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The evolution and revolution in understanding the psoriasis pathway of inflammation has ushered in amazing new treatments that are highly effective at clearing plaque psoriasis. Multiple biologics and new oral and topical non-steroidal medications continue to expand the treatment options available to physicians and patients. Here, I take a closer look at the latest research findings on existing therapies and bring you up to date on new and emerging treatments.

A Choice of Riches

In the last five years, further improvements in biologics have brought clearer skin and improved safety with biologic drugs targeting IL-17 (ixekizumab, brodalumab, and secukinumab) and IL-23 (risankizumab, guselkumab, and tildrakizumab). Selecting the right biologic for your patient means evaluating multiple aspects of each treatment including the efficacy, safety, treatment adherence, health-related quality of life (HRQoL), and contraindications of the target patient. High levels of skin clearance is one outcome of key interest because this has been specifically associated with improvement in HRQoL, psoriasis symptoms, and work productivity. 

A study by Armstrong et al. used a statistical technique known as a network meta-analysis to allow the indirect comparison of biologics and oral treatments for moderate-to-severe plaque psoriasis licensed by the FDA without a head-to-head study. The comparative efficacy analysis of the short-term and long-term Psoriasis Area Severity Index (PASI) response rates using data from their phase 2, 3, or 4 randomized controlled trials demonstrated that brodalumab, guselkumab, ixekizumab, and risankizumab-rzaa had the highest short-term PASI response rates at 10 to 16 weeks from baseline and also long term-term PASI response rates at 44 to 60 weeks.

Real-world evidence is important, because one limitation of clinical trials is that “trial” patients are not always representative of “real-life” patients. In real life, other factors may play a role in the effectiveness and safety of biologics, which include comorbid diseases, physician behaviors, dose modifications, regional guidelines, payer policies, and prescribed co-medication. The probability that a patient will remain on a specific treatment, also known as drug survival, is one important measure of effectiveness in the real-life setting. Drug survival was studied using the United Kingdom registry data, Among 16,122 treatment courses of biologic therapy with either guselkumab, ixekizumab, secukinumab, ustekinumab, or adalimumab,  guselkumab had the highest drug survival concerning effectiveness and safety. The study also showed that factors that influence the effectiveness of biologic therapy include psoriatic arthritis, previous biologic exposure, nail involvement, and ethnicity, confirming that tailoring treatment to individual patients is important.  

Citrate-free ixekizumab

Injection site pain is a common adverse event for biologics and may create a negative patient experience. Ixekizumab, an IL-17 antagonist biologic, offers high skin clearance, durable efficacy, and rapid onset of action, however, injection site reactions have been reported to occur in up to 20 percent of patients. A recently FDA-approved citrate-free formulation of ixekizumab (Taltz, Lilly) is now available. It replaces the original commercial formulation and improves the patient experience with significantly less injection site pain and erythema. 

New kids on the block

Apremilast (Otezla, Amgen) is now approved in adult patients with plaque psoriasis across all severities.

Deucravacitinib (Sotkytu, Bristol Myers Squibb) was just FDA-approved for adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. It is a selective inhibitor of tyrosine kinase 2 (TYK2), a member of the Janus kinase (JAK) family) and works by interrupting the signaling and production of key cytokines such as IL-23 and IL-17 involved in the psoriasis inflammation pathway. The pivotal Phase 3 POETYK PSO-1 and POETYK PSO-2 clinical trials evaluated the safety and efficacy of Sotyktu (6mg once daily) compared to placebo and apremilast (30mg twice daily) demonstrating that 54 percent of deucravacitinib patients achieved clear or almost clear skin compared to 32 percent on apremilast and 7 percent on placebo. Deucravacitinib is the only approved TYK-2 inhibitor worldwide and the first innovation in oral treatment of moderate-severe plaque psoriasis in almost 10 years. The most common adverse events seen with deucravacitinib were upper respiratory tract infections, increases in blood creatine phosphokinase, herpes simplex, mouth ulcers, folliculitis, and acne. Laboratory monitoring includes evaluating for tuberculosis prior to initiating treatment, liver enzymes, and serum triglycerides.

Bimekizumab, still pending FDA approval,  is an investigational biologic that has been studied in multiple Phase 3 studies (BE READY, BE SURE, BE VIVID, BE RADIANT) of adult moderate to severe chronic plaque psoriasis patients. In May 2022, the FDA issued a complete response letter regarding the biologic license application for bimekizumab which indicated that certain pre-approval inspection observations related to the manufacturing process must be resolved. None of the concerns are related to the safety of the drug.  When approved, bimekizumab will be the fourth biologic available within the class of IL-17 inhibitors.

Topical therapies

Two new topical non-steroidal medications have arrived. Vtama (tapinarof, Dermavant), an aryl hydrocarbon receptor agonist, is a novel non-steroidal approved for  the treatment of plaque psoriasis in adults. The most common reactions were folliculitis and contact dermatitis at the application site in up to 24 percent of patients. Most were mild to moderate and did not lead to discontinuation. In the open-label long-term extension study, some patients stay clear or almost clear for an average of 4.6 months without medication. 

Zoryve (roflumilast, Arcutis) cream is a highly potent and selective phosphodiesterase type 4 inhibitor (PDE4) indicated for adults as well as adolescents 12 years and older for plaque psoriasis.  Zoryve is the only topical that has data specifically focusing on the treatment of intertriginous plaques. The common adverse events were diarrhea and headache. Both Vtama and Zoryve offer once-daily application and a high chance of clearance of the localized psoriasis.

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