Neurologic changes that stem from biologic therapy

March 20, 2018

Physicians should be aware of the warning signs that a biologic agent could be to blame when patients experience subacute or rapidly progressive neurologic changes, researchers say.

Biologic therapy-associated neurologic complications are rare but are an important consideration for dermatologists prescribing biologics to treat moderate-to-severe plaque psoriasis, according to a review published in January in the journal Cutis.

Physicians should be aware of the warning signs that a biologic agent could be to blame when patients experience subacute or rapidly progressive neurologic changes, the authors wrote.

Biologic medications have greatly improved psoriasis patients’ quality of life and disease control, but neurologic side effects associated with biologic agents have long been a concern. Concerns stem from some case reports linking TNF-alpha inhibitors with demyelinating diseases, and many recall when the biologic efalizumab was taken off the market in 2009 for causing fatal progressive multifocal leukoencephalopathy.

UNDERSTANDING THE POTENTIAL OF NEUROLOGICAL DEFICITS

The history taking can offer clues about whether some biologics might be better than others for patients at risk of neurologic complications.

“If a patient has a history of any demyelinating disorder, then all TNF inhibitors should be avoided,” says review author Jashin J. Wu, M.D., director of dermatology research at Kaiser Permanente Los Angeles Medical Center. “It's not fully known why, but it seems there may be less risk when using other classes of biologics, so these should be selected instead.”

Among the demyelinating disorders seen with biologic use:  Optic neuritis, which is an inflammatory demyelinating of the optic nerve, has been observed in patients on etanercept, infliximab and adalimumab. Dermatologists and others may see early symptoms including periocular pain and unilateral loss of visual acuity.

Multiple sclerosis also has been seen with use of etanercept, adalimumab and infliximab. Etanercept has been associated, although the incidence is unknown, with transverse myelitis. Efalizumab, adalimumab, infliximab and etanercept have been linked to Guillain-Barre syndrome.

The authors recommend patients on biologic therapies - especially those on TNF-alpha inhibitors - be monitored for signs of demyelinating disorders, including new onset visual, motor or sensory changes, such as ataxia, paresthesias, muscle weakness, impaired vision, hearing and speech problems.

There are few case reports in which use of a TNF-alpha inhibitor is associated with progressive multifocal leukoencephalopathy, but most of those are in the presence of immune suppression, autoimmune disease and other confounding factors. Known cases of biologic-associated leukoencephalopathy are limited to rituximab and the no-longer-available efalizumab.

Though rare, it’s important for dermatologists to note that the type of leukoencephalopathy presents often with subacute, rapidly progressive, focal or multifocal motor, cognitive or visual deficits.

Ustekinumab is rarely associated - two cases ever reported - with reversible posterior leukoencephalopathy syndrome, which can be reversed by controlling blood pressure and stopping use of the biologic agent. Reversible posterior leukoencephalopathy syndrome presents with headache, altered mental status, vision problems and seizures.

There is no data yet to suggest the new biologic, secukinumab, is associated with any neurologic side effects, according to the review. 

PUTTING THE INFORMATION TO PRACTICE

While review authors recommend that dermatologists educate psoriasis patients about neurologic and other risks of using biologic agents, Dr. Wu says he often elects not to address neurologic side effects, unless patients ask.

“I actually do not review any neurologic risks before starting any biologic. There are no boxed warnings, and the risks are so low that it's not worth scaring patients about,” he says.

Dr. Wu says while it’s important for dermatologists to be aware of the possibility of neurologic problems with biologic use, it’s not a concern that should prohibit prescribing in most cases.

Much remains unknown about the long-term neurologic effects of biologic therapy for plaque psoriasis, Dr. Wu says.

“Long-term registries will help further our understanding if there are any long-term neurologic risks,” he says.

 

DISCLOSURES

Dr. Wu is an investigator for AbbVie Inc; Amgen Inc; Eli Lilly and Company; Janssen Biotech, Inc; Novartis; and Regeneron Pharmaceuticals, Inc.

REFERENCE

Lin EJ, Reddy S, Shah VV, Wu JJ. “A review of neurologic complications of biologic therapy in plaque psoriasis,” Cutis. 2018 Jan;101(1):57-60.

 

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