6465 Systematic review of RCT to determine the efficacy and safety of Tiotropium, as add-on to inhaled corticosteroids for mild-persistent asthma in children

Objectives

Systematic review to determine the efficacy and safety of Tiotropium as add-on therapy with inhaled corticosteroids (ICS), compared to placebo with ICS, for mild persistent asthma in 6–12 years children, by measuring peak FEV1.

Methods

PubMed, Embase, web of science, Cochrane Central Register, Clinicaltrials.gov and ICTRP trials were searched, using keywords and MeSH terms. Studies were RCT, published from 2013- 2023, fulfilling the inclusion criteria. Participants: Children 1–17 years with asthma (defined by GINA). Intervention: Tiotropium (high dose 5ug and low dose 2.5ug) add on to low dose ICS, Comparison: placebo with low dose ICS. Primary outcome: Change from baseline-end of treatment in FEV1 peak(0–3h) measured. Prisma flow diagram was used. Jaddad scale determined the quality of methodology.

Results

Five studies with 1696 participants of age 1–17 years. Jaddad scale scored 4(3 studies) and 5 (two studies). Safety and tolerability of tiotropium was comparable with mild or moderate adverse effects. 12 –17 years; moderate persistent Asthma (over 48 weeks): Adjusted mean difference in peak response was higher with the 5– µg dose (174 mL, 95% CI, 76–272 mL), then 2.5 µg dose (134 ml, 95% CI, 34–234 mL). 2.5 µg dose showed numerically higher but statistically insignificant response.¹ 12–17 years; severe persistent Asthma (Over 12 weeks): 5ug tiotropium statistically insignificant (90 mL, 95% CI −19–198; and p=0.104.) 2.5 – µg statistically significant improvements in (111 mL; 95% CI 2–220; and p=0.046).² 6–11 years; moderate persistent Asthma (Over 48 weeks). Statistically significant 2.5 ug and 5 ug dose of tiotropium at 24 weeks. The adjusted mean difference for 5 ug of 164 mL (95% confidence interval CI, 103–225; P < .001) and 170 mL for 2.5 ug (95% CI, 108–231; P < .001).³ 6 –11 Years; severe persistent asthma (over 12 weeks): Statistically significant 5 ug Tiotropium (139 mL; 95% CI, 75–203; and P< .001) and statistically insignificant 2.5–ug dose (35 mL; 95% CI, 228 to 99; and P 5 .27)⁴ 1–5 years; persistent Asthma. 2·5 μg tiotropium showed adjusted mean difference of −0·080 (95% CI −0·312 to 0·152), 5 μg −0·048 (−0·292 to 0·195). Adjusted weekly mean combined daytime asthma symptom scores were not significantly different.⁵

Conclusion

Further trials are suggested to confirm the efficacy and safety of Tiotropium as add-on therapy in milder asthma in children

References

Hamelmann E, et al. Tiotropium add-on therapy in adolescents with moderate asthma: A 1-year randomized controlled trial. J Allergy Clin Immunol. 2016 Aug;138(2):441–450.e8. Hamelmann E, et al. A randomized controlled trial of tiotropium in adolescents with severe symptomatic asthma. Eur Respir J. 2017 Jan 11;49(1):1601100. Vogelberg C, et al. Tiotropium add-on therapy improves lung function in children with symptomatic moderate asthma. J Allergy Clin Immunol Pract. 2018 Nov- Dec;6(6):2160–2162.e9. Szefler SJ, et al. A phase III randomized controlled trial of tiotropium add-on therapy in children with severe symptomatic asthma. J Allergy Clin Immunol. 2017 Nov;140(5):1277–1287. Vrijlandt EJLE, et al. Safety and efficacy of tiotropium in children aged 1–5 years with persistent asthmatic symptoms: a randomized, double-blind, placebo-controlled trial. Lancet Respir Med. 2018 Feb;6(2):127–137.