Expert Opinion on Biological Therapy最新文献

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.

Background: The STELLAR-2 study compared the efficacy, safety, immunogenicity, and pharmacokinetics of Bmab 1200 with reference ustekinumab through Week 52 in patients with moderate-to-severe chronic plaque psoriasis.

Research design and methods: In this double-blind, Phase 3 study, patients were randomized 1:1 to receive Bmab 1200 or reference ustekinumab (45 mg or 90 mg). At Week 16, patients responding to ustekinumab (improvement in Psoriasis Area and Severity Index [PASI] score ≥50%) were re-randomized to continue with reference ustekinumab or switch to Bmab 1200 and followed through Week 52.

Results: Overall, 324 patients completed the study. At Week 52, the mean (SD) percentage reduction in PASI scores from baseline was -95.5% (7.51) for Bmab 1200, -96.6% (5.67) for continued-reference ustekinumab, and -94.7% (7.95) for switched-to-Bmab 1200 groups. Efficacy and safety outcomes were comparable across groups. From 28 to 52 weeks, 37.8% of patients had at least one treatment-emergent adverse event. The incidence of post-switch antidrug antibodies was also comparable (Bmab 1200: 63.7%; continued-reference ustekinumab: 80.2%; switched-to-Bmab 1200: 72.6%).

Conclusions: Bmab 1200 demonstrated clinical biosimilarity to reference ustekinumab through Week 52 even after switching. Long-term comparable efficacy and safety were also maintained.

Trial registration: www.clinicaltrials.gov identifier is NCT05335356 and www.clinicaltrialsregister.eu identifier is 2021-006668-25.

Background: Following the approval of intravenous (IV) infliximab (IFX) in the 1990s, Celltrion developed the first monoclonal antibody biosimilar for IV IFX (Remsima®: Celltrion, South Korea), followed by the first and only subcutaneous IFX, (Remsima® SC). A liquid formulation of IV IFX has been developed that eliminates the need for reconstitution and introduces a 350 mg vial size not previously available with the powder formulation. This study evaluated the operational benefits and cost savings of the liquid formulation of IV IFX compared to the powder formulation, from the perspective of healthcare professionals across seven European countries.

Research design and methods: Semi-structured interviews were conducted with 21 hospital pharmacists and nurses involved in IV IFX preparation from May to June 2025.

Results: Interviewees noted that eliminating reconstitution reduced preparation time by 51% and resource costs by 20% per patient episode compared to the powder formulation, significantly alleviating healthcare professionals' workload.

Conclusions: The liquid formulation of IV IFX streamlines preparation, enhances operational efficiency, and reduces costs compared to the powder formulation. These savings allow resource reallocation to patient care, improving cost-effectiveness of IV IFX therapy. Its adoption is expected to optimize healthcare delivery across European healthcare systems.

Introduction: The introduction of biosimilars changed the management of biologicals in inflammatory bowel disease (IBD) since the approval of CT-P13, the first biosimilar to infliximab, by the European Medicines Agency (EMA) in September 2013 and by the U.S. Food and Drug Administration (FDA) in April 2016. Accumulating evidence in IBD suggests that biosimilar products have equivalent efficacy and safety to reference products and their use was associated with improved access and decrease in medication costs.

Areas covered: This review discusses the current evidence on approved biosimilars of infliximab, adalimumab and ustekinumab in IBD. Authors review data on drug sustainability, efficacy, safety, immunogenicity, non-medical switch data and interchangeability of biosimilar agents.

Expert opinion: The biosimilar concept seems to be successful and has led to increased use of biological/biosimilar agents in the treatment of IBD. Clinical trials with biosimilars in IBD and evidence from real world studies on infliximab and adalimumab biosimilars confirm that safety, efficacy and immunogenicity is comparable to the originator, and that switching from the originator or among biosimilars is safe. While payers are supporting mandatory biosimilar use, on the long run the price race can lead to obstacles and unaffordability of the development of new originator biological agents.

Introduction: From the 1960s and up until 2021, neoadjuvant chemotherapy has represented the standard of care for potentially resectable stage III (N2) Non-Small Cell Lung Cancer (NSCLC). However, in recent years, immunotherapy in the form of Immune Checkpoint Inhibitors (ICIs) has revolutionized oncology treatment strategies and several ICIs have been investigated for the neoadjuvant treatment of NSCLC, both in monotherapy and in combination with other ICIs or chemotherapy.

Areas covered: Therefore, this paper aims to review the currently available data supporting the role of immunotherapy in the neoadjuvant setting, as well as to discuss the challenges associated with it. We undertook a comprehensive literature search of PubMed, Embase, Cochrane Library, of abstracts and posters from annual meetings of American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), and American Association for Cancer Research (AACR) up until November 2024.

Expert opinion: We believe that in the near future ICI plus chemotherapy combinations will represent the new recommended standard of care in the neoadjuvant/perioperative setting. We look forward to the full results coming from the ongoing randomized phase III trials, that will help us guide our choice in terms of patient selection, regimen of choice, and response assessment.

Introduction: Hepatocellular carcinoma (HCC) remains a leading cause of cancer mortality globally. For years, systemic treatment options were limited to tyrosine kinase inhibitors with modest outcomes. The introduction of immunotherapy has transformed the treatment paradigm, establishing immunotherapy as first-line treatment for advanced disease. Among these, tremelimumab -an anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody- is a key therapeutic agent in the evolving management of HCC.

Areas covered: This review offers a detailed examination of the pharmacological characteristics of tremelimumab and synthesizes evidence from clinical trials assessing its efficacy and safety as both monotherapy and in combination for HCC. It also explores ongoing studies and future perspectives on the role of tremelimumab across diverse stages in the management of HCC.

Expert opinion: Tremelimumab has reshaped the treatment of HCC through its use as a single high-dose priming agent in combination with durvalumab. This approach effectively triggers durable immune responses with a favorable safety profile. Ongoing studies are evaluating its potential in earlier and intermediate stages of HCC, particularly as part of neoadjuvant and conversion therapy strategies. However, the lack of predictive biomarkers specific to tremelimumab remains a key limitation. Future research should focus on identifying patients most likely to benefit from tremelimumab-based combinations.

Background: For moderate-to-severe psoriasis, clinical guidelines recommend biologic treatments after failure of at least one traditional systemic therapy. Biologics target different pathways, but a common challenge is loss of efficacy, often requiring a switch. This study explores real-world therapeutic management of moderate-to-severe psoriasis, focusing on biologic treatments.

Methods: A retrospective study was conducted using health records of adult patients currently receiving biologics at Sant'Orsola Hospital in Bologna. Therapeutic sequences were investigated using state sequence analysis. Within-sequence Shannon entropy was calculated and used as the outcome in linear regression models. A directed acyclic graph informed the hierarchical regression models to identify factors influencing treatment duration.

Results: The cohort included 364 patients. Adalimumab was the most common first-line biologic (27%), followed by secukinumab (18%) and etanercept (16%). Nearly half of patients (48%) switched treatments. Increasing age was associated with lower sequence heterogeneity (β = -0.001, p = 0.002). Ustekinumab demonstrated the longest median treatment duration (1,841 days), while etanercept had the shortest (639 days). After adjusting for confounding variables, ustekinumab maintained its positive effect on treatment duration (β = 0.285, p = 0.009).

Conclusion: The treatment duration for ustekinumab was encouraging, supporting its potential role as a durable option in these patients.