OBJECTIVES: Progressive disability due to neurodegeneration is a hallmark feature of cerebrotendinous xanthomatosis (CTX), a rare autosomal recessive disorder of primary bile acid synthesis. With an estimated 200 patients diagnosed in Europe, defining natural history, outcome measures, and treatment benefit in CTX is challenging. Expanded Disability Status Scale (EDSS) scores have been used to monitor progression in CTX patients. To assess the natural history of disability in CTX, we investigated the relationship between age and EDSS in untreated patients, and then assessed whether patients treated with chenodeoxycholic acid (CDCA), the standard of care, had better EDSS scores than expected for their age.

METHODS: The baseline EDSS scores and ages of untreated patients aged 0–64 years [N=82] from two retrospective studies (CDCA-STUK-15-001 [n=30] and CDCA-STRCH-14-001 [n=27]) and a Spanish case series (n=25) were pooled. Simple linear regression was used to calculate the correlation between age and EDSS score. Actual EDSS scores of patients treated with commercially available CDCA (CDCA-STUK-15-001) and pharmacy compounded CDCA (CDCA-STRCH-14-001) were compared with the EDSS score expected for untreated patients at the same age, as derived from the linear regression.

RESULTS: A moderate correlation was observed between EDSS and age for untreated patients (R=0.4764; y=0.1265x-0.6251). Following treatment, EDSS scores were lower than expected in 96% (25/26) of patients treated with commercially available CDCA (mean/median treatment duration 10.77/8.5 years) and in 54% (14/26) treated with locally compounded product (mean/median duration 7.19/6.3 years).

CONCLUSIONS: These results suggest that long-term CDCA treatment may improve disability, as assessed by EDSS scores, when compared with the natural history. Patients treated with the commercial formulation fared better than those treated with the compounded formulation; this may be due to differences in patient cohort demographics, although product differences cannot be ruled out.

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