | ||
| THERAPEUTIC DRUG MONITORING AND MAINTENANCE THERAPY | 651 | ||
| DOSE DE-ESCALATION | 652 | ||
| THERAPEUTIC DRUG MONITORING AND WITHDRAWAL OF COMBINATION THERAPY | 652 | ||
| POST–DRUG HOLIDAY | 653 | ||
| COST-EFFECTIVENESS | 653 | ||
| BIOSIMILARS | 653 | ||
| USTEKINUMAB AND VEDOLIZUMAB | 654 | ||
| FUTURE DIRECTIONS | 654 | ||
| REFERENCES | 654 | ||
| The Evolution of Treatment Paradigms in Crohn's Disease | 661 | ||
| Key points | 661 | ||
| INTRODUCTION | 661 | ||
| HIGHLY EFFECTIVE THERAPIES | 662 | ||
| Highly Effective Therapies | 664 | ||
| Early treatment of high-risk patients | 664 | ||
| Risk prognostication | 665 | ||
| Precision medicine | 665 | ||
| Treat to Target: What Is the Target? | 666 | ||
| Patient-reported outcomes | 666 | ||
| Biomarkers | 667 | ||
| Endoscopy | 667 | ||
| MRI | 669 | ||
| Histopathology | 669 | ||
| PHARMACOKINETICS/PHARMACODYNAMICS | 670 | ||
| CONTROLLED TRIALS OF TREATMENT ALGORITHMS | 670 | ||
| TOWARDS AN INTEGRATED TREATMENT ALGORITHM FOR CROHN'S DISEASE | 671 | ||
| DISCLOSURE | 672 | ||
| REFERENCES | 672 |