The safety and effectiveness of chenodeoxycholic acid treatment in patients with cerebrotendinous xanthomatosis: two retrospective cohort studies

Aad Verrips,Maria Teresa Dotti,Sue Verma,Andrea Mignarri,Bianca M L Stelten,Antonio Federico

doi:10.1007/s10072-019-04169-8

Abstract

ObjectiveTo evaluate the safety and effectiveness of chenodeoxycholic acid (CDCA) treatment in patients with cerebrotendinous xanthomatosis (CTX).MethodsTwo retrospective cohort studies were conducted in CTX patients who underwent CDCA treatment: one in the Netherlands (NL; CDCA-STUK-15-001) and one in Italy (IT; CDCA-STRCH-CR-14-001). Eligible patients were aged 2–75 years, had been diagnosed with CTX, and were treated with CDCA orally for ≥1 year. The impact of CDCA treatment on biochemical markers (including serum cholestanol levels) and disease signs and symptoms were assessed, in addition to the safety and tolerability of CDCA treatment.ResultsA total of 35 patients were screened in the NL study and were diagnosed with CTX at 25.6 (± 13.7 SD) years on average. These patients were treated with CDCA and followed up for a median of 9.00 (range: 0.4–26.3) years. In addition, 28 patients were enrolled in the IT study and were diagnosed at 35.0 (± 11.4 SD) years on average (median duration of CDCA treatment: 5.75 [range: 0.0–25.0] years). Signs and symptoms of disease resolved, improved, or remained stable in many patients, with concomitant improvements in biochemical marker levels (serum cholestanol, p < 0.001; 7α-hydroxy-4-cholesten-3-one, p < 0.001 [IT study]).ConclusionsThe outcomes of these retrospective cohort studies indicate that CDCA is effective in the long-term treatment of CTX, with an acceptable safety profile.

Highlights

Cerebrotendinous xanthomatosis (CTX; OMIM 213700) is a rare, autosomal recessive disorder caused by mutations in Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.Siena, Siena, Italy 3 Catharina Hospital, Eindhoven, the Netherlands 4 Leadiant Biosciences Ltd., London, UKCYP27A1, which lead to a deficiency in sterol 27hydroxylase [1, 2]
Mean serum cholestanol levels significantly decreased from baseline to any post-treatment visit (p < 0.001 at any visit; Fig. 2a)
CTX is a rare neurometabolic disease that results in neurodegeneration, and for which chenodeoxycholic acid (CDCA) treatment is the standard of care [4]

Summary

Introduction

CYP27A1, which lead to a deficiency in sterol 27hydroxylase [1, 2] The latter is important for primary bile acid synthesis, the conversion of cholesterol to chenodeoxycholic acid (CDCA) and cholic acid [2, 3]. Manifestations of CTX can vary, within families but even between twins [5] These include prolonged neonatal jaundice, infantile-onset chronic diarrhoea, juvenile cataracts, tendon xanthomas with onset during adolescence or young adulthood, osteoporosis, and progressive psychiatric and neurological impairment [2, 6]. The latter may include mental retardation, cerebellar syndrome, pyramidal syndrome, peripheral neuropathy, epileptic seizures and dementia [2].

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