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reported as 3.2 per 100,000 persons per year [ 79 ]. Given its high efficacy in treat-
ment of rheumatoid arthritis (RA) and the similarities in pathophysiology between
RA and MS, anti-TNF therapy was once studied for use in the treatment of MS. In
the first open-label phase I trial, infliximab was used to treat two patients with rap-
idly progressive MS [ 80 ]. Both of these patients had an increase in the number of
lesions on brain magnetic resonance imaging (MRI), as well as a rise in leukocytes
in CSF and IgG titers [ 80 ].
There have been a number of reported cases of brain lesions detected on MRI in
patients treated with an anti-TNF therapy [ 81 – 84 ]. The anti-TNF therapies associ-
ated with these reported cases include etanercept, infliximab, and adalimumab [ 81 –
84 ]. Among the 19 patients with RA registered in the FDA Adverse Reporting
System who developed neurological problems associated with demyelinating
lesions of the CNS, 17 of these patients were treated with etanercept and 2 with
infliximab [ 82 ]. The patients’ age ranged from 21 to 56 years, and the average time
of onset of neurological symptoms was 5 months after initiating anti-TNF therapy
[ 82 ].
Patients who develop neurological symptoms after anti-TNF therapy can have
a wide range of symptoms. There have been reports of new-onset MS, worsening
of baseline demyelinating disease, encephalopathy with residual deficit and/or evi-
dence of demyelination on biopsy, optic neuritis, peripheral neuropathies, and
Lhermitte’s sign, which is characterized by an electrical sensation that runs down
the back into the limbs [ 85 ]. In addition, headache, tinnitus, dysarthria, and dys-
phagia have been reported [ 86 ]. The majority of reported cases have partial or
complete resolution of symptoms after discontinuation of anti-TNF therapy
[ 81 – 84 ].
Risk Factors
Although anti-TNF therapy has been associated with demyelinating disease, patients
with one autoimmune disease are thought to be more susceptible to developing
another autoimmune condition including demyelinating diseases [ 87 ]. In a retro-
spective cohort and cross-sectional study consisting of 7988 CD and 12,185 UC
patients matched with 80,666 controls in the era before anti-TNF therapies, demy-
elinating diseases were observed more commonly among patients with IBD than
those without [ 87 ]. Compared to controls, patients with UC had an incidence rate
ratio (IRR) of 2.63 (95% CI 1.29–5.15), and patients with CD had an IRR of 2.12
(95% CI 0.94–4.5) [ 87 ].
While a number of cases of demyelinating diseases have been reported after anti-
TNF therapy [ 78 , 81 – 84 ], it remains unclear whether the relationship between anti-
TNF therapy and demyelinating disease is coincidental or causal. Patients with
demyelinating neurological diseases at baseline are discouraged from using anti-
TNF therapy due to concern for exacerbation of existing disease. However, it is not
U. Wong and R.K. Cross