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

BACKGROUND: Several clinical studies have evaluated the use of tralokinumab (CAT-354) administration in patients with moderate to severe asthma; no consensus on tralokinumab efficacy and safety was reached. Thus, further analysis is required on the efficacy and safety of tralokinumab as an asthma biologic.

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, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from their inception to November 4, 2018. Only randomized clinical trials (RCTs) with tralokinumab versus placebo treatment in patients with moderate to severe asthma were evaluated. Efficacy and safety outcomes were extracted, and a meta-analysis was performed using a random-effects 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 FEV1 was statistically improved in patients receiving tralokinumab at 300 mg every 2 weeks (mean difference [MD], 0.14 L; 95% 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 % changes (MD, 5.82%, 95% CI, 3.58-8.06, and MD, 11.8%, 95% CI, 0.79-22.81, respectively). Also, absolute forced vital capacity 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 300 mg every 2 weeks. Asthma Quality of Life Questionnaire scores were not significantly different, and absolute Asthma Control Questionnaire 6 scores were statistically improved but did not reach the clinically meaningful difference. Tralokinumab treatment did not decrease annualized asthma exacerbation rate in unselected patients with moderate to severe asthma, but it was associated with improved annualized asthma exacerbation rate in patients with severe asthma with high fractional exhaled nitric oxide levels (rate ratio, 0.72; 95% CI, 0.53-0.97). Tralokinumab was not associated with an increased incidence of serious adverse events, but it did show an increase in mild injection-site reactions (odds ratio, 5.92; 95% CI, 1.61-21.76).

CONCLUSION: This pooled analysis of 6 RCTs suggested that tralokinumab was well tolerated and it modestly improved FEV1 and forced vital capacity in patients with moderate to severe asthma. It did not render clinically important improvements in asthma-related quality of life, and nor did it reduce asthma exacerbations.