Autoimmune diseases induced by biological agents. A review of 12,731 cases (BIOGEAS Registry)

Abstract

Biological drugs are therapies designed to target a specific molecule of the immune system that have been linked with the development of autoimmune diseases. Areas covered: The BIOGEAS Registry currently collects information about nearly 13,000 reported cases of autoimmune diseases developed in patients exposed to biologics, including more than 50 different systemic and organ-specific autoimmune disorders, of which psoriasis (n=6375), inflammatory bowel disease (n=845), demyelinating CNS disease (n=803), interstitial lung disease (n=519) and lupus (n=369) were the most frequently reported. The main biologics involved were anti-TNF agents in 9133 cases (adalimumab in 4154, infliximab in 3078 and etanercept in 1681), immune checkpoint inhibitors in 913 (ipilimumab in 524 and nivolumab in 225), B-cell targeted therapies in 741 (rituximab in 678), and growth factor inhibitors in 549 cases (bevacizumab in 544). Even though targeting a particular immune molecule may be associated with an excellent clinical response in most patients, an unexpected autoimmune disease may arise in around 8 out of 10,000 exposed patients. Expert opinion: Following the increased use of biologics, the number and diversity of induced autoimmune diseases is increasing exponentially. Management of these disorders will be an increasing clinical challenge in the daily practice in the next years.

Ocular complications of tumour necrosis factor alpha inhibitors

“…Autoimmune diseases, a paradoxical adverse event, are recognised to be induced by TNFα antagonists, most frequently psoriasis, inflammatory bowel disease, central nervous system (CNS) demyelinating diseases, interstitial lung disease and lupus . Induction of auto‐antibodies and systemic thromboembolic events are described.…”

The Safety Profile of Tumor Necrosis Factor Inhibitors in Ankylosing Spondylitis: Are TNF Inhibitors Safer Than We Thought?

“…Interestingly, the high percentage of patients with TNF inhibitor–induced antinuclear antibodies does not translate into the number of patients with TNF inhibitor–induced autoimmune diseases . Until May 2014 there were only 14 case reports of SLE/lupus‐like syndrome induced by TNF inhibitors in patients with ankylosing spondylitis . The incidence of this phenomenon in patients with ankylosing spondylitis is unknown and can only be estimated based on data from other rheumatic diseases.…”

“…The incidence of this phenomenon in patients with ankylosing spondylitis is unknown and can only be estimated based on data from other rheumatic diseases. The prevalence of SLE/lupus‐like syndrome in all rheumatic patients treated with TNF inhibitors was calculated to be 0.33% according to the BIOGEAS registry (which collects cases by systematic Medline search) . In the BSRBR‐RA registry, the incidence of SLE/lupus‐like syndrome in patients with RA was 1.0/1000 pyrs, with no increased risk compared to TNF inhibitors naive patients after adjusting for baseline differences .…”

“…A second autoimmune disease associated with TNF inhibitor treatment is vasculitis. Although in both the BIOGEAS and BSRBR‐RA registries vasculitis after treatment with TNF inhibitors seems to be more common than in TNF inhibitor–naïve patients (with prevalence of 0.71% and incidence 1.5/1000 pyrs respectively), it may not be true in ankylosing spondylitis; there are only single case reports in the literature of TNF inhibitor–induced vasculitis in patients with ankylosing spondylitis . Hypotheses on possible mechanisms of vasculitis after TNF inhibitor treatment include cytokine imbalance due to the shift from TH1 cell to TH2 cell cytokines production and immune complexes (containing antibodies against TNF inhibitors) inducing hypersensitivity reaction in vessel walls …”

“…There are no observational studies of this AE in ankylosing spondylitis, only case reports. To date, according to the BIOGEAS registry (based on a systematic Medline literature review), there were 18 cases of sarcoidosis occurring during TNF inhibitor therapy in patients with ankylosing spondylitis, with 111 cases in all diseases treated with TNF inhibitors (mostly RA) . Sarcoidosis occurred mainly after ETN (52.3%), followed by ADA (24.3%) and IFX (22.5%).…”