Expert Opinion on Biological Therapy最新文献

Introduction: The successful clinical trials of the type I interferon (IFN) receptor monoclonal antibody, anifrolumab, have proven the benefit of IFN blockade in systemic lupus erythematosus (SLE), and paved the way for novel therapies targeting this pathway.

Areas covered: This review will cover the updated evidence regarding the efficacy and safety of anifrolumab since its positive phase III trial in 2020. In addition, indications of the clinical benefit of emerging IFN-targeting therapies, such as monoclonal antibodies targeting IFN-producing cells and small-molecule inhibitors of IFN signaling, currently in phase II/III clinical trials will be discussed.

Expert opinion: Evidence from clinical trials and real-world studies have revealed the potential for IFN blockade to reduce disease activity and flares, improve glucocorticoid (GC) tapering and increase the attainment of treat-to-target goals in SLE, including in refractory patients. The efficacy of IFN blockade across different SLE disease manifestations and patient subgroups remains under investigation, as well as the ability of such treatments to reduce end organ damage. Regardless, it is clear that IFN blockade has earned a place as part of the standard of care in SLE. Future studies are needed to define whether IFN blockade moves toward being a first-line treatment.

Introduction: Until recently, the biological treatment options for hidradenitis suppurativa (HS) were largely restricted to adalimumab and secukinumab. In 2024, bimekizumab, an IL-17A and IL-17F antibody was introduced to the clinical practice.

Areas covered: Bimekizumab offers a new therapeutic approach for managing HS. It was approved by the U.S Food and Drug Administration (FDA) and European Medicines Agency (EMA) in 2024. The available biologic therapies in HS treatment are described. The data from phase II and phase III clinical trials were analyzed to evaluate the bimekizumab effectiveness in HS treatment. Data from those trials and latest summaries of product characteristics (SmPC) were retrieved to investigate its safety profile. The current preliminary data regarding its long-term effectiveness from BE HEARD EXT (NCT04901195) trial were presented.

Expert opinion: The common side effects of bimekizumab were upper respiratory infections, candida infections and eczematous reactions across all indications. The favorable side effects profile and strong clinical effectiveness proved in clinical trials gave the bimekizumab potential to become the first-choice drug in HS treatment.

Introduction: Osteoporosis is a significant public health issue due to its associated morbidity, mortality, and economic burden. Despite available effective treatments, a treatment gap persists, characterized by delayed diagnosis, undertreatment, and poor adherence. Biosimilars, such as biosimilars for denosumab, offer an opportunity to improve treatment accessibility and affordability for osteoporosis and cancer-related bone loss.

Areas covered: This review explores the current treatment challenges in osteoporosis, the potential of denosumab biosimilars in improving access and outcomes, and the necessity of a multidisciplinary, patient-centered approach.

Expert opinion: The emergence of biosimilars for denosumab offers an opportunity to enhance accessibility and affordability of osteoporosis treatment, as biosimilars provide effective and economic versions of reference biologic therapies. A multidisciplinary approach is vital in managing osteoporosis, central to which is the patient, whose preferences, values, and lifestyle must guide the treatment plan. Healthcare providers play a crucial role in educating patients, promoting adherence to prescribed treatments, and involving patients in their own care to improve health outcomes.

Background: To demonstrate comparative efficacy of AVT03, a proposed denosumab biosimilar, versus reference product (RP) in postmenopausal women with osteoporosis.

Research design and methods: Participants received AVT03 or RP; 60 mg subcutaneous on Day 1 and Month 6. At Month 12, AVT03 group received 3^rd dose while RP group received either a 3^rd dose of RP or a dose of AVT03. Primary endpoints were percent change from baseline in lumbar spine bone mineral density (BMD) at 12 months and area under the effect curve (AUEC)_0-6 months of percent change from baseline (%Cfb) in serum C-terminal telopeptide of type I collagen (sCTX-1). Safety and immunogenicity were evaluated.

Results: The 95% confidence interval (CI)s of the least squares means difference between treatments for percent change from baseline in lumbar spine BMD to Month 12 (-0.58, 0.82) were entirely contained within the prespecified margin (-1.45%, 1.45%), supporting demonstration of comparative efficacy. The 95% CIs of the geometric mean ratio between treatments for AUEC_0-6 months of %Cfb sCTX-1 (0.97, 1.03) were entirely contained within the prespecified margin (0.80, 1.25), supporting demonstration of pharmacodynamic similarity. Safety and immunogenicity profiles were comparable throughout.

Conclusion: Data supported demonstration of comparative efficacy between AVT03 and RP denosumab. Safety and immunogenicity profiles were similar.

Trial registration: www.clinicaltrials.gov identifier is NCT05395091.

Introduction: This systematic review and meta-analysis aimed to compare the efficacy, safety, and immunogenicity of biosimilars and reference biologics (adalimumab, etanercept, infliximab) in the treatment of ankylosing spondylitis (AS).

Methods: We conducted a systematic search of four electronic databases through 6 January 2025, supplemented by trial registry searches for unpublished trials. We included head-to-head randomized controlled trials (RCTs) that compared biosimilars with reference biologics in patients with AS. Effect measures were summarized using random-effects meta-analysis, and the risk of bias was assessed using the Cochrane RoB 2 tool. The overall certainty of evidence was assessed using the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) system.

Results: Six head-to-head RCTs (2,107 participants) were included. Biosimilars demonstrated similar efficacy to reference biologics in achieving ASAS20 (risk ratio [RR] 1.01, 95% confidence interval [CI] 0.96-1.07) and ASAS40 (RR 1.00, 95% CI 0.94-1.05) responses. No significant differences were observed in other efficacy (e.g. disease activity indices), safety (e.g. adverse events), or immunogenicity outcomes (e.g. anti-drug antibodies). Sensitivity and subgroup analyses confirmed the robustness of these findings.

Conclusions: This study provides evidence supporting the clinical equivalence of biosimilars to reference biologics in AS treatment, reinforcing their potential as safe and effective alternatives.

Protocol registration: www.crd.york.ac.uk/prospero identifier is CRD42024528886.

Introduction: Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent episodes of subcutaneous and/or submucosal swelling (angioedema). Current HAE-specific medications primarily focus on either inhibiting plasma bradykinin or kallikrein, or replacing C1-esterase inhibitor, but they are frequently limited in efficacy and accessibility. In contrast, Factor XII (FXII) inhibitors may provide a novel therapeutic approach by targeting the contact system at an upstream level, potentially addressing some of these limitations.

Areas covered: This review explores the role of FXII in HAE and assesses FXII inhibition as a promising prophylactic treatment strategy. By synthesizing findings from both preclinical and clinical studies and real-world observational studies, the review highlights the efficacy, safety, and practical benefits of FXII inhibitors, such as garadacimab.

Expert opinion: FXII inhibition represents a promising new strategy for HAE management and may address current unmet needs in prophylactic therapies. The early experiences of garadacimab highlights FXII as a viable and druggable target, paving the way for broader applications in bradykinin-mediated disorders. Despite its potential, uncertainties remain regarding long-term safety, cost, and accessibility. Future research will help redefine the role of FXII inhibition in advancing personalized care and improving the quality of life for patients with HAE.

Introduction: This systematic review and meta-analysis evaluated the lipid-lowering efficacy and safety of evolocumab in statin-treated patients at high cardiovascular risk, focusing on changes in LDL-C, TG, ApoB, HDL-C, and Lp(a) after 12 weeks.

Methods: A comprehensive search identified randomized controlled trials comparing evolocumab to placebo in adults on statin therapy. Studies reporting baseline and 12-week lipid and safety data were included. Risk of bias was assessed using the Cochrane tool. Random-effects models were used to calculate mean differences (MD) or odds ratios (OR) with 95% confidence intervals (CI).

Results: Five trials with 4,009 participants were analyzed. Evolocumab significantly reduced LDL-C (MD: -64.67; 95% CI: -66.72 to -62.61), TG, ApoB, and Lp(a), and increased HDL-C. No significant difference was observed in total TEAEs (OR: 0.97; 95% CI: 0.84 to 1.14) or serious TEAEs (OR: 1.23; 95% CI: 0.80 to 1.89) versus placebo.

Conclusions: Evolocumab offers robust lipid-lowering benefits with a safety profile comparable to placebo in statin-treated patients. Limitations include short follow-up and variable statin regimens. Further long-term studies are needed to confirm cardiovascular outcome benefits.

Protocol registration: www.crd.york.ac.uk/prospero identifier is CRD42024543525.

Introduction: Denileukin difitox (DD), a recombinant cytotoxic fusion protein composed of full-length human interleukin-2 (IL-2) conjugated to diphtheria toxin's A and B subunits, has shown activity in patients with relapsed and refractory (R/R) mycosis fungoides and the Sezary Syndrome (MF/SS) whose tumor cells expressed CD25, with response rates of 30-44% in advanced and earlier (Stage I-III) stage patients, respectively.

Areas covered: Recently, a newer version of DD with improved purity and bioactivity (DD-cxdl) was developed. A registrational trial of D-cxdl showed similar response rates in R/R MF/SS. The purpose of this review is to describe efficacy and safety data surrounding these medications and highlight the equivalency of these two drugs.

Expert opinion: Both DD and DD-cxdl demonstrate activity in R/R MF/SS with higher response rate in tumor and plaque stage disease. Adverse events grade ≥3 included infusion reactions in 8%, elevated hepatic transaminases in 22%, and capillary leak syndrome in 8%. In addition to direct targeting of CD25 expressing tumor cells, both drugs are also capable of depleting immunoregulatory T-cells. A clinical trial of DD-cxdl in Japan showed that responses were independent of CD25 expression, suggesting multiple mechanisms of action for DD-cxdl in MF/SS and potentially other malignancies.

Background: The impact of traditional systemic drugs to treat psoriasis (ciclosporin, methotrexate, and acitretin) in a subsequent response to biologics has not been adequately addressed in the literature. In clinical practice, it is increasingly necessary to initiate, due to concomitant comorbidities, biologics in patients with psoriasis or psoriatic arthritis (PsA) who have not undergone prior treatment with systemics, i.e. full-naive.

Objectives and methods: This study analyzed the possible impact of non-biological systemic therapies on the effectiveness and drug survival of first-line biologic drug up to 12 months in bio-naive psoriatic and PsA patients consecutively enrolled from January 2017 to March 2021.

Results: Ninety-five patients with severe psoriasis (13.5%) were full-naive. Being full-naive and having or not having undergone methotrexate or cyclosporine therapy did not impact response to subsequent years of biologic therapy. Only acitretin promotes faster response to subsequent biologic drugs with 59.6% and 74.2% of patients achieving Psoriasis Area Severity Index (PASI) 90 at 16 and 28 week, respectively, vs. 50.5% and 65% (p = 0.034 and 0.026). In multivariate analysis, the advantage given by acitretin was lost.

Conclusion: Previous systemic therapy in bio-naive patients does not appear to result in a differential response to biologics during the first year of treatment.