With new and emerging therapies in the works for patients with psoriasis, there’s hope on the horizon for an evolving treatment landscape. Dive in to these different therapies and how they could offer long-lasting relief to these patients.
Psoriasis remains a significant challenge for patients and healthcare providers alike. While established therapies offer relief, the search for even more effective, convenient, and long-lasting options continues. Based on its pathophysiology, it’s no surprise that therapeutic targets are focused on immune and inflammatory mediators. Let's dive into the latest advancements in the psoriasis treatment landscape that highlight new and emerging therapeutics and approaches.
Oral Powerhouses: TYK2 Inhibitors Take Center Stage
Deucravacitinib, the first FDA-approved once daily, oral tyrosine kinase 2 (TYK2) inhibitor for moderate-to-severe psoriasis, marked a significant shift towards convenient administration therapies in 2022. Like many other therapies used to treat immune disorders, deucravacitinib works by modulating cytokine signaling in inflammatory pathways, particularly through interleukin-23 (IL-23). Although TYK2 is a member of the Janus kinase (JAK) family, it may have an improved safety profile because of its selectivity. Additional studies are underway to better characterize the long-term safety and efficacy and define its role as a therapeutic agent in other immune/inflammatory diseases.
Selective IL-17A/F Inhibition: Bimekizumab Emerges
Also a biologic, bimekizumab boasts a unique mechanism as a selective inhibitor of both IL-17A and IL-17F. In phase 3 trials, it's been reported that patients achieved complete (PASI100), or near complete, clearance after receiving bimekizumab for moderate to severe plaque psoriasis at week 16 of the study. In fact, the data suggests that its effects were superior compared to placebo and IL-17A specific inhibitors. While bimekizumab is administered subcutaneously, it has a dosing frequency of every eight weeks after the first 16 weeks.
Targeting IL-36 Pathways
The therapeutic arsenal against psoriasis is expanding beyond IL-17. Generalized pustular psoriasis (GPP) is a rare, chronic condition that can lead to sepsis and even multi-organ failure, requiring emergency attention. Spesolimab, an IL-36 receptor inhibitor is approved for GPP, offering a much-needed treatment option for this specific variant. Data from Phase 2 clinical trials showed a significant reduction of GPP flares in 84 percent of patients. Trials are ongoing evaluating the long-term efficacy of spesolimab in a larger population.
Topical Advancements: Tapinarof and Roflumilast Offer New Options
The realm of topical therapies has also seen exciting developments. Aryl hydrocarbon receptor (AhR) is a transcription factor that is being studied as a therapeutic target for psoriasis. Unlike other targets that are cell surface receptors, AhR is a cytoplasmic complex with known roles in xenobiotic metabolism, essentially helping to maintain cellular homeostasis, pigmentation, and immunity of the dermis. Tapinarof, a novel, non-steroidal cream derived from a roundworm bacterium, exhibits potent anti-inflammatory properties, and offers sustained improvement, four months after treatment cessation.
Another non-steroidal, topical treatment for psoriasis being investigated is roflumilast. Like apremilast, an oral phosphodiesterase-4 (PDE4) inhibitor helps to reduce inflammation, but from inside-out. Whereas, roflumilast, another topical option, also a PDE-4 inhibitor aims to treat chronic psoriasis from the outside, directly. In clinical trials, roflumilast, continues to demonstrate efficacy in managing chronic plaque psoriasis, even those with facial, neck, scalp, and intertriginous area involvements.
So What’s Next?
The future of psoriasis treatment holds immense promise. The landscape of psoriasis treatment is constantly evolving with new and emerging therapies being offered. From more convenient administrations to more targeted biologics, a wider range of tools to achieve optimal disease control and improve patient quality of life is within arm’s reach.
References
Bachelez H, Choon SE, Marrakchi S, et al. Trial of Spesolimab for Generalized Pustular Psoriasis. New England Journal of Medicine. 2021;385(26):2431-2440. doi:10.1056/NEJMoa2111563
Camiña-Conforto G, Mateu-Arrom L, López-Ferrer A, Puig L. Bimekizumab in the Treatment of Plaque Psoriasis: Focus on Patient Selection and Perspectives. Patient Prefer Adherence. 2023;Volume 17:1541-1549. doi:10.2147/PPA.S350760
Dec M, Arasiewicz H. Aryl hydrocarbon receptor role in chronic inflammatory skin diseases: a narrative review. Advances in Dermatology and Allergology. 2024;41(1):9-19. doi:10.5114/ada.2023.135617
Draelos ZD, Adam DN, Hong HC ho, et al. Efficacy and safety of roflumilast cream for chronic plaque psoriasis with facial/neck and intertriginous area involvement: a post hoc analysis from a randomized controlled trial. British Journal of Dermatology. 2023;188(6):810-812. doi:10.1093/bjd/ljad060
EffisayilTM ON: A Study to Test Long-term Treatment With Spesolimab in People With Generalized Pustular Psoriasis Who Took Part in a Previous Study. ClinicalTrials.gov identifier: NCT03886246. Updated January 5, 2024. Accessed May 2, 2024. https://clinicaltrials.gov/study/NCT03886246? intr=Spesolimab&rank=2
Fernández-Gallego N, Sánchez-Madrid F, Cibrian D. Role of AHR Ligands in Skin Homeostasis and Cutaneous Inflammation. Cells. 2021;10(11):3176. doi:10.3390/cells10113176
Kingston P, Blauvelt A, Strober B, Armstrong AW. Deucravacitinib: A Novel TYK2 Inhibitor for the Treatment of Moderate-to-Severe Psoriasis. J Psoriasis Psoriatic Arthritis. 2023;8(4):156-165. doi:10.1177/24755303231201336
Lé AM, Puig L, Torres T. Deucravacitinib for the Treatment of Psoriatic Disease. Am J Clin Dermatol. 2022;23(6):813-822. doi:10.1007/s40257-022-00720-0
Lebwohl MG, Stein Gold L, Strober B, et al. Phase 3 Trials of Tapinarof Cream for Plaque Psoriasis. New England Journal of Medicine. 2021;385(24):2219-2229. doi:10.1056/NEJMoa2103629
Morand E, Merola JF, Tanaka Y, Gladman D, Fleischmann R. TYK2: an emerging therapeutic target in rheumatic disease. Nat Rev Rheumatol. 2024;20(4):232-240. doi:10.1038/s41584-024-01093w
Morita A, Strober B, Burden AD, et al. Efficacy and safety of subcutaneous spesolimab for the prevention of generalised pustular psoriasis flares (Effisayil 2): an international, multicentre, randomised, placebo-controlled trial. The Lancet. 2023;402(10412):1541-1551. doi:10.1016/S0140-6736(23)01378-8
Nicolas SE, Bear MD, Kanaan AO, Coman OA, Dima L. Roflumilast 0.3% Cream: a Phosphodiesterase 4 Inhibitor for the Treatment of Chronic Plaque Psoriasis. Am J Ther. 2023;30(6):e535-e542. doi:10.1097/MJT.0000000000001678
Prieto K, Duong JQ, Feldman SR. Tapinarof cream for the topical treatment of plaque psoriasis in adults. Expert Rev Clin Immunol. 2024;20(4):327-337. doi:10.1080/1744666X.2023.2296607
Thurston AW, Osborne DW, Snyder S, Higham RC, Burnett P, Berk DR. Pharmacokinetics of Roflumilast Cream in Chronic Plaque Psoriasis: Data from Phase I to Phase III Studies. Am J Clin Dermatol. 2023;24(2):315-324. doi:10.1007/s40257-022-00741-9
UCB. BIMZELX® Approved by the U.S. FDA for the Treatment of Adults with Moderate to Severe Plaque Psoriasis. Published October 18, 2023. Accessed May 2, 2024. https://www.ucb.com/sites/ default/files/press_files/93a57a7451a70708.pdf
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