Diana Swift
October 07, 2015
Findings from a Danish population-based study suggest a twofold increased relative risk for central demyelinating diseases in patients with inflammatory bowel disease (IBD) who receive tumor necrosis factor (TNF) inhibitors.
“If true, the observed association could either be attributed to the unmasking of a latent demyelinating disease or to the emergence of a de novo demyelinating disease,” write Nynne Naebo Andersen, MD, a PHD candidate in epidemiology at the Statens Serum Institut in Copenhagen, Denmark, and colleagues, in a research letter published online October 5 in JAMA Internal Medicine.
The authors emphasize that despite the increased relative risk, the absolute risk remains low. Prior case reports have suggested an association between TNF inhibitors in patients with IBD or other immune-mediated diseases and demyelinating diseases in the central nervous system.
Dr Andersen and colleagues used the Danish Civil Registration System to identify a population of 4 million people living in Denmark from January 1, 1999, to December 31, 2012. Unique identifiers in the system allowed the researchers to link those data to data from national health registries for IBD diagnoses, anti-TNF exposure, and central demyelinating diseases, including multiple sclerosis, optic neuritis, transverse myelitis, and others.
Patients exposed to anti-TNF and unexposed patients were matched in ratios of up to 1:4 for sex, age (5-year intervals), and disease duration (<1, 1 – 4, 5 – 9, 10 – 19, and 20 or more years).
Of 54,843 patients with IBD, 4504 were exposed to anti-TNF, and these patients were matched to 16,429 unexposed patients, yielding a study cohort of 20,933 patients. Anti-TNF-exposed patients in the matched cohort had a mean age of 39.4 years (standard deviation, 14.7 years), were 56% female, and had a mean disease duration of 4.0 years (interquartile range, 1.1 – 9.0 years).
A total of 11 central demyelinating events were observed among exposed patients (multiple sclerosis, two cases; optic neuritis, five cases; other diseases, four cases), which translated to 7.5 events per 10,000 person-years (95% confidence interval [CI], 4.1 – 13.5 events). In the unexposed group, the authors identified 17 central demyelinating events (five cases of multiple sclerosis, six cases of optic neuritis, one case of transverse myelitis, and five cases other central demyelinating diseases), which translated to 3.3 events per 10,000 person-years (95% CI, 2.1 – 5.4 events).
The hazard ratio for central demyelinating disease in exposed vs unexposed patients was 2.19 (95% CI 1.02 – 4.71), with an absolute risk difference of 3.9 per 10,000 person-years (95% CI, 0.1 – 12.2).
TNF inhibitors should be used cautiously in patients with a personal or family history of demyelinating conditions, Dr Anderson told Medscape Medical News. “Patients treated with anti-TNF should be closely monitored for demyelination with neurological examinations, and if a patient develops signs of demyelinating during ongoing treatment, therapy should be discontinued promptly,” she noted.
She added that it is important to emphasize to patients, however, that the absolute risk appears to be very limited.
The authors concede that because the rarity of demyelinating diseases limited the study’s statistical power, these preliminary findings could be a result of chance or unmeasured confounding, and therefore need confirmation. The results do, however, “represent the first analytical data of this potential association,” they write.
This study was supported by grants from the Lundbeck Foundation, the Beckett Foundation, the Danish Colitis Crohn Association, the Danish Council for Independent Research, and the Danish Council for Independent Research. Two authors reported receiving travel funding and speakers’ fees from industry.
JAMA Intern Med. Published online October 5, 2015. Abstract