Cover

Front-Matter

Contents

Preface

Physiological Role of TNF in Mucosal Immunology

The Effect of TNF-α on the Regulation of Epithelial Function in Inflammatory Bowel Disease

Abstract

Introduction

TNF-α Signaling Pathways in Intestinal Epithelial Cells

The Regulation of Intestinal Epithelial Cell Differentiation by TNF-α

TNF-α in Tight Junction Modulation

Apoptosis and Necroptosis of Intestinal Epithelial Cells by TNF-α

The Carcinogenesis of Colitis-Associated Colon Cancer by TNF-α

Conclusion and Future Directions

References

Physiological Role of TNF in Mucosal Immunology: Regulation of Macrophage/Dendritic Cell Function

Abstract

Introduction

Defining Mononuclear Phagocyte Subsets in the Intestinal Mucosa

Impact of TNF Signaling on Intestinal Mononuclear Phagocytes

TNF Production by Mononuclear Phagocytes and Its Impact on the Intestinal Microenvironment

Conclusion and Future Directions

References

Physiological Role of TNF in Mucosal Immunology: Regulation of T-Cell Function

Abstract

Introduction

Main Points

Conclusions and Future Directions

Funding

References

Pathophysiological Role of TNF in Inflammatory Bowel Disease: TNF and Its Impact on Barrier Function

Abstract

The Intestinal Mucosal Barrier

Alterations of the Intestinal Barrier in Inflammatory Bowel Disease and the Function of TNF

Conclusion

References

Pathophysiological Role of TNF in Inflammatory Bowel Disease: TNF and Its Effect on Innate Immune Defense

Abstract

Introduction

Main Points

Conclusions and Future Directions

Funding

References

TNF and Its Impact on Adaptive Immune Mechanisms and Chronic Inflammation

Abstract

Introduction

Main Points

Conclusions and Future Directions

References

Mechanism of Action of Anti-TNF Antibodies

Binding of Membrane-Bound TNF

Abstract

Introduction

Main Points

Conclusion

References

Apoptosis of T Cells and Monocytes

Abstract

Introduction

Anti-TNF Agents in the Treatment of Inflammatory Bowel Disease

Induction of Apoptosis by Anti-TNF Action in vitro and in vivo

Mechanisms of Anti-TNF-Induced Apoptosis

Are Apoptosis-Related Mechanisms Relevant to the Clinical Efficacy of Anti-TNF Agents?

Summary

References

Neutralisation of Soluble Tumor Necrosis Factor

Abstract

Introduction

Production of Soluble Tumor Necrosis Factor-Alpha

Mechanism of Action

Neutralisation of Soluble Tumor Necrosis Factor-Alpha

Binding, Affinity and in vitro Potency

Pharmacokinetics of Anti-Tumor Necrosis Factor-Alpha Agents

Future Perspectives

References

General Treatment Considerations

Recommended Screening Procedures before Treatment with Anti-TNF Agents

Abstract

Introduction

Main Points

Conclusions

References

The Risk of Formation of Neutralizing Antibodies

Abstract

Introduction

Formation of Neutralizing Antibodies

Prevention and Suppression of Neutralizing Antibodies

Conclusion

References

TNF Antagonist Trough Concentrations and Treatment Efficacy in Inflammatory Bowel Disease

Abstract

Introduction

Main Points

Conclusions and Future Directions

References

Biosimilars

What Is a Biosimilar?

Abstract

Introduction

Main Points

Conclusions and Future Directions

References

Is Extrapolation of Safety and Efficacy Data Possible?

Abstract

Introduction

Main Points

Conclusions and Future Directions

References

Potential Concerns and Questions

Abstract

Introduction

Evaluation of Biosimilarity

Reference Product Stability

Biosimilar Name

Extrapolation of Indications

Interchangeability/Pharmacovigilance

Conclusions and Future Directions

References

Side Effects of Anti-TNF Therapy

Psoriasis-Like Lesions and Skin Reactions

Abstract

Introduction

Paradoxical Psoriasis and Eczematous Eruptions after Initiation of Anti-TNF Therapy

Allergic Skin Reactions and Infections

Drug-Induced Lupus Erythematosus and Lupus-Like Syndrome

Conclusions and Future Directions

References

The Elicitation of Rheumatic Symptoms at Vascular Sites

Abstract

Introduction

Drug-Induced Vasculitic Syndromes: Entities of Their Own?

Essential Terminological Aspects and Classification

Pathogenic Mechanisms

Clinical Signs and Symptoms

Diagnostic Testing

Treatment Options

Conclusions and Future Directions

References

Serum Reaction, Lupus-Like Syndrome

Abstract

Introduction

Laboratory Findings

Pathogenesis of Anti-TNF Drug-Induced Lupus

Clinical Presentation of Anti-TNF Drug-Induced Lupus

Treatment of Anti-TNF Drug-Induced Lupus

Conclusion and Future Directions

References

Risks of Anti-TNF Therapy

Risk of Non-Hematologic Malignancy with Anti-TNF Therapy in Inflammatory Bowel Diseases

Abstract

Introduction

Skin Cancer

Cervical Cancer

Summary

References

Risk of Lymphoma

Abstract

Introduction

Main Points

Hepatosplenic T-Cell Lymphoma

Risk Interpretation and Better Communication

Conclusions and Future Directions

References

Risk of Serious Infection

Abstract

Introduction

Incidence of Infections in Anti-TNFα Users with Inflammatory Bowel Disease

Tuberculosis

Viral Infection

Conclusion and Future Direction

References

Risk of Post-Operative Infections with Anti-TNF Therapy

Abstract

Introduction

Studies of Peri-Operative Anti-TNF in Crohn’s Disease

Studies of Peri-Operative Anti-TNF in Ulcerative Colitis

Studies of Peri-Operative Anti-TNF in Combined Crohn’s Disease and Ulcerative Colitis

Measuring Peri-Operative Anti-TNF Exposure and Management Recommendations

Summary

References

Anti-TNF Therapy in Crohn’s Disease

The ‘Ideal’ Anti-TNF Patient: Indications for Anti-TNF Therapy in Crohn’s Disease

Abstract

Introduction

Main Points

Conclusions and Future Directions

References

Predictor of Treatment Response

Abstract

Introduction

Disease-Related Predictors

Patient-Related Predictors

A Serological Marker: C-Reactive Protein

Prior Use of Anti-TNF Agents

Concomitant Immunomodulators

Conclusions and Future Directions

References

Step-Up or Top-Down, Combination with Immunosuppression or Not?

Abstract

Introduction

Step-Up or Top-Down

Thiopurines in Accelerated Step-Up

Combination with Immunosuppression

Conclusions and Recommendations

References

Anti-TNF Therapy in Ulcerative Colitis

The ‘Ideal’ Anti-TNF Patient: Indications for Anti-TNF Therapy in Ulcerative Colitis

Abstract

Introduction

Efficacy of Anti-TNF Therapy in Ulcerative Colitis

Anti-TNF Agents as a Rescue Therapy for Severe Refractory Ulcerative Colitis

Is Mucosal Healing an Objective Parameter?

Concomitant Use of Thiopurine with an Anti-TNF Agent for the Treatment of Ulcerative Colitis

Anti-TNF Discontinuation in Ulcerative Colitis – Is it Possible or Not?

Conclusions

References

Predictors of the Treatment Response

Abstract

Introduction

Limitations of Single Predictors

Benefits of Composite Predictors

Mechanisms Leading to Predictors

What Genetic Factors and the Gene Expression Signature Hold

Limitations of Genetics

Benefits of a Gene Expression Signature

Comprehensive Composite Predictors

Conclusions and Future Directions

References

What Is the Right Dosage?

Abstract

Introduction

Infliximab

Adalimumab

Golimumab

Conclusion

References

Anti-TNF Therapy in Special Inflammatory Bowel Disease Situations

Fistulizing and Stricturing Crohn’s Disease

Abstract

Introduction

Therapy of Stricturing Crohn’s Disease

Therapy of Perianal Fistulizing Crohn’s Disease

Therapy of Nonperianal Fistulizing Crohn’s Disease

Conclusions and Future Directions

References

Postoperative Anti-TNF Therapy in the Management of Crohn’s Disease

Abstract

Grant Support

References

Anti-TNF-α Therapy for Extraintestinal Manifestations of Inflammatory Bowel Disease

Abstract

Introduction

Extraintestinal Manifestations in Different Organs

Hypersensitivity and Paradoxical Inflammation Induced by Biological TNF Inhibitors

Neurologic Adverse Reactions

Conclusions

References

Anti-TNF Therapy in Special Situations of the Patient

Anti-TNF Alpha Agents and Breastfeeding

Abstract

Introduction

Physiology of Human Lactation

Physiology of Anti-TNF Alpha Agents and Their Passage into Breast Milk and the Neonate

Potential Effects of Anti-TNF Alpha Agents on Neonatal Health and Immune Function

Summary

References

Anti-TNF Therapy before Surgery

Abstract

Introduction

Postoperative Complications in Patients on Preoperative Anti-TNF Therapy

Conclusion and Future Directions

Grant Support

References

When and How to Stop Anti-TNF Treatment in Inflammatory Bowel Disease

When and How to Stop Anti-TNF Treatment in Inflammatory Bowel Disease: Predictors of Relapse after Stopping Treatment

Abstract

Introduction

Reasons for Anti-TNF Discontinuation in Inflammatory Bowel Disease

Available Studies on Anti-TNF Treatment Cessation in Inflammatory Bowel Disease and Other Immune-Mediated Inflammatory Diseases

Predictive Factors for Relapse

Monitoring and Retreatment of Patients

The Concept of Treatment Cycles

Conclusions

References

Treatment Options after Anti-TNF Failure

Abstract

Introduction

Treatment Options after Primary Failure in Crohn’s Disease

Treatment Options after Primary Failure in Ulcerative Colitis

Treatment Options after Secondary Failure

Conclusions

References

Author Index

Cover