Tumor Necrosis Factor-α Inhibitor Use in Psoriasis Patients With a First-degree Relative With Multiple Sclerosis
August 2015 | Volume 14 | Issue 8 | Original Article | 876 | Copyright © August 2015
Bobbak Mansouri MD, Mary E. Horner MD, Alan Menter MD
Department of Dermatology, Baylor University Medical Center, Dallas, TX
Tumor necrosis factor (TNF)-α inhibitors are currently the gold standard for treating moderate to severe plaque psoriasis and other immune-mediated diseases. The presence of previously existing demyelinating disease is amongst the contraindications to their use. However, controversy surrounds the use of TNF-α inhibitors in patients who are more predisposed to developing multiple sclerosis (MS), specifically first-degree relatives of MS patients. In fact, the major guidelines committees’ recommendations on this issue by the American Academy of Dermatology, the British Association of Dermatologists, and the European S3-Guidelines are not consistent. The data we present suggest that the number needed to treat is at least an order of magnitude smaller than the number needed to harm across all comparisons of anti-TNF-α agents and first-degree relative relationships. Based on these data, physicians could weigh the treatment options available and work closely with neurological colleagues when prescribing anti-TNF-α therapy in this patient population rather than practicing absolute prohibition of anti-TNF-α agents in patients who have a first-degree relative with MS. J Drugs Dermatol.
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-