Expert Opinion on Biological Therapy最新文献

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.

Background: Fecal microbiota transplantation (FMT) is increasingly used in geriatric medicine, including intestinal decolonization of antimicrobial-resistant bacterial pathogens and the treatment of inflammatory bowel disease, graft versus host disease and autism spectrum disorders. The aim of this study was to examine readability of patient-facing FMT information.

Research design and methods: Readability was calculated using Readable software, examining (i) Flesch Reading Ease (FRE), (ii) Flesch-Kincaid Grade Level (FKGL), (iii) Gunning Fog Index, and (iv) SMOG Index and two text metrics [words/sentence, syllables/word] for 234 sources of FMT information, from four categories (abstracts/hospital information/patient-facing information/clinical trials).

Results: Mean readability scores of FMT information for FRE and FKGL were 22.2 ± 1.2 (SEM) (target > 60) and 14.8 ± 0.2 (target < 8), respectively, with mean words/sentence and syllables/word of 19.2 ± 0.4 and 2.0, respectively. There was no significant difference in readability between scientific abstracts and lay summaries. No information was found that had a readability of less than 7th grade (12-13 year olds).

Conclusion: Readability of FMT information for patients is poor, not reaching readability reference standards. Authors of FMT information should consider using readability calculators when preparing FMT information, so that the final material is within recommended readability reference parameters, to support the health literacy and treatment adherence of readers.

Background: Limited real-world studies have evaluated outcomes after switching treatment from a reference product (RP) to a biosimilar product. The objective of this real-world study was to assess the outcomes of switching from RP adalimumab to biosimilar adalimumab-atto in patients with rheumatoid arthritis (RA).

Research design and methods: This was a propensity score matched, non-inferiority study assessing adult patients with RA who switched from RP adalimumab to adalimumab-atto (Switchers) between or received RP adalimumab continuously (Non-Switchers). One-year disease worsening, serious adverse events, and patient out-of-pocket cost outcomes were evaluated. An upper limit of 5% for adalimumab-atto was set as the non-inferiority margin.

Results: After matching, there were 1,172 patients in each group. 24.8% and 31.0% of patients in the Switcher and Non-Switcher groups, respectively, experienced the disease worsening (non-inferiority p < 0.01). The crude rates per 100 patient-years of the safety outcome and mean monthly changes in out-of-pocket costs were 5.6 (95% CI 4.2-7.5) and 7.2 (95% CI 5.2-9.2) (p = 0.21) and -$51 (±$164) and -$11 (±$152) (p < 0.01) in the Switcher and Non-Switcher groups, respectively.

Conclusions: These results provide evidence that switching from RP adalimumab to biosimilar adalimumab-atto did not result in disease worsening or increased adverse events but did deliver modestly lower patient out-of-pocket costs.

Objectives: To assess the effectiveness and safety of Rituximab (RTX) treatment among patients diagnosed with rheumatoid arthritis-associated interstitial lung disease (RA-ILD).

Methods: We performed a systematic review with meta-analysis of studies involving patients with RA-ILD who were treated with RTX. Two investigators independently conducted the research.

Results: Twenty studies met the criteria for data extraction for the systematic review with a good quality assessment according to an 18-criteria checklist using a modified Delphi method. The total number of patients was 14,523, including 1,619 who received RTX. Stabilization or improvement was observed in more than half of the patients in all studies. Evaluation based on pulmonary function tests (PFTs) noted disease progression in fewer than 20% of 7 out of 11 studies. Meta-analysis results revealed that, based on PFTs, the proportion of patients showing functional decline was 14.5% (95%CI, 7.6-25.8%) (95%PI, 2-69%); and according to the pulmonary high-resolution computed tomography (HRCT) evaluation, the proportion of worsening was 19.5% (95%CI, 8.1-40%) (95%PI, 1-84%). An overall acceptable safety profile was noted, with respiratory mortality ranging from 4% to 14%.

Conclusion: Our review suggests that RTX appears to be an effective therapy in patients with RA-ILD, with a satisfactory safety profile.

Protocol registration: https://www.crd.york.ac.uk/prospero identifier is CRD420251049957.

Introduction: Complement inhibition has revolutionized paroxysmal nocturnal hemoglobinuria (PNH) treatment. While eculizumab, the first anti-C5 antibody, reduced intravascular hemolysis (IVH) and thrombotic risk, it required fortnightly infusions and left a significant percentage of patients with persistent anemia. New terminal complement inhibitors, such as long-acting ravulizumab and subcutaneous crovalimab, have allowed for better control of IVH and demonstrated efficacy in patients with specific C5 genetic polymorphisms (crovalimab). Proximal complement inhibitors, including the small molecule pegcetacoplan (C3 inhibitor), the recently approved orally administered iptacopan (factor B inhibitor), and danicopan (factor D inhibitor, in combination with anti-C5), efficiently control C3-mediated extravascular hemolysis. However, these treatments come with an increased risk of serious breakthrough hemolysis events due to reduced half-life and increased sparing of PNH erythrocytes.

Areas covered: In this review, we summarize phase III trials and real-world data to support patient-tailored treatment strategies and offer practical guidance for patient profiling and optimal complement inhibitor selection.

Expert opinion: In this evolving landscape, treatment choice has become increasingly complex. PNH specialists must now balance multiple factors beyond efficacy alone. Disease characteristics such as previous thrombotic events or transfusion needs, as well as drug administration routes, patient preferences toward oral or parenteral administration and expected compliance, will all influence clinical decisions.