A placebo-controlled, parallel-group, randomized withdrawal study of subjects with symptoms of spasticity due to multiple sclerosis who are receiving long-term Sativex® (nabiximols)

Abstract

Background: Open-label studies are not ideal for providing robust evidence for long-term maintenance of efficacy of medicines, especially where medicines provide symptom relief and where long-term use of a placebo may be problematic and not ethical. Objective: To evaluate the maintenance of efficacy of Sativex in subjects who have gained long-term symptomatic relief of spasticity in multiple sclerosis (MS), and to assess the impact of sudden medicine withdrawal. Methods: An enriched enrolment randomized withdrawal study design was used. Eligible subjects with ongoing benefit from Sativex for at least 12 weeks entered this 5-week placebo-controlled, parallel-group, randomized withdrawal study. Each subjects’ previous effective and tolerated dose was continued. Results: A total of 18 subjects per group were enrolled. Demographics showed a mean duration of MS of 16.4 years, spasticity 12.7 years, mean duration of Sativex use of 3.6 years (median 3.4 years) and a mean daily dose of 8.25 sprays. Primary outcome of time to treatment failure was significantly in favour of Sativex ( p = 0.013). Secondary endpoints showed significant changes in the Carer and Subject’s Global Impression of Change scales in favour of Sativex. Conclusions: Maintenance of Sativex efficacy in long-term symptomatic improvement of spasticity to a group of subjects with MS has been confirmed using this study design.

Cannabinoids in neurology – Brazilian Academy of Neurology

“…O extrato de cannabis oral e o THC também se mostrou eficaz apenas nas escalas de auto-avaliação no uso por até 15 semanas, porém, após um ano os resultados indicaram uma melhora também nas escalas objetivas de mensuração da espasticidade. Estes resultados sugerem que esta opção terapêutica pode ser considerada nos pacientes com EM, embora faltem estudos de segurança com uso por longos períodos 6 .…”

Clinical Use of Cannabinoids for Symptom Control in Multiple Sclerosis

“…At therapeutic levels of dosing it has been shown that the abuse potential of the clinical cannabinoids is very low [36][37][38][39]. There is no significant withdrawal syndrome from medicinal use [15,36]. No evidence of tolerance to the effects of nabiximols with subsequent increased dose requirements has emerged in clinical trials to date [40,41].…”

“…In general, a short downward titration period of a few days would seem reasonable, although cannabinoids may take several weeks to be completely eliminated from the body. Patients may experience a return of their symptoms but a withdrawal syndrome is very unlikely, although sleep and mood may be upset temporarily [15].…”

“…However, it would wise to exercise caution in use in severe cardiovascular, liver, kidney, and immunological disease, especially in acute illness. If a prescribed cannabinoid is controlling severe pain or spasticity, and so on, then stopping it suddenly may cause the patients to be plunged into a severe exacerbation of their symptoms, adding to the burden of their other medical problems [15].…”

“…Additionally, Notcutt et al [15] evaluated the ability of nabiximols to provide long-term relief from spasticity by assessing the effect of sudden withdrawal of the medicine after its use for at least 12 weeks, demonstrating the ongoing benefit patients were receiving, whilst also showing no evidence of a withdrawal syndrome. An observational study reviewed the benefits that patients continued to get with long-term use [16]: spasticity, pain, sleep, activities of daily living .…”