Reslizumab 25mg/2.5ml solution for infusion vials

ABSTRACT Background: New, complex, and expensive therapies targeting Interleukin-5 (IL-5) to treat severe eosinophilic asthma are emerging. Objective: To assess efficacy, adverse events, and inter-drug comparison of mepolizumab and reslizumab for treating severe eosinophilic asthma. Design: A systematic review and meta-analysis on randomized, placebo-controlled, clinical trials elucidating two critical (exacerbation rate and oral corticosteroid (OCS) use) and six important clinical outcomes on the efficacy and safety of mepolizumab and reslizumab. Results: Five studies (N = 2197) contributed with data for exacerbation rate, showing a reduction of 53% (95% CI 46; 59) in favour of anti-IL-5, corresponding to –0.94 annual exacerbations (95% CI –1.08;–0.82), thus exceeding the predefined minimal clinical important difference (MCID) of 25% reduction of the estimated ≥2 annual exacerbations. Quality of evidence was considered moderate, with low heterogeneity in study findings (I2 = 0%). One study (N = 135) contributed with data on percentage of patients experiencing ≥50% reduction inoral corticosteroid treatment, showing an effect of 20% (95% CI 2.3;47) in favour of anti-IL-5 treatment (mepolizumab), thus exceeding the predefined MCID of 10%. Quality of evidence was considered low. Compared to placebo, anti-IL-5 showed significant improvements in lung function, asthma control, and asthma-related quality of life, but below the MCIDs. No differences were observed for serious adverse events and number of patients, who dropped out. No studies evaluating sickleave or head-to-head comparisons were identified. By indirect comparison, we found no significant difference between mepolizumab and reslizumab in any ofthe predefined clinical outcomes. OCS treatment reduction could not be compared due to lack of reslizumab studies investigating this outcome. Conclusions: Mepolizumab and reslizumab provide significant and clinically relevant improvements in exacerbation rate and OCS reduction. Indirect, inter-study comparisons revealed no differences between the anti-IL-5 drugs in efficacy or safety measures.

Abstract licence: CC BY 4.0

BACKGROUND: Asthma patients with comorbid chronic rhinosinusitis or nasal polyps (CRS/NP) often experience poor asthma control. However, the comparative efficacies of biological therapies in this subgroup remain unclear. METHODS: A comprehensive search of multiple databases was conducted to identify randomized controlled trials (RCTs) on biological therapies targeting uncontrolled asthma that included CRS/NP data. The outcomes of interest were annual asthma exacerbation rate (AER), pre-bronchodilator forced expiratory volume in one second (pre-BD FEV1), asthma control questionnaire (ACQ) scores, and sinonasal outcome test (SNOT-22) scores. Pairwise meta-analyses were performed based on the presence or absence of CRS/NPs. Subsequently, random-effects network meta-analyses were conducted to perform indirect comparisons of the individual biological therapies. RESULTS: Eleven eligible RCTs evaluating tezepelumab, dupilumab, mepolizumab, and benralizumab were identified. Omalizumab and reslizumab were excluded because subgroup data were not available. Pairwise meta-analyses demonstrated significantly greater improvement effects of biological therapies on all outcomes in patients with CRS/NP than in those without CRS/NP (p < 0.01). In the network meta-analyses, for CRS/NP patients, tezepelumab showed the most pronounced reduction in AER (rate ratio 0.17; 95% confidence interval [CI] 0.09, 0.29), while benralizumab (mean difference [MD] 0.30 L; 95% CI 0.19, 0.40) exhibited the greatest improvement in pre-BD FEV1. Tezepelumab demonstrated the most substantial improvement in the ACQ scores (MD -0.80; 95% CI -1.25, -0.35), whereas mepolizumab (MD -11.80; 95% CI -19.75, -3.85) was associated with the greatest improvement in the SNOT-22 scores. CONCLUSIONS: In the management of asthma with CRS/NP, it is crucial to select biological therapies that consider specific improvements in individual outcomes.

Abstract licence: CC BY-NC-ND

Background and Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous type 2 inflammatory disease for which biologic therapies have expanded treatment options; however, biomarkers capable of guiding biologic selection remain poorly defined. This systematic review aimed to evaluate the available evidence regarding predictive and prognostic biomarkers associated with currently available biologic agents for CRSwNP (omalizumab, dupilumab, mepolizumab, benralizumab, reslizumab, and tezepelumab). Materials and Methods: A systematic search of PubMed/MEDLINE, Embase, Google Scholar, and the Cochrane Library identified studies published between January 2006 and September 2025. Results: Twenty-five eligible studies, including 12 randomized controlled trials, 12 systematic reviews/meta-analyses, and one indirect treatment comparison study, were analyzed. Multiple biomarkers, including blood eosinophils, total IgE, periostin, eotaxins, eosinophil cationic protein, IL-5, TARC, PARC, and urinary leukotriene E4, were evaluated across biologics targeting IgE, IL-4/IL-13, and IL-5 pathways. Conclusions: Although several biomarkers reflected the modulation of type 2 inflammation and disease activity, no validated biomarker has reliably predicted the superiority of one biologic over another. Nasal IL-5 showed potential for predicting the response to anti-IL-5 therapy but requires further validation. Current evidence supports biomarker use primarily for confirming type 2 inflammation rather than guiding biologic selection. Prospective biomarker-driven and head-to-head comparative studies are needed to enable precision medicine approaches in CRSwNP.

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Background: Eosinophilic esophagitis (EoE) is a rare, chronic immune-mediated disorder with limited treatment options. Despite the U.S. Food and Drug Administration (FDA) approval of dupilumab for EoE, other monoclonal antibodies remain unapproved and are used off-label with limited evidence on their efficacy and safety. This systematic review rigorously and comprehensively evaluates the evidence for monoclonal antibody therapies used off-label to treat EoE. Methods: We conducted a systematic review across PubMed, EMBASE, Cochrane Central, and ClinicalTrials.gov, assessing the efficacy and safety of off-label monoclonal antibodies in EoE through clinical outcomes and the FDA Adverse Event Reporting System (FAERS) data. Results: Among ten monoclonal antibodies reviewed, mepolizumab that targets IL-5 showed the most promise with a moderate recommendation based on Level 2 evidence. Others like omalizumab (anti-IgE), dectrekumab (anti-IL-13), and reslizumab (anti-IL-5) showed limited utility. Safety evaluations via the FAERS database revealed significant adverse drug reactions, including serious events like asthmatic crises, pneumonia, and adrenal insufficiency for mepolizumab and reslizumab, as well as chronic obstructive pulmonary disease and gastroenteritis for omalizumab. Dectrekumab's safety profile remains unclear due to a lack of data. Conclusions: While mepolizumab demonstrates potential as an off-label treatment, none of the antibodies reviewed have FDA approval for EoE. Clinicians should consider the balance between local and systemic effects and exercise caution, closely monitoring for adverse effects, particularly in patients with respiratory comorbidities. Continued research is crucial to establish a more robust evidence base for these therapies.

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BackgroundAsthma is a heterogeneous inflammatory disease that can cause substantial morbidity, reduced quality of life, and socioeconomic burden when uncontrolled. Biologic therapies have become central to the management of moderate-to-severe asthma by targeting specific inflammatory pathways.MethodsThis overview of systematic reviews synthesized evidence on the efficacy and safety of biologic agents for uncontrolled asthma. Searches were conducted in Medline (PubMed), Embase, LILACS, Web of Science, and the Cochrane Library using MeSH and Emtree terms structured according to the PICOT framework. Systematic reviews with meta-analyses or network meta-analyses comparing omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, and tezepelumab were included.ResultsIn indirect comparisons, dupilumab and tezepelumab were associated with more favorable outcomes in reducing the annualized exacerbation rate (AER) than benralizumab, mepolizumab, and reslizumab in severe uncontrolled asthma. In eosinophilic asthma, indirect evidence suggested more favorable outcomes with mepolizumab, tezepelumab, and dupilumab across eosinophil-defined subgroups (≥ 400 cells/μL, ≥ 300 cells/μL, ≥ 150 cells/μL, and 1), indirect evidence suggested more favorable outcomes with dupilumab. Regarding asthma control (ACQ), more favorable outcomes were observed with mepolizumab in specific comparisons. Regarding quality of life (AQLQ), more favorable outcomes were observed with omalizumab and tezepelumab in the general and eosinophilic asthma populations, respectively. One indirect comparison suggested lower odds of serious adverse events with mepolizumab.ConclusionThe available evidence suggests that biologic therapies may be effective and generally safe options for uncontrolled asthma, although the methodological quality of most included reviews was critically low. These findings support individualized treatment guided by biomarkers and clinical characteristics and highlight the need for standardized, methodologically rigorous future studies.

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Kimura disease (KD) is a rare, chronic inflammatory disorder characterized by painless subcutaneous tumors and lymphadenopathy, predominantly affecting the head and neck region. Its pathogenesis involves a dysregulated T-helper 2 (Th2) immune response leading to lymphoid hyperplasia and eosinophilic infiltration. As interleukin-5 (IL-5) is the cytokine responsible for eosinophil proliferation and survival, anti-IL-5 therapy may be biologically justified in KD. This study aims to investigate the efficacy of benralizumab, reslizumab, and mepolizumab in the treatment of KD. A systematic review following PRISMA guidelines was performed. Although a comprehensive literature search was performed, no published studies or case reports evaluating reslizumab in KD were identified. Nine case reports (11 patients, mean age 36.5 years, one patient received both agents sequentially) were studied regarding benralizumab and mepolizumab. Data extracted included the used agent, previous and concurrent therapy, efficacy, adverse effects, and recurrence. Mepolizumab showed a therapeutic response in seven out of nine cases, including three complete and four partial responses. Benralizumab showed clinical benefit in all treated patients, although one required salvage surgery. However, these findings must be interpreted with caution due to the limited sample size. Clinical improvement enabled the tapering or discontinuation of concomitant immunosuppressing therapy in most responders. No drug-related adverse events were reported over mean treatment durations of 16 months (median 14 months) for mepolizumab and 23 months (median 12 months) for benralizumab. However, cases included in this study may underreport potential long-term or rare adverse effects. Anti-IL-5 agents offer a potential treatment strategy for refractory or recurrent KD, demonstrating efficacy in tumor reduction and a favorable safety profile. These biologics are a corticosteroid-sparing alternative for resistant cases. Current evidence is limited by the reliance on small, heterogeneous case series. Multicenter prospective registries or international collaborative cohorts are required to validate these findings and standardize dosing regimens.

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