TNF Inhibitor Exposure May Raise Risk of Inflammatory CNS Events

Exposure to tumor necrosis factor (TNF) inhibitors may be associated with an increased risk for inflammatory central nervous system (CNS) events, according to recent findings published in JAMA Neurology.

The authors of the study observed a similar association for both inflammatory demyelinating and nondemyelinating CNS events. “Whether this association represents de novo or exacerbated inflammatory pathways requires further research,” they wrote.

The authors arrived at this conclusion after performing a case-control study (N = 212) of patients with autoimmune diseases with or without inflammatory CNS events who received treatment at Mayo Clinic in Rochester, Minnesota; Jacksonville, Florida; and Scottsdale, Arizona, between January 1, 2003, and February 20, 2019. A total of 106 patients had inflammatory CNS events, while the remaining 106 did not.

Patients whose medical records contained reports of ICD-10 diagnostic codes for FDA-approved autoimmune disease indications for TNF inhibitor use, as well as diagnostic codes for inflammatory CNS events, were included. Potential indications included rheumatoid arthritis, psoriasis and psoriatic arthritis, ankylosing spondylitis, Crohn disease, and ulcerative colitis.

The results of the study indicated that 64 (60%) patients and 42 (40%) controls who had exposure to TNF inhibitors had an increased risk for any inflammatory CNS event, and secondary analyses revealed that this association was strongest among individuals with rheumatoid arthritis.

Neurology Learning Network discussed these findings further with study author Amy Kunchok, MBBS, MMed, from the Department of Neurology at Mayo Clinic in Rochester, Minnesota.

Neurology Learning Network: You and your colleagues aimed to determine whether exposure to TNF inhibitors is associated with risk of inflammatory demyelinating and nondemyelinating CNS events among patients with an autoimmune disease. What prompted you to conduct this study?

Dr Kunchok: In our MS and Autoimmune Neurology clinics at Mayo Clinic, we observed several inflammatory CNS events among patients with systemic autoimmune diseases. We were interested to understand whether there was an association between exposure to TNFα inhibitors and these inflammatory CNS events.

NLN: You and your colleagues found that the use of TNF inhibitors among patients with autoimmune diseases appeared to be associated with increased risk for inflammatory CNS events. Could you elaborate on this finding?

Dr Kunchok: We found that inflammatory CNS events were associated with TNFα inhibitor exposure (adjusted OR, 3.01; 95% CI, 1.55-5.82; P = .001). When stratified into demyelinating and nondemyelinating CNS events, the adjusted OR was similar ((OR, 3.09; 95% CI, 1.19-8.04; P = .02) for inflammatory demyelinating CNS events and for inflammatory nondemyelinating CNS events (adjusted OR, 2.97; 95% CI, 1.15- 7.65; P = .02)).

NLN: Did you anticipate these findings, or were any of them surprising to you?

Dr Kunchok: Although an association between TNFα inhibitor use and inflammatory demyelinating CNS events has been previously postulated, it has still been debated. In this nested case control study, we observed that TNFα inhibitor exposure was associated with inflammatory demyelinating CNS events.

In addition, a novel finding from this study was the association with inflammatory nondemyelinating CNS events such as meningitis and meningoencephalitis.

NLN: What areas of future research are needed after this study?

Dr Kunchok: Further research is needed both at an epidemiological level, including population-based studies to examine the incidence of these inflammatory CNS events among patients exposed to TNFα inhibitors, and also more laboratory research is needed to better understand the complex inflammatory pathways and processes altered by TNFα inhibition.

NLN: What key takeaways do you hope to leave with neurologists and neurology providers on this topic?

Dr Kunchok: TNFα inhibitors are highly effective therapies for patients, and these inflammatory CNS events are likely uncommon. Our study has observed an association, but this does not imply causality. Therefore, we are not cautioning against using these therapies among appropriate patients.

However, we do recommend that when clinicians are assessing patients with both inflammatory demyelinating and nondemyelinating CNS events, a detailed evaluation of the medication history is taken, particularly in patients with coexistent autoimmune diseases who may have a current or past history of biological therapies.

—Christina Vogt

Reference:
Kunchok A, Aksamit AJ, David III JM, et al. Association between tumor necrosis factor inhibitor exposure and inflammatory central nervous system events. JAMA Neurol. 2020;77(8):937-946. doi:10.1001/jamaneurol.2020.1162