Agreement between the results of meta-analyses from case reports and from clinical studies regarding the efficacy of laronidase therapy in patients with mucopolysaccharidosis type I who initiated enzyme replacement therapy in adult age: An example of case reports meta-analyses as an useful tool for evidence-based medicine in rare diseases

Abstract Background Case reports might have a prominent role in the rare diseases field, due to the small number of patients affected by one such disease. A previous systematic review regarding the efficacy of laronidase therapy in patients with mucopolysaccharidosis type I (MPS-I) who initiated enzyme replacement therapy (ERT) in adult age has been published. The review included a meta-analysis of 19 clinical studies and the description of eleven case reports. It was of interest to perform a meta-analysis of those case reports to explore the role of such meta-analyses as a tool for evidence-based medicine in rare diseases. Methods The study included all case reports with standard treatment regimen. Primary analysis was the percentage of case reports showing an improvement in a specific outcome. Only when that percentage was statistically higher than 5%, the improvement was confirmed as such. The outcomes that accomplished this criterion were ranked and compared to the GRADE criteria obtained by those same outcomes in the previous meta-analysis of clinical studies. Results There were three outcomes that had a significant improvement: Urine glycosaminoglycans, liver volume and 6-minute walking test. Positive and negative predictive values, sensitivity and specificity for the results of the meta-analysis of case reports as compared to that of clinical studies were 100%, 88.9%, 75% and 100%, respectively. Accordingly, absolute (Rho = 0.82, 95%CI: 0.47 to 0.95) and relative agreement (Kappa = 0.79, 95%CI: 0.593 to 0.99) between the number of case reports with improvement in a specific outcome and the GRADE evidence score for that outcome were good. Sensitivity analysis showed that agreement between the meta-analysis of case reports and that of the clinical studies were good only when using a strong confirmatory strategy for outcome improvement in case reports. Conclusions We found an agreement between the results of meta-analyses from case reports and from clinical studies in the efficacy of laronidase therapy in patients with MPS-I who initiated ERT in adult age. This agreement suggests that combining case reports quantitatively, rather than analyzing them separately or qualitatively, may improve conclusions in the field of rare diseases.