DOI: 10.6084/m9.figshare.27044377.v1
title: Supplementary materials: Comparing the efficacy of cipaglucosidase alfa plus miglustat with other enzyme replacement therapies for late-onset Pompe disease: a network meta-analysis utilizing patient-level and aggregate data

description: <b>These are peer-reviewed supplementary materials for the article '</b><b>Comparing the efficacy of cipaglucosidase </b><b>alfa plus miglustat with other enzyme </b><b>replacement therapies for late-onset </b><b>Pompe disease: a network meta-analysis </b><b>utilizing patient-level and aggregate data</b><b>' published in the</b><b> </b><b><i>Journal of Comparative Effectiveness Research</i></b><b>.</b><b>Supplementary Table 1:</b> PICOS(+) framework to identify trials for the SLR.<b>Supplementary Table 2</b><b>:</b> Search in MEDLINE, 2022 SLR.<b>Supplementary Table 3:</b> Search in MEDLINE, 2023 SLR update.<b>Supplementary Table 4:</b> Search in EMBASE, 2022 SLR.<b>Supplementary Table 5:</b> Search in EMBASE, 2023 SLR update.<b>Supplementary Table 6:</b> Search in Cochrane Central Register of Controlled Trials.<b>Supplementary Table 7:</b> Search in Cochrane Database of Systematic Reviews.<b>Supplementary Table 8:</b> Search in PROSPERO.<b>Supplementary Table 9:</b> Search in ISRCTN.com.<b>Supplementary Table 10:</b> Search in DARE.<b>Supplementary Table 11</b><b>:</b> Conferences searches, 2022 SLR.<b>Supplementary Table 12:</b> Conferences searches, 2023 SLR update.<b>Supplementary Table 13:</b> Search in ClinicalTrials.gov.<b>Supplementary Table 14:</b> Search on ICTRP.<b>Supplementary Table 15:</b> Search in EU Clinical Trials Register.<b>Supplementary Table 16:</b> Search in Google Scholar and CDER.<b>Supplementary Table 17:</b> List of included publications.<b>Supplementary Table 18</b><b>:</b> Quality assessment according to RoB2 Tool: PROPEL and COMET.<b>Supplementary Table 19:</b> Quality assessment according to ROBINS-I Tool: NEO1/NEO-EXT and COMET OLE.<b>Supplementary Table 20:</b> Efficacy results of included trials at or around 1 year.<b>Supplementary Figure 1:</b> PRISMA flow chart for selection of studies.<b>Supplementary Figure 2:</b> Longitudinal efficacy results from included trials – 6MWD (m) change from baseline.<b>Supplementary Figure 3:</b> Longitudinal efficacy results from included trials – FVC (% predicted) change from baseline.<b>Supplementary Figure 4:</b> Forest plots for 6MWD (m) and FVC (% predicted), base case scenario, all models.<b>Supplementary Figure 5:</b> SUCRA scores, base case scenario, all models.<b>Supplementary Figure 6</b><b>:</b> Forest plots for 6MWD and FVC change from baseline at Week 52<i>,</i> previous ERT duration scenarios.<b>Supplementary Figure 7:</b> Forest plots for 6MWD (m) and FVC (% predicted) at different weeks.<b>Supplementary Table 21:</b> Matching criterion<b>Aim:</b> Late-onset Pompe disease is characterized by progressive loss of muscular and respiratory function. Until recently, standard of care was enzyme replacement therapy (ERT) with alglucosidase alfa. Secondgeneration ERTs avalglucosidase alfa (aval) and cipaglucosidase alfa with miglustat (cipa+mig) are now available. Without head-to-head trials comparing aval with cipa+mig, an indirect treatment comparison is informative and timely for understanding potential clinical differentiation.<b> Materials & methods:</b> A systematic literature review was performed to identify relevant studies on cipa+mig and aval. Using patient-level and aggregate published data from randomized controlled trials (RCTs) and phase I/II and open-label extension (OLE) trials, a multi-level network meta-regression was conducted, adjusting for various baseline covariates, including previous ERT duration, to obtain relative effect estimates on 6-minute walk distance (6MWD, meters [m]) and forced vital capacity (FVC, % predicted [pp]). Analyses of two networks were conducted: Network A, including only RCTs, and network B, additionally including single-arm OLE and phase I/II studies. <b>Results:</b> Network B (full evidence analysis) showed that cipa+mig was associated with a relative increase in 6MWD (mean difference 28.93 m, 95% credible interval [8.26–50.11 m]; Bayesian probability 99.7%) and FVC (2.88 pp [1.07–4.71 pp]; &gt;99.9%) compared with aval. The comparison between cipa+mig and aval became more favorable for cipa+mig with increasing previous ERT duration for both end points. Analysis of network A showed that cipa+mig was associated with a relative decrease in 6MWD(-10.02m[-23.62 to 4.00 m]; 91.8%) and FVC (-1.45 pp [-3.01 to 0.07 pp]; 96.8%)compared with aval. <b>Conclusion:</b> Cipa+mig showed a favorable effect versus aval when all available evidence was used in the analysis.