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The therapeutic armamentarium for patients with psoriasis and psoriatic arthritis (PsA) has been strengthened by research affording more individualized treatment regimens with new therapeutic targets. In this article, new systemic therapies for psoriasis are discussed, including a review of the relevant clinical trials for novel therapeutics and their respective mechanisms of action, patient outcomes, and safety profiles. This article is the final installment in a 3-part series on agents in the pipeline for the management of psoriasis and PsA including topical agents, biologic treatments, and systemic therapies in phase 2 through phase 4 clinical trials. These systemic agents offer patients more targeted treatment regimens with the prospect of enhanced therapeutic efficacy and more favorable side-effect profiles with better tolerability.

Biologic treatments have revolutionized the management of psoriasis and psoriatic arthritis (PsA). Anti-tumor necrosis factor (TNF) α monoclonal antibodies presently are approved by the US Food and Drug Administration (FDA) for treatment of these conditions. In this article, new therapies that target this pathway and other steps in the pathogenesis of psoriasis and PsA are discussed, including IL-12/IL-23, IL-17, T-cell activation in antigen-presenting cells, regulatory T cells, toll-like receptors, and granulocyte-macrophage colony-stimulating factor. This article is the second in a 3-part series on treatments presently in the pipeline for the management of psoriasis and PsA including topical agents, biologic treatments, and systemic therapies in phase 2 through phase 4 clinical trials as well as agents that are recently FDA approved. Pivotal clinical trials, mechanisms of action, patient outcomes, and pertinent safety information will be discussed for each new therapy. As our knowledge of the underlying pathogenesis of psoriasis and PsA deepens, it enables the development of more targeted therapies in the management of these conditions.

In recent years, advances in our understanding of inflammatory mediators and the underlying pathogenesis of psoriasis and psoriatic arthritis have shed light on potential therapeutic targets, which has led to the development of several new promising treatments. In this article, key clinical trials, mechanisms of action, patient outcomes, and relevant safety information for these novel topical medications will be evaluated. This article is the first in a 3-part series on treatments presently in the pipeline for the management of psoriasis and psoriatic arthritis including topical agents, biologic treatments, and systemic therapies in phase 2 and phase 3 clinical trials. With novel approaches to the disease process, these therapies may afford more targeted individualized treatment regimens and offer hope to patients with psoriasis and psoriatic arthritis who have reported a suboptimal therapeutic response to conventional therapies.

Introduction: The National Psoriasis Foundation (NPF) recommends evaluating patient response to treatment at week 12, with a target response of ≤ 1% body surface area (BSA) affected by plaque psoriasis and an acceptable response of BSA ≤ 3% or ≥ 75% improvement. This post hoc analysis compared the achievement of NPF target and acceptable responses for ixekizumab (IXE) versus other biologics. Methods: Outcomes were evaluated at week 12 for patients with moderate-to-severe plaque psoriasis from four head-to-head randomized clinical trials (RCTs; UNCOVER-2, UNCOVER-3, IXORA-R, and IXORA-S) and one real-world prospective observational study (Psoriasis Study of Health Outcomes; PSoHO). RCT patients were treated with IXE or etanercept (ETN; UNCOVER-2/3), guselkumab (GUS; IXORA-R), or ustekinumab (UST; IXORA-S). PSoHO patients were treated with anti-interleukin (IL)-17A biologics (IXE, secukinumab, SEC) and other approved biologics for the treatment of plaque psoriasis. Patients with missing outcomes were imputed as non-responder imputation. For RCT data, statistical comparisons between treatment groups were performed using Fisher's exact test with no multiplicity adjustments. For real-world data, adjusted comparative analyses were performed using frequentist model averaging (FMA) and reported as odds ratio (OR). Results: Across the four head-to-head clinical trials analyzed, significantly higher proportions of patients achieved target and acceptable responses at week 12 with IXE versus ETN, GUS, or UST. Likewise, the proportion of PSoHO patients achieving target and acceptable response at week 12 was higher with IXE compared with other individual biologics. Adjusted comparative analyses showed that IXE had significantly greater odds of target and acceptable response at week 12 versus SEC, GUS, risankizumab (RIS), adalimumab (ADA), UST, and tildrakizumab (TILD) and numerically greater odds of target and acceptable response at week 12 versus brodalumab (BROD). Conclusion: Across both clinical studies and real-world settings, more patients treated with IXE achieved NPF target and acceptable responses at week 12 compared with those treated with other biologics. Trial Registration: UNCOVER-2 (NCT01597245); UNCOVER-3 (NCT01646177); IXORA-R (NCT03573323); IXORA-S (NCT02561806); PSoHO (EUPAS24207). [ABSTRACT FROM AUTHOR]

Introduction: When assessing the effect of a therapy for psoriasis (PsO), it is important to consider speed of response and cumulative response. However, responses among biologics may differ by body regions. This post hoc analysis compares speed of response and cumulative response for ixekizumab (IXE), an interleukin-17A antagonist, and guselkumab (GUS), an interleukin-23p19 inhibitor, in different body regions of patients with moderate-to-severe plaque PsO participating in the IXORA-R study, up to week 24. Methods: The IXORA-R design has been previously described. Patients received the respective on-label dosing of IXE or GUS. The median time to first Psoriasis Area and Severity Index (PASI) 50, 75, 90, and 100 response (50%, 75%, 90%, and 100% improvement from baseline, respectively) and the cumulative days with clear skin for PASI 50, 75, 90, and 100 responses were assessed in four body regions: head, trunk, upper extremities, and lower extremities. Results: A total of 1027 patients were enrolled and received IXE (N = 520) or GUS (N = 507). Median time to first PASI 50, 75, 90, and 100 response was shortest in the head region, followed by the remaining body regions in both IXE and GUS cohorts. In each body region, IXE was significantly faster than GUS (p < 0.001) in achieving PASI 50, 75, 90, and 100. Through 24 weeks, the number of days with clear skin for PASI 90 and 100 was greater in the head region, followed by trunk, upper extremities, and lastly lower extremities in both IXE and GUS cohorts. In each body region, through 24 weeks, patients on IXE experienced a significantly higher number of days with clear skin for PASI 50, 75, 90, and 100 than patients on GUS (p < 0.01). Conclusions: As compared to GUS, IXE provided a faster skin clearance and more days with clear skin in all body regions of patients with moderate-to-severe plaque PsO through 24 weeks. Trial Registration Number: https://www.clinicaltrials.gov/: NCT03573323 (IXORA-R). Plain Language Summary: Psoriasis, a long-term, inflammatory skin disease, impacts patient's lives, and response to treatment varies depending on the body region affected. Here, we assessed the speed of response and cumulative response through 24 weeks in different body regions (head, trunk, upper extremities, and lower extremities) of patients with moderate-to-severe plaque psoriasis treated with currently approved therapies: ixekizumab (IXE), an interleukin-17A antagonist, or guselkumab (GUS), an interleukin-23p19 inhibitor. We calculated the speed of response as the number of weeks to achieve first skin clearance, based on the Psoriasis Area and Severity Index (PASI) tool, and the cumulative response as the number of days with clear skin throughout the 24-week period. We found that the head region achieved skin clearance fastest and had a higher number of days with clear skin compared to the trunk, upper extremities, and lower extremities, in both groups of patients treated with IXE or GUS. Compared to GUS, IXE provided faster skin clearance and a higher number of days with clear skin in all body regions. For example, the head region of patients treated with IXE, as compared to GUS, achieved complete skin clearance twofold faster and experienced 18.7% more days of complete skin clearance. In conclusion, treatment with IXE through 24 weeks provided a faster response and a higher cumulative response than treatment with GUS in all four body regions of patients with moderate-to-severe plaque psoriasis. [ABSTRACT FROM AUTHOR]