Johnny N MahlanguDepartment of Molecular Medicine and Haematology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South AfricaCorrespondence: Johnny N Mahlangu, Department of Molecular Medicine and Haematology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg, 2193, South Africa, Tel +27 11 489 8413, Email johnny.mahlangu@wits.ac.zaAbstract: Emicizumab, a bispecific factor VIIIa-mimetic antibody, has transformed hemophilia A prophylaxis by providing an effective subcutaneous treatment regardless of factor VIII inhibitor status. The HAVEN program established sustained reductions in treated bleeding, favorable safety, and reduced treatment burden across children and adults. More recent evidence has expanded its use into infancy, previously untreated patients, and selected people with moderate or mild hemophilia A, shifting treatment toward prevention before recurrent bleeding and joint damage occur. Real-world experience broadly confirms the trial’s efficacy but also highlights important limitations. Zero treated bleeds does not necessarily indicate absence of pain, synovitis, or progressive arthropathy. At the same time, breakthrough bleeding, laboratory assay interference, rare neutralizing anti-drug antibodies, and thrombotic complications associated principally with excessive activated prothrombin complex concentrate remain clinically relevant. Emicizumab controls bleeding in patients with factor VIII inhibitors but does not induce immune tolerance, leaving unresolved questions regarding inhibitor eradication, delayed factor VIII exposure, and optimal induction of immune tolerance. The next phase of development will require moving beyond uniform weight-based dosing and annualized bleeding rates toward individualized exposure, validated biomarkers, and outcomes that encompass joint structure, physical participation, quality of life, and treatment burden. Emicizumab must also be positioned against next-generation factor VIII mimetics, rebalancing therapies, sustained-exposure factor VIII replacement, and gene therapy. This review critically examines the established and emerging evidence, practical management challenges, unresolved scientific questions, and future therapeutic positioning of emicizumab. Its ultimate impact will depend not only on broader eligibility, but also on precision use, long-term safety, rational treatment sequencing, and equitable global access.Keywords: bispecific antibody, emicizumab, factor VIII inhibitors, hemophilia A, nonfactor therapy, prophylaxis
Francesco Catamerò,1,2 Simone Foti Randazzese,3 Davide Caimmi,4,5 Giovanni Paoletti,6,7 Giorgio Walter Canonica,6,7 Enrico Heffler,6,7 Andrea Giovanni Ledda,8 Stefano Del Giacco,8 Giulia Anna Maria Luigia Costanzo,8 Giuseppe Guida,9,10 Fabio Luigi Massimo Ricciardolo,9– 11 Francesca Bertolini,9 Remo Poto,12 Rory Chan,13 Gilda Varricchi,12,14 Mattia Giovannini1,21Department of Health Sciences, University of Florence, Florence, Italy; 2Allergy Unit, Meyer Children’s Hospital IRCCS, Florence, Italy; 3Pediatric Unit, Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, Pavia, Italy; 4Allergy Unit, Hôpital Arnaud De Villeneuve, University Hospital of Montpellier, Montpellier, Occitanie, France; 5IDESP, UMR 1318, University of Montpellier - INSERM, Montpellier, Occitanie, France; 6Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; 7Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy; 8Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy; 9Department of Clinical and Biological Sciences, University of Turin, Turin, Italy; 10Severe Asthma, Rare Lung Disease and Respiratory Pathophysiology Unit, San Luigi Gonzaga University Hospital, Orbassano, Italy; 11Institute of Translational Pharmacology, National Research Council (IFT-CNR), Palermo, Italy; 12Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy; 13University of Dundee, School of Medicine, Dundee, UK; 14Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, ItalyCorrespondence: Francesco Catamerò, Department of Health Sciences, University of Florence, Viale Pieraccini 24, Florence, 50139, Italy, Email francesco.catamero@unifi.itAbstract: Allergen immunotherapy (AIT) is the only available disease-modifying treatment for IgE-mediated allergic disease. Unlike conventional pharmacotherapy, AIT targets the underlying immune dysregulation driving allergic asthma (AA), with the potential to induce sustained off-treatment benefits. This narrative review examines the available evidence from both randomized controlled trials (RCTs) and real-world evidence to provide an updated and balanced overview of the clinical role of AIT in AA across different age groups. RCTs indicate that AIT can improve asthma symptom scores, reduce medication requirements and exacerbation risk, with additional steroid-sparing effects; however, findings are not consistent across trials. The strongest evidence is confined to house dust mite SLIT tablets, and the most recent Cochrane review judged the evidence insufficient for firm conclusions. Observational database studies enrolling up to 445,000 patients are consistent with these findings, reporting reductions in asthma events, medication use and treatment step-up, although their design precludes causal inference. Beyond symptomatic control, AIT has demonstrated a preventive role by interrupting the allergic trajectory, reducing the risk of new-onset asthma in patients with allergic rhinitis, and slowing progression to more severe asthma phenotypes. Long-term follow-up studies, mostly small and open in design, suggest that benefit may persist for up to 15 years after AIT discontinuation. Preliminary uncontrolled evidence also suggests that AIT may be feasible in selected patients with well-controlled severe asthma. In conclusion, AIT represents a uniquely positioned, disease-modifying strategy in the management of AA, with potential benefits spanning symptom control, prevention of disease onset and progression, and long-term benefits persisting after treatment discontinuation.Keywords: allergen immunotherapy, allergic asthma, SLIT, SCIT, disease-modifying, asthma prevention
Alhanouf Almousa,1 Mohamed Ahmed,2 Rayd Abdulaziz Almehizia,1 Meshal Aldurayhim,1 Gamal Mohamed,3 Almutairdi Abdulelah,4,5 Yousef Binamer,5,6 Ahmed Alshaikh71Pharmaceutical Care Division, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia; 2Formulary Management Department, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia; 3Research Laboratories Department, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia; 4Medicine Department (Gastroenterology), King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia; 5Alfaisal University, Riyadh, Kingdom of Saudi Arabia; 6Dermatology Department, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia; 7Medicine Department (Rheumatology), King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi ArabiaCorrespondence: Alhanouf Almousa, Pharmaceutical Care Division, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia, Email Alhanouf.fm@hotmail.comBackground: Adalimumab-atto, a biosimilar to adalimumab, has been widely adopted for managing autoimmune conditions due to its demonstrated safety, efficacy, and cost-effectiveness in clinical trials. However, real-world data from Saudi Arabian population remains limited.Objective: This study aimed to evaluate the persistence, safety, and clinical outcomes of patients transitioned from originator adalimumab (Humira®) to adalimumab-atto biosimilar (Amgevita®) at a tertiary care center.Methods: A retrospective self-controlled cohort study was conducted, including all patients transitioned to adalimumab-atto between January 1 and December 31, 2022, for non-medical reasons. The primary endpoint was treatment persistence at 12 months. Secondary endpoints included disease stability, adverse events, and reasons for discontinuation.Results: The study included 265 adult patients previously treated with originator adalimumab. The mean age of the cohort was 41 ± 13 years, with 46.8% being female. The most common indications were Crohn’s disease (40.4%), rheumatoid arthritis (16.6%), and plaque psoriasis (12.1%), with a mean disease duration of 11.7 ± 6.7 years. At 12 months, 90.2% of patients persisted with adalimumab-atto, of whom 79.5% remained stable, while 20.5% were classified as unstable Twenty-six patients (9.8%) discontinued therapy, primarily due to insufficient efficacy (13 patients), with one discontinuation attributed to adverse events.Conclusion: Adalimumab-atto demonstrated high treatment persistence and favorable safety outcomes in a diverse population of patients with autoimmune diseases. These findings support the feasibility of continued use of the biosimilar in patients with immune-mediated diseases.Keywords: Adalimumab-atto, biosimilars, non-medical switching, treatment persistence, real-world evidence, immune-mediated diseases
Kamila Zawadzińska-Halat,1 Magdalena Stec,1 Katarzyna Poznańska-Kurowska,2,3 Maciej Pastuszczak11Clinical Department of Dermatology, Medical University of Silesia, Zabrze, Poland; 2Department of Dermatology, Pediatric Dermatology and Oncological Dermatology, Dr. W. Bieganski Regional Hospital, Łódź, Poland; 3Clinic of Occupational Diseases and Environmental Health, Nofer Institute of Occupational Medicine, Łódź, PolandCorrespondence: Maciej Pastuszczak, Email pastuszczak.maciej@gmail.comAbstract: Netherton syndrome is a rare and severe genodermatosis caused by pathogenic variants in SPINK 5, leading to epidermal barrier dysfunction, immune dysregulation, and prominent atopic manifestations. Therapeutic options remain limited, and long-term real-world data on biologic treatment are scarce. We report a retrospective two-center real-world case series of six patients with Netherton syndrome treated with dupilumab, with emphasis on long-term outcomes, safety, and clinical effects beyond eczema control. Five patients were managed at one dermatology referral center and one patient at a second center. Clinical data were collected retrospectively from medical records, including disease severity scores, pruritus, quality of life, genetic findings, comorbidities, treatment duration, adverse events, and additional clinically relevant observations. Dupilumab was initiated because of severe, chronic, and refractory inflammatory skin disease with intense pruritus and impaired quality of life. Follow-up ranged from 13 to 34 months. All patients achieved sustained, clinically meaningful improvement in inflammatory skin lesions, pruritus, and quality of life, although complete remission was not observed. Treatment was well tolerated, including in patients with recurrent infections, immunodeficiency-like features, severe food allergy, and a history of acute lymphoblastic leukemia. Additional observations included improvement in hair abnormalities and sweating in selected patients, reduced infectious burden, improved growth parameters, and absence of further anaphylactic episodes in one patient. These findings suggest that dupilumab may represent a valuable long-term therapeutic option for Netherton syndrome with prominent type 2 inflammatory features. Potential benefits beyond eczema control should be regarded as hypothesis-generating and require confirmation in larger multicenter studies.Keywords: Netherton syndrome, dupilumab, SPINK 5, trichorrhexis invaginata, ichthyosiform erythroderma, biologic therapy, atopic dermatitis
