CONTEXT:

Reslizumab is a humanised anti-interleukin 5 monoclonal antibody that disrupts eosinophil maturation and promotes programmed cell death.

OBJECTIVE:

We carried out a systematic review and meta-analysis to assess the efficacy and safety of the drug in patients with inadequately controlled, eosinophilic asthma.

DATA SOURCES:

The search included the following databases: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. The reference lists of the retrieved studies were also investigated.

STUDY SELECTION:

A literature review was performed to identify all published randomized double-blind, placebo-controlled trials of reslizumab for the treatment of inadequately controlled, eosinophilic asthma.

DATA EXTRACTION:

Two reviewers independently extracted and verified pre-defined data fields.

RESULTS:

Four publications involving a total of 1,366 patients were used in the analysis, including 5 RCTs that compared reslizumab with placebo. For the comparison of reslizumab with placebo, primary efficacy end points: asthma exacerbation (odds ratio (OR) = 0.46, 95% confidence interval (CI) = 0.35 to 0.59, p>0.00001); a forced expiratory volume in 1 s (FEV1) (the standardized mean difference (SMD) = 0.16, 95%CI = 0.10 to 0.23, p>0.00001); Asthma Control Questionnaire (ACQ) score (the SMD = -0.26, 95%CI = -0.36 to -0.16, p>0.00001); and key secondary efficacy end points: blood eosinophil counts (the SMD = -475.62, 95%CI = -528.41 to -422.83, p>0.00001). Safety assessments included the proportion of individuals who withdrawn due to adverse event (AE) (OR = 0.60 95%CI = 0.38 to 1.17, p = 0.16), and Upper respiratory AEs indicated that reslizumab was well tolerated.

LIMITATIONS:

The article didn't research the safety, efficacy of reslizumab with longer term.

CONCLUSIONS:

This meta-analysis indicates that reslizumab to be an effective and safe treatment for inadequately controlled, eosinophilic asthma.

BACKGROUND:

Eosinophilic esophagitis is a chronic allergic disease with insufficient treatment options. Results from animal studies suggest that IL-5 induces eosinophil trafficking in the esophagus.

OBJECTIVE:

We sought to evaluate the effect of reslizumab, a neutralizing antibody against IL-5, in children and adolescents with eosinophilic esophagitis.

METHODS:

Patients with symptom severity scores of moderate or worse and an esophageal biopsy specimen with 24 or more intraepithelial eosinophils per high-power field were randomly assigned to receive infusions of 1, 2, or 3 mg/kg reslizumab or placebo at weeks 0, 4, 8, and 12. The coprimary efficacy measures were changes in peak esophageal eosinophil count and the physician's global assessment score at week 15 (end of therapy).

RESULTS:

Two-hundred twenty-six patients received study medication. Median reductions from baseline to the end of therapy in peak esophageal eosinophil counts were 59%, 67%, 64%, and 24% in the 1, 2, and 3 mg/kg reslizumab (all P < .001) and placebo groups, respectively. All treatment groups, including the placebo group, showed improvements in physician's global assessment scores; the differences between the reslizumab and placebo groups were not statistically significant. The most common adverse events in the reslizumab groups were headache, cough, nasal congestion, and upper respiratory tract infection. One patient in each reslizumab group and 2 in the placebo group had serious adverse events; none were considered related to the study medication.

CONCLUSION:

Reslizumab significantly reduced intraepithelial esophageal eosinophil counts in children and adolescents with eosinophilic esophagitis. However, improvements in symptoms were observed in all treatment groups and were not associated with changes in esophageal eosinophil counts.

The purpose of this study is to determine whether Reslizumab is effective for the treatment of chronic sinusitis.

The primary objective of this study is to assess the absolute bioavailability of reslizumab following administration of a single subcutaneous (sc) dose to healthy non-Japanese participants

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Diethylcarbamazine citrate (DEC) treatment of Loa loa infection is complicated by the development of severe adverse reactions that are correlated with the number of circulating microfilariae in the blood. The cause of these reactions is unknown, but they are accompanied by a dramatic interleukin-5 (IL-5)-dependent increase in eosinophilia and evidence of eosinophil activation. This randomized, placebo-controlled, double-blind pilot study (conducted at the NIH Clinical Center) will assess whether and to what extent the administration of reslizumab (Cinquil ), a humanized monoclonal antibody directed against IL-5, given 3 to 7 days before administration of the anthelminthic drug DEC (at 3 mg/kg 3 times daily for 21 days), prevents the development of eosinophilia in 10 adult subjects with Loa loa infection and 0-5000 microfilariae/mL. Secondary outcomes will include the severity of post-treatment effects, markers of eosinophil activation, and effects of reslizumab on microfilarial clearance.

INTERVENTION:

Patients will recieve reslizuamb (n=21) or placebo (n=11) administered intravenously every 4 weeks for 12 consecutive weeks

CONDITION:

Asthma, Computed tomography, Airways, Reslizumab ; ;

PRIMARY OUTCOME:

In this study the change from baseline in regional image (HRCT) based hyperinflation (iVlobes) and in iVaw after 12 weeks treatment with reslizumab compared to changes in the placebo group

SECONDARY OUTCOME:

iRaw, air trapping, internal lobar airflow distribution, low attenuation or emphysema score, blood vessel density, airway wall thickness. Also correlations between changes in HRCT parameters and SGRQ socire, AQLQ score, FEV1/FVC, FVC, FRC, RV/TLC, FeNO and sputum eosinophils will be assessed.

INCLUSION CRITERIA:

Patients will be aged 18 ‐ 75 years and have a confirmed diagnosis of severe eosinophilic asthma according to ERS/ATS guidelines. All patients will show persistent blood eosinophilia of >0.4 x 10E9/L despite treatment with high doses of inhaled corticosteroids (>1000 ug/day fluticasone equivalent), or >0.15 x 10E9/L despite chronic oral corticosteroid treatment

Introduction: Reslizumab, an anti-interleukin-5 monoclonal antibody, reduced asthma exacerbations and improved lung function and symptoms in pts with inadequately controlled asthma and elevated blood eosinophils (≥400/μL) in three placebo-controlled Phase 3 trials (Bjermer, Eur Respir J 2014; Castro, Lancet Respir Med 2015). Based on interim data, lung function and asthma symptom control benefits were maintained for up to 2 years during an open-label extension study (Murphy, ATS 2015). Herein, we report the effects of reslizumab on asthma-related quality of life during the open-label extension. Methods: Following participation in a prior Phase 3 trial (16-52 weeks duration), reslizumab-naïve and -experienced pts (aged 12-75 years) who enrolled in the extension study received reslizumab 3.0 mg/kg once every 4 weeks for up to 2 years. The objectives (primary and secondary) were to obtain long-term safety and efficacy data. AQLQ was assessed every 24 weeks. This study was approved by relevant Institutional Review Boards; all pts provided written informed consent. Results: Of 1052 pts enrolled in the extension study, 1051 received ≥1 dose of reslizumab (480 reslizumab-naïve; 571 reslizumab-experienced). Baseline mean AQLQ score was better in reslizumabexperienced (5.491) vs -naïve (5.156) pts. Reslizumab-experienced pts maintained their baseline AQLQ scores during treatment, with a small improvement of 0.310 at week 96. Improvement in AQLQ score (0.395) was noted in reslizumab-naïve pts by the first on-treatment assessment (week 24), with a clinically significant (≥0.5 units) improvement of 0.540 at week 96. Clinically important improvements at week 96 were also observed for individual AQLQ domains of emotional function (0.843) and symptoms (0.596). The most common adverse events (AEs; ≥10%) were asthma, nasopharyngitis, and upper respiratory tract infection; incidences of AEs were similar between the two groups. Conclusions: The significant improvement in AQLQ scores observed with reslizumab during placebo-controlled trials was sustained, without diminution, with continued open-label reslizumab 3.0 mg/kg once every 4 weeks for up to 2 years. Reslizumab meaningfully improved AQLQ scores in reslizumabnaïve pts during the treatment period, and was well tolerated in this long-term extension study.

Background/Aim. Reslizumab is humanized monoclonal antibody produced by recombinant DNA technology which binds to circulating interleukin-5 (IL-5) and down-regulates the IL-5 signaling pathway. Reslizumab is indicated for the add-on maintenance treatment of patients 18 years and older with severe eosinophilic asthma phenotype whose symptoms were inadequately controlled with inhaled corticosteroids. The aim of this meta-analysis was to assess the efficacy and safety of reslizumab compared to placebo in patients suffering from inadequately controlled, moderateto- severe asthma with elevated blood eosinophil counts. Methods. Our meta-analysis was based on systematic search of literature and selection of high-quality evidence according to pre-set inclusion and exclusion criteria. The effects of reslizumab and placebo were summarized using Review Manager (RevMan) 5.3.5 and heterogeneity was assessed by the Cochrane Q test and I2 values. Several types of bias were assessed and publication bias shown by Funnel plot and Egger’s regression. Results. The meta-analysis included 5 randomized, placebo-controlled clinical trials. Reslizumab 3.0 mg/kg produced substantial improvements in forced expiratory volume in 1. second (FEV 1) (mean difference 0.15 [0.10, 0.21]) and in forced vital capacity (FVC) (mean difference 0.21 [0.09, 0.32]) over the 15 or 16-week treatment period, substantial decrease versus placebo in Asthma Control Questionnaire (ACQ) score (mean difference -0.28 [-0.41, -0.16]), and substantial increase vs. placebo from baseline in Asthma Quality of Life Questionnaire (AQLQ) total score (mean difference 0.24 [0.06, 0.43]). Also, reslizumab 3.0 mg/kg caused less adverse events versus placebo (OR 0.67 [0.51, 0.88]), especially asthma worsening (OR 0.53 [0.36, 0.77]) or bronchitis (OR 0.42 [0.24, 0.74]). Conclusion. On the basis of published clinical trials reslizumab could be considered as an effective and safe therapeutic option for severe, poorly controlled eosinophilic asthma for the time being.

Dose escalation of reslizumab can ameliorate sputum eosinophilia in severe asthmatics who have persistent sputum eosinophilia despite treatment with reslizumab at the standard dose.