Objective. To determine the pattern of demyelinating disorders (DDs)
occurring during anti-TNF-α 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-α.
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-α 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-α. 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-α was discontinued in 10 patients and 8
received i.v. immunoglobulins. Two patients relapsed after introduction
of another anti-TNF-α. Overall, a causal relationship between anti-TNF-α
and DD was considered as probable in 31 patients and definite in 2 who
had positive rechallenge.
Conclusion. Causal relationship between
anti-TNF-α 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-α
could trigger the demyelinating process, which further evolves
independently.
People treated
with Lemtrada can develop autoimmune thyroid disease, it appears that
people with arthritis treated with anti-tumour necrosis
factor develop demyelinating disease and multiple sclerosis. This is
further evidence that overall blockade of TNF is not a good idea in MS.
Most experimental data may suggest that TNF blockade could be good,
however I think this shows that TNF does lots of different things some could be good and others bad and balance is that its removal at least from the peripheral compartment is bad news.
This can tell us something about biology. Following Lemtrda
administration there is a cytokine storm, quelled by steroids, that
reactive old demylinated lesions