BACKGROUND:In the global Vivacity-MG3 study, nipocalimab (30-mg/kg loading dose; 15-mg/kg every-2-weeks) demonstrated sustained disease control versus placebo plus standard-of-care for generalized myasthenia gravis (gMG); this post-hoc analysis evaluated nipocalimab efficacy for participants with moderate-to-severe ocular symptoms (baseline score of ≥2-points on either ocular-domain item of MG-Activities-of-Daily-Living [MG-ADL]). RESEARCH DESIGN AND METHODS:Mean MG-ADL and Quantitative Myasthenia Gravis total scores change-from-baseline (CFB) through Week (W)24 were assessed using ANCOVA. W24% of participants with ≥2-point improvement in MG-ADL total (meaningful-within-person-improvement) or ocular-domain scores were compared using odds ratios (OR). Longitudinal odds of ≥2-point ocular-domain improvement were evaluated using generalized-estimating-equations logistic models. RESULTS:Nipocalimab (n = 54/77) and placebo-treated (n = 51/76) participants with moderate-to-severe ocular symptoms had similar baseline (mean[SD]) MG-ADL total (10.1[2.8];9.4[1.9]); ocular-domain scores were 4.1 (1.2);3.5 (1.0). At W24, LS-mean(SE) CFB for nipocalimab versus placebo were -4.71 (0.50) versus -3.24 (0.50), p = 0.042 (MG-ADL total) and median (IQR) -2.00 (-3.0 to -0.5) versus -1.00 (-1.5 to 0.0), p = 0.024 (ocular-domain). W24 ≥ 2-point ocular-domain improvements were observed with nipocalimab (40.7%) versus placebo (19.6%; OR = 3.47 [95% CI = 1.34-8.97]; p = 0.010). Adverse events: 77.8% (nipocalimab); 76.5% (placebo). CONCLUSION:These hypothesis-generating results suggest nipocalimab may provide sustained disease control, reduce ocular symptoms, and improve activities-of-daily-living versus placebo in participants with gMG and moderate-to-severe ocular symptoms. CLINICAL TRIAL REGISTRATION:www.clinicaltrials.govidentifier is NCT04951622;www.clinicaltrialsregister.euidentifier is 2020-005732-29.
INTRODUCTION:The molecular and architectural complexity of bispecific antibodies can introduce developability risks beyond those encountered with conventional monospecific antibodies. Therefore, whether developability should be integrated into the discovery process rather than used as a late-stage filter is an increasingly important question. AREAS COVERED:This structured narrative review examines literature identified in PubMed/MEDLINE, Embase, Scopus and Web of Science from database inception, supplemented by citation tracking. Molecular engineering, sequence-, structure-, and machine-learning-based prediction, architecture-related, inherited, and emergent liabilities, and material-efficient tests for assembly, stability, and pharmacokinetic risk are all assessed. For candidate ranking and nomination, a four-tier design-predict-screen-redesign methodology that is iterative and rooted in the goal product profile is suggested. EXPERT OPINION:Developability across bispecific formats cannot be captured by a single computational score or individual assay. Rather, computational predictions should serve to generate testable hypotheses, while candidate nomination requires verified molecular identity, correctly assembled yield, orthogonal testing of purified constructs, and validation under conditions directly relevant to the formulation, administration route, and mechanism of action. Ultimately, field-wide advancement hinges on format-diverse datasets, assay-resolved labels, identity-aware external validation, and prospective evidence.
BACKGROUND:Enfortumab vedotin (EV) has transformed treatment for advanced urothelial carcinoma (aUC), but outcomes vary. Machine learning (ML) with explainable artificial intelligence (XAI) may improve survival prediction. METHODS:Data from 544 aUC patients receiving EV after platinum chemotherapy and immunotherapy (51 centers, 24 countries) were analyzed. Four machine learning (ML) algorithms (Random Survival Forest, XGBoost, Elastic Net-regularized Cox, Support Vector Machine) were trained (80%) and tested (20%) to predict overall survival (OS). SHapley Additive exPlanations (SHAP) analysis (on best performing ML model) provided interpretability. Performance was assessed by C-index and time-dependent area-under-the-curve (AUC). RESULTS:XGBoost (C-index 0.59) and Elastic Net (C-index 0.60) showed best discrimination. XGBoost achieved highest time-dependent AUCs (0.77, 0.87, 0.93 at 1, 2, 3 years). SHAP identified prior immunotherapy (pembrolizumab, atezolizumab/nivolumab), radiotherapy, and upper tract tumors with lower mortality risk; lung, liver, bone, soft tissue metastases increased risk. Eastern Cooperative Oncology Group performance status and metastatic distribution were key predictors. CONCLUSION:ML with XAI identifies clinically plausible survival predictors in EV-treated aUC. XGBoost and Elastic Net offer modest risk stratification, that are hypothesis generating but does not support routine clinical use. Functional status, metastatic pattern, and treatment context are key drivers, providing a foundation for externally validated prognostic tools.
INTRODUCTION:Omalizumab, a humanized anti-immunoglobulin E (IgE) monoclonal antibody approved for chronic spontaneous urticaria (CSU), is increasingly used off-label across a range of dermatoses linked by IgE-mediated and mast cell-driven mechanisms, exemplifying the concept of mechanism-based drug repositioning. AREAS COVERED:This review examines the molecular pharmacology, pleiotropic mechanisms, and clinical evidence for omalizumab in established and emerging dermatologic indications, including CSU, chronic inducible urticarias, bullous pemphigoid, mastocytosis, prurigo nodularis, hyper-IgE syndrome, eosinophilic dermatoses, and other refractory conditions. A literature search of PubMed, Scopus, Embase, and Google Scholar through May 2026 informed the synthesis, with particular emphasis on therapeutic positioning relative to newer targeted biologics and oral agents. EXPERT OPINION:Bullous pemphigoid represents the most clinically compelling near-term indication, supported by a coherent autoreactive-IgE rationale and a candidate predictive biomarker (anti-BP180 IgE); biomarker-stratified trials are now essential to define its role alongside the recently FDA-approved dupilumab. Clinical response does not require elevated baseline IgE, arguing against serum IgE as a strict selection criterion. Biosimilar availability may reposition omalizumab as a cost-effective option, particularly in resource-limited settings, even as newer interleukin IL-4/IL-13, IL-31, and oral Bruton tyrosine kinase (BTK)-targeted therapies reshape treatment algorithms. Biomarker-stratified controlled trials remain the principal research priority.
INTRODUCTION:Islet transplantation has long been considered a potential long-term treatment for type 1 diabetes mellitus (T1DM); however, the need for systemic immunosuppression has limited its clinical utility due to associated toxicity. Gene-edited hypoimmune islets represent a promising immunosuppression-free alternative. Recent first-in-human data demonstrating short-term engraftment and C-peptide production without immunosuppression, with 12-week immune monitoring and extended 14-month follow-up, provide an important proof-of-concept. However, whether short-term immune evasion can translate into durable long-term graft survival remains unclear. AREAS COVERED:We critically evaluate current preclinical and clinical evidence from 2019 to 2026 for gene-edited hypoimmune islets, highlighting key immunological vulnerabilities that may emerge over time. EXPERT OPINION:The central question is no longer whether these islets can evade acute rejection, but whether they can sustain this evasion and efficacy long-term against the human immune system. Several theoretical mechanisms may contribute to delayed graft injury: indirect allorecognition (particularly non-HLA antibody formation), persistence of autoreactive immune memory, β-cell stress-induced neoantigen formation, and susceptibility to viral infection. Durable graft survival will likely require multimodal approaches combining gene-edited islets with adjunct immunomodulation (e.g. teplizumab, low-dose ATG, tegoprubart) and metabolic support. If these long-term challenges can be overcome, gene-edited hypoimmune islets could transform T1DM treatment paradigms.
INTRODUCTION:Chimeric antigen receptor (CAR) T cell therapy has shown efficacy in the treatment of hematological malignancies. However, the application to a broader patient population is still limited by the complex logistics in coordinating the lymphodepleting chemotherapy and the labor-, time-, and cost-intensive ex vivo manufacturing of patients' CAR T cells in specialized centers. By combining recent advances in lipid nanotechnology, RNA chemistry, and viral particle targeting, engineering CAR T cells in the patient's bloodstream is becoming an emerging option that may overcome current limitations. Advanced pre-clinical and early clinical studies support this approach by demonstrating successful engineering of CAR T cells in vivo and producing some anti-tumor responses in clinical trials. AREAS COVERED:We review delivery strategies using viral and non-viral vectors, summarize the translation into clinical application, and outline strategies for optimization. We further discuss current challenges with respect to targeting specificity, genomic safety, pharmacokinetics, host immune responses, and regulatory oversight. EXPERT OPINION:Although still in its infancy, in vivo genetic engineering shows promise for CAR T cell therapy in a wide range of cancer patients. It also has the potential to reprogram patients' immunity in autoimmunity, chronic infections, and regenerative medicine.
INTRODUCTION:Immune checkpoint inhibitors (ICIs) have transformed oncology by targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1), thereby enabling responses across multiple malignancies. Despite these advances, benefits remain limited in many cancers. AREAS COVERED:A narrative literature review was conducted using PubMed, Embase, and the Cochrane Library to identify English-language publications from 1 January 2000, through 31 December 2025. Eligible sources included pivotal trials, real-world studies, reviews, and relevant clinical practice guidelines. EXPERT OPINION:Since 2011, ICIs have permeated virtually all fields of oncology, with meaningful impact across many cancer types. Beyond expanding indications, they offer potential for durable benefit in many responders. In melanoma, head and neck, kidney, liver, and urothelial cancers, PD-L1 testing outside clinical trials is no longer required. Tumor-agnostic efficacy of PD-1 ± CTLA-4 inhibition in microsatellite instability-high cancers is well established. Limited benefit in other cancer subsets highlights the need for biomarker discovery and optimization of therapeutic strategies, including addition of antibody-drug conjugates to ICIs, next-generation checkpoint modulation, personalized neoantigen vaccines, and engineered cellular immunotherapy. Effective future therapies should also address comprehensive profiling of tumor cells, their molecular expression patterns, and constantly changing dynamics of the tumor microenvironment.
INTRODUCTION:Allergen immunotherapy (AIT) is the only disease-modifying treatment for IgE-mediated allergic disorders, including allergic rhinitis and asthma, with established long-term clinical efficacy and immunological tolerance induction. AREAS COVERED:This review synthesizes current evidence on the potential extra-allergic effects of AIT, focusing on respiratory tract infections (RTIs), SARS-CoV-2 outcomes, and selected immune-mediated conditions. AIT modulates key immunopathological pathways by promoting regulatory T and B cell responses, increasing allergen-specific IgG4, and rebalancing Th1/Th2 immunity. Emerging data suggest that these effects may extend beyond allergy control, with observational and limited clinical studies indicating reduced RTIs burden, decreased medication use, and enhanced antiviral responses, including improved interferon-mediated epithelial immunity. Preliminary findings also suggest an association between AIT and milder COVID-19 outcomes. Evidence regarding autoimmune conditions, such as alopecia areata, remains limited and largely anecdotal. EXPERT OPINION:Although AIT demonstrates promising immunomodulatory properties beyond allergic disease, current evidence is heterogeneous and primarily observational, precluding causal inference. The broader clinical relevance of these effects remains to be established. Well-designed prospective studies integrating clinical and mechanistic endpoints are required to clarify the extent and clinical significance of AIT-induced systemic immune modulation.
INTRODUCTION:Psoriasis is a chronic immune-mediated disease with physical and psychosocial burden that is not fully captured by measures of skin lesion characteristics. Advances in therapies, including multiple biologic treatments, have improved disease control, but gaps remain in aligning treatment with patient-reported outcomes and preferences. AREAS COVERED:The purpose of this paper is to discuss how patient centered approaches to psoriasis treatment have changed over time and what methods have been used to provide this treatment. A PubMed search was performed to identify articles that could provide information for our review. EXPERT OPINION:Many current therapies are highly effective in improving skin clearance, but they vary in how well they address factors that matter to patients, such as symptom burden, convenience, and side effects. The literature highlights the importance of incorporating patient-reported outcomes and shared decision-making when selecting treatments. Tailoring therapy based on individual preferences, comorbidities, and lifestyle is increasingly emphasized. A more patient-centered approach to psoriasis treatment is needed. Incorporating patient perspectives into clinical decision-making can improve satisfaction, adherence, and overall outcomes.
BACKGROUND:Following the approval of the first denosumab biosimilar in Canada, patients receiving long-term denosumab treatment for osteoporosis may be switched from the reference biologic to the biosimilar. Supporting patient-reported satisfaction following a switch will be critical to ensure treatment adherence, and foster patient confidence and ongoing acceptance of denosumab biosimilars. METHODS:This cross-sectional, multicenter, real-world survey in Canada included adults with osteoporosis switched from reference (Prolia®, Amgen) to biosimilar (Jubbonti®, Sandoz) denosumab (n = 435). Data collected included demographics, disease and treatment history, and patient experience and satisfaction with switching. Key endpoints assessed overall satisfaction with the switch (based on a five-point scale) and the perceived importance of economic benefits and improved treatment access. RESULTS:Most patients (83.1%) expressed satisfaction with the switch, and 84.8% reported being satisfied with the explanation provided about the biosimilar. Clear and adequate communication was significantly associated with overall switch satisfaction (p < 0.001). Better affordability of a biosimilar was considered important by 72.7% of respondents. CONCLUSION:In this real-world survey, respondents reported high satisfaction with the switch from reference to biosimilar denosumab, particularly when the transition was accompanied by clear communication from their healthcare provider. Findings should be interpreted considering limitations inherent to cross-sectional survey research.
INTRODUCTION:The therapeutic landscape of moderate-to-severe plaque psoriasis has been transformed by interleukin-17 (IL-17) and interleukin-23 (IL-23) inhibitors, which offer superior effectiveness compared to older biologics. However, a substantial proportion of patients experience primary or secondary treatment failure, necessitating a therapeutic switching. AREAS COVERED:This review integrates real-world evidence from studies identified through a PubMed search for publications on sequencing and switching between IL-17 and IL-23 inhibitors in plaque psoriasis. The most relevant studies were selected, and their clinical outcomes were evaluated to provide an overview of current evidence on switching strategies. EXPERT OPINION:Key findings indicate that interclass switching (between IL-17 and IL-23 pathways) generally outperforms intraclass switching, with IL-23 inhibitors demonstrating robust effectiveness after IL-17 failure and vice versa. Safety profiles are favorable across all switching scenarios. Future directions include biomarker-guided selection and precision medicine approaches to optimize first-line therapy choice and subsequent sequencing.
INTRODUCTION:Autoimmune blistering diseases and autoimmune connective tissue diseases with prominent skin involvement are increasingly managed with biologic and targeted therapies. We review the evidence supporting these approaches and their practical positioning. AREAS COVERED:We performed a PubMed/MEDLINE literature review (inception to February 2026) on biologic therapies for pemphigus, pemphigoid spectrum disorders, LABD, EBA, cutaneous lupus erythematosus, and dermatomyositis, including selected non-biologic small molecules, focusing on validated cutaneous outcomes. Evidence is strongest for B-cell depletion in pemphigus (including dose-optimization strategies) and for IL-4/IL-13 pathway blockade in BP, with additional data for anti-IgE therapy in selected BP phenotypes. In CLE, the most consistent cutaneous datasets involve pDC/type I interferon-axis modulation and BAFF inhibition, largely derived from systemic lupus cohorts; TYK2 inhibition has shown controlled benefit in CLE. In dermatomyositis, CDASI-based evidence is strongest for IVIg, with anti-IFNβ therapy and the TYK2/JAK1 inhibitor brepocitinib (positive in a phase 3 trial) showing cutaneous benefit; other biologics show limited trial signals. EXPERT OPINION:Biologic/targeted therapies should be positioned by disease phenotype and evidence strength, prioritizing steroid-sparing strategies in pemphigus and BP and using CLASI/CDASI-anchored outcomes to interpret lupus and dermatomyositis data. Evidence for rare AIBDs remains mostly case-level and should be framed accordingly.
INTRODUCTION:In health systems outside the United States (US) with longer biosimilar experience, use has shifted from a question of adoption to one of implementation. Tenders, formularies, and payer policies are progressively driving reference-product-to-biosimilar, biosimilar-to-biosimilar, switchback transitions, and retransitioning in routine care, posing significant clinical, operational, and governance difficulties. AREAS COVERED:This structured narrative review examines evidence published from 1 January 2015 to 15 March 2026 on repeated switching within a single reference-product family. It focuses on efficacy, safety, immunogenicity, persistence, switchback, clinician-led and non-medical switching, nocebo mechanisms, communication, patient education, device support, pharmacovigilance, and traceability. EXPERT OPINION:While data on repeated and cross-switching are promising yet nascent, particularly outside tumor necrosis factor (TNF) inhibitors and beyond short-term follow-up periods, current evidence unequivocally supports initial switching. Successful outcomes depend upon pharmacovigilance, traceability, structured communication, and device support, in addition to molecular comparability. Injection-site pain during adalimumab transitions may be attributed to citrate content, pH, injection volume, or device variations, and should not be prematurely categorized as a nocebo effect. Explicit governance frameworks for repeated-switch programs and prospective, implementation-sensitive evidence are requisite for future clinical advancements.
INTRODUCTION:In neovascular age-related macular degeneration (AMD), complete resolution of retinal fluid has traditionally been regarded as the hallmark of successful treatment, yet accumulating evidence suggests that residual subretinal fluid (SRF) may not be uniformly harmful. In this report, the cumulative evidence supporting and qualifying an 'SRF-tolerating' treatment approach is summarized. AREAS COVERED:Relevant articles were identified through a search of the PubMed/MEDLINE database until April 2026, using terms including 'subretinal fluid,' 'intraretinal fluid,' 'neovascular AMD,' and 'anti-vascular endothelial growth factor.' The report discusses post hoc analyses of major clinical trials (CATT, VIEW, HARBOR, ARIES, and In-Eye), the randomized FLUID study, real-world cohorts, and a recent meta-analysis, covering the association of residual SRF with visual acuity and macular atrophy, contrasting evidence linking large-volume, fluctuating, or prolonged SRF with poorer outcomes, and the distinct behavior of SRF in type 3 macular neovascularization. EXPERT OPINION:The impact of persistent SRF on outcomes has not yet been fully established, and its clinical significance is likely to depend on its volume, location, stability, duration, and the underlying lesion subtype. An SRF-tolerating approach may be considered in selected patients, but strict monitoring of fluid status and visual acuity are required to prevent undertreatment.
INTRODUCTION:Regenerative medicine offers a sophisticated array of interdependent technologies designed to restore healthy, functional tissue across diverse therapeutic scenarios. In particular, combining biologic matrices with growth factors holds promise for counteracting degenerative processes and restoring tissue function, but translational and standardization challenges limit clinical implementation. AREAS COVERED:This review examines current strategies combining biologic matrices with growth factor-based therapies, focusing on biological, translational, regulatory, and standardization challenges. The literature was identified through a non-systematic search of PubMed, Scopus, and Web of Science using keywords related to regenerative medicine, biomaterials, growth factors, combination products, and standardization, with emphasis on relevant preclinical studies, clinical evidence, and regulatory literature. The review also proposes an algorithm-based treatment framework structured into three operational pillars: (I) Primary Regenerative Target, (II) Bio-functional Configuration, and (III) Phase-Adapted Biological Stimulation. EXPERT OPINION:Pursuing a universal regenerative product is unrealistic because of inherent inter-patient variability. Instead, reproducibility should rely on standardized patient-specific decision pathways that align biological objectives with material engineering, supporting a transition from product-based to algorithm-based standardization.
BACKGROUND AND OBJECTIVES:Comparative real-world data on originator and biosimilar adalimumab in hidradenitis suppurativa (HS) are limited. We compared effectiveness, persistence, and safety of originator (ADL-O) versus three biosimilars (ADL-B1, ADL-B2, ADL-B3) in routine care. RESEARCH DESIGN AND METHODS:Retrospective cohort of 146 biologic-naive HS patients initiating adalimumab (January 2020-November 2025) at three tertiary centers in Turkiye. Primary outcomes were Week-12 HiSCR50 and IHS4-55 responses, compared using overlap weighting. Persistence was assessed by 24-week restricted mean survival time (RMST). Safety was summarized descriptively. RESULTS:Baseline characteristics were well balanced across groups. Overlap-weighted Week-12 analyses excluding the ADL-B3 evaluable subset (n = 118) showed no evidence of differential effectiveness: HiSCR50 RR 1.05 (95% CI 0.78-1.42); IHS4-55 RR 1.07 (95% CI 0.76-1.52). Inclusion of ADL-B3 as a sensitivity analysis did not alter the findings. Among Week-52 evaluable ADL-O and ADL-B1 patients, HiSCR50 was 68.8% in both groups. Product-level 24-week RMST was 23.4 versus 22.3 weeks (difference -1.1 weeks, 95% CI - 2.7 to 0.5). Safety comparisons were descriptive given limited sample size. CONCLUSIONS:No statistically significant difference in short-term effectiveness was detected between originator and biosimilar adalimumab in HS. The findings reflect absence of evidence for a difference rather than equivalence. Larger prospective studies with immunogenicity assessment are needed.
INTRODUCTION:The clinical translation of pluripotent stem cell-derived therapies has entered a new phase following conditional approval of first-in-class allogeneic induced pluripotent stem cell (iPSC)-derived products in Japan. These approvals highlight both the therapeutic promise of iPSC technologies and regulatory challenges associated with evaluating complex cell-based interventions. AREAS COVERED:This report examines the evidentiary basis supporting recent approvals and reviews key biological characteristics of allogeneic iPSC-derived therapies, including pluripotency-associated instability, immunological constraints, and manufacturing-related genomic variability. Drawing on recent clinical studies and relevant experimental literature, we analyze how these multilayered risks evolve over extended time horizons and assess their implications for the interpretation of early-phase clinical data and current regulatory frameworks. EXPERT OPINION:We argue that the central challenge extends beyond limited clinical evidence to a fundamental mismatch between the temporal dynamics of biological risk and the duration of conventional clinical evaluation. As a result, early clinical observations may systematically underestimate long-term risks. Conditional approval pathways should therefore incorporate safeguards aligned with this temporal uncertainty, including long-term follow-up, rigorous post-approval evaluation, and enhanced transparency in biological and manufacturing data. Aligning regulatory design with intrinsic properties of pluripotent stem cell-derived therapies will be essential for ensuring safe and responsible clinical translation.
INTRODUCTION:Inborn errors of immunity (IEI) are rare genetic defects that disrupt immune function, often resulting in life-threatening infections, malignancies, and immune dysregulation. Allogeneic hematopoietic stem cell transplantation (HSCT), a curative option for some diagnoses, is limited by donor availability and the risks of graft-versus-host disease. This review explores the 30-year evolution of autologous gene therapy as a vital alternative to allogeneic HSCT for IEIs. AREAS COVERED:Literature search using PubMed for gene therapy for IEI in the last 20 years. We trace the transition from early gamma-retroviral gene addition, which successfully restored immunity in severe combined immunodeficiency (SCID) but carried high risks of insertional mutagenesis and leukemogenesis, to the adoption of safer self-inactivating lentiviral vectors. The field is rapidly advancing beyond viral gene addition toward highly precise gene‑editing technologies, including CRISPR/Cas9 and base/prime editing, which offer targeted correction with minimized genotoxicity. EXPERT OPINION:Recent milestones in diseases such as Wiskott -Aldrich syndrome (WAS) and chronic granulomatous disease (CGD) highlight enormous scientific success, yet significant barriers to accessibility, manufacturing, and affordability remain. Overcoming this requires innovative regulatory frameworks and collaborative funding models. Streamlining development and ensuring equitable access are essential next steps to establishing gene therapy as a safe alternative.
BACKGROUND:Achieving simultaneous 'dual remission' in both upper and lower airways is the clinical goal for comorbid asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). This multicentric observational study evaluated the 24-month real-world effectiveness of dupilumab in reaching these stringent endpoints. METHODS:A retrospective study of 205 adult patients was conducted. Remission was defined by SANI criteria for asthma and modified EPOS/EUFOREA-DUPIREAL benchmarks for CRSwNP. Complete recovery required dual remission plus normosmia restoration. RESULTS:At 24 months, 77.4% of patients with severe asthma achieved CRSwNP remission, significantly higher than the 61.8% in the moderate asthma group (p = 0.0309). Dual remission was reached by 22.9% of the overall cohort. High baseline FeNO (≥50 ppb) was the strongest predictor for dual remission (34.5%) and normosmia restoration (19.2%). Prior surgery did not hinder long-term outcomes; surgical patients achieved complete recovery significantly faster at 12 months (16.7% vs. 3%, p = 0.0115). A higher surgical burden positively predicted olfactory restoration (OR = 4.0 per revision, p = 0.045). CONCLUSIONS:Dupilumab is highly effective over the long term, exhibiting a structural 'catch-up" effect. While high baseline Type 2 biomarkers and surgical history are positive prognostic indicators, the persistent "clinical-functional gap' suggests earlier intervention is critical to prevent irreversible neuroepithelial damage. CLINICAL TRIAL REGISTRATION:www.clinicaltrials.gov identifier is NCT07574294.
