Adverse Reactions to Biologics

Description

In many areas of medicine physicians still face the great challenge of finding therapies that will meet the patients’ needs. In dermatology the challenge has arisen on multiple fronts through advances in the understanding of the immunopathogenesis of many inflammatory and malignant cutaneous disorders. Breakthroughs, combined with significant developments in targeted immunotherapy, have resulted in improved outcomes as these newer therapies are being used for both approved indications and as off-label therapies for various chronic inflammatory skin disorders and many forms of skin cancer. In the expectation that by truly understanding the safety profile of these targeted therapies patients’ outcomes will be significantly improved, this book offers insights into topics such as adverse reactions, infectious complications and the perioperative use of biologics in psoriasis, immunogenicity of biologic therapies, paradoxical reactions, safety of biologics used to treat autoimmune bullous diseases and primary cutaneous lymphomas, adverse reactions and skin manifestations of therapies targeting melanoma and non-melanoma skin cancer and other neoplastic diseases. Eminent researchers with extensive clinical experience have contributed to this publication, providing an in-depth overview of the latest knowledge in this field.

Informations

• Publié par: S. Karger AG
• Date de parution: 07 novembre 2017
• Nombre de lectures: 0
• EAN13: 9783318061017
• Langue: English
• Poids de l'ouvrage: 2 Mo

Extrait

Adverse Reactions to Biologics
Current Problems in Dermatology
Vol. 53
Series Editor
Peter Itin Basel
Gregor B.E. Jemec Roskilde
 
Adverse Reactions to Biologics
Volume Editors
Lluís Puig Barcelona
Wayne Gulliver St. John’s, NL
25 figures, 24 in color, and 12 tables, 2018
_______________________ Lluís Puig Hospital de la Santa Creu i Sant Pau Department of Dermatology Barcelona (Spain)
_______________________ Wayne Gulliver Faculty of Medicine Division of Medicine and Dermatology St. John’s, NL (Canada)
Library of Congress Cataloging-in-Publication Data
Names: Puig Sanz, Lluís, editor. | Gulliver, Wayne, editor.
Title: Adverse reactions to biologics / volume editors, Lluís Puig, Wayne Gulliver.
Other titles: Current problems in dermatology ; v. 53. 1421-5721
Description: Basel; New York : Karger, 2018. | Series: Current problems in dermatology, ISSN 1421-5721 ; vol. 53 | Includes bibliographical references and index.
Identifiers: LCCN 2017046401| ISBN 9783318061000 (hard cover : alk. paper) | ISBN 9783318061017 (electronic version)
Subjects: | MESH: Skin Diseases--drug therapy | Biological Products--adverse effects | Biological Products--therapeutic use
Classification: LCC RL110 | NLM WR 650 | DDC 616.5/06--dc23 LC record available at https://lccn.loc.gov/2017046401
 
Bibliographic Indices. This publication is listed in bibliographic services, including Current Contents ® and Index Medicus.
Disclaimer. The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publisher and the editor(s). The appearance of advertisements in the book is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
Drug Dosage. The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
© Copyright 2018 by S. Karger AG, P.O. Box, CH–4009 Basel (Switzerland)
www.karger.com
Printed on acid-free and non-aging paper (ISO 9706)
ISSN 1421–5721
e-ISSN 1662–2944
ISBN 978–3–318–06100–0
e-ISBN 978–3–318–06101–7
 
Contents
Preface
Puig, L. (Barcelona); Gulliver, W. (St. John’s, NL)
Introduction – Biologics in Dermatology: Indications and Off-Label Usage
Puig, L. (Barcelona); Gulliver, W. (St. John’s, NL)
Adverse Reactions to Biologics in Psoriasis
Lockwood, S.J.; Prens, L.M.; Kimball, A.B. (Boston, MA)
Clinical Trial and Registry Data
Gooderham, M. (Peterborough, ON/Waterloo, ON/Kingston, ON); Papp, K. (Waterloo, ON)
Immunosuppression/Infections across Indications
Al-Khalili, A.; Dutz, J.P. (Vancouver, BC)
The Immunogenicity of Biologic Therapies
Garcês, S. (Indianapolis, IN); Demengeot, J. (Oeiras)
Paradoxical Reactions: Anti-Tumor Necrosis Factor Alpha Agents, Ustekinumab, Secukinumab, Ixekizumab, and Others
Puig, L. (Barcelona)
Bullous Diseases
Corbaux, C.; Joly, P. (Rouen)
Adverse Reactions of Antibody-Therapy for Primary Cutaneous Lymphomas: Rituximab, Brentuximab Vedotin, Alemtuzumab, and Mogamulizumab
Saulite, I. (St. Gallen/Riga); Guenova, E. (St. Gallen/Zurich); Hoetzenecker, W. (St. Gallen/Linz)
Adverse Reactions to Biologics: Melanoma (Ipilimumab, Nivolumab, Pembrolizumab)
Hwang, S.J.E.; Fernández-Peñas, P. (Sydney)
Skin Manifestations of Targeted Antineoplastic Therapy
Sanmartín, O. (Valencia)
Author Index
Subject Index
 
Preface
In many areas of medicine, we still face the great challenge of finding therapies that will fulfill our patient’s unmet needs. In dermatology, we have risen to the challenge on multiple fronts through advances in the understanding of both the genetics and immunopathogenesis of many inflammatory and malignant cutaneous disorders. This, combined with significant advances in targeted immunotherapy, has resulted in improved outcomes as these newer therapies are being used for both approved and off-label therapies for multiple chronic cutaneous disorders and multiple forms of skin cancer.
As in dermatology, many other specialties also have patients benefiting from targeted therapy. Many of these therapies come with an adverse event profile that includes a range of cutaneous disorders. All of these therapies have an adverse event profile with a wide spectrum ranging from mild reactions such as upper respiratory tract infection or morbilliform drug eruption to life-threatening disorders that include severe infections, anaphylactic reactions or toxic epidermal necrolysis.
As clinicians we always manage our patients on the basis of risk and benefit. Thus, we felt it would be important to gather a group of experts to evaluate the present state of knowledge with respect to adverse events to biologics used in patients with chronic cutaneous disorders or skin cancers, as well as biologics used by other specialties that significantly impact the skin. The expectation is that by truly understanding the risk of these targeted therapies, we will better manage our patients, resulting in significantly improved outcomes while striving to keep the risk to a minimum. We sincerely thank the authors for their valuable contribution in helping us understand the adverse reactions to biologics, and we know that many patients will benefit from the work as we disseminate this substantive body of information that we hope will have value to the practicing physician.
Lluís Puig , Barcelona Wayne Gulliver , St. John’s, NL
 
Introduction – Biologies in Dermatology: Indications and Off-Label Usage
The use of biologies in dermatology has been the subject of some recent excellent reviews [ 1 – 3 ] and highlights the number of eutaneous disorders for which these targeted therapeutics are both indicated for use or being used off-label. As well, of interest to the dermatologist, a significant number of biologics which have been developed for non-dermatological use have been associated with a multitude of cutaneous adverse events. It is, therefore, imperative that the dermatologist be familiar with adverse events associated with biological agents used in dermatological and non-dermatological diseases.
As dermatologists, we were first introduced to biologics about 14 years ago with the marketing authorization of alefacept, an immunoglobulin G1 (IgG1) recombinant dimeric fusion protein targeting LFA-3 [ 2 ] and indicated for the treatment of moderate-to-severe psoriasis. The primary endpoint of a 75% improvement in the psoriasis area severity index was achieved in approximately 20% patients, with some noted to have a lasting response of up to 1 year [ 2 ]. In 2016, ixeki-zumab, a humanized IgG4 antibody that neutralizes IL-17A, was approved by the FDA for the treatment of moderate-to-severe psoriasis [ 1 ]. Approximately 89% of ixekizumab-treated patients achieve PASI 75 improvement. The adverse event profiles of both molecules, while different, are acceptable. Today multiple biologics have been approved and are indicated for the treatment of moderate-to-severe chronic plaque psoriasis, and have efficacy and safety profiles that allow continuous use with a risk-benefit ratio that is acceptable to the regulators. This was not the case in the past, and in 2009 efalizumab was voluntarily withdrawn from the market when the severe but rare side effect of progressive multifocal leukoencephalopathy (PML) was observed.
In 2017, dermatologists have a multitude of options to treat moderate-to-severe psoriasis and these include drugs that target tumor necrosis factor (TNF), namely etanercept, infliximab, and adalimumab. In addition to the approved indication of moderate-to-severe psoriasis, adalimumab is also approved for the treatment of hidradenitis suppurativa (HS). As well, TNF antagonists have been used off-label in the treatment of pyoderma gangrenosum, chronic spontaneous urticaria, ur-ticarial vasculitis, and atopic dermatitis [ 1 ].
The anti-IL-12/23 molecule ustekinumab is also approved for the treatment of moderate-to-severe chronic plaque psoriasis and has also been used off-label in the treatment of HS [ 1 ].
In 2015-2016, we saw the arrival of anti-IL-17s including secukinumab and ixekizumab, again both approved for the treatment of moderate-to-severe psoriasis. It is theorized that IL-17 may play a role in other inflammatory skin disorders such as HS, and the expectation is that drugs targeting IL-17 will also be explored