Expanded knowledge opens doors to improved psoriasis treatments

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Mark Lebwohl, MD: ‘If we’re going to subject patients to the risks of liver biopsies, we should limit biopsies to those patients who are at most risk from methotrexate.’

The development of psoriasis treatments, from understanding its pathophysiology, to comorbidities, to the development of a variety of medications was covered March 21 in “Translating Evidence into Practice: Psoriasis Guidelines.”

‘Psoriasis: From the Bench to the Bedside’

Craig A. Elmets, MD, department of dermatology, University of Alabama at Birmingham, traced research into the causes of psoriasis in his presentation. “Psoriasis is one of the great success stories in translating basic research observations into new and improved therapeutics,” he said.

Dr. Elmets explained the pathogenesis of the disease, linking the activation of T-cells that contribute to dysregulated interplay between the epidermis and dermis, the cutaneous microvasculature, and the immune system. When activated, T-cells produce cytokines that affect the skin, bring in other inflammatory cells, and cause the release of other cytokines and biologically active molecules.

Genetics also are an important component of psoriasis, with 30 percent of psoriasis patients having a relative with the condition. At least nine chromosomal regions, PSOR1-PSOR9, are recognized as susceptibility lock, and PSOR1 has received the most attention, he said.

Genetic loci correspond well with evidence that immunologic hyperactivity is a feature of psoriasis, and this could help drive safer and more effective methods of therapy. When genetic profiles are developed, they could be used to tailor therapies and identify those at risk of developing psoriasis, Dr. Elmets said.

Current treatments include tumor necrosis factor (TNF) inhibitors such as secukinumab, ixekizumab, and alefacept, as well as efalizumab and brodalumab, which are in phase III trials.

‘Psoriasis Comorbidities and Prevention of Risk Factors’

Joel M. Gelfand, MD, MSCE, associate professor at Perleman School of Medicine, University of Pennsylvania, said that several comorbidities are associated with psoriasis, including heart attack, stroke, cardiovascular death, metabolic syndrome, diabetes, psoriatic arthritis, mood disorders, Crohn’s disease, and T-cell lymphoma.

Cardiovascular diseases are most common, and the risk is similar to that conferred by diabetes, he said. Patients treated with severe psoriasis are 30 times more likely to develop major adverse cardiac events (MACE) than melanoma.

Metabolic problems start early, according to emerging pediatric data. The prevalence of metabolic syndrome in pediatric patients with psoriasis is 30 percent, versus 7.4 percent in control groups in one study.

Another study reports that psoriasis is associated with increased vascular inflammation independent of traditional risk factors, and is equivalent to 10 years of aging, Dr. Gelfand said.

“Cardiovascular risk factors are under-screened and under-managed in psoriasis patients,” he said, and it has been suggested that psoriasis be aggressively treated to lower the risk of cardiovascular disease. Trials are underway to study the impact of anti-inflammatory treatment on cardiovascular risk.

In addition, other comorbidities emerging among patients with psoriasis include sleep apnea, nonalcoholic steatohepatitis (NASH), and chronic obstructive pulmonary disease (COPD).

‘New Developments in Psoriatic Arthritis’

Alice Gottlieb MD, PhD, chair and dermatologist in chief, and Harvey B Ansell professor of dermatology at Tufts University School of Medicine, said in her presentation that psoriatic arthritis could be associated with significantly higher rates of comorbid conditions than psoriasis. Those comorbidities include hyperlipidemia, hypertension, depression, diabetes, cardiovascular disease, obesity, and cancer.

Psoriatic arthritis is common and easy to diagnose, she said, adding that dermatologists can be the first to detect arthritis and can help prevent disability with early treatment.

After describing the pathogenesis of the disease, Dr. Gottlieb reviewed the use of therapies, including oral therapies, with a focus on apremilast, and TNF inhibitors, such as ustekinumab, secukinumab, and brodalumab.

Dr. Gottlieb concluded by saying that the current treatment algorithm for psoriasis is determined by whether psoriatic arthritis is present. Treatments for patients with psoriatric arthritis, when NSAID treatments have failed, include methotrexate (MTX), TNF blockers or a combination of the two.

‘Comorbidities in the Setting of Psoriasis Treatment Options That Make Sense’

Craig L. Leonardi, MD, clinical professor of dermatology at Saint Louis University, discussed the use of several treatments for psoriasis. He reviewed the use of drugs that are safe or not safe for patients with comorbidities, such diabetes, hypertension, skin cancer, alcoholism, dyslipidemia, cardiovascular disease, and psoriatic arthritis, as well as for pregnant patients.

Psoriasis is a significant cardiovascular risk factor, he said, adding that methotrexate reduces the incidence of vascular diseases in patients with psoriasis. In addition, TNF blockers are associated with a lower incidence of first cardiovascular events in patients with rheumatoid arthritis.

Dr. Leonard recommended that when using TNF blockers, physicians should look at all options in this class of medications and start patients on the lowest possible doses regardless of patient weight. He also reviewed the safety of several TNF blockers, many of which are still being tested, and recommended that physicians continue to monitor data from these studies.

Psoriasis treatment is not stepwise and the choice of therapy depends on individual patient characteristics, he said.

‘Guidelines: Systemic Therapies’

Mark Lebwohl, MD, Sol and Clara Kest professor and chairman of the department of dermatology at Mount Sinai School of Medicine, discussed the treatment of psoriasis using traditional systemic treatment. He focused on links between the use of methotrexate for treating psoriasis and the risks of liver fibrosis, and the dangers of liver biopsies.

“If we’re going to subject patients to the risks of liver biopsies, we should limit biopsies to those patients who are at most risk from methotrexate,” he said.

Psoriasis patients with type 2 diabetes, obesity, or alcohol abuse are at high risk of developing liver fibrosis during methotrexate treatment, Dr. Lebwohl said, and he emphasized a 2009 National Psoriasis Foundation consensus statement: “In patients without risk factors for hepatic fibrosis, liver biopsies may not be indicated or the frequency markedly reduced.”

Dr. Lebwohl reviewed strategies for monitoring patients at risk for developing liver fibrosis. For patients at low risk, a better course is to monitor liver function tests monthly for the first six months of treatment, and every one to two months thereafter. Options for methotrexate treatments in patients with psoriasis and rheumatoid arthritis include amlodipine and cyclosporine, and those patients also should be closely monitored.

‘Improving Physician Communication and Patients’ Adherence’

Steven R. Feldman, MD, PhD, professor of dermatology, pathology & public health sciences, and director of the Psoriasis Treatment Center at Wake Forest University School of Medicine, discussed difficulties getting patients to use medications.

“Treatments only work if patients use them,” Dr. Feldman said. “There are three reasons for poor treatment outcomes — poor compliance, poor compliance, and poor compliance. A lot of patients don’t even fill their prescriptions.”

Keys in improving patient adherence include building physician trust with patients, involving patients in treatment planning so using medications is easier, avoid scaring patients with an emphasis on side effects, scheduling return visits, and giving clearly written instructions, he said.

Dr. Feldman also discussed challenges in treating scalp psoriasis, recommending a regimen that begins with clearing followed by maintenance When tachyphylaxis does occur, get patients to use topical clobetasol.

‘Phototherapy for Psoriasis with Case Study’

Henry W. Lim, MD, chairman and C.S. Livingood chair of the department of dermatology at Henry Ford Hospital discussed phototherapy for patients with psoriasis, focusing on narrowband UVB, targeted phototherapy, and PUVA.

In patients with psoriasis, PUVA is better than narrowband UVB, which is better than broadband UVB, he said. The protocol for narrowband UVB is to begin with a dose of 70 percent of the minimal erythema dose (MED) three times a week, and increase treatments by 10-15 percent in the first 40 treatments. Noticeable improvements should occur in 20-30 treatments, he said.

When using targeted phototherapy, the patient should have treatments twice a week for 10 treatments, and there should be noticeable improvement in six to 10 treatments. Treatments should be discontinued after 15-20 treatments.

For PUVA, patient selection is important and should be avoided for pediatric patients, pregnant women, nursing mothers, or those with a history of melanoma, lupus or xeroderma. The maximum dose is 70 mg two or three times a week, and noticeable improvement should be seen in 20-30 treatments.

‘Biosimilars in Our Psoriasis Therapeutic Armamentarium: The Future’

Alan Menter, MD, chief of dermatology at the Psoriasis Research Institute at Baylor University Medical Center, said biosimilars are important because they are less expensive than biologics. He discussed the biosimilar manufacturing process, differences between biosimilars and generics, and the availability of biosimilars in the near future.

Biosimilars are approved biologics with comparable quality, safety, and efficacy to a reference product, and they are recognized around the world as safe and effective, Dr. Menter said. Biosimilars are manufactured at the same standards as biologics and they must match the molecule profile with the originator.

“In the end, the biosimilar must closely match the original product at all levels,” he said.

However, biosimilar development needs more time and a greater budget, and is far more complex than standard generics development, Dr. Menter said. Infliximab biosimilars were approved in Europe in 2013, and inflectra, an infliximab biosimliar, was approved in Canada in 2014. Seven biosimilar agents are under development for adalimumab, whose patent expires at the start of 2017.

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