Association of Lonafarnib Treatment vs No Treatment With Mortality Rate in Patients With Hutchinson-Gilford Progeria Syndrome
Abstract
IMPORTANCE: Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare fatal premature aging disease. There is no approved treatment.
OBJECTIVE: To evaluate the association of monotherapy using the protein farnesyltransferase inhibitor lonafarnib with mortality rate in children with HGPS.
DESIGN, SETTING, AND PARTICIPANTS: Cohort study comparing contemporaneous (birth date ≥1991) untreated patients with HGPS matched with treated patients by age, sex, and continent of residency using conditional Cox proportional hazards regression. Treatment cohorts included patients from 2 single-group, single-site clinical trials (ProLon1 [n = 27; completed] and ProLon2 [n = 36; ongoing]). Untreated patients originated from a separate natural history study (n = 103). The cutoff date for patient follow-up was January 1, 2018.
EXPOSURE: Treated patients received oral lonafarnib (150 mg/m2) twice daily. Untreated patients received no clinical trial medications.
MAIN OUTCOMES AND MEASURES: The primary outcome was mortality. The primary analysis compared treated patients from the first lonafarnib trial with matched untreated patients. A secondary analysis compared the combined cohorts from both lonafarnib trials with matched untreated patients.
RESULTS: Among untreated and treated patients (n = 258) from 6 continents, 123 (47.7%) were female; 141 (54.7%) had a known genotype, of which 125 (88.7%) were classic (c.1824C>T in LMNA). When identified (n = 73), the primary cause of death was…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 258 participants or records.
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