In this episode of Topical Conversations, Brad Glick, DO, and Jason Hawkes, MD, discuss the use of IL-17 inhibitors in managing psoriasis and psoriatic arthritis, with a focus on ixekizumab. Their conversation highlights the immunologic basis of IL-17, the safety and efficacy of ixekizumab, and its role in addressing the complex interplay of skin and joint symptoms in psoriatic disease.
The role of IL-17 in psoriasis
They begin by explaining that IL-17 plays a dual role in skin health. It provides natural protection against infections like candidiasis; however, excessive levels of IL-17 can drive keratinocyte hyperproliferation, leading to the scaling and plaque formation characteristic of psoriasis.
Ixekizumab, by targeting IL-17A, helps normalize keratinocyte activity and significantly improves psoriasis symptoms. This mechanism of action also explains why some patients develop candidiasis during treatment, as blocking IL-17 reduces natural defenses against infections like candidiasis.
Managing safety concerns
While ixekizumab does not cause inflammatory bowel disease (IBD), it can exacerbate symptoms in patients with preexisting IBD. For patients who present with both psoriasis and IBD, clinicians need to carefully weigh the benefits of improved skin symptoms against the potential for worsening gastrointestinal issues. Monitoring and patient education are essential to ensure that risks are understood and managed effectively.
Candidiasis, a known side effect of IL-17 inhibition, also requires consideration. By understanding the underlying immunologic mechanisms, dermatologists can counsel patients appropriately and address concerns about this potential complication.
Efficacy of ixekizumab in psoriasis
Clinical trials, including the UNCOVER studies, have demonstrated ixekizumab’s high efficacy in psoriasis treatment. The trials revealed significant rates of disease clearance, with about half of patients achieving PASI 100. These outcomes represent a substantial improvement over earlier treatments like methotrexate and TNF inhibitors.
However, patient characteristics such as body weight can influence outcomes. For patients with higher body weights, efficacy may decrease, potentially due to the pro-inflammatory effects of adipose tissue. These findings highlight the importance of tailoring treatment approaches to individual patient profiles.
Ixekizumab and psoriatic arthritis
Psoriatic arthritis (PsA), a common comorbidity of psoriasis, remains challenging to treat. While ixekizumab and other IL-17 inhibitors have shown moderate efficacy in managing joint symptoms, they are highly effective for skin improvement. Dermatologists must set realistic expectations with patients, explaining that while dramatic skin improvements are likely, joint symptoms may respond more slowly or to a lesser degree.
Exploring future approaches
Emerging research is investigating the potential synergy of IL-17 inhibitors with GLP-1 receptor agonists. This approach aims to address systemic inflammation associated with obesity, which is linked to higher risks of diabetes, cardiovascular disease, and poorer psoriasis outcomes. By targeting both psoriasis and metabolic health, this strategy could offer comprehensive benefits, though further studies are needed to clarify its impact.
Key takeaways for dermatologists
Ixekizumab represents a significant advancement in psoriasis treatment, due to its high efficacy and targeted action. While considerations such as candidiasis risk and IBD management are important, this IL-17 inhibitor remains a strong option for dermatologists, with its potential for future innovations further underscoring its value in advancing patient care.
In the first DermInsider - A Virtual Grand Rounds Series session of the year, join leading experts Dr. Bhutani and Dr. Serota for a dynamic deep dive into one of the most exciting frontiers in psoriatic disease management. Dr. Del Rosso moderates this 45-minute activity that explores the rapidly emerging role of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and their potential impact beyond metabolic disease. Don't miss out on this opportunity to catch up on breakthrough insights and emerging evidence on this hot topic!“We have some really interesting data on the horizon that’s going to hopefully help more providers feel confident about using [GLP-1] medications in conjunction with their psoriasis medications that they are used to using.” – Tina Bhutani, MD MASBest of FC25: GLP-1RAs in Psoriasis – Catching Up on The ScienceThis activity is supported by an educational grant from Lilly.
Got a few minutes? Join our expert faculty for their rapid-fire tips on getting started with GLP-1 receptor agonists for patients with psoriasis and obesity.“When we are treating patients with obesity and psoriasis in weight management, really focus on the health gains. It’s not about what people are losing, it’s about what they are gaining in this process.” – Angela Fitch, MDPlease visit the “Educational Resources” page to access the handouts developed by faculty on GLP's in psoriatic disease mentioned in this activity.This activity is supported by an educational grant from Lilly.
In this 20-minute Seminar in Depth from the 2025 Fall Clinical Dermatology Conference, the faculty explore what differentiates TYK2 inhibitors from traditional JAK inhibitors, as well as how to identify patients with psoriasis who may benefit from oral small molecule therapy.“When thinking about a medication, you need to take a number of things into consideration: location of disease, disease severity, and age. Age plays a big role when I think about what medication I’m going to choose for a patient – Are they of child-bearing age? Are they young and they live in group housing or a dorm?” – Benjamin Lockshin, MDFC25: Encapsulating Progress With New and Emerging TYK2 Inhibitors for Psoriasis: An Online ActivityThis activity is supported by an educational grant from Bristol Myers Squibb.