INTRODUCTION
Tumor necrosis factor (TNF)-α inhibitors are the mainstay
in treating multiple immune-mediated diseases. In 2008, the American Academy of Dermatology (AAD) working group recommended TNF-α inhibitor avoidance in patients
with multiple sclerosis (MS)1 due to the well-established increase in MS exacerbations in patients on anti-TNF-α therapy2 – a recommendation echoed by the European S33 and British Association of Dermatologists’ (BAD) guidelines.4 However, the AAD guidelines further recommend this avoidance in patients with a first-degree relative with MS.1 While neither the BAD nor the European S3 guidelines committees specifically make this restrictive recommendation, the BAD guidelines do reference the AAD’s recommendation. Further discussion and insight regarding the avoidance of all anti-TNF-α therapies in patients with first-degree relatives with MS, we believe, is warranted.
Multiple sclerosis is an autoimmune demyelinating disease also linked to elevated levels of TNF-α5 and was therefore targeted in early anti-TNF-α studies. In a phase II study of the anti-TNF-α agent lenercept, MS patients experienced an increase in attack frequency (P= 0.007) and exacerbations occurred earlier (P = 0.006) in the lenercept group versus the placebo group.2 As such, all current anti-TNF-α safety labels as well as all guidelines committee recommendations correctly urge TNF-α inhibitor avoidance in patients with MS or other demyelinating diseases.
1,3,4
There is a strong genetic component to MS in addition to environmental
influences.1,6,7 While it is unclear if developing
symptoms of demyelinating diseases secondary to anti-TNF-α therapy occur as a result of a genetic predisposition or not, it is likely that genetic variants do predispose these patients to having such reactions. Additionally, though these various guidelines do aim to protect patients with MS and their first-degree relatives from developing demyelinating disease if placed on anti-TNF-α therapy, there continues to be reports in the literature of patients on anti-TNF-α therapy experiencing demyelinating events.8 Fortunately, between 37% and 97% of these patients either partially or fully recover following discontinuation
of therapy, and as such, likely do not represent patients with true demyelinating disease but rather reversible, demyelinating adverse reactions to therapy. It has even been reported that some patients’ symptoms abate without discontinuation
of therapy altogether.9 Therefore, recommending outright avoidance of TNF-α inhibitors in patients who may not develop MS, but whose psoriasis requires TNF-α inhibitors, is worthy of consideration.
No studies to date have examined the risks and benefits of TNF-α inhibitors in first-degree relatives of persons with MS. However, by utilizing the calculated lifetime risk (LR), relative risk (RR), and incidence of MS in the general population and in first-degree relatives of MS patients, one can extrapolate the attributable risk and subsequently the number needed to harm (NNH) in first-degree relatives of MS patients who have psoriasis.
According to calculated data from 18 family and twin studies,6 the age-adjusted LR of developing MS in the general popula-
