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According to the Italian Medicines Agency (AIFA) guidelines, patients with moderate-to-severe psoriasis can access biological therapies in case of treatment failure or contraindication to at least one conventional systemic treatment. However, no studies have been conducted to investigate the potential influence of previous conventional systemic treatments on the efficacy of subsequently prescribed biologics. The purpose of this study was to evaluate whether patients treated with bimekizumab, a monoclonal anti-interleukin (IL)-17A/F drug, achieve Psoriasis Area and Severity Index (PASI) 90 at different times based on prior use of cyclosporine or methotrexate. Fifty-four patients were enrolled in this study; 29 had previously been treated with methotrexate and 25 with cyclosporine. There was a statistically significant difference in efficacy (measured by mean PASI score) at week 4 (p<0.01), with patients treated with methotrexate responding faster to bimekizumab. Females previously on treatment with cyclosporine responded better and faster, followed by females on methotrexate and then men on methotrexate. Men on cyclosporine showed a later response to bimekizumab. Our study confirmed that bimekizumab is a fast and effective biologic treatment for psoriasis. Patients previously treated with methotrexate responded faster to bimekizumab than those formerly treated with cyclosporine.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by painful nodules, abscesses, and draining tunnels in areas such as the axillae, groin, and inframammary regions. It typically emerges in early adulthood, with a global prevalence of approximately 1%, though regional variations exist. HS significantly affects patients’ quality of life and imposes considerable socioeconomic burdens. It is frequently associated with metabolic syndrome, inflammatory arthritis, and inflammatory bowel disease, reflecting its underlying systemic inflammatory nature. The pathogenesis of HS involves innate immune mechanisms, including macrophages, neutrophils, interleukin (IL)-1β, tumor necrosis factor-alpha (TNF-α), and granulocyte colony-stimulating factor, alongside adaptive immune responses mediated by T cells (IL-17, interferon-gamma [IFN-γ]) and B cells, which contribute to autoantibody formation and tertiary lymphoid structures. Chronic inflammation results in irreversible tissue damage, tunnel formation, and severe scarring. Treatment strategies vary based on disease severity. Early inflammatory stages benefit from pharmacological therapies, while later stages require a combination of medical and surgical interventions, with surgery often necessary for advanced cases. The introduction of targeted biologic therapies, including TNF-α (adalimumab) and IL-17 inhibitors (secukinumab, bimekizumab), has expanded treatment options beyond traditional antibiotic regimens. Effective management focuses on early intervention to prevent irreversible damage, control symptoms such as pain, and address systemic comorbidities. A timely diagnosis, along with a multidisciplinary and personalized approach, is essential for improving patient outcomes and quality of life.

Interleukin (IL)-17A is a key driver of inflammation and the principal target of anti-IL-17 therapeutic monoclonal antibodies. IL-17A, and its structurally similar family member IL-17F, have been shown to be functionally dysregulated in certain human immune-mediated inflammatory diseases such as psoriasis, psoriatic arthritis, and axial spondyloarthritis. Given the overlapping biology of these two cytokines, we postulated that dual neutralization of IL-17A and IL-17F may provide a greater depth of clinical response in IL-17-mediated diseases than IL-17A inhibition alone. We identified 496.g1, a humanized antibody with strong affinity for IL-17A but poor affinity for IL-17F. Affinity maturation of 496.g1 to 496.g3 greatly enhanced the affinity of the Fab fragment for IL-17F while retaining strong binding to IL-17A. As an IgG1, the affinity for IL-17A and IL-17F was 3.2 pM and 23 pM, respectively. Comparison of 496.g3 IgG1 with the commercially available anti-IL-17A monoclonal antibodies ixekizumab and secukinumab, by surface plasmon resonance and in a human IL-17A functional assay, showed that 496.g3 and ixekizumab display equivalent affinity for IL-17A, and that both antibodies are markedly more potent than secukinumab. In contrast to ixekizumab and secukinumab, 496.g3 exhibited the unique feature of also being able to neutralize the biological activity of IL-17F. Therefore, antibody 496.g3 was selected for clinical development for its ability to neutralize the biologic function of both IL-17A and IL-17F and was renamed bimekizumab (formerly UCB4940). Early clinical data in patients with psoriasis, in those with psoriatic arthritis, and from the Phase 2 studies in psoriasis, psoriatic arthritis, and ankylosing spondylitis, are encouraging and support the targeted approach of dual neutralization of IL-17A and IL-17F. Taken together, these findings provide the rationale for the continued clinical evaluation of bimekizumab in patients with immune-mediated inflammatory diseases.

IntroductionBimekizumab is a monoclonal antibody that targets Interleukin-17 A and F, approved for the treatment of moderate-to-severe plaque psoriasis. While bimekizumab has been evaluated in several phase-III clinical trials, real-world evidence is still very limited.MethodThis multicenter retrospective study included patients affected by plaque psoriasis treated with bimekizumab from May 1, 2022 to April 30, 2023, at 19 Italian referral hospitals. Patients affected by moderate-to-severe plaque psoriasis eligible for systemic treatments were included. The effectiveness of bimekizumab was evaluated in terms of reduction in psoriasis area and severity index (PASI) compared with baseline at weeks 4 and 16. The main outcomes were the percentages of patients achieving an improvement of at least 75% (PASI75), 90% (PASI90) and 100% (PASI100) in PASI score.ResultsThe study included 237 patients who received at least one injection of bimekizumab. One hundred and seventy-one patients and 114 reached four and 16 weeks of follow-up, respectively. Complete skin clearance was achieved by 43.3% and 75.4% of patients at weeks 4 and 16, respectively. At week 16, 86.8% of patients reported no impact on their quality of life. At week 16, there were no significant differences between bio-naïve and bio-experienced patients in terms of PASI75, PASI90 and PASI100. The most commonly reported adverse events (AEs) were oral candidiasis (10.1%). No severe AEs or AEs leading to discontinuation were observed throughout the study.ConclusionOur experience supports the effectiveness and tolerability of bimekizumab in a real-world setting with similar results compared with phase-III clinical trials.

The interleukin 17 (IL-17) family, a subset of cytokines consisting of IL-17A-F, plays crucial roles in host defence against microbial organisms and the development of inflammatory diseases, including psoriasis (PsO), axial spondyloarthritis (axSpA), and psoriatic arthritis (PsA). IL-17A is the signature cytokine produced by T helper 17 (Th17) cells and is considered the most biologically active form. The pathogenetic involvement of IL-17A in these conditions has been confirmed, and its blockade with biological agents has provided a highly effective therapeutical approach. IL-17F is also overexpressed in the skin and synovial tissues of patients with these diseases, and recent studies suggest its involvement in promoting inflammation and tissue damage in axSpA and PsA. The simultaneous targeting of IL-17A and IL-17F by dual inhibitors and bispecific antibodies may improve the management of Pso, PsA, and axSpA, as demonstrated in the pivotal studies of dual specific antibodies such as bimekizumab. The present review focuses on the role of IL-17F and its therapeutic blockade in axSpA and PsA.

Hidradenitis suppurativa (HS) is a chronic, debilitating inflammatory disorder of the hair follicles affecting areas rich in apocrine glands. Moderate-to-severe forms often require biologic therapies, including bimekizumab, a humanized monoclonal antibody that selectively inhibits IL-17A and IL-17F. Secukinumab, a fully human monoclonal antibody targeting IL-17A, and adalimumab, an anti-TNFα monoclonal antibody and the first biologic approved for HS, also represent established therapeutic options, reducing inflammatory lesions and pain with variable long-term response among patients. Approved in Europe and the USA in 2024 for HS, bimekizumab has shown promising efficacy in the BE HEARD I and II clinical trials, with significantly higher HiSCR response rates compared to placebo and improvements sustained through 48 weeks; the BE HEARD EXT extension study confirmed durable benefits at two years, with reduced disease severity and improved quality of life. This review included six studies (two trials, three case series, and one case report), highlighting consistent results in real-world settings, though limited by the drug's recent introduction. Observational studies reported significant reductions in IHS4, pain, and DLQI scores, with complete remission in some cases. The most frequent adverse events were mucocutaneous candidiasis, generally mild and manageable. Dual inhibition of IL-17A and IL-17F represents an innovative therapeutic approach for HS, with potentially greater efficacy than selective inhibitors. However, further large-scale, long-term real-world data are needed to confirm the drug's safety and effectiveness and to define the optimal role of bimekizumab in HS management.

Pyoderma gangrenosum (PG) is an inflammatory neutrophilic dermatosis with no FDA‐approved treatments. Current therapies, including corticosteroids and immunomodulators, often show limited efficacy and nonspecific, conferring to higher risk of adverse events. We report a case of a 60‐year‐old male with recalcitrant PG successfully treated with bimekizumab, an IL‐17 inhibitor. After two doses of monthly 320 mg subcutaneous injections, the patient experienced marked pain reduction and lesion resolution, with no adverse effects to‐date. This case highlights the efficacy of bimekizumab as a potential treatment for PG, warranting further controlled studies.

Background Bimekizumab, a monoclonal IgG1 antibody that selectively inhibits IL-17F in addition to IL-17A, showed efficacy to 2 years in patients with axial spondyloarthritis (axSpA). In this post hoc analysis, we compare the impact of shorter versus longer symptom duration on the efficacy of bimekizumab to Week 104. Methods Efficacy outcomes by symptom duration (≤ 2 [ASAS early axSpA definition] versus > 2 years; ≤ 5 versus > 5 years) were assessed across patients from BE MOBILE 1 and 2 (non-radiographic [NCT03928704]/radiographic axSpA [NCT03928743]) and the combined open-label extension (NCT04436640). (Relative) odds ratios and (relative) differences were calculated to compare 16-week bimekizumab versus placebo treatment effect and 104-week outcomes, and infer the significance of differences, between symptom duration subgroups. Analyses were neither powered for these comparisons nor multiplicity adjusted, and should be interpreted accordingly. Results Improved disease activity, physical function, fatigue, health-related quality of life and objective signs of inflammation were seen with bimekizumab versus placebo at Week 16 regardless of symptom duration. Outcomes were then sustained or improved with bimekizumab to Week 104 across all subgroups. 16-week bimekizumab versus placebo treatment effect was comparable between subgroups (e.g., ≤ 2-year versus > 2-year symptom duration relative odds ratio [95% CI] for ASDAS < 2.1 in BE MOBILE 1: 0.82 [0.22, 3.08]). Significant differences were observed for some 104-week outcomes between symptom duration subgroups across both studies (e.g., ≤ 5-year versus > 5-year symptom duration odds ratio [95% CI] for ASDAS < 2.1 in BE MOBILE 2: 1.94 [1.02, 3.68]), all favouring the shorter symptom duration subgroups. Conclusions Bimekizumab was efficacious to 2 years regardless of symptom duration, with comparable 16-week treatment effect but generally better 104-week outcomes in the shorter versus longer symptom duration subgroups. Trial registration Registered on ClinicalTrials.gov; NCT03928704 (BE MOBILE 1; 23rd April 2019), NCT03928743 (BE MOBILE 2; 23rd April 2019), NCT04436640 (BE MOVING; 15th June 2020).

The paradigm of psoriasis as a Th17-driven disease has evolved in the last years towards a much deeper knowledge of the complex pathways, mechanisms, cells, and messengers involved, highlighting the crucial role played by the IL-17 family of cytokines. All IL-17 isoforms signal through IL-17R. Five subunits of IL-17R have been described to date, which couple to form a homo- or hetero-receptor complex. Characteristically, IL-17RA is a common subunit in all hetero-receptors. IL-17RA has unique structural—containing a SEFIR/TILL domain—and functional—requiring ACT-1 for signaling—properties, enabling Th17 cells to act as a bridge between innate and adaptive immune cells. In psoriasis, IL-17RA plays a key role in pathogenesis based on: (a) IL-17A, IL-17F, and other IL-17 isoforms are involved in disease development; and (b) IL-17RA is essential for signaling of all IL-17 cytokines but IL-17D, whose receptor has not been identified to date. This article reviews current evidence on the biology and role of the IL-17 family of cytokines and receptors, with focus on IL-17RA, in psoriasis and some related comorbidities, and puts them in context with current and upcoming treatments.

Bimekizumab, a novel humanized monoclonal IgG1 antibody that neutralizes both IL-17A and IL-17F, was recently approved the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy. Bimekizumab represents the latest anti IL-17 treatment available for the management of moderate to severe psoriasis. Bimekizumab safety and efficacy profiles were evaluated in four Phase III clinical trials, which evaluated bimekizumab versus placebo and ustekinumab (BE VIVID), versus placebo (BE READY), versus adalimumab (BE SURE), and versus secukinumab (BE RADIANT). Overall, bimekizumab displayed promising results in terms of both efficacy and safety, allowing reach PASI90 and PASI100 in short time (as early as week 4) and maintain it in the long term (52 weeks), with acceptable safety profile. Also, bimekizumab showed a rapid onset of response and a higher efficacy when compared to adalimumab, ustekinumab and secukinumab, with comparable safety profile. Herein, we carried out a comprehensive literature review of the available literature data about bimekizumab in the treatment of moderate to severe psoriasis.