Pattern of demyelination occurring during anti-TNF-α therapy: a French national survey

Objective. To determine the pattern of demyelinating disorders (DDs) occurring during anti-TNF-alpha therapy. Methods. Between June 2005 and April 2008, 1800 French rheumatologists and internists were contacted to report cases of DDs occurring in patients treated with anti-TNF-alpha. Results. After a median of 10.2 (1.5-39.9) months of treatment, 33 patients developed DDs: 22 had CNS and 11 peripheral nervous system (PNS) involvement. Underlying diseases were RA (n = 16), AS (n = 11), PsA (n = 4), JIA (n = 1) and PM (n = 1). Anti-TNF-alpha was infliximab (n = 15), etanercept (n = 12) or adalimumab (n = 6). CNS involvement was encephalic lesions (n = 16), transverse myelitis (n = 8) or retrobulbar optic neuritis (n = 5). Cerebrospinal fluid (CSF) analysis in 16 patients and MRI in 20 patients were abnormal. All patients discontinued anti-TNF-alpha. Fifteen patients required steroids. Twenty patients initially improved. Five patients developed multiple sclerosis. PNS involvement was chronic (n = 9) or acute inflammatory demyelinating polyneuropathy (n = 2). CSF analysis revealed an increased protein level in nine patients. Nerve conduction studies confirmed DD in all these patients. Anti-TNF-alpha was discontinued in 10 patients and 8 received i.v. immunoglobulins. Two patients relapsed after introduction of another anti-TNF-alpha. Overall, a causal relationship between anti-TNF-alpha and DD was considered as probable in 31 patients and definite in 2 who had positive rechallenge. Conclusion. Causal relationship between anti-TNF-alpha and induction of DD remains unclear, but in some cases the chronology of clinical events is suggestive. Nevertheless, DD might persist despite treatment discontinuation, suggesting that anti-TNF-alpha could trigger the demyelinating process, which further evolves independently.