medwireNews: Exposure to tumor necrosis factor (TNF) inhibitors is associated with a 36% higher risk for inflammatory central nervous system (CNS) diseases relative to conventional therapies, a pooled analysis suggests.
The association was found “irrespective of background autoimmune disease or TNF inhibitor type,” note Shiyu Xiao (Sichuan Provincial People’s Hospital, Chengdu, China) and colleagues in JAMA Neurology.
They write: “Physicians should carefully balance the risks and benefits when prescribing anti-TNF agents and ensure necessary monitoring and timely intervention once treatment is initiated.”
Given that inflammatory CNS events have an “exceptionally low incidence,” they carried out a pooled analysis of 18 observational studies evaluating the association between exposure to TNF inhibitors for autoimmune diseases and the incidence of any inflammatory CNS events, including demyelinating and non-demyelinating diseases. Of these, 14 were cohort studies, three were case-control studies, and one was a cross-sectional design.
Included were 1,118,428 patients aged 25–63 years with autoimmune diseases, who had more than 5.6 million patient–years of follow-up, 258,897 of whom received TNF inhibitors, including the monoclonal antibodies adalimumab, infliximab, golimumab, or certolizumab pegol, and the TNF receptor and antibody fusion protein, etanercept. The rate of new-onset inflammatory CNS events in these patients after starting TNF-inhibitor treatment ranged from 2.0 to 13.4 per 10,000 person–years.
The most common autoimmune diseases included rheumatic diseases in nine studies and inflammatory bowel disease in five studies, with the remaining four studies covering a broader range of autoimmune diseases.
In the primary analysis, patients given TNF inhibitors were more likely to experience any inflammatory CNS event than those given other conventional treatments, such as antirheumatic drugs, nonsteroidal anti-inflammatory drugs, and other biologic or Janus kinase inhibitors, with a significant pooled risk ratio (RR) of 1.36.
This was “mainly attributed to demyelinating diseases,” the researchers note, which occurred at a significant RR of 1.38, compared with a nonsignificant 1.24 for non-demyelinating diseases.
All the results held up across subgroups, suggesting that “these results were relatively stable,” the researchers write.
In further analysis, there was no significant difference in the risk for inflammatory CNS events between patients with rheumatic diseases or inflammatory bowel disease, nor between those with rheumatoid arthritis compared with other rheumatic diseases, such as psoriatic diseases and ankylosing spondylitis.
Three studies looked at the effects of different types of TNF inhibitors and showed no difference in the risk for inflammatory CNS events among the anti-TNF monoclonal antibodies except for certolizumab pegol, which showed a significant 39% higher risk compared with etanercept. However, the results “should be interpreted with caution as the number of studies is very small and lack a plausible mechanistic explanation,” Xiao et al note.
They say that the findings need “to be interpreted in a clinical context, particularly given the low absolute risk and the substantial benefit of TNF inhibitor therapy.”
The team suggests that “[s]imilar to any drug treatment, weighing the benefits and adverse effects is necessary to make an informed choice and provide appropriate neurological counseling to facilitate shared decision-making.”
Future studies on the topic should aim for “more comprehensive data and rigorous designs to minimize confounding (eg, disease severity) and selection bias,” say the researchers, who also recommend assessment of the risks and benefits of novel autoimmune disease therapies being used as alternatives to TNF inhibitors.
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