A systematic review to evaluate the effectiveness of enzyme replacement therapy for lysosomal storage disorders in comparison to the treatment of similar diseases with higher prevalence
Abstract
Significant challenges exist when submitting orphan drugs for reimbursement in a health care system. An assessment of value for money is undertaken by comparing the costs and clinical effectiveness of the new technology to that of an existing treatment. Orphan drugs rarely have standard treatments, with which to contrast a new technology. We aimed to compare the clinical effectiveness of enzyme replacement therapy (ERT) for rare diseases, to that of recommended drugs for comparable but non-rare diseases (lifelong treatment, shortened life expectancy due to the disease), using number needed to benefit (NNTB).
A systematic review was performed to identify randomised controlled trials (RCTs) of ERT treatments in three rare diseases; Fabry Disease, Hunter Syndrome (MPS II) and Gaucher Disease Type 1. MEDLINE, MEDLINE In-Process Citations and Daily Update, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, Health Technology Assessment Database, ClinicalTrials.gov, metaRegister of Controlled Trials and the WHO International Clinical Trials Registry Platform were searched from inception to August 2012. We identified comparator studies from the NICE (UK) or IQWiG/G-BA (Germany), websites to 2012. For each study, NNTB analyses were performed for the primary outcome of all (recommended) drug doses, at all follow-up times.
Ten ERT RCTs were identified (8 in Fabry Disease, 2 in Hunter Syndrome, 0 in Gaucher Disease). Eleven analyses were performed for ERTs; NNTB calculated from the mean absolute risk difference ranged from 1.4 to 17.2 (median = 2.7). Seven comparator disease studies were identified in multiple sclerosis, rheumatoid arthritis, type 2 diabetes mellitus, peripheral arterial disease and Alzheimer disease. Thirty-nine analyses were performed for the comparator studies; NNTB ranged from -61.8 to 330.8 (median = 4.6).
The median value of NNTB values was lower for ERT studies than for comparator studies, suggesting that ERT therapies for rare diseases were more effective than existing recommended drugs for comparable diseases. Caution should be applied to the interpretation of these results because the analyses were limited by risk of bias, study size and the lack of identical outcomes. Comparing the effectiveness of orphan drugs with non-orphan drugs using NNTB may provide additional clinical effectiveness information for reimbursement decision making.
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