Systematic review of available evidence on 11 high-priced inpatient orphan drugs

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Abstract

Background

Attention for Evidence Based Medicine (EBM) is growing, but evidence for orphan drugs is argued to be limited and inferior. This study systematically reviews the available evidence on clinical effectiveness, cost-effectiveness and budget impact for orphan drugs.

Methods

A systematic review was performed in PubMed, Embase, NHS EED and HTA databases for 11 inpatient orphan drugs listed on the Dutch policy rule on orphan drugs. For included studies, we determined the type of study and various study characteristics.

Results

A total of 338 studies met all inclusion criteria. Almost all studies (96%) focused on clinical effectiveness of the drug. Of these studies, most studies were case studies (41%) or observational studies (39%). However, for all orphan diseases at least one experimental or quasi-experimental study was found, and a randomized clinical trial was available for 60% of the orphan drugs. Eight studies described the cost-effectiveness of an orphan drug; an equal number described an orphan drug’s budget impact.

Conclusions

Despite the often heard claim that RCTs are not feasible for orphan drugs, we found that an RCT was available in 60% of orphan drugs investigated. Cost-effectiveness and budget impact analyses for orphan drugs are seldom published.

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Most cited references 15

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Randomized, Controlled Trials, Observational Studies, and the Hierarchy of Research Designs

John Concato, Nirav Shah, Ralph Horwitz (2000)

New England Journal of Medicine, 342(25), 1887-1892

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Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy

J. Wraith, Maurizio Scarpa, Michael Beck … (2007)

Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is a rare X-linked recessive disease caused by deficiency of the lysosomal enzyme iduronate-2-sulphatase, leading to progressive accumulation of glycosaminoglycans in nearly all cell types, tissues and organs. Clinical manifestations include severe airway obstruction, skeletal deformities, cardiomyopathy and, in most patients, neurological decline. Death usually occurs in the second decade of life, although some patients with less severe disease have survived into their fifth or sixth decade. Until recently, there has been no effective therapy for MPS II, and care has been palliative. Enzyme replacement therapy (ERT) with recombinant human iduronate-2-sulphatase (idursulfase), however, has now been introduced. Weekly intravenous infusions of idursulfase have been shown to improve many of the signs and symptoms and overall wellbeing in patients with MPS II. This paper provides an overview of the clinical manifestations, diagnosis and symptomatic management of patients with MPS II and provides recommendations for the use of ERT. The issue of treating very young patients and those with CNS involvement is also discussed. ERT with idursulfase has the potential to benefit many patients with MPS II, especially if started early in the course of the disease.

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Long-term efficacy and safety of laronidase in the treatment of mucopolysaccharidosis I.

Emil Kakkis, N Kolodny, Robert M. Rapoport … (2008)

Our goal was to evaluate the long-term safety and efficacy of recombinant human alpha-l-iduronidase (laronidase) in patients with mucopolysaccharidosis I. All 45 patients who completed a 26-week, double-blind, placebo-controlled trial of laronidase were enrolled in a 3.5-year open-label extension study. Mean patient age at baseline was 16 (range: 6-43) years. All patients had attenuated disease (84% Hurler-Scheie, 16% Scheie phenotypes). Clinical, biochemical, and health outcomes measures were evaluated through the extension phase. Changes are presented as the mean +/- SEM. All 40 patients (89%) who completed the trial received at least 80% of scheduled infusions. As shown in earlier trials, urinary glycosaminoglycan levels decreased within the first 12 weeks and liver volume decreased within the first year. Percent predicted forced vital capacity remained stable, with a linear slope of -0.78 percentage points per year. The 6-minute walk distance increased 31.7 +/- 10.2 m in the first 2 years, with a final gain of 17.1 +/- 16.8 m. Improvements in the apnea/hypopnea index (decrease of 7.6 +/- 4.5 events per hour among the patients with significant baseline sleep apnea) and shoulder flexion (increase of 17.4 degrees +/- 3.6 degrees) were most rapid during the first 2 years. Improvements in the Child Health Assessment Questionnaire/Health Assessment Questionnaire disability index (decrease of 0.31 +/- 0.11, signifying a clinically meaningful improvement in activities of daily living) were gradual and sustained over the treatment period. Laronidase infusions were generally well tolerated except in 1 patient who experienced an anaphylactic reaction. Infusion-associated reactions, which occurred in 53% of the patients, were mostly mild, easily managed, and decreased markedly after 6 months. One patient died as a result of an upper respiratory infection unrelated to treatment. Antibodies to laronidase developed in 93% of the patients; 29% of the patients were seronegative at their last assessment. This trial demonstrates the long-term clinical benefit and safety of laronidase in attenuated patients with mucopolysaccharidosis I and highlights the magnitude and chronology of treatment effects. Prompt diagnosis and early treatment will maximize treatment outcomes.

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Author and article information

Journal

Journal ID (nlm-ta): Orphanet J Rare Dis

Journal ID (iso-abbrev): Orphanet J Rare Dis

Title: Orphanet Journal of Rare Diseases

Publisher: BioMed Central

ISSN (Electronic): 1750-1172

Publication date Collection: 2013

Publication date (Electronic): 16 August 2013

Volume: 8

Page: 124

Affiliations

[1 ]Institute for Medical Technology Assessment, Department of Health Policy & Management, Erasmus University Rotterdam, Burgemeester Oudlaan 50, P.O. Box 1738, 3000DR Rotterdam, The Netherlands

Article

Publisher ID: 1750-1172-8-124

DOI: 10.1186/1750-1172-8-124

PMC ID: 3751719

PubMed ID: 23947946

SO-VID: 387bc7c9-14bc-4c48-b896-938e09e0a056

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Systematic review of available evidence on 11 high-priced inpatient orphan drugs

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Abstract

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Point-of-Care Testing for Infectious Diseases Super Collection

Most cited references 15

Randomized, Controlled Trials, Observational Studies, and the Hierarchy of Research Designs

Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy

Long-term efficacy and safety of laronidase in the treatment of mucopolysaccharidosis I.

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