Cysteamine (Cystagon(R)) adherence in patients with cystinosis in Spain: successful in children and a challenge in adolescents and adults

Abstract

BackgroundCysteamine has improved survival and prognosis in cystinosis. Increasing numbers of patients reach adulthood and face new challenges such as compliance that wanes over time. The aim of this study was to evaluate adherence to cysteamine treatment in a group of cystinotic patients in Spain in an attempt to identify potential therapy pitfalls and improve the overall care of affected individuals. Despite the impact of cysteamine on prognosis, there is a paucity of data regarding adherence.MethodThirty-four cystinotic patients (21 male) 38% ≥18 years were enrolled in a voluntary, anonymous survey. Replies were obtained from patients (15/34), mothers (11/34), fathers (4/34) and both parents (4/34).ResultsPatient age (median and interquartile range) at diagnosis was 1 year (0.57–1), and patient age at Cystagon® initiation was also 1 year (0.8–1.8). Sixteen (47%) were kidney transplant (KTx) recipients; six were retransplanted. Age at first KTx 10 years (8.7–13.7). Patient understanding of multiorgan involvement in cystinosis: 4.1 organs reported; eye 97% and kidney 91%. Cysteamine was given by mother (100%) and father (83%) in <11 year olds, or self-administered (94%) in ≥11 year olds. Four daily doses in 89% versus 56% in <11 year olds or ≥11 year olds, with fixed schedule in 94% versus 50% in <11 or ≥11 year olds and progressive loss of reminders over time. Furthermore, 44% complained of unpleasant smell. Motivation for treatment compliance was 100% versus 40% in <11 versus ≥11 year olds, respectively. Disease impact in patients <18 years is as follows: school (29%), social (14%), ‘feeling different’ (10%); in patients ≥18 years: ‘feeling different’ (62%), professional (39%) and job absenteeism (31%). Referring physician: paediatric nephrologist (94%) and nephrologist (63%) in <11 versus ≥11 year olds. Ophthalmological follow-up: 83% versus 38% in <11 versus ≥11 year olds. Patient opinion of physician expertise: paediatric nephrologist (94%) and nephrologist (44%). New treatment options (65%) and better information (42%) were demanded to improve adherence.ConclusionTreatment with Cystagon is effective in young patients. However, adherence diminishes over time in adolescents and adults despite disease impact. Strategies such as better information on the disease, patient self-care promotion and facilitated transition to adult healthcare services are required to improve compliance and the clinical management of cystinosis.

Cistinosis en pacientes adolescentes y adultos: Recomendaciones para la atención integral de la cistinosis

“…Otros factores de riesgo no menos importantes y no exclusivos de cistinosis son: el conocimiento limitado sobre la enfermedad, la falta de motivación, la transición inadecuada del paciente a los servicios de adultos y el impacto de la enfermedad en la calidad de vida 7,9,10 . Otros factores de riesgo no menos importantes y no exclusivos de cistinosis son: el conocimiento limitado sobre la enfermedad, la falta de motivación, la transición inadecuada del paciente a los servicios de adultos y el impacto de la enfermedad en la calidad de vida 7,9,10 .…”

Central nervous system complications in adult cystinosis patients

“…Compliance to treatment is a major challenge, particularly in adults. 19 Indeed, overall median cystine level in this study is high at 2.0. In our French historical cohort, we also found a clinical effect of cysteamine on the incidence of neurological complications: the incidence of neuromuscular disorders was significantly reduced when cysteamine was started before 5 years in comparison with the absence of treatment.…”

“…A numerical value of compliance was assigned to each year of age and the median score was calculated for each patient. Median follow-up of cystine dosages was 22 years (range [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24].…”

Management of bone disease in cystinosis: Statement from an international conference

“…The recommended dosage is 60 to 90 mg/kg/d or 1.3‐1.95 g/m 2 /d, intended to achieve a leukocyte cystine level <1.0 nmol half‐cystine/mg of protein. Oral cysteamine has an unpleasant taste and smell, and induces nausea and other digestive complaints, so only one third of patients strictly comply with the dosage regimen, particularly in adolescence . Patients with gastric side effects of cysteamine therapy can benefit from medications such as omeprazole or ranitidine …”

“…Oral cysteamine has an unpleasant taste and smell, and induces nausea and other digestive complaints, so only one third of patients strictly comply with the dosage regimen, particularly in adolescence. 11,14 Patients with gastric side effects of cysteamine therapy can benefit from medications such as omeprazole or ranitidine. 15 Other tissue and organ damage occur in cystinosis due to the accumulation of intracellular cystine.…”