Expert Opinion on Biological Therapy最新文献

Introduction: Belimumab (BEL), an anti B-lymphocyte stimulator monoclonal antibody, is the only approved biological therapy for systemic lupus erythematosus (SLE) and lupus nephritis (LN).

Areas covered: This review discusses BEL's real-world use and its positioning in clinical practice guidelines, focusing on the evolution of its application and patient profile over the last decade in Spain.

Expert opinion: Initially used for refractory and non-major SLE manifestations, BEL's application has expanded. International guidelines now recommend earlier use of BEL in treatment algorithms. With its 2021 approval for LN, BEL is increasingly used for renal manifestations and as a first-line therapy. Safety data confirm its tolerability without a significant increase in severe infections. However, real-world evidence in Spain reveals discrepancies with these recommendations for both SLE and LN. The optimal patient for BEL treatment is one with mild, moderate, or severe SLE that cannot be controlled with hydroxychloroquine (HCQ), with or without glucocorticoids (GC) and immunosuppressants (IS), in patients with a disease duration of ≤2 years, no initial organ damage, GC doses ≥5 mg/day, and a high risk of severe flares. Further studies are needed to determine the optimal timing for BEL initiation to improve patient outcomes and modify the disease course.

Background: The aim of this study is to confront the effectiveness of anti-IL 17 versus anti-IL 23 mAb in treating palmoplantar psoriasis by comparing the incidence of patients that required a therapy switch to another mAb class. Furthermore, we calculated the mean time intercurrent the beginning therapy with mAbs and the necessity to switch class due to ineffectiveness.

Research design and methods: We enrolled 116 patients with moderate to severe palmoplantar psoriasis. Patients with the pustular variant were excluded from this study. We performed statistical analysis to calculate the incidence of therapy switch in anti-IL 17 and anti-IL 23 mAb therapies.

Results: The results of both univariate and multivariate statistical analysis demonstrated that patients in therapy with anti-IL 23 mAb have a lower incidence of therapy switch compared to patients in therapy with anti-IL 17 drugs. The median switch time is 105 months. No other significant factors predictive of therapy switch were found.

Conclusions: This real-life evidence confirms the reduced necessity of therapy switch in patients with palmoplantar psoriasis treated with anti-IL 23 antibodies, compared to those treated with IL 17 inhibitors.

Introduction: Patients with relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL) have a poor median survival rate when treated with traditional salvage therapies. Bispecific antibodies (BsAbs) are an emerging class of 'off-the-shelf' immunotherapies that show promising efficacy in this population. Odronextamab is a CD20×CD3 targeting bispecific antibody that is being investigated in multiple subtypes of relapsed/refractory B-NHL.

Areas covered: This article describes the development of odronextamab from pre-clinical work through to ongoing clinical trials in relapsed/refractory B-NHL. The structure, safety, efficacy and administration of odronextamab are discussed. Studies were selected for inclusion by performing a search in PubMed, EMBASE, Cochrane Library and relevant conference abstracts from 2014 to 2024. The clinicaltrials.gov website and reference lists of the included studies were also reviewed.

Expert opinion: Odronextamab has demonstrated manageable safety and promising efficacy in multiple subtypes of relapsed/refractory B-NHL. The low rates of immune effector cell-associated neurotoxicity syndrome ;(ICANS) and high response rates in rare aggressive subtypes of B-NHL are particularly noteworthy. High rates of severe infections remain a challenge with BsAbs, with further prophylactic efforts required to reduce the risk. Clinical trials of combination therapies with odronextamab are required to improve the utility of this BsAb across a wider range of settings and subtypes of B-NHL.

Introduction: Antibody-based immunotherapies are a class of therapeutics under active investigation in clinical trials for the treatment of acute myeloid leukemia (AML). Our review provides a comprehensive examination of trials published to date, focusing on recurrent challenges and promising aspects of antibody-based therapeutics.

Areas covered: We described antibody-based immunotherapies for AML, specifically, an overview of the most prominent antigen targets in published clinical trials investigating monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptor therapies. Manuscripts and abstracts describing clinical trials investigating antibody-based therapies for AML published through December 2024, identified by searching Google Scholar and PubMed, were included.

Expert opinion: Antibody-based immunotherapies for AML have encountered limitations, including imperfect target antigens with significant associated toxicity such as myelosuppression, in addition to challenges specific to the AML patient population. The majority of trials have targeted CD33, CD123, CD371 (CLL1/Clec12), and CD47. For successful implementation of antibody-based therapeutics in AML treatment, future directions require creative applications of antibody-based therapeutics specifically engineered to minimize limiting toxicities and tailoring of therapies for this unique patient population.

Introduction: Ulcerative colitis (UC) is a chronic, relapsing and remitting, inflammatory bowel disease. Monoclonal antibodies targeting interleukin (IL)-23p19 have been developed to treat chronic inflammatory diseases mediated by aberrant IL23/Th17 responses, including psoriasis, psoriatic arthritis, and Crohn's disease. More recently, these agents have been evaluated for the treatment of moderately-to-severely active UC.

Areas covered: In this review, we summarize and discuss phase 2 and pivotal phase 3 clinical trials informing the efficacy and safety of mirikizumab (AMAC, LUCENT, SHINE), risankizumab (INSPIRE, COMMAND), and guselkumab (QUASAR, VEGA). The literature search included original research publications, secondary publications, and preliminary data from conference abstracts presented at international gastroenterology meetings from the past 5 years.

Expert opinion: The approval of IL23p19 antagonists expand the armamentarium of effective and safe therapies for patients living with moderately-to-severely active UC. These agents demonstrate potent efficacy for both inducing and maintaining symptomatic and objective disease endpoints, including endoscopic, histologic, and biomarker remission. These well-tolerated agents are effective in both advanced treatment-naïve and experienced patients. Accordingly, IL23p19 antagonists have potential to be used in a diverse population of patients with UC, and as potential platform therapies for future combinations with other targeted immunomodulatory agents.

Introduction: Adding monoclonal antibodies to chemotherapy drastically changed the landscape of advanced colorectal cancer. The prediction of benefit from anti-EGFR therapies is mainly based on the absence of mutations in RAS and BRAF genes, the primary tumor sidedness and microsatellite MSS/MSI status. Molecular hyperselection may optimize the outcome of patients receiving anti-EGFR while detecting additional resistance alterations, both in chemo-naïve and in chemo-refractory settings.

Areas covered: Our review focuses on negative molecular hyperselection, both on tissue samples and ctDNA, and the impact of this further patient selection on response rate and survival outcomes. We searched electronic database, selecting relevant English-language publications from 2017 to 2024.

Expert opinion: Negative hyperselection beyond RAS and BRAF in advanced colorectal cancer appears to be a powerful tool for predicting outcomes to anti-EGFR therapy and spare patients from unnecessary treatment. This improvement appears in both naïve and pre-treated patients. However, data come mainly from retrospective studies. Therefore, to validate and integrate these findings in the clinical practice, prospective studies should be conducted. It will be interesting to elucidate the role of ctDNA in this setting and the choice of molecular techniques, considering costs and accessibility, to guarantee its implementation in the clinic.

Objectives: Many biosimilars have been approved in both the United States of America (U.S.A.) and European Union (EU). We aim to highlight how regulatory challenges and divergent requirements between both agencies exist.

Methods: A comprehensive review of biosimilars approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) was conducted. We aimed to highlight similarities and differences in approaches taken by the agencies regarding the use of non-local (i.e. non -US and non-EU) reference medicinal products in biosimilar development. A search of the six most frequent classes of biosimilars authorized (cutoff date: 12 June 2024) by these agencies were identified and their public assessment reports reviewed.

Results: The review highlighted that pharmacokinetic (PK) bioequivalence studies are often replicated, the current process is inefficient and not entirely necessary when critical quality attributes are considered.

Conclusion: This article provides a comparative analysis of biosimilar approvals in EU and US regulatory agencies, focusing on non-local reference medicinal product (RMP) utilization and bioequivalence demonstration. The findings contribute to literature on biosimilar development and regulatory considerations, enhancing understanding of harmonization opportunities in biosimilar approval processes, potentially improving global access to high-quality, cost-effective biosimilars.