Expert Opinion on Biological Therapy最新文献

Introduction: Recombinant human erythropoietin (rHuEPO) and its derivatives, which are called erythropoiesis-stimulating agents (ESAs), have long been indispensable molecules to treat patients with anemia due to their high effectiveness in stimulating erythropoiesis. Previous studies have indicated the additional effects of EPO besides erythropoiesis such as suppressing inflammation and apoptosis.

Areas covered: This review summarizes the physiology of EPO and its receptors, describes the pathways other than erythropoiesis activated by recombinant human EPO and their derivatives, and discusses the potential benefits of non-erythropoietic EPO receptor agonists (ERAs). Literature search was conducted using Google Scholar and PubMed databases.

Expert opinion: Previous studies indicate the protective effects of ESAs in various disease models, some of which are independent of their erythropoietic feature. However, ESAs contain safety concerns, especially when administered in high dose to fully bring out their favorable effects. ERAs that only activate the non-erythropoietic reactions by EPO seem to be equally beneficial in improving outcome without serious adverse effects, which raises expectations for their further investigation in large clinical trials. So far, non-erythropoietic ERAs are not clinically available yet, and clinicians should understand the risks associated with ESAs upon their usage.

Introduction: Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disorder and has a considerable impact on patients' quality of life. Dupilumab, the first biologic approved for moderate-to-severe AD, is a human monoclonal antibody targeting the interleukin (IL)-4 receptor α, thereby blocking both IL-4 and IL-13 signaling, key drivers of type 2 inflammation in AD. Its introduction has marked a paradigm shift in the management of AD and paved the way for future therapies. As real-world evidence on biologics and Janus kinase (JAK) inhibitors is rapidly emerging, comprehensive and up-to-date reviews are important.

Areas covered: This review primarily summarizes real-world data on dupilumab, with a focus on its effectiveness and safety in clinical practice, highlighting recent findings and their implications for optimizing patient management.

Expert opinion: Real-world evidence consistently confirms the high effectiveness, favorable safety profile, and long-term treatment durability of dupilumab across various patient subgroups, including children, elderly, and patients with different underlying immune and genetic profiles. Additionally, dupilumab has demonstrated beneficial effects in patients with comorbid asthma and food allergies. Emerging data further support its potential safety during pregnancy, breastfeeding, and (non-)live vaccinations. Dose tapering is often successful and lowers the socio-economic impact of dupilumab.

Introduction: Interleukin (IL)-23 is a cytokine implicated in the pathogenesis of ulcerative colitis (UC). Guselkumab, a selective IL-23 antagonist, was approved for the treatment of moderately-to severely active UC in 2024/5.

Areas covered: The review briefly summarizes the pathophysiology of the IL-23 pathway and summarizes the available evidence on the efficacy and safety of guselkumab in UC. We discuss future challenges and clinical dilemmas in the use of guselkumab.

Expert opinion: Guselkumab has demonstrated efficacy across all endpoints with a favorable safety profile. No direct comparisons are available between individual IL-23 antagonists or with ustekinumab, the IL-12/23 antagonist, which limits decision-making in clinical practice. Combining two biologics as advanced combination treatment is an attractive strategy to break the therapeutic efficacy ceiling in UC - a proof-of-concept phase 2 trial combining guselkumab and golimumab has shown promise, the combination is currently undergoing evaluation in a larger ongoing trial.

Background: Pediatric rheumatic diseases impose substantial significant physical, emotional, and social burdens. Biologic therapies have revolutionized disease management; however, few data exist exploring caregivers' lived experiences with pediatric biologic therapy.

Research design and methods: A cross-sectional survey was conducted between August and October 2025 across three pediatric rheumatology centers in Türkiye. Primary caregivers of 156 children receiving biologic disease-modifying antirheumatic drugs (bDMARDs) for ≥3 months completed structured questionnaires assessing demographics, knowledge, perceptions, emotions, treatment experiences, satisfaction, and support needs.

Results: Among caregivers, 42% initially reported fear and 33% expressed trust or reliance upon treatment recommendation. Overall satisfaction with clinic services was high (98%), and 79% perceived marked improvement in their child's well-being and daily functioning. Perceived insufficiency of information was associated with increased fear and concern (p = 0.005). Subcutaneous, weekly regimens predominated, and mothers more often reported difficulty with administration (p = 0.042). Longer treatment duration was associated with more positive perceptions (p = 0.049), while adverse events were linked to lower perceived efficacy (p = 0.035).

Conclusion: Caregiver perceptions significantly affect adherence and satisfaction. Structured caregiver education and psychosocial support should be integrated into routine pediatric rheumatology practice to strengthen adherence and family-centered care.

Background: Anti-IL-23 monoclonal antibodies have shown strong efficacy in achieving complete clearance (PASI 100) in psoriasis. Real-world evidence is needed to confirm these outcomes and define predictors of response.

Research design and methods: We performed a monocentric retrospective study on 243 adults with moderate-to-severe psoriasis treated with guselkumab, risankizumab, or tildrakizumab at the University of Pisa. The primary endpoint was PASI 100 achievement; secondary endpoints were maintenance and predictors of response. Survival analysis and Cox regression were applied.

Results: PASI 100 was achieved in 67.4% of patients, on average at 27 weeks. Among responders, 81.7% maintained clearance for a mean of 90 weeks. Palmoplantar involvement reduced the likelihood of achieving PASI 100 (HR 0.575), while facial involvement (HR 2.261) and longer disease duration (HR 1.020) favored maintenance. Prior cyclosporine use (HR 0.644) and higher baseline PASI (HR 0.973) were negative predictors. No unexpected safety issues were observed.

Conclusions: Anti-IL-23 therapies are effective in achieving and sustaining PASI 100 in routine care. Outcomes are influenced by disease localization, duration, prior treatments, and baseline severity. Limitations include retrospective design, single-center setting, and absence of comparators.

Introduction: Medical management of juvenile idiopathic arthritis (JIA) presents a significant challenge in pediatric rheumatology. Ideally, the treatment target is remission, though achieving this remains complex. Interleukin-6 (IL-6) inhibitors (IL-6is) play an important role, targeting the inflammatory pathways central to JIA pathogenesis. However, their optimal use is debated.

Areas covered: This narrative review examined JIA care needs and IL-6 inhibition. A SPIDER-based literature search of PubMed/MEDLINE, Semantic Scholar, WorldCat, Cochrane Library, Embase, CINAHL, ICTRP, and ClinicalTrials.gov (to May 2025), identifying 56 studies from 246 records published between 2018 and 2025. Key unmet needs include difficulty controlling the disease, diagnostic delay, shortcomings in biomarker research, and multidisciplinary support. Tocilizumab, a well-studied IL6i, showed efficacy in symptom reduction, disease control, and reduced glucocorticoid use.

Expert opinion: Addressing gaps in JIA management, such as delayed diagnosis and inadequate disease control, is essential. Experts advocate for early IL6i use within a treat-to-target framework, optimizing outcomes and minimizing glucocorticoid use. Recognizing benefits for highrisk JIA subtypes, experts support earlier tocilizumab integration into treatment algorithms, offering valuable options for refractory oligoarthritis and uveitis. Ultimately, bridging gaps in JIA management and reshaping real-world outcomes hinges on integrating clinical insight and research outcomes - a process driven by precision medicine.

Introduction: Myasthenia gravis (MG) is an autoimmune disease caused by autoantibodies targeting the neuromuscular junction. MG, characterized clinically by fluctuating muscle weakness and fatigability, is traditionally treated primarily with corticosteroids and nonspecific immunosuppressive drugs. Despite their documented efficacy in a proportion of patients, current standard-of-care treatments are associated with moderate-to-severe side effects that underline the need for new targeted therapies. Nipocalimab, a fully human monoclonal antibody, binds to the neonatal Fc receptor (FcRn) with high affinity and specificity, causing selective reduction of circulating IgG and pathogenic IgG autoantibodies. The phase 3 study Vivacity-MG3 confirmed nipocalimab as an efficacious and safe treatment providing sustained disease control in seropositive patients with generalized MG (gMG).

Areas covered: The efficacy and safety of nipocalimab in gMG from the phase 2 study Vivacity-MG (NCT03772587) and the phase 3 study Vivacity-MG3 (NCT04951622).

Expert opinion: Clinical studies have demonstrated that nipocalimab provided rapid and sustained reduction of total IgG and pathogenic IgG autoantibodies together with sustained disease control over 6 months in a broad population of seropositive patients with gMG, with an acceptable safety profile. The long-term impact of nipocalimab on the course of gMG needs to be further investigated in real-world settings.

Introduction: Advances in frontline multiple myeloma (MM) treatment, through combinatorial regimens with diverse mechanisms of action, have created a need for alternative agents at relapse. BCMA-targeting CAR-T therapies have already demonstrated superiority over conventional options. Belantamab mafodotin, a first-in-class BCMA-directed antibody - drug conjugate (ADC), has shown significant benefit in combination with proteasome inhibitors or immunomodulators, as an accessible alternative to CAR-T therapy.

Areas covered: Belantamab mafodotin-based regimens were approved for the treatment of MM from second line of therapy in UK (April 2025) and EU (July 2025) and is under extended review by the FDA after concerns raised regarding its safety profile. This review discusses its mechanism of action, along with efficacy and safety data, to evaluate its role in the evolving MM treatment landscape.

Expert opinion: Belantamab mafodotin offers a distinct therapeutic profile: off-the-shelf availability compared to CAR-Ts, lower infection risk than T-cell engagers, and a mechanism of action distinct from both T-cell - redirecting and standard therapies. Ocular keratopathy is a class-specific adverse event that is manageable with appropriate measures. Its relatively low incidence of life-threatening infections supports its use, particularly in frail patients. Ongoing trials suggest a feasible integration into frontline regimens to further improve clinical outcomes.

Background: This study compared the pharmacokinetics (PK), safety, and immunogenicity of the Tocilizumab biosimilar, BAT1806 SC (Tocilizumab biosimilar, Subcutaneous Injection), with Tocilizumab (RoActemra®) in healthy Chinese male subjects.

Research design and methods: In this randomized, double-blind, parallel-group phase I clinical study, healthy Chinese male subjects (Number (N) = 300) were randomized 1:1 to receive 162 mg/0.9 mL either BAT1806 SC or Tocilizumab subcutaneously.

Results: The mean drug concentration-time curve trend and PK parameters were similar between BAT1806 SC and Tocilizumab. The 90% CIs (Confidence Interval), of the GMRs (Geometric Mean Ratio) of AUC_0-inf (area under the curve from zero to infinity) (97.07%), and AUC_0-t (area under the curve from time 0 to the last measured) (97.18%) and C_max (95.72%) were all within the bioequivalence limits [80.00%-125.00%]. The TEAE was very similar between the BAT1806 SC group (89.4%) and the Tocilizumab group (91.3%). No serious adverse events such as TEAEs (Treatment-related adverse events) leading to early discontinuation or deaths were reported. The ADA (anti-drug antibodies) incidence was 67 (44.4%) and 49 (32.9%) in the BAT1806 SC group and Tocilizumab group. This study revealed that immunogenicity had no significant effect on the PK or safety of the Tocilizumab.

Conclusion: This study demonstrated bioequivalent PK, comparable safety, and immunogenicity profiles of BAT1806 SC and Tocilizumab in healthy subjects.

Trial registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT05968508).

Objective: Biologic agents have been used in colchicine-resistant familial Mediterranean fever (FMF) patients and in patients with comorbidities including juvenile idiopathic arthritis (JIA). The main aim of our study was to evaluate the use of biological agents in pediatric patients with FMF and to assess the factors influencing the initiation of biological treatment.

Materials and methods: Our study included 832 pediatric FMF patients, who were followed up at Ankara Etlik City Hospital. Demographic data, clinical and laboratory characteristics, genetic results, treatments and treatment responses of the patients were retrospectively reviewed.

Results: Of the patients enrolled in the study, 107 (12.9%) had received biological treatment. The reduction in attack frequency and changes in laboratory parameters including white blood cell count, absolute neutrophil count, neutrophil/lymphocyte ratio, hemoglobin, platelet count, mean platelet volume, C-reactive protein, erythrocyte sedimentation rate and serum amyloid A levels were statistically significant in patients receiving (anti-interleukin-1) treatment.

Conclusion: The initiation of biological treatment was higher in patients with younger symptom onset, in patients with JIA comorbidity, and in patients with homozygous exon 10 or compound heterozygous exon 10 mutation. Gender, delay in diagnosis, comorbidities other than JIA, family history of FMF, amyloidosis or chronic kidney disease did not increase the initiation of biological treatment.