Exploring Oral Options for Psoriasis Therapies

In the ever-evolving landscape of psoriasis treatment, oral therapies continue to play a crucial role. Ben Lockshin, MD, FAAD, assistant professor at Georgetown University’s Department of Dermatology, and director of the clinical trials center at US Dermatology Partners in Washington, DC, shared his insights on the latest advancements in oral options for psoriasis therapies during the session “Oral Options for Psoriasis Therapies” at the 2024 Fall Clinical Dermatology Conference for PAs and NPs in Scottsdale, Arizona.¹

In an interview with Dermatology Times, Lockshin explained how far we have come in oral treatment options for psoriasis, the future outlook, and patient populations that benefit most from orals.

Classic Oral Treatments

The classic oral treatments for psoriasis include methotrexate (MTX), cyclosporine (CyA), and fumaric acid. These medications have been staples in psoriasis management, particularly in countries like Germany, where they are frequently prescribed for moderate to severe cases. Fumaric acid, for example, has demonstrated efficacy with a PASI 75 response rate of 40.3% and a PASI 90 response rate of 22.3%. PASI (Psoriasis Area and Severity Index) scores are critical in assessing the effectiveness of psoriasis treatments, with PASI 75 and 90 indicating 75% and 90% improvement.²

Newer Generation Oral Therapies

“We live in an exciting time because we've got new topical therapies, multiple oral therapies, and obviously, an array of biologic agents and patient preferences change,” Lockshin said. The newer generation of oral therapies includes apremilast (Otezla; Amgen) and deucravacitinib (Sotytku; Bristol Myers Squibb). Apremilast is an oral phosphodiesterase 4 inhibitor that modulates the inflammatory response. It is approved for psoriasis (Ps), psoriatic arthritis (PsA), and oral ulcers associated with Behçet's disease.³ Deucravacitinib, a more recent addition, has shown promising results in terms of efficacy and tolerability.⁴

Clinical Data Supporting Apremilast

In a phase 3 trial involving 595 patients with mildtomoderate plaque psoriasis inadequately controlled or intolerant to at least 1 topical therapy, apremilast demonstrated significant improvements. At week 16, the primary endpoint of clear or almost clear skin, as measured by a 2+ point reduction in sPGA (static Physician’s Global Assessment) scores, was achieved.⁵

Pediatric Use of Apremilast

Apremilast has also been evaluated in pediatric patients aged 6-17 with moderate to severe plaque psoriasis. A study involving 245 patients showed significant improvements at 16 weeks, confirming its efficacy and safety in younger populations.⁶

Comparison Between Apremilast and Deucravacitinib

Deucravacitinib offers the convenience of once-daily dosing and has demonstrated superior efficacy to Apremilast, with a similar adverse event profile. Phase 3 trials (POETYK PSO-1 & PSO-2) showed that deucravacitinib sustained PASI 75 and 90 responses well from week 52 through 4 years, making it a compelling option for long-term management, according to investigators.⁷

Both apremilast and deucravacitinib have manageable safety profiles. Long-term data for deucravacitinib indicate that rates of major adverse cardiovascular events (MACE) and other serious conditions are comparable to those seen with other psoriasis treatments. Regular monitoring is essential, but these therapies are generally safe for most patients.⁷

Oral Options vs. Injectables

The choice between oral and injectable treatments often depends on patient preference and specific clinical scenarios. Some patients prefer the convenience of oral medications, while others may opt for injectables due to their efficacy. Comparative studies, like the IMMpulse phase IV study, are providing valuable data on patient outcomes and preferences.⁸

“I like oral therapies to initiate prior to thinking about a biologic,” Lockshin explained. “There are 3 patient types that are great for oral therapies. One is the dabblers, the patients that are kind of tepid about starting systemic therapy. Given the fact that it's a small molecule, there's less of a chance of immunogenicity. There's a possibility if they want to stop, they can stop and then restart without much concern. In addition, I like using orals for younger patient populations that don't want to have injectable medications in their dorm fridge or, you know if they have roommates. So thinking about all options fits into their lifestyle a lot better. And then the last one is for those patients with a little bit more mild disease. I think that oral options actually fit in quite nicely into the treatment algorithms.”

Future of Oral Therapies

Several new oral therapies are in clinical development, aiming to enhance efficacy, safety, and patient quality of life. Lockshin concluded, “In this newer generation of managing patients with psoriasis, I think that the introduction of new deucravacitinib allows us to achieve the same meaningful response rates, as we do with some of the injectable medications with a once daily pill. I think this really has changed the way that we look at oral therapies and the management of patients with moderate severe psoriasis.”

References

1. Lockshin B. Oral options for psoriasis therapies. Presented at: 2024 Fall Clinical Dermatology Conference for PAs and NPs; May 31-June 2; Scottsdale, AZ
2. Atwan A, Ingram JR, Abbott R, et al. Oral fumaric acid esters for psoriasis. Cochrane Database Syst Rev. 2015;2015(8):CD010497. Published 2015 Aug 10. doi:10.1002/14651858.CD010497.pub2
3. Papp K, Reich K, Leonardi CL, et al. Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1). J Am Acad Dermatol. 2015;73(1):37-49. doi:10.1016/j.jaad.2015.03.049
4. Strober B, Thaçi D, Sofen H, et al. Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: Efficacy and safety results from the 52-week, randomized, double-blinded, phase 3 Program fOr Evaluation of TYK2 inhibitor psoriasis second trial. J Am Acad Dermatol. 2023;88(1):40-51. doi:10.1016/j.jaad.2022.08.061
5. Stein Gold L, Papp K, Pariser D, et al. Efficacy and safety of apremilast in patients with mild-to-moderate plaque psoriasis: Results of a phase 3, multicenter, randomized, double-blind, placebo-controlled trial. J Am Acad Dermatol. 2022;86(1):77-85. doi:10.1016/j.jaad.2021.07.040
6. Fiorillo L, Becker E, de Lucas R, et al. Efficacy and safety of apremilast in pediatric patients with moderate-to-severe plaque psoriasis: 16-week results from SPROUT, a randomized controlled trial. J Am Acad Dermatol. 2024;90(6):1232-1239. doi:10.1016/j.jaad.2023.11.068
7. Strober B, Blauvelt A, Warren RB, et al. Deucravacitinib in moderate-to-severe plaque psoriasis: Pooled safety and tolerability over 52 weeks from two phase 3 trials (POETYK PSO-1 and PSO-2). J EurAcad Dermatol Venereol. Published online March 7, 2024. doi:10.1111/jdv.19925
8. Stein Gold LF, Bagel J, Tyring SK, et al. Comparison of risankizumab and apremilast for the treatment of adults with moderate plaque psoriasis eligible for systemic therapy: results from a randomized, open-label, assessor-blinded phase IV study (IMMpulse) [published correction appears in Br J Dermatol. 2024 May 06;:]. Br J Dermatol. 2023;189(5):540-552. doi:10.1093/bjd/ljad252