A Closer Look at IL-17 Inhibitors in Psoriasis

Panelists discuss how IL-17 is a key pro-inflammatory cytokine in plaque psoriasis pathogenesis. It stimulates keratinocyte proliferation, promotes neutrophil recruitment, induces antimicrobial peptides, and up-regulates other inflammatory mediators, creating a self-perpetuating inflammatory cascade in lesional skin.

Panelists discuss how IL-17 inhibitors differ in their targets within the IL-17 pathway. Secukinumab and ixekizumab block IL-17A, reducing inflammation in psoriasis and arthritis. Brodalumab inhibits IL-17RA, affecting multiple IL-17 cytokines, but carries suicide risk warnings. Bimekizumab targets IL-17A and IL-17F, potentially enhancing efficacy but with added risk of infections. These differences impact efficacy, safety, and patient selection in inflammatory diseases.

Panelists discuss how IL-17 inhibitors are biologics that target the inflammatory cytokine IL-17 pathway. They demonstrate rapid onset of action, with measurable improvement in most patients within 2 to 4 weeks and peak efficacy by 12 to 16 weeks. They achieve high rates of skin clearance in psoriasis patients and maintain efficacy with long-term use.

Panelists discuss how inhibition of IL-17 in psoriasis treatment significantly improves quality of life by reducing inflammation, skin lesions, itching, and pain. Patients report better psychological well-being, increased social confidence, and improved daily functioning as inflammatory pathways are interrupted.

Panelists discuss how IL-17 inhibitors are considered for plaque psoriasis based on disease severity, comorbidities, and patient preference. Selection factors include efficacy, safety, access, and cost. Clinical trial data guide choices, but real-world factors impact use. Dosing varies: secukinumab (300 mg weekly for 5 weeks, then monthly), ixekizumab (160 mg at week 0, then 80 mg biweekly for 12 weeks, then monthly), brodalumab (210 mg weekly for 3 weeks, then biweekly), and bimekizumab (320 mg every 4 weeks for 16 weeks, then every 8 weeks). Dosing and device options influence prescribing decisions.

Panelists discuss how IL-17 inhibitors are generally well-tolerated, but common adverse effects include infections, particularly candidiasis, and potential increased suicidal ideation risk. Patients should be informed of candidiasis risk, especially with bimekizumab (Gordon, 2022), and monitored for mood changes, as IL-17s and IL-23s may impact mental health (Blauvelt, 2023). Open discussions help assess risks while ensuring treatment benefits.

Panelists discuss how when prescribing an IL-17 inhibitor, key safety considerations include infection risk (particularly tuberculosis and fungal infections), inflammatory bowel disease exacerbation, allergic reactions, neutropenia, immunogenicity, vaccination timing, pregnancy/breastfeeding status, malignancy history, and monitoring requirements for adverse events.

Panelists discuss how long-term data confirm the sustained efficacy and safety of IL-17 inhibitors in psoriasis. Secukinumab (Bissonnette, 2018; Langley, 2022) and ixekizumab (Blauvelt, 2021) show durable PASI responses over 5 years. Brodalumab’s 5-year pharmacovigilance (Lebwohl, 2024) and 120-week data (Puig, 2020) support its long-term use. Bimekizumab’s 4-year data (Blauvelt, 2024; Gordon, 2024) demonstrate continued efficacy, with 5-year results anticipated at AAD 2025.

Panelists discuss how head-to-head trials in psoriasis provide direct efficacy and safety comparisons between IL-17 inhibitors and other drug classes. Studies like BE RADIANT, BE VIVID, and IXORA-R highlight bimekizumab’s and ixekizumab’s superiority over secukinumab and ustekinumab. CLARITY and COBRA compare IL-17 to IL-23 inhibitors, while IMMerge and BE BOLD explore risankizumab’s role. These trials inform treatment decisions by guiding biologic selection based on efficacy, durability, and safety.

Panelists discuss how medical professionals anticipate new IL-17 inhibitor data, particularly from head-to-head trials like BE BOLD. Interest is growing in sonelokimab, an IL-17A/F nanobody (Papp, 2021). Further research is needed on long-term efficacy, safety, and optimal patient selection.