Indirect Treatment Comparison of Lanadelumab and a C1-esterase Inhibitor in Pediatric Patients with Hereditary Angioedema

Overview

Journal J Comp Eff Res

Date 2025 Jan 21

PMID 39836016

Authors

Maureen Watt

Rachel Goldgrub

Mia Malmenas

Katrin Haeussler

Affiliations

Soon will be listed here.

Abstract

To compare the efficacy and safety of lanadelumab versus other approved long-term prophylaxis (LTP) treatments in patients with pediatric hereditary angioedema (HAE) aged <12 years. A systematic literature review was conducted to identify studies of LTP in patients with HAE aged <12 years. Two studies met the inclusion criteria in an indirect treatment comparison of efficacy and safety data in pediatric HAE patients. These were for lanadelumab (SPRING, NCT04070326) and intravenous-C1-esterase inhibitor (C1-INH[IV], NCT02052141). A propensity score analysis used individual patient-level data from both studies in a logistic regression model to estimate inverse probability weights. To avoid convergence issues and an underpowered analysis due to the small sample size (n = 29), the base case was defined as Poisson regression analyses on monthly attack rate adjusting for one covariate (baseline attack rate). Model selection among unadjusted, adjusted and weighted regression models was conducted through the Akaike and Bayesian Information Criteria. Lanadelumab 150 mg every 2 weeks (Q2W) reduced the monthly HAE attack rate by 82.1% versus C1-INH(IV) 1000 IU twice weekly (every 3-4 days [BIW]; rate ratio [RR], 0.1792 [95% CI: 0.0296-1.0853]) and by 88.9% versus C1-INH(IV) 500 IU BIW (RR: 0.1107 [95% CI: 0.0234-0.5239]). Treatment with lanadelumab Q2W reduced the risk of total adverse events by 56.2% versus C1-INH(IV) 1000 IU BIW (RR:0.4377 [95% CI: 0.1536-1.2469]) and by 66.0% versus C1-INH(IV) 500 IU BIW (RR: 0.3401 [95% CI: 0.1234-0.9371]). This exploratory analysis suggested a trend toward greater efficacy and fewer adverse events with lanadelumab 150 mg Q2W compared with C1-INH(IV) BIW 1000 IU and 500 IU in pediatric patients with HAE. Future studies could potentially assess larger samples over longer periods of time for the long-term preventative efficacy, safety and tolerability of lanadelumab and C1-INH(IV).

References

Farkas H, Martinez-Saguer I, Bork K, Bowen T, Craig T, Frank M . International consensus on the diagnosis and management of pediatric patients with hereditary angioedema with C1 inhibitor deficiency. Allergy. 2016; 72(2):300-313. PMC: 5248622. DOI: 10.1111/all.13001. View

Zanichelli A, Magerl M, Longhurst H, Aberer W, Caballero T, Bouillet L . Improvement in diagnostic delays over time in patients with hereditary angioedema: findings from the Icatibant Outcome Survey. Clin Transl Allergy. 2018; 8:42. PMC: 6182796. DOI: 10.1186/s13601-018-0229-4. View

Riley R, Lambert P, Staessen J, Wang J, Gueyffier F, Thijs L . Meta-analysis of continuous outcomes combining individual patient data and aggregate data. Stat Med. 2007; 27(11):1870-93. DOI: 10.1002/sim.3165. View

Manresa M, Smith L, Casals-Diaz L, Fagundes R, Brown E, Radhakrishnan P . Pharmacologic inhibition of hypoxia-inducible factor (HIF)-hydroxylases ameliorates allergic contact dermatitis. Allergy. 2018; 74(4):753-766. DOI: 10.1111/all.13655. View

Zuraw B . The pathophysiology of hereditary angioedema. World Allergy Organ J. 2013; 3(9 Suppl):S25-8. PMC: 3666152. DOI: 10.1097/WOX.0b013e3181f3f21c. View

Farkas H, Reshef A, Aberer W, Caballero T, McCarthy L, Hao J . Treatment Effect and Safety of Icatibant in Pediatric Patients with Hereditary Angioedema. J Allergy Clin Immunol Pract. 2017; 5(6):1671-1678.e2. DOI: 10.1016/j.jaip.2017.04.010. View

Betschel S, Badiou J, Binkley K, Borici-Mazi R, Hebert J, Kanani A . The International/Canadian Hereditary Angioedema Guideline. Allergy Asthma Clin Immunol. 2019; 15:72. PMC: 6878678. DOI: 10.1186/s13223-019-0376-8. View

Lumry W, Manning M, Hurewitz D, Davis-Lorton M, Fitts D, Kalfus I . Nanofiltered C1-esterase inhibitor for the acute management and prevention of hereditary angioedema attacks due to C1-inhibitor deficiency in children. J Pediatr. 2013; 162(5):1017-22.e1-2. DOI: 10.1016/j.jpeds.2012.11.030. View

Schoffl C, Wiednig M, Koch L, Blagojevic D, Duschet P, Hawranek T . Hereditary angioedema in Austria: prevalence and regional peculiarities. J Dtsch Dermatol Ges. 2019; 17(4):416-423. PMC: 6850089. DOI: 10.1111/ddg.13815. View

Zuraw B, Cicardi M, Longhurst H, Bernstein J, Li H, Magerl M . Phase II study results of a replacement therapy for hereditary angioedema with subcutaneous C1-inhibitor concentrate. Allergy. 2015; 70(10):1319-28. PMC: 4755045. DOI: 10.1111/all.12658. View

Upton J, Poder T, Begin P . Early introduction without screening is a good deal, if caregivers will buy it. Allergy. 2018; 74(2):213-215. DOI: 10.1111/all.13584. View

10.

Aygoren-Pursun E, Soteres D, Nieto-Martinez S, Christensen J, Jacobson K, Moldovan D . A randomized trial of human C1 inhibitor prophylaxis in children with hereditary angioedema. Pediatr Allergy Immunol. 2019; 30(5):553-561. PMC: 6851661. DOI: 10.1111/pai.13060. View

11.

Maurer M, Lumry W, Li H, Aygoren-Pursun E, Busse P, Jacobs J . Lanadelumab in Patients 2 to Less Than 12 Years Old With Hereditary Angioedema: Results From the Phase 3 SPRING Study. J Allergy Clin Immunol Pract. 2023; 12(1):201-211.e6. DOI: 10.1016/j.jaip.2023.09.009. View

12.

Levy D, Caballero T, Hussain I, Reshef A, Anderson J, Baker J . Long-Term Efficacy of Subcutaneous C1 Inhibitor in Pediatric Patients with Hereditary Angioedema. Pediatr Allergy Immunol Pulmonol. 2020; 33(3):136-141. PMC: 7499895. DOI: 10.1089/ped.2020.1143. View

13.

Banerji A, Riedl M, Bernstein J, Cicardi M, Longhurst H, Zuraw B . Effect of Lanadelumab Compared With Placebo on Prevention of Hereditary Angioedema Attacks: A Randomized Clinical Trial. JAMA. 2018; 320(20):2108-2121. PMC: 6583584. DOI: 10.1001/jama.2018.16773. View

14.

Magerl M, Schiffhorst G, Fanter L, Muller G, Hirche C, Berkemeier F . Patient-level indirect treatment comparison of lanadelumab versus pdC1-INH i.v. in hereditary angioedema patients: PATCH study. Allergy. 2023; 79(1):215-224. DOI: 10.1111/all.15861. View

15.

Reshef A, Grivcheva-Panovska V, Kessel A, Kivity S, Klimaszewska-Rembiasz M, Moldovan D . Recombinant human C1 esterase inhibitor treatment for hereditary angioedema attacks in children. Pediatr Allergy Immunol. 2019; 30(5):562-568. PMC: 6851822. DOI: 10.1111/pai.13065. View

16.

Craig T, Zuraw B, Longhurst H, Cicardi M, Bork K, Grattan C . Long-Term Outcomes with Subcutaneous C1-Inhibitor Replacement Therapy for Prevention of Hereditary Angioedema Attacks. J Allergy Clin Immunol Pract. 2019; 7(6):1793-1802.e2. DOI: 10.1016/j.jaip.2019.01.054. View

17.

Maurer M, Magerl M, Betschel S, Aberer W, Ansotegui I, Aygoren-Pursun E . The international WAO/EAACI guideline for the management of hereditary angioedema-The 2021 revision and update. Allergy. 2022; 77(7):1961-1990. DOI: 10.1111/all.15214. View

18.

Zuraw B, Banerji A, Bernstein J, Busse P, Christiansen S, Davis-Lorton M . US Hereditary Angioedema Association Medical Advisory Board 2013 recommendations for the management of hereditary angioedema due to C1 inhibitor deficiency. J Allergy Clin Immunol Pract. 2014; 1(5):458-67. DOI: 10.1016/j.jaip.2013.07.002. View