Sativex® in the treatment of pain of neurological origin or symptoms of Multiple Sclerosis: Interim analysis of a long-term, open label, safety and tolerability study

Abstract

The efficacy and tolerability of Sativex®, a highly standardised cannabisbased medicine, has been investigated in a series of randomised, double-blind, placebo-controlled studies, in symptomatic multiple sclerosis (MS) and chronic pain patients. Study medication was added to patients’ existing therapies. Patients self titrated their medication: each 100microlitre oro-mucosal spray delivered 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg of cannabidiol (CBD). Patients completing the randomised studies were eligible to enter a long-term, open label, safety and tolerability study, where they discontinued their randomised therapy and re-titrated using Sativex®. Diaries of daily dosing and weekly symptom severity were completed, with clinic visits at 8-weekly intervals. As of November 2003, 261 (65%) of the 404 enrolled patients were ongoing. Withdrawals were mainly due to adverse events (n 57, 14%), withdrawal of consent (n 36, 9%) or lack of efficacy (n 24, 6%). Treatment-related adverse events were not uncommon (n 341, 84.4%), but serious, treatment-related adverse events were reported in only 11 patients (2.7%). Sustained improvement in mean Numerical Rating Scale (NRS) symptom scores were observed in patients who completed 52 weeks of extension study treatment (mean NRS score spasticity Baseline (BL, Sativex®) 5.49; BL (Placebo) 5.39, Week 52 (Sativex®) 3.29; Central neuropathic pain in MS (BL, Sativex®) 6.5, (BL, Placebo) 6.4, Week 52 (Sativex®) 2.83; Peripheral neuropathic pain (BL, Sativex®) 7.29, (BL, Placebo) 7.21, Week 52 (Sativex®) 5.07). Based on the mean number of sprays per day in 118 patients who reached 52 weeks treatment (Week 12 9.21 Week 52 7.89), there was no evidence of tolerance to Sativex®. Patients consistently reported little or no intoxication (mean intoxication Visual Analog Scale (VAS) scores (0-100) 2.26 – 4.84) for the same period. This interim analysis demonstrates that Sativex® is well tolerated and provides sustained long-term symptom relief.