There are many positive developments in psoriasis treatment. Novel biologics such as interleukin 23 inhibitors and small molecule inhibitors provide improved effectiveness and a wider range of choices. Progress in topical treatments utilizing microneedles and nanoparticles enhances drug delivery, while personalized medicine directed by biomarkers offers the possibility of customized therapy and improved results.
Psoriasis is a chronic inflammatory skin disease that affects 2–3% of the global population. Current therapies include topical treatments, phototherapy, oral systemic treatments, and biologics.
A literature review published in the International Journal of Molecular Sciences reviewed the challenges faced by current psoriasis therapies and their future prospects.
Challenges Persist in Current Psoriasis Treatment
Biologic agents have transformed the psoriasis treatment landscape; however, several challenges persist. Primary and secondary treatment failures are major challenges. In primary treatment failure, certain patients do not respond to treatment. There is a need for better predictive tools to identify individuals likely to benefit from specific biologic drugs.
Secondary failure is characterized by decreased efficacy in patients who initially responded well to treatment. While combining biologics with methotrexate prolongs drug responses in other immune-mediated diseases, only limited evidence supports its use in conjunction with biologics for psoriasis. Switching biologics may be a good option for secondary failure. Several studies demonstrated that patients who switched to an alternative biologic agent showed comparable improvements in Psoriasis Area and Severity Index (PASI) scores to biologic-naive patients.
Another major challenge is the high cost of biologic therapies, which imposes burdens on patients and healthcare systems. A patient survey highlighted the demand for a more cost-effective treatment option. The impending expiration of some biologic patents will pave the way for biosimilars, potentially reducing costs.
The treatment of mild psoriasis relies heavily on localized therapies. There is a need for more targeted systemic therapies for patients with mild disease who do not respond well to topical treatments. Specific psoriasis subtypes (such as scalp, genital, palmoplantar, etc.) present distinct challenges in treatment satisfaction and management, requiring future research to develop more effective and tailored approaches for these patients.
Novel Biologic Agents and Small Molecule Inhibitors Hold Potential for Future Psoriasis Treatment
Mirikizumab, an interleukin (IL)-23 inhibitor, targets the IL-23/Th17 pathway. It has shown promise in clinical trials, with significant improvements in psoriatic skin lesions. Deucravacitinib, a selective tyrosine kinase 2 inhibitor, has demonstrated efficacy in reducing symptoms and improving quality of life in clinical trials. IL-36 inhibitors, namely A-552 and spesolimab, have shown efficacy in recent trials.
Studies have also indicated the therapeutic potential of IL-37 and IL-38 for psoriasis. Retinoic-acid-receptor-related orphan receptor gamma-t (RORγt) inhibitors modulate the Th17-cell-mediated immune response in psoriasis and show potential as a new therapeutic approach. VTP-43742, an oral RORγt inhibitor, has demonstrated a 23–29% reduction in PASI score after 4 weeks in a phase IIa study.
Rho-associated protein kinase 2 (ROCK2) inhibitors reduce the production of pro-inflammatory cytokines, providing a new avenue for targeted therapy. KD025, a ROCK2 inhibitor, resulted in a 50% reduction in PASI scores in 46% of psoriasis vulgaris patients.
Various Novel Therapeutic Approaches Show Potential for Psoriasis Treatment
Microneedles are used for transdermal drug delivery. Clinical trials and animal studies have shown their effectiveness in improving drug permeation and therapeutic outcomes in psoriasis. Lipid-based, metallic, and polymeric nanoparticles have been extensively investigated for transdermal drug delivery in psoriasis and have shown promising results in improving drug permeation and therapeutic outcomes. Nanofiber-based drug delivery systems have also emerged, which allow for the controlled release of anti-psoriatic agents, leading to enhanced efficacy.
Source:
Lee, H. J., & Kim, M. (2023). Challenges and future trends in the treatment of psoriasis. International Journal of Molecular Sciences, 24(17), 13313. https://doi.org/10.3390/ijms241713313
