Genes predict the best biologics for psoriasis

Personalised medicine will mean more effective treatment and better quality of life, says an Australian expert.

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Researchers have pinpointed genetic markers that predict the effectiveness of biologic treatments for psoriasis, potentially enabling patients to have faster access to the best medication for their disease.

The research has been welcomed by leading Australian dermatologist and researcher, Professor Dedee Murrell, who said personalised medicine would make a huge difference to patients’ quality of life.

“They get to clear skin faster, and it wouldn’t waste government money giving them medications that were, for them, not so effective,” said the head of St George Hospital’s Department of Dermatology and professor of dermatology at UNSW.

“In the long run these kinds of tests will probably save money and achieve happier patients quicker,” she told The Medical Republic.

“This is a way to optimise the response of the patient, and they might even predict who’s going to have an adverse reaction to these drugs.

“This is exactly what we need, so that we can guide the best treatment for the patient. Typically, most of the new biologics do work for most patients, but they might not completely clear the patient.”

The Spanish researchers, whose work was published in Experimental Dermatology, identified several genetic polymorphisms as predictive markers of psoriasis treatment efficacy in both the short and long term.

They found patients showed diverse responses to biological treatments due to genetic differences.

“As a result, there is a need for novel pharmacogenetic markers associated with treatment efficacy to facilitate personalised medicine,” they wrote.

“Although these findings need validation in a larger cohort of patients, their application in clinical settings could enhance treatment optimisation, achieve higher response rates, reduce side effects and costs and ultimately improve the quality of life for patients.”

The researchers took salivary samples from patients and analysed a set of 21 single nucleotide polymorphisms related to psoriasis and other immunological diseases.

They then assessed treatment effectiveness and patient improvement through the Relative Psoriasis Area and Severity Index (PASI). The associations between single nucleotide polymorphisms and PASI factors were assessed at three and 12 months for IL-17, IL-23, IL-12&23 and TNF-α inhibitors.

The researchers said they found significant statistical associations between several single nucleotide polymorphisms and PASI<1 and PASI90 values at three and 12 months after the onset of treatment.

“Among them, those related to TLR2, TLR5, IL12B, TNFAIP3, SLC12A8, HLA-C, TIRAP and PGLYRP4 genes were the most significant in the maintenance of long-lasting clinical responses in psoriatic patients treated with biological agents.”

The researchers noted that the study was observational and added that additional studies were necessary in more extensive patient cohorts and a higher number of patients.

Professor Murrell said most patients would improve between 75% and 90% when taking biologics. But she said more patients wanted complete skin clearance and weren’t satisfied with 75% clearance.

Patients could cycle through different drugs for several years hoping to find one that completely cleared their psoriasis, she said.

“Meanwhile, according to the government criteria, the patient should be fine because they’ve improved by 75%,” she said.

“But if the 75% is in the covered areas … and the visible parts that they’re embarrassed about are still affected, even if they’re small areas, then to the patient they’re not happy.

“And we’re not happy as doctors because we want them to be clear where they’re embarrassed about their problem.”

Professor Murrell said the genetic tests used in the research were not readily available in Australia or were expensive.

“If they were available, we could tailor the treatment for patients from the beginning,” she said.

Professor Murrell said psoriasis affected patients’ mental health, employment and relationships.

“Some people don’t go to work when they’re absolutely looking terrible with psoriasis, or people won’t give them a job because they think it’s contagious,” she said.

“If it’s all over their face and scalp, they can’t go out in public, or they can’t walk because their feet are covered in sores and painful. Some patients suicide because of psoriasis, or they become profoundly depressed, or they can’t have a relationship.”

Professor Murrell said genetic testing had previously been used to determine which people of Han Chinese background had severe adverse reactions to anti-convulsant medications.

“The test used to cost $200 in Australia, so neurologists weren’t ordering it because patients didn’t want to pay for it,” she said.

“Then it was like a lotto. You’d see people coming into hospital, especially Chinese patients, with horrendous skin reactions that can affect your eyes. So now the test is available for patients going on to these anticonvulsants.”

Experimental Dermatology 2024, online 4 January