The Safety and Efficacy of Anti-IL-13 Treatment with Tralokinumab (CAT-354) in Moderate to Severe Asthma: A Systematic Review and Meta-analysis

Abstract Background Several clinical studies have evaluated the use of tralokinumab (CAT-354) administration in patients with moderate to severe asthma; no consensus of tralokinumab efficacy and safety were reached. Thus, the efficacy and safety of tralokinumab as an asthma biologic requires further analysis and evaluation. Objective To assess the efficacy and safety of subcutaneous injection of tralokinumab in patients with moderate to severe asthma. Methods Clinical trials were identified from MEDLINE, EMBASE, CENTRAL, and ClinicalTrials.gov from its inception to November 4, 2018. Only randomized clinical trials (RCTs) with tralokinumab versus placebo treatment in moderate to severe asthma patients were evaluated. Efficacy and safety outcomes were extracted, and a meta-analysis was performed using a random-effect model. The Cochrane Collaboration’s risk of bias assessment tool was used to assess the risk of bias. Results Five studies describing 6 RCTs (including 2928 adults with moderate to severe asthma) were pooled and analyzed in this study. Absolute forced expiratory volume in 1 second (FEV1) was statistically improved in patients receiving tralokinumab at 300 mg every 2 weeks (Mean difference [MD] 0.14 L, 95% confidence interval [CI] 0.08,0.21) and 600 mg every 2 weeks (MD 0.20 L, 95% CI 0.01,0.39), as well as FEV1 percentage changes (MD 5.82 %, 95% CI 3.58, 8.06; MD 11.8 %, 95% CI 0.79, 22.81). Also, absolute forced vital capacity (FVC) volume changes (MD 0.11 L, 95% CI 0.01, 0.21) and percentage changes (MD 4.44 %, 95% CI 0.84, 8.04) improved in tralokinumab at 300mg every 2 weeks. Asthma Quality of Life Questionnaire (AQLQ) scores were not significantly different, and absolute Asthma Control Questionnaire-6 (ACQ-6) scores were statistically improved but did not reach the clinically meaningful difference. Tralokinumab treatment did not decrease annualized asthma exacerbation rate (AAER) in unselected moderate to severe asthma patients, but it was associated with improved AAER in severe asthmatic patients with high FeNO levels (Rate ratio [RR] 0.72, 95% CI 0.53, 0.97). Tralokinumab was not associated with an increased incidence of serious adverse events, but did show an increase in mild injection site reactions (OR 5.92, 95% CI 1.61, 21.76). Conclusions This pooled analysis of six randomized clinical trials suggested that trakolinumab was well tolerated and modestly improved FEV1 and FVC. It did not render clinically important improvements in asthma related quality of life, nor did it reduce asthma exacerbations.