Adalimumab-associated antiphospholipid syndrome: a case report and review of the literature

Abstract

This study aims for the presentation of the first reported case of adalimumab-associated antiphospholipid syndrome (APS) and review of the literature on adalimumab-induced vasculitis and APS. A case of APS associated with adalimumab use in a 67-year-old woman is reported. The English medical literature was reviewed for antitumor necrosis factor (TNF) agents and their association with APS and vasculitis. Adalimumab is a fully humanized monoclonal antibody targeted against TNF alpha that is widely used in the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis, and Crohn's disease. Literature review reveals several cases of anti-TNF-induced vasculitis including cases associated with adalimumab. We report the first case of adalimumab-induced APS in a 67-year-old woman who developed APS and vasculitis associated with de novo positive anti-cardiolipin (aCL) antibody following the third dose of adalimumab therapy for the treatment of spondyloarthropathy. This is the first case demonstrating that a short course of adalimumab therapy may induce immunoglobulin M aCL autoantibodies leading to APS. With the growing use of anti-TNF medications in immune-mediated and inflammatory diseases, adalimumab and other anti-TNF medications should be considered as a possible explanation for APS.

16th International Congress on Antiphospholipid Antibodies Task Force Report on Antiphospholipid Syndrome Treatment Trends

“…This trial should clarify the role of anti-TNF therapy for this APS manifestation. It is important to note that there are reported cases of the development 135,136 or exacerbation 137 of APS while using anti TNF therapy. These drugs currently have no role in other disease manifestations and may have deleterious effects.…”

Safety of Anti-Tumor Necrosis Factor Therapies in Arthritis Patients

“…Autoimmune AEs with cutaneous manifestations also included intermediate bullous and cicatricial pemphigoid (122) and granuloma annulare (123). Other autoimmune AEs in patients treated with anti-TNF biologicals included de novo or exacerbation of autoimmune hepatitis (124)(125)(126)(127)(128) and antiphospholipid syndrome (129,130). IFX is believed to lead to the unmasking of autoimmune hepatitis by binding to transmembrane TNF on the cell surface, thus inducing apoptosis and leading to the release of nucleosomes (131).…”

Digital ischaemia secondary to adalimumab-induced antiphospholipid syndrome

“…In contrast, antiphospholipid syndrome (APS) induced by anti-TNF agents has been less commonly described. Prior to this case, only a few examples of anti-TNF-induced APS have been reported in the literature in which immunological and clinical features of APS were documented 4 5. Both venous and arterial events have been described while under treatment with adalimumab, infliximab and etanercept 6–8.…”