The 2019 European Academy of Dermatology and Venereology Congress was held in Madrid, Spain. During this conference, a symposium was held discussing IL-23 inhibition in psoriasis. Here are some of the highlights.
This symposium gave an overview of the current treatment landscape for psoriasis, clinical developments, and recent clinical trials.
Due to the pathophysiology of the disease, there is a rationale for using multiple classes of biologics. Researchers believe that IL-23 and IL-187 have different roles in both psoriasis and PsA (psoriatic arthritis). Therefore, the inhibitors will have different clinical behaviors.
As scientists have come to better understand the pathophysiology of psoriasis, cytokine-targeted therapies have expanded. But it is important to realize that there will never be one magic therapy for all patients. Individualized and targeted approaches to care are crucial. The IL-23/12, the IL-17, and the IL-23 pathways show this.
Currently, guselkumab, risankizumab, and tildrakizumab are the IL-23 inhibitors approved in the United States and European Union. Additionally, it’s expected that mirikizumab may be approved within the next couple of years. These inhibitors have shown efficacy, safety, and a maintenance of response in clinical trials.
Unfortunately, comorbidities are a common problem for psoriasis patients. This is due to the inflammatory nature of the condition. Comorbidities can include PsA, cardiovascular disease, obesity, inflammatory bowel disease (IBD), and various psychological disorders such as depression and anxiety.
There is reason to believe that IL-23 could benefit patients who are dealing with comorbidities. Ultimately, researchers contend that a multidisciplinary treatment plan is important to effectively care for patients.
PsA is found in up to 48% of patients and researchers estimate that there is a high rate of under-diagnosis. But fortunately, when it is diagnosed early, early treatment can substantially improve outcomes. This diagnosis usually comes from dermatologists.
When treated with guselkumab in a clinical trial, patients diagnosed with PsA and psoriasis achieved positive results which were maintained for up to three years. Additionally, patients reported an improved quality of life.
Individuals with psoriasis have an increased risk of having a higher BMI, and therefore a higher risk of obesity. They also have a higher risk of developing metabolic syndrome. Likewise, those who are obese have a higher risk of psoriasis. These individuals are also likely to face a decreased efficacy of treatment.
In the ECLIPSE trial, guselkumab had a response in >80% of participants at week 48. This response was across all BMIs. The VOYAGE trials noted consistent response across all subgroups of psoriasis patients for those who received the therapy for up to 3 years.
Inflammatory Bowel Disease
Researchers aren’t entirely sure of how psoriasis and IBD are interconnected. They suspect it could be due to immune dysfunction, genetic abnormalities, the dysregulation of the gut microbiota, or systemic inflammation.
In the IM-UNITI clinical trial, ustekinumab produced clinical response and remission for patients with Crohn’s disease.
Psoriasis is often correlated with anxiety, depression, and alcohol abuse. For this reason it is recommended that psoriasis patients are always screened for potential psychological comorbidities. Thankfully, these conditions can all be treated simultaneously.
For psoriasis patients dealing with depression and anxiety, guselkumab has been shown to produce better results than adalimumab treatments.
Head to Head
The ECLIPSE clinical trial was the very first study to investigate guselkumab (an IL-23 inhibitor) side by side secukinumab (an IL-17 inhibitor). 84% of those taking guselkumab reached the trial’s primary endpoint. Only 70% of those taking secukinumab reached the same endpoint. Each drugs’ previous safety profile was maintained.
Additionally important to note is the fact that the majority of patients treated with guselkumab documented an improved quality of life.
More research is still needed, especially regarding long term outcomes. However, results so far have been very promising. Overall, they show that IL-23 may be an effective treatment for psoriasis and the comorbidities that unfortunately often accompany it.