Psoriasis treatment has significantly improved since the mid-2000s with the arrival of biologic drugs.

Therapies, including TNF-α inhibitors and interleukin inhibitors, have advanced enough to target not only PASI 75 but PASI 90 and PASI 100 in psoriasis treatment.

As physicians can prescribe biological medicines with various mechanisms of action, they can choose the optimal drug to treat severe psoriasis, considering the drug’s effectiveness, safety, and convenience.

AbbVie’s Skyrizi (risankizumab) is the most recently developed interleukin-23 (IL-23) inhibitor. The drug can be taken only four times a year, and its high rate of PASI 100 achievement and long-acting effect have drawn much attention.

In Korea, Skyrizi was released with health insurance benefits in June 2020.

Korea Biomedical Review had a virtual interview with Melinda Jennifer Gooderham, a professor at Queens University in Canada. She participated in major clinical trials of Skyrizi with abundant experience in severe psoriasis treatment.

She shared the latest knowledge of psoriasis treatment and explained how clinical care has changed since the arrival of Skyrizi.

Question: The emergence of various biologic drugs has greatly improved the treatment goal in severe psoriasis. How high is the purpose of severe psoriasis treatment now?

Answer: When biologic drugs first came out, people used to set PASI 50, an improvement of half of the symptoms, as the criteria to measure effectiveness. At the time, no treatment achieved PASI 50. So, patients were very pleased with PASI 50 achievement alone. Later, TNF-α inhibitors raised the treatment goal to PASI 75. Recently, more effective new biologic agents such as IL-17 inhibitor and IL-23 inhibitor came out, pushing the goal to PASI 90 and even PASI 100 where the skin becomes completely clean.

Q: Korea has yet to offer guidelines for the use of biological drugs in severe psoriasis. Can you explain Canadian or international guidelines?

A: Canada provides guidelines for psoriasis treatment. Although they are an old version, they aim for the same goal as the international guidelines. It set “achieving nearly clear or completely clear skin (PASO 90 or PASI 100)” as the treatment goal. Also, there are specific guidelines according to the patient’s situation. For example, they explain what criteria should be used for toxin treatment and treat patients with a history of inflammatory bowel disease. In addition, Canada is trying to provide temporary guidelines for areas where information is insufficient because it was not addressed in clinical trials.

Q: Researchers have developed various interleukin inhibitors, such as an IL-12/23 inhibitor, an IL-17 inhibitor, and an IL-23 inhibitor, as they found the pathological mechanism of psoriasis. What are your criteria for prescribing these drugs to treat severe psoriasis?

A: I prescribe an IL-23 inhibitor first unless there is a specific reason not to. It is effective and convenient to use. However, if the patient has a significant disease burden for psoriatic arthritis and the rheumatologist recommends using other drugs, I sometimes recommend an IL-17 inhibitor.

When there is specific comorbidity, some drugs are suitable, and others should be avoided. For example, suppose the patient has an inflammatory bowel disease such as ulcerative colitis or Crohn’s disease. In that case, you should consider a TNF-α inhibitor or an IL-23 inhibitor first and avoid an IL-17 inhibitor.

For patients with psoriasis and hidradenitis suppurativa, you may choose a TNF-α inhibitor such as adalimumab, which is indicated for both diseases. The patient’s comorbidity is also an important factor in selecting a drug.

I also consider the patient’s lifestyle. For example, many of the patients I care for are long-distance truck drivers. As they drive to and from both ends of the continent for a long time, some of them cannot return home for months. In these cases, it is desirable to prescribe a drug with a long interval. However, no matter how effective a drug is, if it does not fit the patient’s lifestyle and is not administered right, we cannot see the expected effect. So, you have to consider the patient’s lifestyle, as well as the drug’s efficacy.

Q: You participated in major clinical trials of Skyrizi. Can you evaluate Skyrizi based on your research or prescribing experience?

A: I participated in the IMMvent study, which compared Skyrizi with adalimumab, and the IMMhance study that evaluated the re-treatment effect in patients who discontinued Skyrizi. I also participated in the phase 2 trial of Skyrizi, a study in patients with psoriatic arthritis, and the LIMMitless research, an extension clinical trial. As the extension study includes my 39 patients, I have been doing a long-term follow-up. I have been treating some patients for over six years as they were enrolled from the phase 2 study through the extension study. I’ve been prescribing Skyrizi for a long time, but no patient discontinued the drug use or was excluded from the study due to safety issues.

Skyrizi completely changed the lives of the majority of trial participants. Most of the patients are fairly satisfied with the Skyrizi treatment outcome. A patient left the study for a while to have a child and resumed treatment after giving birth.

Based on my experience of Skytizi treatment and patients’ evaluations, the treatment outcome is quite encouraging. Therefore, unless you have to use another drug for a specific reason, Skyrizi is suitable for almost all psoriasis patients.

Q: Korea applies special exempted health insurance calculations to severe psoriasis treatment, reducing the patient’s burden by allowing them to pay only 10 percent of the medical cost. However, the calculations have a condition that the patient has to receive phototherapy. So, many criticize this system for failing to reflect reality. How is the situation in Canada?

A: Canada has a health insurance system similar to Korea's, although it differs from province to province. Phototherapy is set as the reimbursement criteria in Canada, like Korea. The problem is that there are too few hospitals that provide phototherapy. From the perspective of hospitals, phototherapy requires installing equipment and hiring nurses while the reimbursement rate is low. In other words, access to phototherapy is considerably low.

Some patients try phototherapy, but most do not prefer it. For example, one of my patients spent four hours of a round trip to receive two-minute phototherapy. This treatment should be done three times a week. So, unless the patient is a retiree or jobless, it is extremely difficult to maintain phototherapy. I heard that phototherapy criteria are exempted for such an unavoidable case.

Q: Recently, the concept of “cumulative life course impairment” (CLCI) has been introduced in psoriasis treatment. It is affecting people’s perception of therapy. What is CLCI, and how should a doctor treat psoriasis based on CLCI?

A: Even though a patient has been suffering from the disease for a long time, the physician’s observation of the patient’s condition can be fragmented at the time of the hospital visit. However, the real pain and difficulty of psoriasis patients accumulate over a long time. For example, what started as a few skin rashes can affect all over the body eventually. Then, it will affect the patient’s all aspects of life, including relations with other people, studies, social life, and marriage.

CLCI implies the meaning that psoriasis could have a long-term, significant impact on the patient’s life. The long-term influences include not only psychological but physical ones such as psoriatic arthritis. The earlier psoriatic arthritis is treated, the less damage it causes. So, CLCI suggests that physicians should help change the patient’s overall life by getting rid of psoriasis variable through early treatment intervention before the patient has to make important decisions in life.