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Demyelinating Disease in Patients Treated with TNF Antagonists in Rheumatology: Data from BIOBADASER, a Pharmacovigilance Database, and a Systematic Review

https://doi.org/10.1016/j.semarthrit.2011.05.003Get rights and content

Objectives

To estimate the rate of demyelinating diseases in patients with rheumatic diseases treated with tumor necrosis factor (TNF) antagonists and to describe the cases reported to 3 different pharmacovigilance sources.

Methods

All confirmed cases of demyelinating disease, optic neuritis, and multiple sclerosis (MS) in patients with rheumatic diseases treated with TNF-antagonists were reviewed from 3 different sources: (1) the Spanish Registry of biological therapies in rheumatic diseases (BIOBADASER); (2) the Spanish Pharmacovigilance Database of Adverse Drug Reactions (FEDRA); and (3) a systematic review (PubMed, EMBASE, and the Cochrane Library). In BIOBADASER, the incidence rate per 1000 patients was estimated with a 95% confidence interval (95% CI).

Results

In 21,425 patient-years in BIOBADASER, there were 9 patients with confirmed demyelinating disease, 4 with optic neuritis, and 1 with MS. In addition, 22 patients presented polyneuropathies, paresthesias, dysesthesias, facial palsy, or vocal cord paralysis without confirmed demyelination. The incidence rate of demyelinating disease in patients with rheumatic diseases exposed to TNF-antagonists in BIOBADASER was 0.65 per 1000 patient-years (95% CI: 0.39-1.1). The incidence of MS in BIOBADASER was 0.05 (95% CI: 0.01-0.33), while the incidence in the general Spanish population was 0.02 to 0.04 cases per 1000. Compared with BIOBADASER, cases in FEDRA (n = 19) and in the literature (n = 48) tend to be younger, have shorter exposure to TNF-antagonists, and recover after discontinuation of the drug.

Conclusions

It is not clear whether TNF antagonists increase the incidence of demyelinating diseases in patients with rheumatic diseases. Differences between cases depending on the pharmacovigilance source could be explained by selective reporting bias outside registries.

Section snippets

Methods

The information presented herein was obtained from the following sources: (1) the Spanish Registry of adverse events of biological therapies in rheumatic diseases (BIOBADASER); (2) the Spanish Pharmacovigilance Database of Adverse Drug Reactions (FEDRA); and (3) a systematic literature review on demyelinating diseases reported as an adverse event of TNF antagonists.

Cases of Demyelinating Diseases in the BIOBADASER Registry

Up to 1 September 2008, BIOBADASER contained information on 9256 patients receiving anti-TNF therapies, with a total exposure of 21,425 patient-years. Exposure of patients with rheumatoid arthritis (RA) was 13,075 patient-years, with ankylosing spondylitis (AS) 2870 patient-years, and with psoriatic arthritis (PsA) 2873 patient-years. Nine patients had a confirmed demyelinating disease—of which 1 was a case of Guillain Barre's syndrome and the other were unspecified lesions—4 had optic

Discussion

We have investigated the characteristics and incidence of demyelinating cases in patients with rheumatic diseases treated with TNF antagonists. Notably, the information obtained depended on the source: literature review, spontaneous pharmacovigilance system, or a biologics registry, reflecting the different nature of the safety system and ratifying the more pragmatic view of the registries. As an example, MS represents nearly half of the cases reported to FEDRA, but only 7% of the BIOBADASER

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    This work was partially supported by the RETICS Program, RD08/0075 (RIER), Instituto de Salud Carlos III (ISCIII). BIOBADASER is supported by the Sociedad Española de Reumatología and the Spanish Agency of Medicines and Health care Products. Grants in approximately equal amounts (all under 25,000€/year) from Roche, Abbott, BMS, Schering, and Wyeth contribute to the support of the registry.

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