Background Tumor Necrosis Factor alpha (TNF) plays a major role in the pathogenesis of multiple sclerosis (MS). However, attempts to use TNF Inhibitor (TNF-I) for the treatment of MS have been unsuccessful and even led to increased MS-attack frequency. Several case-reports and small patient-series have implicated TNF-I treatment with occurrence of both central and peripheral demyelinating conditions1. All patients in Denmark with inflammatory arthritis requiring treatment with TNF-I are registered in the national database DANBIO with continuous recordings of clinical, serological and radiographic data. Likewise, all patients with an established diagnosis of MS are included in the Danish Multiple Sclerosis Registry (DMSR) with a coverage exceeding 95% of all eligible cases.
Objectives To investigate whether TNF-I treatment in arthritis patients is associated with an increased risk of MS based on prospectively registered observational data from the DANBIO registry and DMSR.
Methods By linking data from DANBIO and DMSR we identified all individuals with new onset MS in a cohort of 30 490 patients (62.5% rheumatoid arthritis, 8.9% ankylosing spondylitis, 14.1% psoriatric arthritis, 14.6% other arthritides). Among these, 10 296 started TNF-I therapy during follow-up from January 2000 to the end of 2012. Patients registered with MS before entry were excluded from the analyses. Standardized Incidence Ratios (SIR) of MS among ever TNF-I users and TNF-I naïve were estimated using standardized incidence rates of MS from the general populations and person-years at risk.
Results During 113 506 person-years of follow-up there were 7 incident cases of MS, yielding an overall SIR of 1.27 (95% CI 0.51-2.62). There was no difference between SIR of MS observed in patients ever starting TNF-I therapy (SIR=1.30, 95% CI 0.35-3.32) or TNF-I naïve patients (SIR=1.24, 95% CI 0.26-3.63).
Conclusions We were unable to demonstrate an increased risk of MS in arthritis patients treated with TNF-I. However, this does not necessarily exclude that inhibition of TNF could lead to demyelinating conditions in susceptible patients. Based on several published cases of demyelinating adverse events occurring after TNF-I treatment the disease manifestations may deviate from the common pattern of recurrent episodes found in classical MS and thus escape inclusion into DMSR.
Theibich A, Dreyer L, Magyari M, Locht H. Demyelinizing neurological disease after treatment with tumor necrosis factor alpha-inhibiting agents in a rheumatological outpatient clinic: description of six cases. Clin Rheumatol. 2014 May;33(5):719-23. doi: 10.1007/s10067-013-2419-8. Epub 2013 Nov 8.
Acknowledgements Thanks to all the departments of rheumatology in Denmark for reporting to the DANBIO registry.
Disclosure of Interest None declared