Over the past two decades, understanding of the pathogenesis of psoriasis has improved, opening new avenues toward treatment. Although these treatments, like biologics, are highly effective, they are also limited by cost and administration issues. Despite these discoveries, there has been little progress in traditional topical treatments and there is still no cure for this chronic disease.
A review1 Published in Dermatology and Therapy looked at some of the most recent advances being collectively researched in psoriasis treatment clinical trials over the past year. A major theme, the study found, was several small-molecule oral drugs in various phases of clinical trials that could help alleviate some of the limitations of biologic therapies.
Most of the newer and highly effective drugs to treat psoriasis target the IL-23/IL-17 axis, the pathway by which psoriatic inflammation is believed to be triggered. Drugs like tumor necrosis factor-α, IL-12/23 and IL-17 inhibitors target these pathways and have produced superior results in treating moderate to severe psoriasis, but the study notes also that progress in treating milder cases of psoriasis has stalled somewhat.
Treatments for mild psoriasis still focus on systemic medications with a high risk of toxicity, such as methotrexate, or traditional topicals that are less effective and carry a risk of long-term consequences. report noted.
So, although newer medications have led to better skin cleansing and better quality of life, their cost is higher and these medications typically involve injections or infusions that can create a barrier for many patients. According to the study, the lack of progress in other systemic and topical medications highlights gaps in psoriasis treatment and the need for new treatments.
- Some treatments currently in trial were identified in the study and include therapies such as:
- IL-36 inhibitors
- IL-23 inhibitors
- IL-17 inhibitors
- Phosphodiesterase 4 inhibitors
- Janus kinase inhibitors
- Receptor-interacting serine protein kinase 1 inhibitors
- Orphan C receptor inhibitors related to retinoic acid receptors
- Adenosine A3 receptor agonists
- Aryl hydrocarbon receptor modulators
- CXC chemokine receptor 2 antagonists
Many of these drugs are in late stages of clinical trials and leverage the effectiveness of biologics but offer an oral delivery option. There are also choices geared towards treating mild psoriasis instead of reserving these treatments for more serious forms of the disease.
There are also several drugs in early stages of clinical trials for which data is limited, but which also offer more oral treatment options. These include a reactive aldehyde species inhibitor (ADX-629); an antagonist of peptide receptors linked to the calcitonin gene (rimegepant); and a sphingosine-1-phosphate receptor 1 agonist.
Finally, the study highlighted recently FDA-approved treatments for psoriasis, a list that includes deucravacitinib, an oral tyrosine kinase 2 inhibitor; spesolimab, an anti-IL-36 receptor antibody; and other nonsteroidal topical agents.
The study authors believe that progress in developing new treatments will continue at a rapid pace, particularly as understanding of the disease evolves. The research team noted that the main focus of these new treatments is data on long-term effectiveness and safety.
This article was originally published on dermatologytimes.com and has been lightly edited.
