TNF Inhibitor Use May Raise Risk of MS and Neuropathy in AS Patients

Use of tumor necrosis factor alpha (TNF) inhibitors is linked to a higher risk of inflammatory disorders affecting the nervous system among people with ankylosing spondylitis (AS) and psoriatic arthritis (PsA), a long-term study based on nationwide data from Sweden and Denmark suggests.

Specifically, the potential of greater risk was seen for a demyelinating disease like multiple sclerosis (MS), or for polyneuropathy, its researchers report.

The study, “Risk of neuroinflammatory events in arthritis patients treated with tumour necrosis factor alpha inhibitors: a collaborative population-based cohort study from Denmark and Sweden,” was published in the journal Annals of the Rheumatic Diseases.

TNF is a signaling protein that helps drive inflammation. Intended to block this protein, TNF inhibitors are a mainstay of treatment for several conditions, including AS, PsA, and rheumatoid arthritis (RA). Examples of existing therapies are Enbrel (etanercept), Humira (adalimumab), infliximab (brand names Remsima, Remicade), Simponi (golimumab), and Cimzia (certolizumab pegol).

This type of treatment is associated with neuroinflammatory conditions — those characterized by inflammation in the nervous system. In particular, high levels of TNF have been found in disease-associated brain lesions of MS patients and in their cerebrospinal fluid — that surrounding the brain and spinal cord. But clinical trials testing TNF inhibitors in MS patients have led to unfavorable results.

Aiming to analyze whether TNF inhibitors use changes the risk of developing a neuroinflammatory disease, researchers analyzed separately nationwide data from Denmark and from Sweden. In total, 175,520 people with RA, PsA, or AS were analyzed and followed for up to 17 years. Within this group, 43,909 (25%) patients were treated at least once with a TNF inhibitor.

Although the exact rates of treatment use varied by location and disease type, patients on TNF inhibitors were generally younger at the study’s start and at diagnosis than non-treated patients in both countries. They also had a longer disease duration and higher disease activity.

Patients with AS or PsA (analyzed together) showed a higher, yet rare, risk of neuroinflammatory conditions if using use of TNF inhibitors. These included MS, other diseases characterized by loss of myelin — the protective sheath of nerve fibers — and polyneuropathy (degeneration of peripheral nerves).

In those on TNF inhibitors, the incidence rates of such conditions per 1,000 person-years were 0.59 (in Sweden) and 0.87 (in Denmark), compared to 0.40 (Sweden) and 0.19 (Denmark) in people not taking these therapies. (Person-years is a measure that sums follow-up duration in each patient, and is higher with more years in a study.)

These rates correspond to a higher risk associated with TNFi use of 1.5 times in Sweden, and 3.4 times in Denmark.

Among those on TNF inhibitors and experiencing a neuroinflammatory event, the average time to such a complication was 3.1 to 3.8 years, at an average age 43 to 46, depending on the country.

No such risk was seen when analyzing the use of TNF inhibitors to treat RA.

These data suggest that among people with AS and PsA, the use of TNF inhibitors is associated with an increased risk for neuroinflammatory conditions.

“This information will be important for risk communication and evaluation in clinical practice,” the researchers wrote, “even though the absolute risk is low.” They also said that further studies are needed to better understand the biological mechanisms underlying this link.