Increased risk of inflammatory CNS diseases following anti-TNF therapy for autoimmune diseases

Compared with conventional therapies, exposure to tumour necrosis factor (TNF) inhibitors is associated with increased risk of inflammatory central nervous system (CNS) diseases, irrespective of background autoimmune disease or TNF inhibitor type, a recent meta-analysis has found.

The systematic review and meta-analysis of 18 multinational, observational studies, which included 1,118,428 patients with autoimmune diseases such as inflammatory bowel disease (IBD), inflammatory arthritis, rheumatoid arthritis and psoriatic arthritis, found that compared with conventional therapies, exposure to TNF inhibitors (adalimumab, infliximab, certolizumab pegol, golimumab and etanercept) used to treat the patients’ autoimmune diseases was associated with a 36 percent increased risk of any inflammatory CNS events such as multiple sclerosis, demyelinating events and optic neuritis (risk ratio [RR] 1.36; 95 percent confidence interval [CI], 1.01–1.84). Patients who received conventional therapies were not exposed to TNF inhibitors and were typically treated with conventional synthetic disease-modifying antirheumatic drugs, nonsteroidal anti-inflammatory drugs for rheumatic diseases, and 5-aminosalicylic acid for IBD. [JAMA Neurol 2024;doi:10.1001/jamaneurol.2024.3524] 

Secondary analyses revealed a similar risk of inflammatory CNS diseases across different types of underlying autoimmune diseases (RR for rheumatic diseases: 1.36; 95 percent CI, 0.84–2.21; IBD: 1.49; 95 percent CI, 0.93–2.40; p for subgroup = 0.74) and TNF inhibitors (RR for anti-TNF monoclonal antibodies vs etanercept, 1.04; 95 percent CI, 0.93–1.15).

The investigators noted that in a real-world analysis of patients with autoimmune diseases, the risk of inflammatory CNS events did not differ between TNF inhibitors and other biologics or Janus kinase inhibitors. Consequently, the relative risk needs to be interpreted in a clinical context, particularly given the low absolute risk and the substantial benefit of TNF inhibitor therapy. [Arthritis Care Res (Hoboken) 2024;76:1203-1209; JAMA Neurol 2020;77:933-935]

Autoimmune diseases are a group of chronic inflammatory disorders characterized by aberrant immune response to self-antigens. With a prevalence of up to 10 percent worldwide, autoimmune diseases are the third most prevalent disease category after heart disease and cancer, representing a significant global health burden. [Lancet 2023;401:1878-1890; J Intern Med 2015;278:369-395]

The authors thus concluded that, as with any drug treatment, physicians should carefully balance the risks and benefits when prescribing anti-TNF agents, provide appropriate neurological counselling to facilitate shared decision-making, and ensure necessary monitoring and timely intervention once treatment is initiated.