A review of adverse events in plaque psoriasis

Dr. Fernandez

As the list of treatments for plaque psoriasis grows, so does the list of adverse events associated with biologic treatment. In this article, we summarize adverse events associated with common treatments for plaque psoriasis.

Determining the best course of care for patients starts with the first patient appointment, says Anthony P. Fernandez, M.D., Ph.D., director of medical dermatology at Cleveland Clinic in Ohio. “Nothing’s perfect. Every therapy has potential side effects. We want to take a good medical history to learn of other therapies our patients are taking and to learn of any comorbidities they may have. It is often more important to determine what patients should not take as opposed to trying to pick the ideal treatment option,” he said.  

Dr. Fernandez recently reviewed adverse events associated with treatments for plaque psoriasis during a Medical Dermatology Therapy Update educational session.

TRADITIONAL TREATMENTS
In psoriatic disease, traditional therapies include tumor necrosis factors (TNF), interleukin (IL) inhibitors and small molecule inhibitors. Some treatments are associated with long-term adverse effects. For example, the long-term use of first-line therapy methotrexate is associated with liver damage. 

IN THIS ARTICLE:

CONDITION:

DRUGS:

ADVERSE EVENTS:

“It had been recommended that after three to four grams of methotrexate cumulatively, patients should get a liver biopsy, which in and of itself is a procedure that is associated with risk. We’ve gone away from biopsies with other liver toxicity screening options, but it is still on our minds that keeping a patient on a medication like methotrexate chronically can be harmful,” he said.

Renal insufficiency is the big concern with long-term cyclosporin use in psoriasis patients. “So, it has generally been recommended that we use cyclosporin for no more than about a year for patients with psoriasis,” Dr. Fernandez says.

Providers also have to consider the more acute adverse effects that can result from methotrexate and cyclosporin use. The standard of care when using them to treat psoriasis is to do serologic tests, including complete blood counts and metabolic panels, every month initially and then every several months for patients who are on stable doses of the medicines.

“Acitretin is another traditional psoriasis treatment that requires us to routinely check labs. In particular, we check lipid panels to monitor for cholesterol and triglyceride abnormalities, and metabolic panels to monitor for signs of liver inflammation,” Dr. Fernandez said.

The advent of biologics and small molecule inhibitors have revolutionized moderate-to-severe psoriasis treatment, but adverse events associated with these treatments can manifest early in patients.

TNF INHIBITORS
Treatment should begin with a check for evidence of latent tuberculosis. In early clinical trials for tumor necrosis factor (TNF) inhibitors, the start of TNF treatment reactivated latent tuberculosis in some patients. TNF inhibitors have also been linked with precipitating or worsening congestive heart failure and they are contraindicated in patients with demyelinating medical conditions, such as multiple sclerosis, or a family history of one. TNF inhibitors have also been associated with the development of psoriasis-like rashes, which can make treatment problematic.

Biologics in general are associated with the development of infections, such as upper respiratory or gastroenteritis infections. IL-17 inhibitors appear to be uniquely associated with an increased risk of developing mycocutaneous candidiasis infections, including oral thrush or even esophageal candidiasis. IL-17 inhibitors can sometimes trigger flares for patients with inflammatory bowel disease, such as Crohns disease or ulcerative colitis.

IL-23 INHIBITORS
IL-23 inhibitors, including guselkumab and investigational risankizumab and tildrakizumab, have been associated with nasopharyngitis, upper respiratory infections, gastroenteritis and a rare incidence of malignancy or major cardiovascular events.

SMALL MOLECULE INHIBITORS
The oral small molecule apremilast is associated with gastrointestinal events, such as nausea and diarrhea, and upper respiratory tract infections which tend to resolve in the first couple of months of treatment.

LONG-TERM DATA

The Psoriasis Longitudinal Assessment and Registry (PSOLAR), as well as the ESPRIT, the Abbvie-sponsored 10-year registry of patients taking adalimumab (Humira, Abbvie).

“There have been studies published using data in those databases looking at a number of different safety parameters for biologic agents. There has been a very mild increased risk of serious infections with the biologics,” he said.

“The nice thing about these registries is that many patients tend to be enrolled and we are looking at real-world data,” he says.

DISCLOSURES
Dr. Fernandez is an advisor for Abbvie and does speaking and teaching for Abbvie and Celgene.

REFERENCE:
Medical Dermatology Therapy Update, Cleveland Clinic, Cleveland, Ohio. April 25-27, 2018.