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Meta-Analysis
. 2019 Oct 21;14(1):230.
doi: 10.1186/s13023-019-1202-6.

Agreement between results of meta-analyses from case reports and clinical studies, regarding efficacy and safety of idursulfase therapy in patients with mucopolysaccharidosis type II (MPS-II). A new tool for evidence-based medicine in rare diseases

Miguel Sampayo-Cordero  1 , Bernat Miguel-Huguet  2 , Almudena Pardo-Mateos  3 , Andrea Malfettone  4 , José Pérez-García  4   5 , Antonio Llombart-Cussac  4   6 , Javier Cortés  4   5 , Marc Moltó-Abad  7 , Cecilia Muñoz-Delgado  8 , Marta Pérez-Quintana  9 , Jordi Pérez-López  7
Affiliations
Meta-Analysis

Agreement between results of meta-analyses from case reports and clinical studies, regarding efficacy and safety of idursulfase therapy in patients with mucopolysaccharidosis type II (MPS-II). A new tool for evidence-based medicine in rare diseases

Miguel Sampayo-Cordero et al. Orphanet J Rare Dis. .

Abstract

Background: A preliminary exploratory study shows solid agreement between the results of case reports and clinical study meta-analyses in mucopolysaccharidosis Type I (MPS-I) adult patients. The aim of the present study is to confirm previous results in another patient population, suffering from mucopolysaccharidosis Type II (MPS-II).

Methods: A systematic review and meta-analysis of case reports published by April 2018 was conducted for MPS-II patients treated with enzyme replacement therapy (ERT). The study is reported in accordance with PRISMA and MOOSE guidelines (PROSPERO database code CRD42018093408). The assessed population and outcomes were the same as previously analyzed in a meta-analysis of MPS-II clinical studies. The primary endpoint was the percent of clinical cases showing improvement in efficacy outcome, or no harm in safety outcome after ERT initiation. A restrictive procedure to aggregate case reports, by selecting standardized and well-defined outcomes, was proposed. Different sensitivity analyses were able to evaluate the robustness of results.

Results: Every outcome classified as "acceptable evidence group" in our case report meta-analysis had been graded as "moderate strength of evidence" in the aforementioned meta-analysis of clinical studies. Sensitivity, specificity, and positive-negative predictive values for results of both meta-analyses reached 100%, and were deemed equivalent.

Conclusions: Aggregating case reports quantitatively, rather than analyzing them qualitatively, may improve conclusions in rare diseases and personalized medicine. Additionally, we propose some methods to evaluate publication bias and heterogeneity of the included studies in a meta-analysis of case reports.

Keywords: Case reports; Clinical studies; Enzyme replacement therapy; Evidence-based medicine; Meta-analysis; Mucopolysaccharidosis type II; Systematic review.

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Conflict of interest statement

We wish to draw the attention of the Editor to the following facts which may be considered as potential conflicts of interest and to significant financial contributions to this works:

Miguel Sampayo-Cordero has received consulting and advisor fees from: Nestle Health Science, Laboratorios Leti, Roche and Allergan. In addition, Miguel Sampayo has received research funding fees from Nestle Health Science.

Bernat Miguel-Huguet declares no conflict of interest.

Almudena Pardo Mateos has been contracted in the past by Shire and by Genzyme.

Andrea Malfettone declares no conflict of interest.

José Pérez-García has received consulting and advisor fees from: Roche and Eli Lilly.

Antonio Llombart-Cussac has received consulting and advisor fees from Roche, GlaxoSmithKline, Novartis, Celgene, Eisai, and AstraZeneca and has stock options, patents and intellectual property from MedSIR.

Javier Cortés has received consulting and advisor fees from: Roche, Celgene, Cellestia, AstraZeneca, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo and Erytech. In addition, Javier Cortés has received honorarias from: Roche, Novartis, Celgene, Eisai, Pfizer and Samsung. Add more, Javier Cortés has received research funding fees to the institution from Roche. Finally, Javier Cortés has stock options, patents and intellectual property from MedSIR.

Marc Moltó-Abad has received research support from Shire; has received fees from Sanofi/Genzyme, Shire and Alexion for participation in their respective registries. In addition, this work used laronidase, a product manufactured by Shire, to evaluate the efficacy of ERT in MPS II patients.

Cecilia Muñoz-Delgado as received consulting fees, fees as a speaker, and research support from Shire and Genzyme.

Marta Pérez-Quintana as received consulting fees, fees as a speaker, and research support from Shire.

Jordi Pérez-López has received consulting fees, fees as a speaker, and research support from Shire.

Figures

Fig. 1
Fig. 1
Flow diagram of case reports of patients with MPS-II published between January 2008 to April 2018
Fig. 2
Fig. 2
Agreement between the evidence score from the case report meta-analysis and the SOE from the clinical study meta-analysis. Strong confirmatory method. 6MWT: 6-min walk test; CI: Confidence interval; IRR: Infusion-related reaction; JROM: Joint range of motion; QoL: Quality of life; Rho: Spearman correlation coefficient; SOE: Strenght of evidence; uGAGs: Urinary glycosaminoglycans
See this image and copyright information in PMC

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