“Imiglucerase Treatment Associated with Reduction of Bone Claims in Gaucher Patients: Analysis of US Claims Data”
Authors: Nalysnyk Lubomyra , Selzer Martin , Hamed Alaa , Weinreb Neal J. 
Published: October 2019

Abstract
BACKGROUND: Gaucher disease type 1 (GD1) is a rare, genetic, multisystemic disorder caused by a deficiency of acid ß-glucosidase and characterized by an accumulation of lipid glucosylceramide in organs such as the spleen, liver and bone marrow. The key clinical features include anemia, thrombocytopenia, hepatosplenomegaly, and skeletal disease. Bone involvement is one of the most frequent, debilitating complications of GD1 that can have significant negative impact on patients’ quality of life due to pain, disability, and need for orthopedic intervention. Several studies have shown that treatment with imiglucerase improves bone density, decreases the occurrence of bone crisis, and ameliorates bone pain.
OBJECTIVE: To examine the impact of treatment with imiglucerase on bone claims in Gaucher patients before and after initiation of treatment using US administrative claims data.
METHODS: A retrospective study of medical claims data was conducted using Optum’s Clinformatics Data Mart database. Gaucher patients treated with imiglucerase between January 1, 1997 and June 30, 2013 were identified. Adult and pediatric patients were eligible for this study and were required to have at least 3 months continuous insurance coverage prior to their first treatment with imiglucerase (index date), at least 3 months follow-up post-index date, and at least 4 imiglucerase administrations within the first 3 months. The number of claims associated with bone disease and number of patients reporting these claims before and after treatment initiation with imiglucerase were assessed. The percentage of patients with bone claims and the average bone claims per patient were used to compare pre- and post-treatment data. Bone claims with the following treatment diagnoses were included: osteoporosis, pathological fracture, joint pain, necrosis, and unspecified bone problems.
RESULTS: A total of 107 GD patients were evaluated in the pre-treatment period; 59 (55%) were male and 48 (45%) were female; there were 85 (79%) adults (18 years and older) and 22 (21%) pediatric patients. Among the 107 GD patients, 31 patients (29%) reported bone claims within 3 months prior to treatment initiation with imiglucerase. During the first year of post-treatment initiation, a significant reduction in the number of patients with bone claims was observed in all 3-month intervals when compared to the pre-treatment period. The same results were observed for the average bone claims per patient, except it did not reach statistical significance for the 6-9 month period.
Results for all patients are presented in the Table below.
Table: Bone Claims Before and After Treatment Initiation with Imiglucerase Time interval N evaluated N (%) of patients with bone claims Total # of bone claims Average # of bone claims per patient (SD) Baseline/3 months prior to treatment 107 31 (29%) 99 0.93 (1.922) 0-3 months after treatment 105 10 (9.5%*) 32* 0.3 (1.161)* 3-6 months after treatment 98 12 (12.2%)* 30* 0.31 (1.04)* 6-9 months after treatment 80 7 (8.8%)* 49* 0.61 (2.447) 9-12 months after treatment 72 7 (9.7%)* 14* 0.19 (0.685)*
N = Number of patients
* Statistically significant compared to baseline at a cumulative probability level > 0.95.
Note: Statistical significance for % of patients is evaluated as a difference in proportions. Data has been adjusted for outliers.
When data were analyzed separately for adult and pediatric populations, similar trends were observed with more pronounced results among pediatric patients. For pediatric patients, 5 patients reported bone claims prior to initiation of treatment and no bone claims in the first 6 months after treatment initiation.
CONCLUSION: A reduction in the number of bone claims and number of patients with bone claims was observed after initiation of treatment with imiglucerase in Gaucher patients in the US. These results suggest that imiglucerase treatment is associated with a reduction of bone complaints in both adult and pediatric patients. Differences in bone claim frequencies between adult and pediatric patients after treatment initiation with imiglucerase also suggest that early treatment can mitigate the development of chronic bone disease and can result in a reduction of associated medical claims.

Disclosures
Nalysnyk: Genzyme, a Sanofi Company: Employment. Selzer:Genzyme, a Sanofi Company: Employment. Hamed:Genzyme, a Sanofi Company: Employment. Weinreb:Genzyme, A Sanofi Company: Consultancy, Honoraria, Speakers Bureau.