Improving Outcomes in Patients with Psoriasis and Psoriatic Arthritis: A Focus on Interleukin Inhibitors

Psoriasis (PsO) and psoriatic arthritis (PsA) are common inflammatory conditions that significantly impact patients' quality of life. Joseph Merola, MD, presented at Fall Dermatology Week an in-depth exploration of the role of interleukin (IL) inhibitors in improving outcomes for patients with these diseases. This session covered the pathogenesis, burden of disease, and therapeutic interventions for PsO and PsA, with a specific focus on IL inhibitors.

Dr Merola reiterated that psoriasis is primarily a disease of the skin, characterized by excessive keratinocyte proliferation leading to the formation of plaques. The pathogenesis of PsO is driven by a complex interplay of innate and adaptive immune responses. Central to this process are the IL-23 and IL-17 pathways. IL-23 stimulates the differentiation of T-helper (Th) cells into Th17 cells, which produce IL-17, IL-22, and other pro-inflammatory cytokines that contribute to keratinocyte activation and the subsequent development of psoriasis. Keratinocytes are not passive participants; they actively contribute to the inflammatory cycle, perpetuating the disease.

PsA shares similar immune mechanisms with PsO, involving Th17 cells and cytokines like IL-23 and IL-17. However, in PsA, the inflammatory response extends beyond the skin, affecting the joints and leading to synovitis, enthesitis, and, in severe cases, bone erosion and deformity. Both diseases, although distinct in manifestation, share common immune pathways, which provides a rationale for using similar treatments for both.

PsO, even in its mild form, significantly burdens patients. The UPLIFT survey demonstrated that even patients with mild PsO experience substantial impacts on their quality of life, as measured by the Dermatology Life Quality Index. Despite the high burden of disease, many patients with moderate to severe PsO are undertreated, with a substantial proportion still relying on topical treatments or receiving no systemic therapy at all. This indicates a gap in PsO management, with many patients not receiving the appropriate care for their disease severity.

Similarly, PsA is often undiagnosed, with studies showing that a large percentage of patients with psoriasis have PsA that remains unidentified until later in their disease course. Early diagnosis of PsA is crucial, as delays of even 6 months can lead to worse outcomes, including joint damage and functional disability. Dermatologists are often the first health care providers to see psoriasis patients, and they play a critical role in screening for PsA. This includes assessing symptoms, such as joint pain, stiffness, and swelling, as well as using tools like the PEST PsA screening tool and the "PSA" mnemonic to identify at-risk patients.

Next, Dr Merola shared that the treatment of PsO and PsA has evolved significantly with the advent of biologic therapies targeting specific cytokines. IL-23 and IL-17 inhibitors are now at the forefront of therapeutic strategies due to their potent ability to suppress the immune pathways responsible for both skin and joint disease.

IL-23 plays a pivotal role in the pathogenesis of both PsO and PsA, making IL-23 inhibitors an important class of biologics. Ustekinumab, an older IL-23 inhibitor, targets the shared P40 subunit of IL-12 and IL-23. More recently, IL-23-specific inhibitors, such as guselkumab, tildrakizumab, and risankizumab, have been developed. These drugs block the P19 subunit of IL-23, effectively inhibiting its downstream effects on Th17 cell differentiation and cytokine production, which are central to the inflammatory processes in PsO and PsA.

IL-17 inhibitors, including secukinumab and ixekizumab, target the IL-17A cytokine, which is a key effector in both PsO and PsA. These drugs block IL-17A homodimers and heterodimers, effectively reducing the inflammatory response that drives disease pathology. Brodalumab, another IL-17 inhibitor, blocks the IL-17 receptor, preventing the action of all IL-17 family members (A, C, and E). A newer agent, bimekizumab, targets both IL-17A and IL-17F, showing promise in treating PsO, although it has yet to be approved for PsA.

Dr Merola stressed that when approaching the treatment of PsO, it is essential to assess the severity of disease, the presence of PsA, and the impact on the patient's quality of life. For patients with PsO alone, the treatment approach depends on disease severity, with topical treatments used for mild disease and systemic therapies, including biologics, considered for moderate to severe cases. The presence of PsA necessitates a more aggressive systemic treatment approach, often combining biologics with other disease-modifying agents.

For PsA, treatment must be tailored to the specific domains of disease, such as peripheral arthritis, axial disease, enthesitis, and dactylitis. Various outcome measures are used to assess the efficacy of treatment across these domains, including the American College of Rheumatology scores for peripheral arthritis and the Minimal Disease Activity measure, which evaluates overall disease control across multiple domains. Radiographic progression, indicating joint damage and erosion, is another critical outcome that needs to be monitored.

Dr Merola concluded that IL-23 and IL-17 inhibitors represent significant advancements in the treatment PsO and PsA. These biologic therapies target the central immune pathways driving both conditions, providing more effective options for achieving disease control and improving patient outcomes. However, despite these advancements, undertreatment remains a concern, particularly in patients with mild to moderate disease. Early diagnosis and intervention, especially in the case of PsA, are essential to prevent long-term damage and improve patient quality of life. As the field continues to evolve, dermatologists and rheumatologists must remain vigilant in screening, diagnosing, and treating patients with PsO and PsA to ensure optimal outcomes.

Reference
Merola J. Improving outcomes in patients with psoriasis and psoriatic arthritis: a focus on interleukin inhibitors. Presented at: Dermatology Week; November 13–16, 2024; Virtual.