Long-term Treatment of Cerebrotendinous Xanthomatosis (CTX) with Chenodeoxycholic Acid (CDCA) and CS-514

Abstract Objective To evaluate the safety and effectiveness of chenodeoxycholic acid (CDCA) treatment in patients with cerebrotendinous xanthomatosis (CTX). Methods Two 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. Results A 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]). Conclusions The outcomes of these retrospective cohort studies indicate that CDCA is effective in the long-term treatment of CTX, with an acceptable safety profile.

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Long-term treatment effect in cerebrotendinous xanthomatosis depends on age at treatment start

Neurology ◽

10.1212/wnl.0000000000006731 ◽

2018 ◽

Vol 92 (2) ◽

pp. e83-e95 ◽

Cited By ~ 14

Author(s):

Bianca M.L. Stelten ◽

Hidde H. Huidekoper ◽

Bart P.C. van de Warrenburg ◽

Eva H. Brilstra ◽

Carla E.M. Hollak ◽

...

Keyword(s):

Term Treatment ◽

Cerebrotendinous Xanthomatosis ◽

Neurologic Symptoms ◽

Screening Programs ◽

Treatment Start ◽

Long Term Treatment ◽

Disability Status ◽

Long Term Follow Up

ObjectiveTo evaluate the effect of chenodeoxycholic acid treatment on disease progression in cerebrotendinous xanthomatosis (CTX).MethodsIn this retrospective cohort study, we report the clinical long-term follow-up characteristics of 56 Dutch patients with CTX. Age at diagnosis was correlated with clinical characteristics and with the course of modified Rankin Scale (mRS) and Expanded Disability Status Scale (EDSS) scores at follow-up.ResultsMedian follow-up time was 8 years (6 months–31.5 years). Patients diagnosed and treated before the age of 24 years had a significantly better outcome at follow-up. When considering only patients with a good treatment adherence (n = 43), neurologic symptoms, if present, disappeared in all patients who were diagnosed before the age of 24 and treated since. Furthermore, treatment prevented the development of new neurologic symptoms during follow-up. In contrast, 61% of the patients diagnosed and treated after the age of 24 showed deterioration of the neurologic symptoms, with parkinsonism as a treatment-resistant feature. There was an improvement or stabilization in favor of patients diagnosed and treated before the age of 24 compared to those treated after the age of 24: 100% vs 58% for mRS scores and 100% vs 50% for EDSS scores, respectively.ConclusionsTreatment start at an early age can reverse and even prevent the development of neurologic symptoms in CTX. This study emphasizes the importance of early diagnosis in CTX and provides a rationale to include CTX in newborn screening programs.

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