Authors: Basir Afzaal Gill, Anum Ijaz, Noor Fatima, Arsalan Ahmed, Ayesha Noor, Samia Sharif, Ishrat Fatima, Amna Saeeda, Hansa Devi, Muhammad Nabeel Saddique
Categories: Research, Asthma, Monoclonal antibody, Depemokimab, Meta-Analysis
Source: BMC Immunology
Authors: Basir Afzaal Gill, Anum Ijaz, Noor Fatima, Arsalan Ahmed, Ayesha Noor, Samia Sharif, Ishrat Fatima, Amna Saeeda, Hansa Devi, Muhammad Nabeel Saddique
Asthma is a complex and heterogeneous disease that significantly impacts quality of life. Eosinophilic asthma, characterized by elevated eosinophil levels, leads to inflammation and hypersensitivity. Many patients remain inadequately managed, resulting in frequent exacerbations and hospitalizations despite standard treatment options. Depemokimab, a long-acting monoclonal antibody that targets IL-5, could offer a novel approach for managing severe eosinophilic asthma.
A systematic search was conducted across the PubMed, Cochrane Library, Embase, ClinicalTrials.gov, and Scopus databases up to January 2025. Dichotomous outcomes were pooled as risk ratios (RR), and continuous outcomes were represented as mean differences (MD) from baselines, with 95% confidence intervals (CIs), using a random-effects model. Statistical analysis was performed using RevMan (version 5.4).
Two randomized controlled trials (n = 762) were included. Depemokimab significantly reduced the annualized rate of exacerbations (MD -0.59, 95% CI [-0.76 to -0.42], P < 0.00001) and improved the St. George’s Respiratory Questionnaire (SGRQ) score (MD -2.93, 95% CI [-5.48 to -0.38], P = 0.02). It also significantly decreased the annualized rate of exacerbations requiring hospitalization or emergency department visits (RR 0.33, 95% CI [0.15 to 0.75], P = 0.008). No significant differences were observed in changes to the Asthma Control Questionnaire (ACQ-5) score, pre-bronchodilator FEV1, or asthma-related diaries. Safety outcomes indicated significantly lower risks for pneumonia, nasopharyngitis, rhinitis, and back pain in the Depemokimab group. However, an increased risk of allergic rhinitis was noted (RR 2.71, 95% CI [1.22 to 6.02], P = 0.01). No significant differences were observed in serious adverse events or other adverse events.
Depemokimab demonstrates promising efficacy in reducing clinically significant exacerbations and improving quality of life measures in patients with severe eosinophilic asthma, with a generally favorable safety profile. However, the current evidence is limited to two trials with relatively short follow-up periods. Further research with larger, more diverse patient populations and extended long-term follow-up is needed to establish the drug’s definitive place in therapeutic algorithms and to comprehensively evaluate potential long-term safety concerns before widespread clinical implementation can be recommended.
The online version contains supplementary material available at 10.1186/s12865-025-00777-6.
Approximately 300 million people worldwide suffer from asthma, with an estimated 50% of severe asthma cases representing the eosinophilic subtype [1]. Patients with eosinophilic asthma are more likely to experience severe exacerbations, which can be debilitating. Furthermore, eosinophilic asthma may not respond well to traditional asthma treatments, such as inhaled corticosteroids [2]. Eosinophilic asthma is associated with type 2 inflammation, which involves the activation of immune cells, such as eosinophils and T-helper 2 cells. This process includes the production of cytokines, such as interleukin-5 (IL-5), which plays a key role in the maintenance of eosinophilic inflammation [3, 4].
The standard stepwise approach to treating asthma has proven to be less effective in managing asthma with the eosinophilic subtype [5]. Considering the distinct pathophysiology of eosinophilic asthma, which involves the key role of interleukin-5 (IL-5), researchers have recently developed targeted therapies aimed at blocking the IL-5 receptor. These novel treatments have shown promising results in the management of eosinophilic asthma [5].
Researchers have identified many monoclonal antibodies targeting IL-5 or its receptor that show promising results in treating eosinophilic asthma [6, 7]. By identifying patients with elevated eosinophil levels, clinicians can predict responsiveness to these therapies, which have significantly reduced asthma severity, exacerbations, and hospitalizations.
The recent introduction of Depemokimab, a novel anti-IL-5 monoclonal antibody, has expanded treatment options for patients with chronic asthma [8]. This innovative therapy offers comparable efficacy and safety to existing IL-5 inhibitors, but with a distinct its modified amino acid structure allows for less frequent dosing, enabling twice-yearly administration. This significant reduction in dosing frequency can improve patient compliance and quality of life, particularly for those with severe or uncontrolled asthma.
This meta-analysis focused on evaluating the efficacy of Depemokimab in reducing annualized exacerbation rates and improving patient-reported outcomes, as well as assessing the safety profile of the intervention by analyzing the incidence of adverse events compared to placebo in patients with eosinophilic asthma.
This systematic review and meta-analysis was outlined and performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist and the Cochrane Handbook of Systematic Reviews of Intervention [9, 10].
The PubMed, Embase, Cochrane, ClinicalTrials.gov, and Scopus databases were systematically searched for articles related to Depemokimab in severe asthma with an eosinophilic phenotype in January 2025. Our search included studies with title, abstract, and keyword search fields, aimed at finding the greatest number of studies with the following ((((“Asthma“[Mesh]) OR (Asthmas)) OR (Asthma, Bronchial)) OR (Bronchial Asthma)) AND (Depemokimab). The line-by-line search strategy for each database is presented in Supplementary files (Appendix 1).
Studies were included in this systematic review and meta-analysis if they met the following inclusion (1) the study design was limited to randomized controlled trials (RCTs) to ensure the highest level of evidence; (2) the intervention involved Depemokimab administered at any dosage regimen, which is the primary focus of this review; (3) the study included a comparator group receiving either a placebo or standard asthma treatments, such as inhaled corticosteroids or other biologic agents, to enable an appropriate comparison of outcomes; (4) the study reported at least one of the following (i) annualized asthma exacerbation rates, (ii) reduction in eosinophil counts, (iii) changes in lung function or quality-of-life measures (e.g., FEV1, ACQ, AQLQ), or (iv) adverse events and treatment-related safety profiles; and (5) the study was published in a peer-reviewed journal and written in English.
Studies were excluded from this review based on the following (1) Studies that did not directly address the research question or objectives of the systematic review, thus providing data unrelated to the efficacy or safety of Depemokimab for severe eosinophilic asthma were excluded; (2) Study designs other than RCTs, such as case series, observational studies, case reports, reviews, or editorials, were excluded due to their inherently lower methodological rigor; (3) Studies involving participants without an eosinophilic asthma phenotype or studies focused exclusively on pediatric populations (age < 12 years) were excluded, as they did not meet the specified population criteria for this review; (4) Studies that evaluated biologics other than Depemokimab were excluded to maintain focus on the specific intervention of interest; (5) Studies that did not report key efficacy or safety outcomes related to asthma management or lacked sufficient data for analysis were excluded; and (6) Non-peer-reviewed articles, conference abstracts with insufficient data, or unpublished studies were excluded to ensure the inclusion of only high-quality, rigorously evaluated evidence.
The retrieved references were initially screened based on titles, abstracts, and relevant outcomes to evaluate their eligibility according to the predefined inclusion and exclusion criteria. This process was carried out by four independent reviewers (A.I., A.A., A.N., and I.F.). Conference presentations and grey literature were excluded from the literature search to uphold the rigor of the review process. After the primary screening, secondary screening was conducted by five additional independent reviewers (B.G., S.S., N.F., A.I., and H.A.), who evaluated the full-text articles for eligibility based on the predefined criteria.
The aggregate-level data from the included studies were extracted by three independent reviewers (S.S., A.N., and H.) regarding study characteristics, interventions, comparisons, and outcomes. The primary outcomes of interest included the annualized rate of clinically significant asthma exacerbations, changes from baseline in the St. George’s Respiratory Questionnaire (SGRQ) total score, and various asthma-related symptom measures such as the Asthma Control Questionnaire (ACQ-5), along with the Forced Expiratory Volume in 1 s (FEV1). Safety outcomes, including serious adverse events (SAEs) and other relevant adverse events, were also extracted. All data were organized and entered into a standardized Excel sheet. A third independent reviewer was employed to resolve any discrepancies. Additionally, data from Kaplan–Meier plots and other graphical representations were extracted using WebPlotDigitizer, a web-based tool [11]. The standard error and range were transformed into means and standard deviations (SD) using the Meta-Analysis Accelerator, another web-based tool [12].
The risk of bias for each included study was independently assessed by the reviewers using the Cochrane Risk of Bias 2.0 (RoB 2.0) tool [13]. This tool assesses the risk of bias across five (1) Selection Bias (from random sequence generation and allocation concealment), (2) Performance Bias (from deviations from the intended interventions), (3) Detection Bias (from the blinding of outcome assessors), (4) Attrition Bias (from incomplete outcome data), and (5) Reporting Bias (from selective reporting of outcomes). Each study was categorized as having a low risk, some concerns, or high risk of bias in each domain, based on the information provided in the study reports. Any discrepancies in bias assessments were resolved through discussions with a third independent reviewer. This risk of bias was visualized using Risk-of-Bias VISualization (robvis), a web-based tool developed with R and Shiny application [14].
The main endpoint of this meta-analysis is the reduction in the annualized rate of asthma exacerbations, comparing the effects of Depemokimab with those of placebo. This primary outcome of interest is defined in the original trials (SWIFT-1 and SWIFT-2) as those requiring systemic corticosteroid use and/or resulting in an emergency department visit or hospitalization. Detailed stratification such as exacerbations requiring ICU care or duration of corticosteroid therapy were not reported in the original trial publications, limiting our ability to further refine these endpoints. Secondary endpoints included changes in quality of life, measured by the St. George’s Respiratory Questionnaire (SGRQ) and the Asthma Control Questionnaire (ACQ-5), which evaluate improvements in patient-reported symptoms and overall asthma control.
Pooled outcome estimates for Depemokimab were calculated for dichotomous outcomes as risk ratios (RR) and for continuous outcomes as mean differences (MD), each accompanied by 95% confidence intervals (CI). Statistical heterogeneity among the included studies was assessed using I² and X² statistics, with I² values of < 50% indicating low heterogeneity, 50–75% indicating moderate heterogeneity, and >75% indicating significant heterogeneity. Random-effects models were applied to account for variability between studies, with the Mantel-Haenszel method employed for dichotomous outcomes and the Inverse Variance method used for continuous outcomes. Sensitivity analyses were conducted to assess the robustness of the results, particularly focusing on studies with larger sample sizes. Due to the inclusion of fewer than 10 studies per outcome, funnel plots were not used for publication assessment bias [10]. All statistical analyses were performed using Review Manager 5.4.1 (The Cochrane Collaboration). A p-value of < 0.05 was deemed statistically significant.
The refined search string resulted in 55 articles from various information source databases. After removing 21 duplicate studies, 34 relevant studies remained. These studies were then screened based on their titles and abstracts. After reviewing the full texts of the possibly relevant studies, 2 studies that met the selection criteria were included in this systematic review and meta-analysis. The study selection process is illustrated in the PRISMA flowchart (Fig. 1).Fig. 1PRISMA flowchart for study selection process
The risk of bias for the included randomized controlled trials was evaluated using the Cochrane Risk of Bias 2.0 (RoB 2.0) tool, assessing five randomization process, deviations from intended interventions, missing outcome data, measurement of the outcome, and selection of the reported result. Both SWIFT-1 and SWIFT-2 trials were judged to have an overall low risk of bias. These trials demonstrated adequate random sequence generation and allocation concealment, minimal deviations from intended interventions, low levels of missing outcome data, and blinded outcome assessment. In both trials, outcome reporting followed a pre-specified protocol, reducing the risk of selective reporting bias (Figs. 2 and 3).Fig. 2Traffic light plot for risk of bias assessment using the Cochrane RoB 2.0 toolFig. 3Summary plot for risk of bias assessment across included studies
Across the included studies, the pooled patient population had a mean age of approximately 53 years, with a slight female predominance. Most participants were White, followed by Asian and other ethnic groups. The average duration of asthma exceeded 20 years, with an onset typically in early adulthood. Most patients received medium to high doses of inhaled glucocorticoids, and a minority were on maintenance oral corticosteroids. Elevated blood eosinophil counts (≥ 150 cells/µL) were common, reflecting the eosinophilic phenotype. Baseline lung function was moderately impaired, with mean pre-bronchodilator FEV₁ around 2.2 L and reversibility averaging 17–19%. Asthma control was suboptimal at baseline, and a considerable proportion of patients had experienced two or more exacerbations in the previous year. Nasal polyps were reported in up to 17% of patients. Overall, the study populations were well-matched and representative of patients with uncontrolled, eosinophilic asthma (Table 1).
Table 1Baseline characteristics and demographics of patients in SWIFT 1 and SWIFT 2 trialsCharacteristicSWIFT 1SWIFT 2Depemokimab (n = 250)Placebo (n = 132)Depemokimab (n = 252)Placebo (n = 128)Male, n (%)106 (42%) 53 (40%) 92 (37%)47 (37%)Female, n (%)144 (58%)79 (60%)160 (63%)81 (63%)Age, years (mean ± SD)54.1 ± 13.853.6 ± 14.953.6 ± 16.051.2 ± 16.6White, n (%)207 (83%)109 (83%)181 (72%)91 (71%)Asian, n (%)43 (17%)23 (17%)52 (21%)23 (18%)Other Ethnicities, n (%)––19 (7%)14 (11%)Duration of Asthma, years (mean ± SD)22.5 ± 16.120.0 ± 16.325.6 ± 18.724.1 ± 17.9Age at Asthma Onset, years (mean ± SD)31.6 ± 18.733.5 ± 18.928.0 ± 20.927.0 ± 21.6Total IgE (U/mL)144.4180.4158.3189.3Inhaled Glucocorticoid Use – Medium dose, n (%)118 (47%)61 (46%)94 (37%)60 (47%)Inhaled Glucocorticoid Use – High dose, n (%)132 (53%)71 (54%)158 (63%)68 (53%)Maintenance Oral Glucocorticoids, n (%)8 (3%)13 (10%)13 (5%)6 (5%)ACQ-5 Score (mean ± SD)1.9 ± 0.71.8 ± 0.71.8 ± 0.71.8 ± 0.7Pre-BD FEV₁, L (mean ± SD)2.22 ± 1.122.34 ± 1.102.20 ± 1.072.13 ± 1.00Pre-BD FEV₁ % Predicted (mean ± SD)62.3 ± 14.560.8 ± 16.662.5 ± 16.060.9 ± 15.7FEV₁ Reversibility (%), mean ± SD16.5 ± 15.317.9 ± 15.317.6 ± 17.519.4 ± 17.3Eosinophil Count ≥ 150 cells/µL at screening, n (%)224 (90%)123 (93%)219 (87%)118 (92%)Eosinophil Count ≥ 300 cells/µL in past 12 mo, n (%)127 (51%)61 (46%)151 (60%)66 (52%)No. of Asthma Exacerbations a) Leading to use of oral or systemic glucocorticoids in ≤ 12 mo-no. (%)01(< 1)000100002210(84)118(89)188(75)90(70)332(13)9(7)36(14)17(13)42(1)3(2)14(6)7(5)> 45(2)2(2)14(6)14(11) b) Leading to hospitalization in ≤ 12 mo-no. (%)0233(93)125(95)233(92)111(87)113(5)4(3)6(2)12(9)≥ 24(2)3(2)13(5)5(4)Nasal Polyps – Previous, n (%)42 (17%)15 (11%)38 (15%)18 (15%)Nasal Polyps – Current, n (%)25 (10%)10 (8%)24 (10%)13 (10%)
The efficacy and safety outcomes of Depemokimab compared to placebo, including exacerbation rates, lung function, asthma control, and adverse events, are summarized in Tables 2 and 3.Table 2Week 52 efficacy outcomes in SWIFT 1 and SWIFT 2 Trials – Depemokimab vs. PlaceboOutcome MeasureSWIFT 1SWIFT 2DepemokimabPlaceboDepemokimabPlaceboYear20232024Participants (n)250132252128Annualized Exacerbation Rate0.46 ± 0.521.11 ± 1.350.56 ± 0.611.08 ± 1.36SGRQ Change from Baseline (Δ Score)−13.3 ± 17.23−9.67 ± 17.47−14.8 ± 16.31−12.49 ± 16.20Hospital/ED Visits (Events/Total)5/25013/13213/25214/128ACQ-5 Change from Baseline (Δ Score)−0.82 ± 1.03−0.77 ± 1.03−0.81 ± 1.02−0.70 ± 1.00Pre-Bronchodilator FEV₁ Change (L)0.16 ± 0.400.16 ± 0.410.24 ± 0.440.18 ± 0.44ANSD Weekly Mean Score Change−1.39 ± 1.63−1.30 ± 1.64−1.18 ± 1.39−0.97 ± 1.37ADSD Weekly Mean Score Change−1.33 ± 1.45−1.25 ± 1.47−1.13 ± 1.26−0.93 ± 1.26SGRQ St. George’s Respiratory Questionnaire, ACQ-5 Asthma Control Questionnaire (5-item), FEV₁ Forced Expiratory Volume in 1 s, ANSD Asthma Nighttime Symptom Diary, ADSD Asthma Daily Symptom Diary, ED Emergency Department, Δ Score Change from baseline, ± SD Mean ± Standard DeviationTable 3Safety outcomes of included studies (SWIFT 1 & SWIFT 2)Adverse EventSWIFT 1SWIFT 2Depemokimab (n = 250)Placebo (n = 132)Depemokimab (n = 251)Placebo (n = 129)Serious Adverse Events15221913Asthma Events35128Other Adverse Events1457813880Influenza21259Respiratory Tract Infection (RTI)91174Lower RTI10758Upper RTI3922296Rhinitis154233(Duplicate) Rhinitis171676Back Pain61177Headache17133012Hypertension10778Pneumonia1304COVID-1951303820Nasopharyngitis37324544Pharyngitis82101Sinusitis146117
All 2 included studies reported the annualized rate of clinically significant exacerbations up to 52 weeks in a total of 762 patients (Depemokimab: 502; 260). There is a statistically significant mean reduction in the annualized rate of clinically significant exacerbations up to 52 weeks in Depemokimab (MD −0.59, 95% CI: [−0.76 to −0.42], I^2^ = 0%, P = 0.00001) (Fig. 4A).Fig. 4A Forest plot for annualized rate of clinically significant exacerbations up to 52 weeks for Depemokimab vs. placebo. B Forest plot for change from baseline in St. George’s Respiratory Questionnaire (SGRQ) total score at week 52 for Depemokimab vs. placebo. C Forest plot for annualized rate of exacerbations requiring hospitalization and/or emergency department visits up to 52 weeks for Depemokimab vs. placebo. **D **Forest plot for change from baseline in Asthma Control Questionnaire (ACQ-5) total score at week 52 for Depemokimab vs. placebo. E Forest plot for change from baseline in pre-bronchodilator FEV1 at week 52 for Depemokimab vs. placebo. F Forest plot for change from baseline in Asthma Nighttime Symptom Diary (ANSD) weekly mean score at week 52 for Depemokimab vs. placebo. G Forest plot for change from baseline in Asthma Daily Symptom Diary (ADSD) weekly mean score at week 52 for Depemokimab vs. placebo
All 2 included studies reported change from baseline in St. George’s Respiratory Questionnaire (SGRQ) total score at week 52 in a total of 738 patients (Depemokimab: 486; 252). There is a statistically significant mean reduction in SGRQ in Depemokimab (MD −2.93, 95% CI [−5.48 to −0.38], I^2^ = 0%, P = 0.02) (Fig. 4B).
All 2 included studies reported the annualized rate of exacerbations requiring hospitalization and/or ED visit up to 52 weeks in a total of 762 patients (Depemokimab: 502; 260). There is a statistically significant reduced risk of the annualized rate of exacerbations requiring hospitalization and/or ED visit up to 52 weeks with Depemokimab (RR 0.33, 95% CI: [0.15 to 0.75], I^2^ = 44%, P = 0.008) (Fig. 4C).
All 2 included studies reported change from baseline in Asthma Control Questionnaire (ACQ-5) total score at week 52 in a total of 740 patients (Depemokimab: 487; 253). There is no difference in Asthma Control Questionnaire (ACQ-5) total score at week 52 between the two groups (MD −0.08, 95% CI: [−0.24 to 0.07], I^2^ = 0%, P = 0.31) (Fig. 4D).
All 2 included studies reported change from baseline in pre-bronchodilator FEV1 at week 52 in a total of 720 patients (Depemokimab: 475; 245). There is no difference in pre-bronchodilator FEV1 at week 52 between the two groups (MD 0.03, 95% CI: [−0.04 to 0.09], I^2^ = 0%, P = 0.45) (Fig. 4E).
All 2 included studies reported change from baseline in Asthma Nighttime Symptom Diary (ANSD) weekly mean score at week 52 in a total of 629 patients (Depemokimab: 417; 212). There is no difference in Asthma Nighttime Symptom Diary (ANSD) weekly mean score at week 52 between the two groups (MD −0.17, 95% CI: [−0.41 to 0.08], I^2^ = 0%, P = 0.18) (Fig. 4F).
All 2 included studies reported change from baseline in Asthma Daily Symptom Diary (ADSD) weekly mean score at week 52 in a total of 691 patients (Depemokimab: 455; 236). There is no difference in ADSD weekly mean score at week 52 between the two groups (MD −0.15, 95% CI: [−0.36 to 0.06], I^2^ = 0%, P = 0.15) (Fig. 4G).
The two included studies assessed safety outcomes following administration of Depemokimab or placebo, in a total of 762 patients (Depemokimab: 501, 261). The pooled analysis shows a statistically significant reduced risk of pneumonia (RR 0.12, 95% CI: [0.02 to 0.69], I^2^ = 0%, P = 0.02), nasopharyngitis (RR 0.56, 95% CI: [0.43 to 0.73], I^2^ = 0%, P < 0.0001), rhinitis (RR 0.57, 95% CI: [0.33 to 0.99], I^2^ = 0%, P = 0.05) and back pain (RR 0.38, 95% CI: [0.19 to 0.77], I^2^ = 0%, P = 0.007) in the Depemokimab group. However, there is a statistically significant increased risk of allergic rhinitis (RR 2.71, 95% CI: [1.22 to 6.02], I^2^ = 0%, P = 0.01) in the Depemokimab group.
There is no difference in serious adverse events (RR 0.51, 95% CI: [0.25 to 1.06], I^2^ = 60%, P = 0.07), asthma (RR 0.59, 95% CI: [0.27 to 1.31], I^2^ = 9%, P = 0.20), other (non-serious) adverse events (RR 0.93, 95% CI: [0.82 to 1.06], I^2^ = 0%, P = 0.27), influenza (RR 1.21, 95% CI: [0.06 to 24.83], I^2^ = 91%, P = 0.90), lower respiratory tract infection (RR 0.52, 95% CI: [0.22 to 1.19], I^2^ = 25%, P = 0.12), COVID-19 (RR 0.93, 95% CI: [0.68 to 1.27], I^2^ = 0%, P = 0.64), respiratory tract infection (RR 0.55, 95% CI: [0.27 to 1.11], I^2^ = 0%, P = 0.09), pharyngitis (RR 2.91, 95% CI: [0.85 to 9.93], I^2^ = 0%, P = 0.09), headache (RR 0.96, 95% CI: [0.52 to 1.76], I^2^ = 41%, P = 0.89), sinusitis (RR 1.00, 95% CI: [0.52 to 1.92], I^2^ = 0%, P = 0.99), upper respiratory tract infection (RR 1.43, 95% CI: [0.55 to 3.74], I^2^ = 75%, P = 0.47), and hypertension (RR 0.59, 95% CI: [0.30 to 1.17], I^2^ = 0%, P = 0.13) (Figure S1-S16).
This systematic review and meta-analysis evaluated the efficacy and safety of Depemokimab in patients with severe eosinophilic asthma, extracting data from two randomized, placebo-controlled trials [15, 16]. Depemokimab significantly reduced the annualized rate of clinically significant exacerbations over 52 weeks, showing a consistent and clinically meaningful effect (MD −0.59) with no observed heterogeneity. There was also a modest but significant improvement in health-related quality of life, reflected by reduced SGRQ scores. The reduced risk of severe exacerbations requiring hospitalization or emergency care also endorses its benefit in high-risk patients.
These outcomes were observed in a well-defined population with severe eosinophilic asthma. Participants had long disease duration (mean ~ 23 years), high eosinophil counts (≥ 150 cells/µL), and poor asthma control at baseline (ACQ-5 > 1.8, frequent exacerbations). Nearly all were on medium- to high-dose inhaled corticosteroids, and some required maintenance oral corticosteroids, reflecting difficult-to-control disease despite optimized therapy.
Though quality of life improved, Depemokimab did not significantly change lung function (pre-bronchodilator FEV₁), asthma symptom diaries (ADSD/ANSD), or ACQ-5 scores. This suggests its primary effect is on exacerbation frequency, while its impact on daily symptoms and pulmonary function may be limited due to shorter follow-up. Given asthma’s chronic, multifactorial nature, symptom improvement may depend on factors like airway remodeling, comorbidities (e.g., nasal polyps), and environmental exposures.
From a safety standpoint, Depemokimab was generally well tolerated. Pooled analysis showed reduced risks of pneumonia, nasopharyngitis, rhinitis, and back pain. A small but significant increase in allergic rhinitis was observed, potentially relevant in predisposed individuals. No increase was noted in serious adverse events or infection-related complications, including COVID-19 or influenza, supporting a favorable safety profile in patients exposed to chronic corticosteroids.
Additionally, the inclusion of participants with long-standing, severe asthma, limits generalizability to milder phenotypes. The 52-week follow-up may not capture long-term effects, and subgroup data (e.g., age, comorbidities) were limited. Lastly, the small number of trials restricts detection of rare events and broader applicability.
Current asthma treatment guidelines classify medications based on symptom severity into relievers and long-term controllers. Bronchodilators (short-acting beta agonists or muscarinic antagonists) and systemic corticosteroids are standard for acute exacerbations, while combinations of long-acting beta agonists (LABA) and inhaled corticosteroids (ICS), long-acting muscarinic antagonists (LAMA) and ICS (ICS), oral corticosteroids (OCS) with or without other therapeutics, leukotriene receptor antagonists, mast cell stabilizers, and biologics are frontline options for long-term control [16].
Biologics have improved outcomes in severe eosinophilic asthma, particularly in reducing exacerbations, enhancing lung function, lowering hospitalizations, and improving symptoms. Among other biologics, IL-5 and IL-5R antagonists have shown promising outcomes. Table 1 compares FDA-approved IL-5 and IL-5R therapies with Depemokimab in terms of administration, and cost [17–21]. To establish its comparative efficacy against these approved biologics, head-to-head, randomized, double-blinded trials with balanced populations to account for confounders, need to be conducted (Tables 4 and 5).Table 4Comparison of FDA-approved IL-5/IL-5R and TSLP inhibitors with Depemokimab in terms of target, administration, dosing, and costDrug NameTargetAdministrationDosingPrice ComparisonKey NotesMepolizumabIL-5SC/IV100 mg SC/75 mg IV every 4 weeks~2,700Weight-based dosing; administered in a clinic; IV infusion onlyBenralizumabIL-5RαSC30 mg SC every 4 weeks for 3 doses, then every 8 weeks~$3,100Induces eosinophil apoptosis via ADCC; convenient less frequent dosing after initial phaseDepemokimabIL-5SC100 mg every 6 monthsNo cost estimates availablePipeline drug, may offer improved complianceSC Subcutaneous, IV IntravenousCosts are approximate and can vary by insurance, region, and discounts
Table 5Asthma concomitant medications taken by ≥ 5% of patients in either treatment arm/studyRespiratory MedicationSWIFT 1SWIFT 2Depemokimab (n = 250)Placebo (n = 132)Depemokimab (n = 252)Placebo (n = 128)ICS, n (%)Prior to treatment250(100)132(100)252(100)128(100)During treatment250(100)132(100)252(100)128(100)Long-acting β2 agonist, n (%)Prior to treatment247(99)131(> 99)249(99)126(98)During treatment245(98)129(98)244(97)124(97)Leukotriene receptor antagonist, n (%)Prior to treatment80(32)39(30)116(46)65(51)During treatment77(31)34(26)109(43)62(48)SCS, n (%)Prior to treatment93(37)53(40)93(37)46(36)During treatment83(33)68(52)88(35)66(52)Long-acting anticholinergic, n (%)Prior to treatment69(28)35(27)87(35)46(36)During treatment66(26)33(25)81(32)48(38)Short-acting anticholinergic, n (%)Prior to treatment31(15)17(13)23(9)12(9)During treatment19(8)10(8)12(5)8(6)Anti-infectives, n (%)Prior to treatment37(15)19(14)27(11)7(5)During treatment25(10)20(15)21(8)19(15)Xanthine, n (%)Prior to treatment21(8)10(8)23(9)8(6)During treatment19(8)14(11)20(8)10(8)Mucolytics, n (%)Prior to treatment23(9)9(7)19(8)7(5)During treatment24(10)16(12)18(7)15(12)
Depemokimab is a promising option for patients with severe eosinophilic asthma, showing efficacy in reducing exacerbations and improving symptoms. Its long-acting profile may improve compliance and reduce treatment burden, making it a potentially practical addition to practice guidelines. Policymakers should consider its potential for cost-effectiveness and efficient healthcare resource allocation. However, while Depemokimab demonstrated efficacy in reducing clinically significant exacerbations, its impact on other key asthma outcomes—such as lung function, symptom burden, and corticosteroid use—remains less clear. This may be partly attributable to the design and reporting focus of the SWIFT-1 and SWIFT-2 trials, which did not prioritize or consistently report these secondary endpoints. Additionally, the inclusion criterion for eosinophilic phenotype in these trials was a blood eosinophil count ≥ 150 cells/µL; lower than the ≥ 300 cells/µL threshold used in other IL-5 targeting studies. This broader inclusion may have enrolled patients with a less pronounced type 2 inflammatory signature, potentially attenuating effects beyond exacerbation control. A key limitation of this meta-analysis, therefore, is the inability to assess treatment response across specific clinical subgroups—such as varying eosinophil levels, oral corticosteroid (OCS) use, or comorbid nasal polyposis—due to the lack of stratified outcome data in the original trials. Although exacerbations were defined as those requiring systemic corticosteroids or resulting in emergency visits or hospitalization, the trials did not report further granularity, such as duration of corticosteroid use or ICU admission, limiting deeper subgroup resolution. Broader use of Depemokimab will require real-world evidence and long-term safety data. Future research should explore its effects across diverse subgroups, including a larger corticosteroid-dependent population, varying age, ethnicity, and comorbidities, and incorporate direct comparisons with existing biologics.
Depemokimab demonstrates significant efficacy in reducing exacerbations in patients with severe eosinophilic asthma, particularly in high-risk populations. While statistically significant improvements in quality of life were observed, they did not reach the threshold for clinical significance. Similarly, no significant improvement was demonstrated in daily symptom control or lung function. Nonetheless, Depemokimab’s long-acting nature and favorable safety profile make it a promising option for managing difficult-to-control asthma. Further real-world evidence and long-term studies are needed to assess its broader applicability, long-term safety, and potential for cost-effectiveness compared to existing biologic therapies.
Supplementary Material 1.