TNF Inhibitors Associated with Neurological Adverse Events

EULAR 2022—Neurological demyelinating adverse events have occurred, in rare instances, in patients with inflammatory joint disease treated with tumor necrosis factor (TNF) inhibitors. An in-depth investigation into the association between TNF inhibitors and neurological events in these patients was presented by Bénédicte Delcoigne, PhD, MSc, Department of Medicine, Solna-Clinical Epidemiology Department, the Karolinska Institute, Stockholm, Sweden, during the European Alliance of Associations for Rheumatology (EULAR) European Congress of Rheumatology 2022.¹

The study sought to estimate the incidence of neurological events in patients with rheumatoid arthritis (RA) and/or spondyloarthritis (SpA) who were beginning treatment with TNF inhibitors. Neurological events included demyelinating disease of the central nervous system (CNS), multiple sclerosis and inflammatory neuropathy. The study also evaluated the incidence of neurological events in patients treated with etanercept compared with the incidence in patients treated with other TNF inhibitors.

Methods

Treatment cohorts comprised patients initiating TNF inhibitors between 2001 and 2018 from clinical rheumatology registers in Denmark, Finland, Iceland, Norway and Sweden. Demographic data, including age and sex, co-medication with methotrexate and clinical variables (e.g., CRP and disease duration [<1 year, 1–5 years, >5 years]), were extracted and used as covariates. Crude incidence rates for neurological events and subtypes were estimated using multiple ICD-10 codes. Data from all five countries were pooled.

One patient could contribute to more than one treatment episode if different agents were prescribed and/or if new diseases were identified. The risk of neurological events between patients treated with etanercept and other TNF inhibitors was compared using Cox regression, with time since treatment start adjusted for the noted covariates, robust standard errors and stratified by country.

The Results

The study found 52,682 treatment starts, including 33,885 for patients with RA. The breakdown for these patients by country was 8,259 for Denmark, 3,765 for Finland, 723 for Iceland, 1,353 for Norway and 19,785 for Sweden. The majority (75%) of patients were women, with a mean age of 56 years.

The study also found 46,549 treatment starts in 28,772 patients with SpA, with a breakdown by country of 7,000 for Denmark, 2,885 for Finland, 962 for Iceland, 2,684 for Norway and 15,241 for Sweden. Of the patients with SpA, 47% were women, with a mean age of 45 years.

The crude incidence rates for neurological events showed some variation by diagnosis. Patients with SpA had rates of demyelinating disease about two times higher than the rates of patients with RA, as well as rates for multiple sclerosis about three times higher than the corresponding rates in patients with RA (P<0.01). However, the rates of inflammatory neuropathy were similar in both patients with RA and SpA.

When the incidence of neurological events in patients treated with etanercept was compared with patients treated with other TNF inhibitors, all Cox regression hazard ratios were statistically non-significant and close to 1. This finding indicates no difference in the rate of neurologic events between these agents. These results are important from a safety perspective for patients starting TNF inhibitor treatment for inflammatory joint and related diseases. Patients, including those with neurologic diseases, such as multiple sclerosis, may become reluctant to start these agents if they learn about theses side effects from press coverage. Therefore, safety data such as this—which is often difficult to study—is welcome to alleviate such fears.

Michele B. Kaufman, PharmD, BCGP, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.

Reference

1. Delcoigne B, Kopp TI, Arkema E, et al. Exposure to specific tumor necrosis factor inhibitors and risk of demyelinating and inflammatory neuropathy in patients with inflammatory arthritis. A collaborative observational study across five Nordic rheumatology registers (OP0060). Ann Rheum Dis. 2022;81(suppl 1):41.