Autoimmune diseases induced by biological agents: A double-edged sword?
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.
References (38)
- et al.
Autoimmune diseases induced by TNF-targeted therapies
Best Pract Res Clin Rheumatol
(2008) - et al.
Autoimmune diseases induced by TNF-targeted therapies: analysis of 233 cases
Medicine (Baltimore)
(2007) - et al.
Assessment of antibodies to double-stranded DNA induced in rheumatoid arthritis patients following treatment with infliximab, a monoclonal antibody to tumor necrosis factor alpha: findings in open-label and randomized placebo-controlled trials
Arthritis Rheum
(2000) - et al.
A systematic review of the off-label use of biological therapies in systemic autoimmune diseases
Medicine (Baltimore)
(2008) - et al.
Vasculitis induced by tumor necrosis factor-targeted therapies
Curr Rheumatol Rep
(2008) - et al.
Anti-TNF-induced lupus
Rheumatology (Oxford)
(2009) - et al.
Systemic lupus erythematosus induced by anti-tumour necrosis factor alpha therapy: a French national survey
Arthritis Res Ther
(2005) - et al.
Safety analyses of adalimumab (HUMIRA) in global clinical trials and US postmarketing surveillance of patients with rheumatoid arthritis
Ann Rheum Dis
(2006) Drug-induced vasculitis
Curr Opin Rheumatol
(2008)- et al.
Sarcoid-like granulomatosis in patients treated with tumor necrosis factor blockers: 10 cases
Rheumatology (Oxford)
(2009)
Treatment with tumour necrosis factor alpha antagonists in patients with rheumatoid arthritis induces anticardiolipin antibodies
Ann Rheum Dis
Anticardiolipin antibodies in rheumatoid patients treated with etanercept or conventional combination therapy: direct and indirect evidence for a possible association with infections
Ann Rheum Dis
Etanercept plus standard therapy for Wegener's granulomatosis
N Engl J Med
The frequency of anticardiolipin antibodies and genetic mutations associated with hypercoagulability among patients with Wegener's granulomatosis with and without history of a thrombotic event
J Rheumatol
Increased MRI activity and immune activation in two multiple sclerosis patients treated with the monoclonal anti-tumor necrosis factor antibody cA2
Neurology
TNF neutralization in MS: results of a randomized, placebo-controlled multicenter study. The Lenercept Multiple Sclerosis Study Group and The University of British Columbia MS/MRI Analysis Group
Neurology
Tumor necrosis factor-alpha antagonists and neuropathy
Muscle Nerve
Treatment with infliximab may contribute to the development of peripheral neuropathy among the patients with rheumatoid arthritis
Clin Rheumatol
Guillain–Barré and Miller Fisher syndromes occurring with tumor necrosis factor alpha antagonist therapy
Arthritis Rheum
Cited by (265)
Incidence of Anti-Drug Antibodies to Monoclonal Antibodies in Asthma: A Systematic Review and Meta-Analysis
2023, Journal of Allergy and Clinical Immunology: In PracticeIxekizumab exposure associated with myelitis: A case report and a literature review
2021, Journal of NeuroimmunologyIsolated myelitis in a patient with Behcet's disease during golimumab therapy
2021, Journal of Neuroimmunology
- 1
The members of the BIOGEAS are listed in Appendix A.