Clinical Takeaway
Pharmaceutical-grade cannabidiol (Epidiolex) reduced drop seizure frequency in Lennox-Gastaut syndrome patients at thresholds below the traditional 50% benchmark, with caregiver-reported outcomes confirming that even smaller reductions translated to meaningful real-world improvements. The Caregiver Global Impression of Change scale proved a reliable anchor for defining what counts as a clinically important response in this population.
#21 Clinically Meaningful Reduction in Drop Seizures in Patients with Lennox-Gastaut Syndrome Treated with Cannabidiol: Post Hoc Analysis of Phase 3 Clinical Trials.
Citation: Specchio Nicola et al.. Clinically Meaningful Reduction in Drop Seizures in Patients with Lennox-Gastaut Syndrome Treated with Cannabidiol: Post Hoc Analysis of Phase 3 Clinical Trials.. CNS drugs. 2025. PMID: 40775196.
Design: 5 Journal: 0 N: 2 Recency: 2 Pop: 2 Human: 1 Risk: -2
Quality Gate Alerts:
- Preclinical only
Abstract: BACKGROUND AND OBJECTIVE: In clinical trials of patients with Lennox-Gastaut syndrome (LGS), a ≥ 50% reduction in drop seizure frequency is generally accepted as a key endpoint. However, smaller reductions (< 50%) may yet be impactful for patients in real-world settings. This exploratory analysis evaluated the threshold for a clinically important response in drop seizures that is associated with the Caregiver Global Impression of Change (CGIC) scale score in patients with LGS treated with cannabidiol (CBD) oral solution and assessed the suitability of CGIC as an anchor for meaningful change. METHODS: This exploratory post hoc analysis included patients with LGS (N = 215, age 2-55 years) receiving CBD (Epidiolex® [USA]/Epidyolex® [EU]; 100 mg/mL oral solution) in two phase 3 randomized placebo-controlled trials (NCT02224690, April-October 2015, and NCT02224560, June- December 2015). Reduction in drop seizures (involving sudden loss of muscle tone) was anchored to CGIC scores of "slightly improved" or better or "much improved" or better, to determine the threshold at which seizure reduction can be considered clinically meaningful to patients. Spearman's correlation indicated suitability of anchors (absolute value ≥ 0.30 deemed appropriate). RESULTS: In the 215 patients receiving CBD with a CGIC score recorded, CGIC was "slightly improved" or better in 60% of patients, and "much improved" or better in 31% after 14 weeks of treatment. With a CGIC rating of "slightly improved" or better, the best threshold for a clinically important response in drop seizure reduction was – 30.6% (57.7% of patients). Mean and median percentage reductions in drop seizures were – 46.9% and – 58.6%, respectively. Using "much improved" or better, the best threshold was – 49.6% (40.5% of patients). Mean and median percentage reductions in drop seizures were – 57.6% and – 66.0%, respectively. Spearman's correlation was 0.47. CONCLUSION: Anchoring to CGIC of "slightly improved" or better, the th