Elsevier

Autoimmunity Reviews

Volume 9, Issue 3, January 2010, Pages 188-193
Autoimmunity Reviews

Autoimmune diseases induced by biological agents: A double-edged sword?

https://doi.org/10.1016/j.autrev.2009.10.003Get rights and content

Abstract

Biological agents are increasingly used for a rapidly-expanding number of rheumatic and systemic autoimmune diseases, with a growing number of reports of the paradoxical induction of autoimmune processes, overwhelmingly associated with anti-TNF agents. In this review, we analyze the clinical characteristics and outcomes of autoimmune diseases developing after biological therapies through a baseline Medline search as one of the objectives of the BIOGEAS project, created by the Spanish Society of Internal Medicine. The latest update of our registry (15 July 2009) included more than 800 cases of autoimmune diseases secondary to biological therapies, including a wide variety of both systemic (lupus, vasculitis, sarcoidosis and antiphospholipid syndrome) and organ-specific (interstitial lung disease, uveitis, optic neuritis, peripheral neuropathies, multiple sclerosis and autoimmune hepatitis) autoimmune processes. The majority of cases appeared between one month and one year after initiation of the biological agent and complete resolution was observed in nearly 75% of cases after cessation of therapy. The induced autoimmune diseases with the poorest outcomes were interstitial lung disease, inflammatory ocular disease and central nervous system demyelinating diseases.

Introduction

Biological therapies are increasingly used for a rapidly-expanding number of rheumatic and autoimmune diseases. These agents have been studied extensively during the past decade and have demonstrated acceptable safety and tolerability profiles. However, an emerging number of clinical and analytical autoimmune adverse events are reported, ranging from asymptomatic immunological alterations to life-threatening systemic autoimmune disease [1]. Paradoxically, for many of these drug-related autoimmune processes, current treatment indications include the very biological agent producing the adverse event.

The available safety data on autoimmune diseases induced by biological agents rely mainly on case reports, and information regarding their management and clinical significance is very limited. The purpose of this review is to analyze the clinical characteristics, outcomes and patterns of association with the different biological agents used in all reported cases of patients developing autoimmune diseases after biological therapy.

Section snippets

Classification of autoimmune diseases induced by biological agents

Autoimmune processes appearing after the use of biological agents were first described in the initial studies of infliximab in patients with rheumatoid arthritis (RA) [2]. Since then, the number and diversity of autoimmune diseases triggered by anti-tumor necrosis factor (TNF) agents has increased in parallel with their increasing use, and cases of autoimmune diseases induced by other licensed biological agents have also been reported. In 2006, the Study Group on Autoimmune Diseases (GEAS) of

Outcomes of induced autoimmune diseases

Autoimmune diseases associated with biological agents may appear during the first day of treatment or after years of use. Of the 498 reported cases in which the time of onset of autoimmune disease was detailed, the mean time was 40.52 ± 2.67 weeks (ranging from 1 day to 7 years) (Table 2). The majority of cases (68%) appeared between one month and one year after initiation of the biological agent. Autoimmune hepatitis and peripheral neuropathy appeared after a mean time of nearly one year, while

Conclusion

Biological agents are increasingly used for a rapidly-expanding number of rheumatic and systemic autoimmune diseases, with a growing number of reports of the paradoxical induction of autoimmune processes, overwhelmingly associated with anti-TNF agents. However, most available information comes from uncontrolled studies and therefore solid conclusions are not possible. Significant concerns include the variable incidence of these autoimmune diseases according to different ethnic groups, the

Take-home messages

  • An emerging number of clinical and analytical autoimmune adverse events are reported, ranging from asymptomatic immunological alterations to life-threatening systemic autoimmune diseases.

  • The last update of the BIOGEAS Registry (15 July 2009) included more than 800 cases of autoimmune diseases secondary to biological therapies.

  • A careful clinical and immunological evaluation accompanying the initiation of biological therapies is recommended, identifying preexisting clinical features suggestive of

Acknowledgments

The BIOGEAS Study group was supported financially by educational grants from Roche and Abbott.

The authors wish to thank David Buss for his editorial assistance.

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    1

    The members of the BIOGEAS are listed in Appendix A.

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