Dear Editor, Plaque psoriasis is the most common form of psoriasis, presenting as erythematous plaques with silvery scales on the scalp and extensor surfaces of the body1,2. These plaques produce tiny pinpoint bleeding spots when removed1. The disease is characterized by periods of remission and exacerbation, typically triggered by trauma, infections, medications, or stress2. It is increasingly recognized not only as a dermatological condition but also as a systemic inflammatory disease involving multiple systems1,2. Other clinical variants of psoriasis include guttate psoriasis, erythrodermic psoriasis, inverse psoriasis, and pustular psoriasis, each with distinct clinical features and varying severity1. Psoriasis affects both males and females, with earlier onset seen in females and individuals with a positive family history1. Psoriasis is driven by the interaction between dendritic cells, T-cells, and keratinocytes, with interleukin-23 (IL-23)/Th17 pathways acting as the key mediators for inflammation and rapid skin cell buildup1,2. Activated dendritic cells produce IL-23, which promotes the survival and differentiation of Th17 cells1. These cells secrete proinflammatory cytokines such as IL-22, IL-17F, and IL-17A, leading to keratinocyte hyperproliferation1. Tumor necrosis factor-alpha also plays a synergistic role in the amplification of inflammation1,2. The cure for psoriasis has not been achieved, but several therapies are available for the management of skin involvement, including topical therapies, oral systemic therapies, phototherapy, and biologics1. Topical therapies remain the first line in the management of mild disease1. These include vitamin D analogs, corticosteroids, topical retinoids like tazarotene, and calcineurin inhibitors for sensitive areas1. These agents work by decreasing keratinocyte proliferation and reducing inflammation1,2. However, adherence can be limited due to local side effects or inconvenience1,2. For moderate disease, phototherapy (preferably narrowband ultraviolet B) along with conventional systemic agents, namely methotrexate, ciclosporin, and acitretin, are used1. Phototherapy induces T-cell apoptosis and alters the cytokine profile, while systemic agents act through varying immunomodulatory mechanisms1. Ciclosporin suppresses calcineurin-mediated T-cell activation, methotrexate inhibits dihydrofolate reductase and reduces T-cell activity, and acitretin modulates keratinocyte differentiation1. Despite their effectiveness, these therapies are limited by cumulative toxicity, organ-specific adverse effects, and a need for laboratory monitoring1. The US Food and Drug Administration has recently approved IcotydeTM (Icotrokinra) as an oral treatment for moderate-to-severe plaque psoriasis in patients ≥12 years who weigh at least 40 kg and are candidates for phototherapy or systemic therapy3. Icotrokinra is a novel, first-in-class IL-23 receptor antagonist that can be taken orally once daily to manage plaque psoriasis3. IL-23 is a key component of the immune signaling pathway involved in psoriasis-related inflammatory reactions2. By inhibiting this pathway, Icotrokinra helps reduce the inflammation that drives plaque formation and other symptoms of plaque psoriasis2,3. The approval was based on Phase 3 ICONIC clinical development program, comprising four randomized controlled trials3. ICONIC-ADVANCE 1 (NCT06143878) and ICONIC-ADVANCE 2 (NCT06220604) enrolled 1505 adults in whom Icotrokinra was assessed against placebo for two co-primary endpoints: Investigator’s Global Assessment (IGA) 0/1 response and at least 90% improvement in the Psoriasis Area and Severity Index (PASI) from baseline (PASI 90)4,5. The results were evaluated at Week 16, where Icotrokinra showed improved outcomes compared to placebo3–5. ICONIC-LEAD (NCT06095115) and ICONIC-TOTAL (NCT06095102) included a total of 995 participants, out of whom 72 individuals were pediatric subjects aged ≥12 years who weighed at least 40 kg, proving its efficacy in the pediatric age-group as well6,7. The primary endpoints in ICONIC-LEAD (NCT06095115) were PASI 90 and IGA 0/1 response, while in ICONIC-TOTAL (NCT06095102), the primary endpoint was IGA 0/1 response6,7. Icotrokinra was evaluated against placebo and demonstrated improvements across all endpoints6,7. Icotrokinra is well-tolerated, with the most common adverse effects (≥1%) including headache, cough, fungal infections, fatigue, and nausea3. Treatment with Icotrokinra should be avoided in the presence of an ongoing clinically significant infection until the infection resolves or is adequately treated3. Potential adverse effects should be monitored in individuals with renal impairment and an estimated glomerular filtration rate <60 mL/min3. IcotydeTM (Icotrokinra) represents a newer therapeutic option for moderate-to-severe plaque psoriasis that may help address certain unmet needs, particularly in individuals with an inadequate response, intolerance, or contraindications to existing systemic and biologic therapies. By targeting key inflammatory pathways involved in psoriasis, it expands the available treatment landscape and offers an additional mechanism of action that may be useful in broadening therapeutic options. However, while clinical trial data demonstrate efficacy and adequate safety, long-term data is still required to better determine the durability of response, safety, and potential long-term adverse effects of the drug.
Abid et al. (Wed,) studied this question.