No treatments have as yet shown clinical efficacy in the modification of progressive multiple sclerosis in the absence of relapses. This prospective study investigated whether oral dronabinol (Δ9-tetrahydrocannabinol) might slow the course of progressive multiple sclerosis when compared with placebo.
Patients were randomised in a 2:1 ratio to either dronabinol 3.5mg twice daily, increasing to maximum 28mg daily (n=329), or matching placebo (n=164) for 36 months. The study had two primary endpoints: time to expanded disability status scale (EDSS) score progression of at least 1 point from a baseline EDSS score of 4.0, 4.5, or 5.0 or at least 0.5 points from a baseline EDSS score of 5.5 or greater; and change from baseline to end of study in the physical impact subscale of the patient-reported 29-item multiple sclerosis impact scale (MSIS-29-PHYS).
The authors reported that the adjusted hazard ratio (HR) for first EDSS score progression event in patients randomly assigned to dronabinol compared with those assigned to placebo was 0.92 (95% CI 0.68–1.23; p=0.57). A multilevel model fitted to repeated measures of MSIS-29-PHYS score showed no evidence of an effect of treatment (estimated effect -0.9 points, 95% CI -2.0 to 0.2; p=0.11). There were 114 patients (35%) in the dronabinol arm who experienced at least one serious adverse event compared with 46 (28%) of patients who received placebo. The number and nature of serious adverse events reported did not differ significantly between groups.
The authors noted that the loss to follow-up in this study was around the level expected, but more patients dropped out of the dronabinol arm, which coincided with a larger number of adverse events than the placebo arm. Low progression rates makes the identification of a treatment effect less likely, and further work is necessary to determine optimum inclusion criteria for trials of progressive multiple sclerosis. Prespecified and exploratory subgroup analysis suggested that dronabinol might have a slight potentially beneficial effect in terms of EDSS score progression and other outcome measures in less disabled patients (baseline EDSS score <6.0). Conversely, dronabinol might have a slight potentially negative effect in patients with higher EDSS scores. This potential benefit in lower disability groups requires further investigation and might have relevance for inclusion criteria in future clinical trials in progressive multiple sclerosis.