抗白细胞介素-13和抗白细胞介素-4药物与安慰剂、抗白细胞介素-5或抗免疫球蛋白-E药物对哮喘患者的疗效比较
2021/11/24
摘要
背景：用针对细胞因子或其受体的特异性单克隆抗体靶向免疫球蛋白E途径和白细胞介素-5途径对重症哮喘患者有效。然而，有些患者对这些生物制剂的反应并不理想。针对白细胞介素-4受体通路的白细胞介素-4和白细胞介素-13对哮喘生物学具有多重影响，因此已开发针对白细胞介素-4和白细胞介素-13（单独或联合）的治疗方法。
目的：评估抗白细胞介素-13或抗白细胞介素-4药物与安慰剂、抗免疫球蛋白E药物或抗白细胞介素-5药物治疗儿童、青少年或成人哮喘的疗效和安全性。
搜索方法：我们从Cochrane Airways试验登记簿（该登记簿由集团信息专家维护）以及美国国立卫生研究院正在进行的试验登记ClinicalTrials.gov和世界卫生组织国际临床试验登记平台的搜索中确定了研究。搜索于2020年10月16日进行。
选择标准：我们纳入平行随机对照试验，比较抗白细胞介素-13或-4药物（或靶向白细胞介素-13和白细胞介素-4的药物）与安慰剂在诊断为哮喘的青少年和成人（16岁或以上）或儿童（年龄小于16岁）的疗效；参与者可以接受他们通常的短效或长效药物（例如吸入皮质类固醇（ICS），长效β-肾上腺素能受体激动剂（LABA），长效毒蕈碱拮抗剂（LAMA）和/或白三烯受体拮抗剂），条件是他们不是随机治疗的一部分。
数据收集和分析：我们使用Cochrane的标准方法。
主要结果：我们共纳入了41项随机对照试验。其中29项研究为定量分析提供了数据，随机分配10604名哮喘患者接受抗白细胞介素-13（干预）或抗白细胞介素-4药物（干预）或安慰剂（对照）治疗。在比较物是抗免疫球蛋白E或抗白细胞介素-5剂的情况下，未发现相关研究。研究持续时间为2至52周（中位数16周）。纳入研究的参与者的平均年龄为22至55岁。只有五项研究纳入儿童和青少年，占本次荟萃分析的参与者总数的不到5%。大多数参与者有中度或重度不受控制的哮喘。大多数（29/21）纳入研究允许或要求伴随ICS使用。19项研究不允许使用维持性全身皮质类固醇，5项研究允许或要求使用维持性全身皮质类固醇（5项研究未报告信息）。关于最常评估的抗白细胞介素-13/-4药物，四项研究评估了dupilumab（300 mg每周一次（Q1W），200 mg每两周一次（Q2W），300 mg Q2W，200 mg每四周一次（Q4W），300mg Q4W，各自通过皮下（SC）注射施用）；8项研究评估了lebrikizumab（37.5 mg Q4W，125 mg Q4W，250 mg Q4W，每次通过SC注射给药）；9项研究（3259名参与者）评估了tralokinumab（75 mg Q1W，150 mg Q1W，300 mg Q1W，150 mg Q2W，300 mg Q2W，600 mg Q2W，300 mg Q4W，均通过SC注射给药；1/5通过静脉内（IV）注射施用10mg/kg）；将所有抗白细胞介素-13或-4药物与安慰剂进行比较。多数研究偏倚风险低或不清楚（提供的细节不足）；九项研究有高风险的失访偏倚，三项研究有高风险的报告偏倚。以下结果与主要结果有关，接受tralokinumab与安慰剂相比，需住院或急诊（ED）就诊的恶化率可能较低（OR 0.68,95%CI 0.47-0.98；中度确定性证据；只可用于tralokinumab（抗白细胞介素-13）的数据）。在接受抗白细胞介素-13/-4药物的参与者中，调整后的哮喘生活质量问卷评分与安慰剂相比的平均改善为0.18单位（95%CI为0.12至0.24；高确定性证据）；但这改善并不是临床相关的显著改善。报告全因严重不良事件（抗白细胞介素-13/-4药物与安慰剂，OR 0.91,95%CI 0.76-1.09；中度确定性证据）的患者比例可能很少或没有差异。就次要终点而言，急性加重需口服皮质类固醇激素的患者比例（抗白细胞介素-13/-4药物与安慰剂相比，OR 0.98，95%CI 0.72-1.32；低确定性证据）。基于哮喘控制问卷评分（抗白细胞介素-13/-4药物与安慰剂，平均差异-0.19；95%CI-0.24至-0.14），抗白细胞介素-13/-4药物可能改善哮喘控制；但这个结果的改善并不是临床相关的显著改善。与接受安慰剂的患者相比，接受抗白细胞介素-13/-4药物治疗的患者发生任何不良事件的比例更高（OR 1.16,95%CI 1.04-1.30；高确定性证据）；用抗白细胞介素-13/-4药物治疗的参与者中最常报告的不良事件是上呼吸道感染，鼻咽炎，头痛和注射部位反应。接受抗白细胞介素-13/-4药物与安慰剂相比，需要口服皮质类固醇（OCS）或住院或急诊就诊的恶化率可能较低（比率0.71，95%CI 0.65至0.77；低确定性证据）。对于不同类别的药剂（抗白细胞介素-13或抗白细胞介素-4），研究持续时间和疾病严重程度，各亚组的结果通常是一致的。基于T辅助2（TH2）炎症类别的亚组分析表明，在具有较高水平的炎性生物标志物（血液嗜酸性粒细胞，呼出的一氧化氮和血清骨膜素）的患者中效果更佳。
作者的结论：根据全部证据，与安慰剂相比，抗白细胞介素-13/-4药物可能与需要住院或急诊就诊的恶化减少有关，但代价是患者不良事件增加。没有发现与健康相关的生活质量或哮喘控制的临床相关改善。因此，抗白细胞介素-13或抗白细胞介素-4药物可能适用于对其他治疗无反应的中度至重度不受控制的哮喘患者。这些结论通常得到基于观察期长达一年的研究的中度或高度确定性证据的支持。
Anti-interleukin-13 and anti-interleukin-4 agents versus placebo, anti-interleukin-5 or anti-immunoglobulin-E agents, for people with asthma
Andrew Gallagher, Michaela Edwards, Parameswaran Nair, Stewart Drew, Aashish Vyas, Rashmi Sharma, Paul A Marsden, Ran Wang, David Jw Evans
Abstract
Background: Targeting the immunoglobulin E pathway and the interleukin-5 pathway with specific monoclonal antibodies directed against the cytokines or their receptors is effective in patients with severe asthma. However, there are patients who have suboptimal responses to these biologics. Since interleukin-4 and interleukin-13, signalling through the interleukin-4 receptor, have multiple effects on the biology of asthma, therapies targeting interleukin-4 and -13 (both individually and combined) have been developed.
Objectives: To assess the efficacy and safety of anti-interleukin-13 or anti-interleukin-4 agents, compared with placebo, anti-immunoglobulin E agents, or anti-interleukin-5 agents, for the treatment of children, adolescents, or adults with asthma.
Search methods: We identified studies from the Cochrane Airways Trials Register, which is maintained by the Information Specialist for the Group and through searches of the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. The search was carried out on the 16 October 2020.
Selection criteria: We included parallel-group randomised controlled trials that compared anti-interleukin-13 or -4 agents (or agents that target both interleukin-13 and interleukin-4) with placebo in adolescents and adults (aged 16 years or older) or children (younger than 16 years), with a diagnosis of asthma; participants could receive their usual short- or long-acting medications (e.g. inhaled corticosteroids (ICS), long-acting beta adrenoceptor agonists (LABA), long-acting muscarinic antagonists (LAMA), and/or leukotriene receptor antagonists) provided that they were not part of the randomised treatment.
Data collection and analysis: We used standard methods expected by Cochrane.
Main results: We identified and included 41 RCTs. Of these, 29 studies contributed data to the quantitative analyses, randomly assigning 10,604 people with asthma to receive an anti-interleukin-13 (intervention) or anti-interleukin-4 agent (intervention), or placebo (comparator). No relevant studies were identified where the comparator was an anti-immunoglobulin agent or an anti-interleukin-5 agent. Studies had a duration of between 2 and 52 (median 16) weeks. The mean age of participants across the included studies ranged from 22 to 55 years. Only five studies permitted enrolment of children and adolescents, accounting for less than 5% of the total participants contributing data to the present review. The majority of participants had moderate or severe uncontrolled asthma. Concomitant ICS use was permitted or required in the majority (21 of 29) of the included studies. The use of maintenance systemic corticosteroids was not permitted in 19 studies and was permitted or required in five studies (information not reported in five studies). Regarding the most commonly assessed anti-interleukin-13/-4 agents, four studies evaluated dupilumab (300 mg once every week (Q1W), 200 mg once every two weeks (Q2W), 300 mg Q2W, 200 mg once every four weeks (Q4W), 300 mg Q4W, each administered by subcutaneous (SC) injection); eight studies evaluated lebrikizumab (37.5 mg Q4W, 125 mg Q4W, 250 mg Q4W each administered by SC injection); and nine studies (3259 participants) evaluated tralokinumab (75 mg Q1W, 150 mg Q1W, 300 mg Q1W, 150 mg Q2W, 300 mg Q2W, 600 mg Q2W, 300 mg Q4W, each administered by SC injection; 1/5/10 mg/kg administered by intravenous (IV) injection); all anti-interleukin-13 or-4 agents were compared with placebo. The risk of bias was generally considered to be low or unclear (insufficient detail provided); nine studies were considered to be at high risk for attrition bias and three studies were considered to be at high risk for reporting bias. The following results relate to the primary outcomes. The rate of exacerbations requiring hospitalisation or emergency department (ED) visit was probably lower in participants receiving tralokinumab versus placebo (rate ratio 0.68, 95% CI 0.47 to 0.98; moderate-certainty evidence; data available for tralokinumab (anti-interleukin-13) only). In participants receiving an anti-interleukin-13/-4 agent, the mean improvement versus placebo in adjusted asthma quality of life questionnaire score was 0.18 units (95% CI 0.12 to 0.24; high-certainty evidence); however, this finding was deemed not to be a clinically relevant improvement. There was likely little or no difference between groups in the proportion of patients who reported all-cause serious adverse events (anti-interleukin-13/-4 agents versus placebo, OR 0.91, 95% CI 0.76 to 1.09; moderate-certainty evidence). In terms of secondary outcomes, there may be little or no difference between groups in the proportion of patients who experienced exacerbations requiring oral corticosteroids (anti-interleukin-13/-4 agents versus placebo, rate ratio 0.98, 95% CI 0.72 to 1.32; low-certainty evidence). Anti-interleukin-13/-4 agents probably improve asthma control based on asthma control questionnaire score (anti-interleukin-13/-4 agents versus placebo, mean difference -0.19; 95% CI -0.24 to -0.14); however, the magnitude of this result was deemed not to be a clinically relevant improvement. The proportion of patients experiencing any adverse event was greater in those receiving anti-interleukin-13/-4 agents compared with those receiving placebo (OR 1.16, 95% CI 1.04 to 1.30; high-certainty evidence); the most commonly reported adverse events in participants treated with anti-interleukin-13/-4 agents were upper respiratory tract infection, nasopharyngitis, headache and injection site reaction. The pooled results for the exploratory outcome, the rate of exacerbations requiring oral corticosteroids (OCS) or hospitalisation or emergency department visit, may be lower in participants receiving anti-interleukin-13/-4 agents versus placebo (rate ratio 0.71, 95% CI 0.65 to 0.77; low-certainty evidence). Results were generally consistent across subgroups for different classes of agent (anti-interleukin-13 or anti-interleukin-4), durations of study and severity of disease. Subgroup analysis based on category of T helper 2 (TH2) inflammation suggested greater efficacy in patients with higher levels of inflammatory biomarkers (blood eosinophils, exhaled nitric oxide and serum periostin).
Authors' conclusions: Based on the totality of the evidence, compared with placebo, anti-interleukin-13/-4 agents are probably associated with a reduction in exacerbations requiring hospitalisation or ED visit, at the cost of increased adverse events, in patients with asthma. No clinically relevant improvements in health-related quality of life or asthma control were identified. Therefore, anti-interleukin-13 or anti-interleukin-4 agents may be appropriate for adults with moderate-to-severe uncontrolled asthma who have not responded to other treatments. These conclusions are generally supported by moderate or high-certainty evidence based on studies with an observation period of up to one year.
背景：用针对细胞因子或其受体的特异性单克隆抗体靶向免疫球蛋白E途径和白细胞介素-5途径对重症哮喘患者有效。然而，有些患者对这些生物制剂的反应并不理想。针对白细胞介素-4受体通路的白细胞介素-4和白细胞介素-13对哮喘生物学具有多重影响，因此已开发针对白细胞介素-4和白细胞介素-13（单独或联合）的治疗方法。
目的：评估抗白细胞介素-13或抗白细胞介素-4药物与安慰剂、抗免疫球蛋白E药物或抗白细胞介素-5药物治疗儿童、青少年或成人哮喘的疗效和安全性。
搜索方法：我们从Cochrane Airways试验登记簿（该登记簿由集团信息专家维护）以及美国国立卫生研究院正在进行的试验登记ClinicalTrials.gov和世界卫生组织国际临床试验登记平台的搜索中确定了研究。搜索于2020年10月16日进行。
选择标准：我们纳入平行随机对照试验，比较抗白细胞介素-13或-4药物（或靶向白细胞介素-13和白细胞介素-4的药物）与安慰剂在诊断为哮喘的青少年和成人（16岁或以上）或儿童（年龄小于16岁）的疗效；参与者可以接受他们通常的短效或长效药物（例如吸入皮质类固醇（ICS），长效β-肾上腺素能受体激动剂（LABA），长效毒蕈碱拮抗剂（LAMA）和/或白三烯受体拮抗剂），条件是他们不是随机治疗的一部分。
数据收集和分析：我们使用Cochrane的标准方法。
主要结果：我们共纳入了41项随机对照试验。其中29项研究为定量分析提供了数据，随机分配10604名哮喘患者接受抗白细胞介素-13（干预）或抗白细胞介素-4药物（干预）或安慰剂（对照）治疗。在比较物是抗免疫球蛋白E或抗白细胞介素-5剂的情况下，未发现相关研究。研究持续时间为2至52周（中位数16周）。纳入研究的参与者的平均年龄为22至55岁。只有五项研究纳入儿童和青少年，占本次荟萃分析的参与者总数的不到5%。大多数参与者有中度或重度不受控制的哮喘。大多数（29/21）纳入研究允许或要求伴随ICS使用。19项研究不允许使用维持性全身皮质类固醇，5项研究允许或要求使用维持性全身皮质类固醇（5项研究未报告信息）。关于最常评估的抗白细胞介素-13/-4药物，四项研究评估了dupilumab（300 mg每周一次（Q1W），200 mg每两周一次（Q2W），300 mg Q2W，200 mg每四周一次（Q4W），300mg Q4W，各自通过皮下（SC）注射施用）；8项研究评估了lebrikizumab（37.5 mg Q4W，125 mg Q4W，250 mg Q4W，每次通过SC注射给药）；9项研究（3259名参与者）评估了tralokinumab（75 mg Q1W，150 mg Q1W，300 mg Q1W，150 mg Q2W，300 mg Q2W，600 mg Q2W，300 mg Q4W，均通过SC注射给药；1/5通过静脉内（IV）注射施用10mg/kg）；将所有抗白细胞介素-13或-4药物与安慰剂进行比较。多数研究偏倚风险低或不清楚（提供的细节不足）；九项研究有高风险的失访偏倚，三项研究有高风险的报告偏倚。以下结果与主要结果有关，接受tralokinumab与安慰剂相比，需住院或急诊（ED）就诊的恶化率可能较低（OR 0.68,95%CI 0.47-0.98；中度确定性证据；只可用于tralokinumab（抗白细胞介素-13）的数据）。在接受抗白细胞介素-13/-4药物的参与者中，调整后的哮喘生活质量问卷评分与安慰剂相比的平均改善为0.18单位（95%CI为0.12至0.24；高确定性证据）；但这改善并不是临床相关的显著改善。报告全因严重不良事件（抗白细胞介素-13/-4药物与安慰剂，OR 0.91,95%CI 0.76-1.09；中度确定性证据）的患者比例可能很少或没有差异。就次要终点而言，急性加重需口服皮质类固醇激素的患者比例（抗白细胞介素-13/-4药物与安慰剂相比，OR 0.98，95%CI 0.72-1.32；低确定性证据）。基于哮喘控制问卷评分（抗白细胞介素-13/-4药物与安慰剂，平均差异-0.19；95%CI-0.24至-0.14），抗白细胞介素-13/-4药物可能改善哮喘控制；但这个结果的改善并不是临床相关的显著改善。与接受安慰剂的患者相比，接受抗白细胞介素-13/-4药物治疗的患者发生任何不良事件的比例更高（OR 1.16,95%CI 1.04-1.30；高确定性证据）；用抗白细胞介素-13/-4药物治疗的参与者中最常报告的不良事件是上呼吸道感染，鼻咽炎，头痛和注射部位反应。接受抗白细胞介素-13/-4药物与安慰剂相比，需要口服皮质类固醇（OCS）或住院或急诊就诊的恶化率可能较低（比率0.71，95%CI 0.65至0.77；低确定性证据）。对于不同类别的药剂（抗白细胞介素-13或抗白细胞介素-4），研究持续时间和疾病严重程度，各亚组的结果通常是一致的。基于T辅助2（TH2）炎症类别的亚组分析表明，在具有较高水平的炎性生物标志物（血液嗜酸性粒细胞，呼出的一氧化氮和血清骨膜素）的患者中效果更佳。
作者的结论：根据全部证据，与安慰剂相比，抗白细胞介素-13/-4药物可能与需要住院或急诊就诊的恶化减少有关，但代价是患者不良事件增加。没有发现与健康相关的生活质量或哮喘控制的临床相关改善。因此，抗白细胞介素-13或抗白细胞介素-4药物可能适用于对其他治疗无反应的中度至重度不受控制的哮喘患者。这些结论通常得到基于观察期长达一年的研究的中度或高度确定性证据的支持。
(中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校)
(Cochrane Database Syst Rev. 2021 Oct 19;10(10):CD012929. doi: 10.1002/14651858.CD012929.pub2.)
(Cochrane Database Syst Rev. 2021 Oct 19;10(10):CD012929. doi: 10.1002/14651858.CD012929.pub2.)
Anti-interleukin-13 and anti-interleukin-4 agents versus placebo, anti-interleukin-5 or anti-immunoglobulin-E agents, for people with asthma
Andrew Gallagher, Michaela Edwards, Parameswaran Nair, Stewart Drew, Aashish Vyas, Rashmi Sharma, Paul A Marsden, Ran Wang, David Jw Evans
Abstract
Background: Targeting the immunoglobulin E pathway and the interleukin-5 pathway with specific monoclonal antibodies directed against the cytokines or their receptors is effective in patients with severe asthma. However, there are patients who have suboptimal responses to these biologics. Since interleukin-4 and interleukin-13, signalling through the interleukin-4 receptor, have multiple effects on the biology of asthma, therapies targeting interleukin-4 and -13 (both individually and combined) have been developed.
Objectives: To assess the efficacy and safety of anti-interleukin-13 or anti-interleukin-4 agents, compared with placebo, anti-immunoglobulin E agents, or anti-interleukin-5 agents, for the treatment of children, adolescents, or adults with asthma.
Search methods: We identified studies from the Cochrane Airways Trials Register, which is maintained by the Information Specialist for the Group and through searches of the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. The search was carried out on the 16 October 2020.
Selection criteria: We included parallel-group randomised controlled trials that compared anti-interleukin-13 or -4 agents (or agents that target both interleukin-13 and interleukin-4) with placebo in adolescents and adults (aged 16 years or older) or children (younger than 16 years), with a diagnosis of asthma; participants could receive their usual short- or long-acting medications (e.g. inhaled corticosteroids (ICS), long-acting beta adrenoceptor agonists (LABA), long-acting muscarinic antagonists (LAMA), and/or leukotriene receptor antagonists) provided that they were not part of the randomised treatment.
Data collection and analysis: We used standard methods expected by Cochrane.
Main results: We identified and included 41 RCTs. Of these, 29 studies contributed data to the quantitative analyses, randomly assigning 10,604 people with asthma to receive an anti-interleukin-13 (intervention) or anti-interleukin-4 agent (intervention), or placebo (comparator). No relevant studies were identified where the comparator was an anti-immunoglobulin agent or an anti-interleukin-5 agent. Studies had a duration of between 2 and 52 (median 16) weeks. The mean age of participants across the included studies ranged from 22 to 55 years. Only five studies permitted enrolment of children and adolescents, accounting for less than 5% of the total participants contributing data to the present review. The majority of participants had moderate or severe uncontrolled asthma. Concomitant ICS use was permitted or required in the majority (21 of 29) of the included studies. The use of maintenance systemic corticosteroids was not permitted in 19 studies and was permitted or required in five studies (information not reported in five studies). Regarding the most commonly assessed anti-interleukin-13/-4 agents, four studies evaluated dupilumab (300 mg once every week (Q1W), 200 mg once every two weeks (Q2W), 300 mg Q2W, 200 mg once every four weeks (Q4W), 300 mg Q4W, each administered by subcutaneous (SC) injection); eight studies evaluated lebrikizumab (37.5 mg Q4W, 125 mg Q4W, 250 mg Q4W each administered by SC injection); and nine studies (3259 participants) evaluated tralokinumab (75 mg Q1W, 150 mg Q1W, 300 mg Q1W, 150 mg Q2W, 300 mg Q2W, 600 mg Q2W, 300 mg Q4W, each administered by SC injection; 1/5/10 mg/kg administered by intravenous (IV) injection); all anti-interleukin-13 or-4 agents were compared with placebo. The risk of bias was generally considered to be low or unclear (insufficient detail provided); nine studies were considered to be at high risk for attrition bias and three studies were considered to be at high risk for reporting bias. The following results relate to the primary outcomes. The rate of exacerbations requiring hospitalisation or emergency department (ED) visit was probably lower in participants receiving tralokinumab versus placebo (rate ratio 0.68, 95% CI 0.47 to 0.98; moderate-certainty evidence; data available for tralokinumab (anti-interleukin-13) only). In participants receiving an anti-interleukin-13/-4 agent, the mean improvement versus placebo in adjusted asthma quality of life questionnaire score was 0.18 units (95% CI 0.12 to 0.24; high-certainty evidence); however, this finding was deemed not to be a clinically relevant improvement. There was likely little or no difference between groups in the proportion of patients who reported all-cause serious adverse events (anti-interleukin-13/-4 agents versus placebo, OR 0.91, 95% CI 0.76 to 1.09; moderate-certainty evidence). In terms of secondary outcomes, there may be little or no difference between groups in the proportion of patients who experienced exacerbations requiring oral corticosteroids (anti-interleukin-13/-4 agents versus placebo, rate ratio 0.98, 95% CI 0.72 to 1.32; low-certainty evidence). Anti-interleukin-13/-4 agents probably improve asthma control based on asthma control questionnaire score (anti-interleukin-13/-4 agents versus placebo, mean difference -0.19; 95% CI -0.24 to -0.14); however, the magnitude of this result was deemed not to be a clinically relevant improvement. The proportion of patients experiencing any adverse event was greater in those receiving anti-interleukin-13/-4 agents compared with those receiving placebo (OR 1.16, 95% CI 1.04 to 1.30; high-certainty evidence); the most commonly reported adverse events in participants treated with anti-interleukin-13/-4 agents were upper respiratory tract infection, nasopharyngitis, headache and injection site reaction. The pooled results for the exploratory outcome, the rate of exacerbations requiring oral corticosteroids (OCS) or hospitalisation or emergency department visit, may be lower in participants receiving anti-interleukin-13/-4 agents versus placebo (rate ratio 0.71, 95% CI 0.65 to 0.77; low-certainty evidence). Results were generally consistent across subgroups for different classes of agent (anti-interleukin-13 or anti-interleukin-4), durations of study and severity of disease. Subgroup analysis based on category of T helper 2 (TH2) inflammation suggested greater efficacy in patients with higher levels of inflammatory biomarkers (blood eosinophils, exhaled nitric oxide and serum periostin).
Authors' conclusions: Based on the totality of the evidence, compared with placebo, anti-interleukin-13/-4 agents are probably associated with a reduction in exacerbations requiring hospitalisation or ED visit, at the cost of increased adverse events, in patients with asthma. No clinically relevant improvements in health-related quality of life or asthma control were identified. Therefore, anti-interleukin-13 or anti-interleukin-4 agents may be appropriate for adults with moderate-to-severe uncontrolled asthma who have not responded to other treatments. These conclusions are generally supported by moderate or high-certainty evidence based on studies with an observation period of up to one year.
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