Immune-mediated adverse effects of biologicals used in the treatment of rheumatic diseases

Andrea T. Borchers, Naama Leibushor, Gurtej S. Cheema, Stanley M Naguwa, M. Eric Gershwin

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Biological agents represent a major advance in the treatment of rheumatic diseases, most particularly in the prevention of irreversible structural damage. While generally well tolerated, their increasing use continues to reveal a variety of immune-mediated adverse effects. The most frequent adverse events are infusion reactions and injection site reactions, but despite their fairly common occurrence the precise mechanisms are not fully understood. Another adverse event that became appreciated early in the era of biologicals is the increased risk of Mycobacterium tuberculosis and other granulomatous infections in patients treated with tumor necrosis factor (TNFα) antagonists. Although it is evident that this enhanced susceptibility to intracellular infections must be due to immunosuppression arising from the blockade of TNFα, the mechanisms have not been fully elucidated; such an understanding is likely to provide important insights into the role of TNFα in granulomatous and other infectious diseases. In addition, the biologicals may paradoxically induce autoimmunity. The development of autoantibodies is seen in a considerable proportion of patients, but clinical autoimmune disease develops much less commonly, including systemic lupus erythematosus, multiple sclerosis and other demyelinating diseases, psoriasis, sarcoidosis, and interstitial lung disease. The mechanisms leading to their induction are very poorly understood, but an intriguing hypothesis is that interferon α provides a common link, at least for lupus, psoriasis and possibly sarcoidosis. Finally, the potential risk of infection with use of the biologicals is an issue that clinicians should always be aware of. These comments aside, the biologics are the most important advance in the treatment of rheumatic disease in the history of rheumatology and their usage has not only greatly helped patient care, but also provided key data on the immunobiology of the disease processes.

Original languageEnglish (US)
Pages (from-to)273-288
Number of pages16
JournalJournal of Autoimmunity
Volume37
Issue number4
DOIs
StatePublished - Dec 2011

Fingerprint

Rheumatic Diseases
Tumor Necrosis Factor-alpha
Sarcoidosis
Psoriasis
Infection
Interstitial Lung Diseases
Biological Factors
Rheumatology
Demyelinating Diseases
Biological Products
Autoimmunity
Mycobacterium tuberculosis
Systemic Lupus Erythematosus
Autoantibodies
Immunosuppression
Interferons
Autoimmune Diseases
Multiple Sclerosis
Communicable Diseases
Patient Care

Keywords

  • Autoimmunity
  • Biologic agents
  • Immunosuppression
  • Infection and immunity

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Immune-mediated adverse effects of biologicals used in the treatment of rheumatic diseases. / Borchers, Andrea T.; Leibushor, Naama; Cheema, Gurtej S.; Naguwa, Stanley M; Gershwin, M. Eric.

In: Journal of Autoimmunity, Vol. 37, No. 4, 12.2011, p. 273-288.

Research output: Contribution to journalArticle

@article{772484cb4b004ed682d69cc51841ec0b,
title = "Immune-mediated adverse effects of biologicals used in the treatment of rheumatic diseases",
abstract = "Biological agents represent a major advance in the treatment of rheumatic diseases, most particularly in the prevention of irreversible structural damage. While generally well tolerated, their increasing use continues to reveal a variety of immune-mediated adverse effects. The most frequent adverse events are infusion reactions and injection site reactions, but despite their fairly common occurrence the precise mechanisms are not fully understood. Another adverse event that became appreciated early in the era of biologicals is the increased risk of Mycobacterium tuberculosis and other granulomatous infections in patients treated with tumor necrosis factor (TNFα) antagonists. Although it is evident that this enhanced susceptibility to intracellular infections must be due to immunosuppression arising from the blockade of TNFα, the mechanisms have not been fully elucidated; such an understanding is likely to provide important insights into the role of TNFα in granulomatous and other infectious diseases. In addition, the biologicals may paradoxically induce autoimmunity. The development of autoantibodies is seen in a considerable proportion of patients, but clinical autoimmune disease develops much less commonly, including systemic lupus erythematosus, multiple sclerosis and other demyelinating diseases, psoriasis, sarcoidosis, and interstitial lung disease. The mechanisms leading to their induction are very poorly understood, but an intriguing hypothesis is that interferon α provides a common link, at least for lupus, psoriasis and possibly sarcoidosis. Finally, the potential risk of infection with use of the biologicals is an issue that clinicians should always be aware of. These comments aside, the biologics are the most important advance in the treatment of rheumatic disease in the history of rheumatology and their usage has not only greatly helped patient care, but also provided key data on the immunobiology of the disease processes.",
keywords = "Autoimmunity, Biologic agents, Immunosuppression, Infection and immunity",
author = "Borchers, {Andrea T.} and Naama Leibushor and Cheema, {Gurtej S.} and Naguwa, {Stanley M} and Gershwin, {M. Eric}",
year = "2011",
month = "12",
doi = "10.1016/j.jaut.2011.08.002",
language = "English (US)",
volume = "37",
pages = "273--288",
journal = "Journal of Autoimmunity",
issn = "0896-8411",
publisher = "Academic Press Inc.",
number = "4",

}

TY - JOUR

T1 - Immune-mediated adverse effects of biologicals used in the treatment of rheumatic diseases

AU - Borchers, Andrea T.

AU - Leibushor, Naama

AU - Cheema, Gurtej S.

AU - Naguwa, Stanley M

AU - Gershwin, M. Eric

PY - 2011/12

Y1 - 2011/12

N2 - Biological agents represent a major advance in the treatment of rheumatic diseases, most particularly in the prevention of irreversible structural damage. While generally well tolerated, their increasing use continues to reveal a variety of immune-mediated adverse effects. The most frequent adverse events are infusion reactions and injection site reactions, but despite their fairly common occurrence the precise mechanisms are not fully understood. Another adverse event that became appreciated early in the era of biologicals is the increased risk of Mycobacterium tuberculosis and other granulomatous infections in patients treated with tumor necrosis factor (TNFα) antagonists. Although it is evident that this enhanced susceptibility to intracellular infections must be due to immunosuppression arising from the blockade of TNFα, the mechanisms have not been fully elucidated; such an understanding is likely to provide important insights into the role of TNFα in granulomatous and other infectious diseases. In addition, the biologicals may paradoxically induce autoimmunity. The development of autoantibodies is seen in a considerable proportion of patients, but clinical autoimmune disease develops much less commonly, including systemic lupus erythematosus, multiple sclerosis and other demyelinating diseases, psoriasis, sarcoidosis, and interstitial lung disease. The mechanisms leading to their induction are very poorly understood, but an intriguing hypothesis is that interferon α provides a common link, at least for lupus, psoriasis and possibly sarcoidosis. Finally, the potential risk of infection with use of the biologicals is an issue that clinicians should always be aware of. These comments aside, the biologics are the most important advance in the treatment of rheumatic disease in the history of rheumatology and their usage has not only greatly helped patient care, but also provided key data on the immunobiology of the disease processes.

AB - Biological agents represent a major advance in the treatment of rheumatic diseases, most particularly in the prevention of irreversible structural damage. While generally well tolerated, their increasing use continues to reveal a variety of immune-mediated adverse effects. The most frequent adverse events are infusion reactions and injection site reactions, but despite their fairly common occurrence the precise mechanisms are not fully understood. Another adverse event that became appreciated early in the era of biologicals is the increased risk of Mycobacterium tuberculosis and other granulomatous infections in patients treated with tumor necrosis factor (TNFα) antagonists. Although it is evident that this enhanced susceptibility to intracellular infections must be due to immunosuppression arising from the blockade of TNFα, the mechanisms have not been fully elucidated; such an understanding is likely to provide important insights into the role of TNFα in granulomatous and other infectious diseases. In addition, the biologicals may paradoxically induce autoimmunity. The development of autoantibodies is seen in a considerable proportion of patients, but clinical autoimmune disease develops much less commonly, including systemic lupus erythematosus, multiple sclerosis and other demyelinating diseases, psoriasis, sarcoidosis, and interstitial lung disease. The mechanisms leading to their induction are very poorly understood, but an intriguing hypothesis is that interferon α provides a common link, at least for lupus, psoriasis and possibly sarcoidosis. Finally, the potential risk of infection with use of the biologicals is an issue that clinicians should always be aware of. These comments aside, the biologics are the most important advance in the treatment of rheumatic disease in the history of rheumatology and their usage has not only greatly helped patient care, but also provided key data on the immunobiology of the disease processes.

KW - Autoimmunity

KW - Biologic agents

KW - Immunosuppression

KW - Infection and immunity

UR - http://www.scopus.com/inward/record.url?scp=82955217794&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=82955217794&partnerID=8YFLogxK

U2 - 10.1016/j.jaut.2011.08.002

DO - 10.1016/j.jaut.2011.08.002

M3 - Article

C2 - 21907543

AN - SCOPUS:82955217794

VL - 37

SP - 273

EP - 288

JO - Journal of Autoimmunity

JF - Journal of Autoimmunity

SN - 0896-8411

IS - 4

ER -