Registry Forge: drug repurposing cohort report

Cohort overview

58Participants in the motor neuron disease cohort 10Deaths on or before the cut-off 16Confirmed alive at the cut-off 32Vital status unknown after last contact 14Medicines with at least 5 exposed participants

Cohort: any motor neuron disease code in the problem list (ICD-10-CM G12.20 to G12.29, ICD-9-CM 335.20 to 335.29, plus the SNOMED CT and Mondo codes listed in the module). Cohort entry is the earliest such code. Exposure criterion: any. Follow-up runs from cohort entry to the data cut-off, ending earlier at death, at the last confirmed alive date or at the last dated record; nobody is assumed alive at the cut-off.

ALS clinical-interest medicines

Shown whether or not they meet the minimum exposure count. The status column describes the regulatory history only. Evidence types say what each record shows: an order, a dispense, an administration, a participant-reported use, or a C-CDA medication list entry that does not say whether the medicine was taken. Counts below 5 are held back for cell size, together with the year range, record count and evidence types for that medicine.

Medicine	Status	In cohort	Participants	Years with records	Records	Evidence types
Riluzole Rilutek, Tiglutik, Exservan · ATC N07XX02	FDA-approved for ALS (1995)	Recorded in cohort	48	2021 to 2024	240	dispense, document_list, order
Edaravone Radicava, Radicava ORS · ATC N07XX14	FDA-approved for ALS (2017)	Recorded in cohort	14	2021 to 2024	14	order
Tofersen Qalsody · ATC N07XX22	FDA-approved for SOD1 ALS (2023, accelerated)	Not recorded	0	–	0	–
Dextromethorphan-quinidine Nuedexta · ATC N07XX59	FDA-approved for PBA; off-label-of-interest in ALS	Recorded in cohort	11	2021 to 2024	11	order
Sodium phenylbutyrate-taurursodiol Relyvrio, Albrioza · ATC N07XX19	FDA-approved for ALS 2022; withdrawn 2024 after PHOENIX	Not recorded	0	–	0	–

Medication summary by ATC class

Kaplan-Meier medians are measured from a landmark 12 months after cohort entry, among participants alive and under follow-up at the landmark, because exposure is assessed through month 12. “Not reached” means fewer than half of that group died during follow-up. These are crude descriptive figures with no adjustment for site of onset, disease stage, age or any other difference between the groups, so a difference between the two columns says nothing about the effect of the medicine.

Methods and limitations

This module assembles the cohort and assigns exposure following the approach of Reimer et al. (Lancet Digital Health, 2026). It does not run propensity score matching or survival regression; those steps need a prespecified analysis plan, dedicated tools and covariates such as site of onset, time from symptom onset, ALSFRS-R and FVC. drug_repurposing_cohort.csv is the input to that work.

Limitations include small groups, confounding by indication (a medicine prescribed for a comorbidity marks a different group of participants), incomplete medication histories in the records a registry receives, evidence that a medicine was ordered rather than taken, deaths missed when vital status has not been linked, and coded diagnoses that have not been checked against the clinical record. Treat every result as a question for a prespecified study.

cure_id_review_worksheet.csv lists each exposed participant and medicine in the shape of a CURE ID case report so a clinical reviewer can decide whether any use is reportable. It is a local review worksheet, not a CURE ID submission. Medicines approved for ALS, and the withdrawn phenylbutyrate-taurursodiol, are not in it.