New oral therapy offers hope for long-term psoriasis management

Recent developments in biologics have expanded treatment options for psoriasis beyond traditional topical, phototherapy, and systemic therapies.

However, as a chronic disease requiring long-term treatment, there is still a strong need for additional treatment options to improve patient adherence and improve quality of life.

In a 2020 survey of 3,806 psoriasis patients in Japan, North America, and Europe, about 84 percent reported that they “need better treatments.” The need is particularly strong among patients with moderate psoriasis. In a 2021-2022 survey of adult U.S. patients with psoriasis, 66.5 percent of 835 patients who were being treated or had never been treated for psoriasis said they would be “willing to be treated with a new oral treatment option.”

The first TYK2 inhibitor, Sotyktu (deucravacitinib), became available for health insurance coverage in April last year, about eight months after it was approved in Korea in August 2023. This expanded treatment options beyond the existing general therapies. Sotyktu is a novel mechanism of action that selectively inhibits TYK2, a central link in the IL-23/IL-17 pathway, a key pathway in developing psoriasis.

The long-term clinical efficacy and safety of Sotyktu are noteworthy. The POETYK PSO-1,2 and LTE clinical studies analyzed patients who received Sotyktu continuously for four years and demonstrated consistent clinical efficacy from 52 weeks of treatment through four years. In the fourth year, the PASI (psoriasis area severity index) 75 response rate was 71.7 percent, and the Static Physician's Global Assessment (sPGA) 0/1 response rate was 57.2 percent. No significant adverse events were seen with long-term treatment. The POETYK PSO-3 clinical study in Asian patients, including those in Korea, also demonstrated clinical efficacy with a PASI 75 response rate of 68.8 percent and sPGA 0/1 achievement rate of 55.6 percent at week 16.

Recently, major university hospitals in Korea have also started prescribing Sotyktu through the pharmaceutical committee.

Korea Biomedical Review sat down with Park Eun-joo, professor of dermatology at Hallym University Sacred Heart Hospital, to discuss the clinical significance of the new treatment option and the outlook for psoriasis treatment in the future.

Question: How do you choose a psoriasis treatment based on severity?

Answer: Psoriasis is classified as mild, moderate, or severe, depending on its severity, and the appropriate treatment is applied according to the stage. Topical treatments are usually used for mild psoriasis. If you only have one or two lesions on your skin, topical treatments can effectively reduce symptoms. Topical treatments are often used as an adjunct to systemic treatments.

If symptoms are not controlled by topical treatments alone, phototherapy can be tried. Before using biologics, systemic treatments, including immunosuppressants, are used. These include cyclosporine, methotrexate, and, more recently, dimethyl fumarate (Skilarence in trademark).

If these treatments are not sufficiently effective, biologics or newer therapies, such as the recently introduced TYK2 inhibitor Sotyktu, are used stepwise.

Q: Oral treatments for psoriasis have recently been introduced. How does Sotyktu differ from previous treatments?

A: In the past, conventional therapy was used to suppress the immune response before biologics were used. These drugs are not specific to psoriasis but rather suppress the immune response.

Sotyktu, on the other hand, is an oral drug with a mechanism of action similar to biologics. It inhibits an intracellular signal called TYK2, which inhibits interleukin (IL)-23, the main trigger of psoriasis, and IL-17. In other words, Sotyktu is an innovative treatment because, like biologics, it targets specific pathogenesis of psoriasis but is an oral drug.

Q: Different psoriasis medications target different interleukins. What about Sotyktu?

A: Sotyktu inhibits IL-23. It's important to note that IL-23 ultimately inhibits IL-17, and it inhibits not just IL-23 but also IL-12 and interferon (IFN)-α and β. This is an additional benefit compared to traditional biologics.

Notably, IFN-α and IFN-β are very important in the acute phase of psoriasis. In other words, besides inhibiting IL-23, Sotyktu inhibits IFN-α and IFN-β, making it more effective than other biologics in the event of a sudden flare-up.

Q: What are the advantages of oral psoriasis medications?

A: In Korea, biologics have been used for several years, and the perception that a single injection can significantly improve psoriasis has spread. However, for patients with a phobia of injections, adolescents, and pediatric patients, oral medications may be more suitable. Younger patients can be more stressed by the anxiety of injections. Oral medications also have the advantage of being easier to dose.

Q: Which patients do you prioritize prescribing oral medications for?

A: For patients who prefer oral medications, Sotyktu can be used aggressively. It is also likely to help patients with acute flare-ups. In addition, there are cases of paradoxical psoriasis, where the psoriasis worsens despite using psoriasis medications. In this case, IFN-α and IFN-β are involved, which is why Sotyktu may be more effective than other biologics.

Q: You said that Sotyktu is no less effective than existing biologics. Are there key clinical data to support this?

A: Sotyktu's key clinical trials include POETYK PSO-1 and 2, global phase 3 trials, and POETYK PSO-3 in Asia. POETYK PSO-3 demonstrated a PASI 75 achievement rate of about 68 percent at week 16, and the recent Japanese POETYK PSO-4 study showed an even higher 76 percent achievement rate.

Notably, Sotyktu's PASI 75 reach rates are higher in Asians. This is relatively higher than the data from POETYK PSO-1 and 2, which may be due to Asians' lower BMI. Similar effects can be expected in Korea. In addition, the effectiveness of specialty areas, such as scalp and nails, was also high.

Q: Domestic prescription data for Sotyktu is still lacking. What should doctors be careful about when prescribing it?

A: There were initial concerns that TYK2 inhibitors may cause side effects like those of JAK inhibitors. However, multiple clinical studies have not reported any serious side effects related to thromboembolism or immunosuppression, so regular blood tests are unnecessary.

However, given the high incidence of tuberculosis in Korea, it is recommended that basic immune-related tests, such as TB screening and white blood cell counts, be performed at the beginning of treatment. While side effects during treatment are possible, we do not anticipate any that would require discontinuation or cause serious concern at this time.

Q: In what order do you anticipate prescribing the medications to patients at the point of care in the future?

A: Patients on compassionate use can choose between oral and biological agents and switch if the first treatment is ineffective. Therefore, we expect a pattern of using Sotyktu as a first-line agent and switching to a biologic if it is ineffective.

However, biologics should be considered first for patients with very severe lesions. This is because Sotyktu has a relatively slow onset of action compared to injectables. However, given that psoriasis treatment is a long-term process and given Sotyktu's four-year safety data, it may be a good option for patients who prefer oral medications.

In addition, clinical studies are underway on the adolescent population of psoriatic arthritis. If approved for these additional indications, Sotyktu will further expand the patient population that can benefit from the drug.

Q: What systemic improvements could be made to the treatment of psoriasis?

A: I suggest two main improvements.

First, expanding the severity criteria. Only patients with a PASI score of 10 or higher are considered severe, but we must recognize patients with psoriasis in special areas even if their PASI score is not that high.

Second, supporting early treatment. Recent studies have shown that starting treatment within one to two years of onset is associated with lower relapse rates, even after discontinuing medication. This shows that early and aggressive treatment is important for disease modification.

However, under the current insurance system, it is difficult for patients in the early stages of the disease, when symptoms are not severe, to obtain coverage for aggressive treatments, such as Sotyktu or biologics. Therefore, it is necessary to expand insurance coverage to allow for early aggressive treatment, even before severe symptoms appear.

Q: What are the main directions of current psoriasis research?

A: Currently, there are two main research directions. First, we are studying how disease control and active treatment affect the prevention and improvement of psoriatic arthritis. Second, we are evaluating how effective these therapeutic approaches are in reducing the burden of cardiovascular disease.

Q: What would you like to say to psoriasis patients?

A: Psoriasis is not just a skin disease but a systemic inflammatory disease. Without proper treatment, inflammation can affect the joints and cardiovascular system. It's important not to rely on folk remedies but to visit your neighborhood dermatological clinics for early and aggressive treatment. The Korean Society for Psoriasis is constantly working on this.