Abstract
Proceedings of an Almirall-sponsored satellite symposium held at the 34th Congress of the European Committee for Treatment and Research in Multiple Sclerosis in Berlin, Germany, 10 October 2018.
Spasticity is a common and frequently disabling symptom of multiple sclerosis (MS). Within 10 years of disease onset, about a third of MS patients report spasticity of at least moderate intensity [Citation1]. Aside from the direct physical disability, MS spasticity-associated symptomatology such as pain, spasms, reduced mobility, sleep disruption and bladder disorders interferes with patients’ ability to perform daily activities and reduces their quality of life [Citation2,Citation3].
Common first-line medications for MS spasticity include baclofen, tizanidine and benzodiazepines [Citation4]. Although initial response to treatment can be positive, the effect of these medications tends to wane over time. Moreover, achieving optimal symptomatic benefit from conventional oral antispasticity agents can be limited by undesired effects such as dose-limiting effects on the central nervous system, increased risk of falls and withdrawal syndrome [Citation4]. A 2014 burden of disease study found that patients’ and physicians’ satisfaction with available oral antispasticity medications was low and that the level of dissatisfaction rose with increasing spasticity severity [Citation2].
Tetrahydrocannabinol (THC):cannabidiol (CBD) oromucosal spray is a second-line treatment for MS spasticity [Citation4,Citation5]. In Europe, THC:CBD oromucosal spray is indicated for symptom improvement in adult patients with moderate-to-severe MS spasticity who have not responded adequately to other antispasticity medication and who demonstrate clinically significant improvement in spasticity-related symptoms during an initial trial of therapy [Citation5]. A large gap follows to third-line treatment which is intrathecal baclofen [Citation4]. Preventing or delaying escalation to invasive therapy requires careful management to preserve use of first- and second-line treatment options for as long as possible.
Approval of THC:CBD oromucosal spray in Europe in 2011 was supported by a broad range of studies, with the foremost being a two-phase enriched-design clinical trial involving 572 patients with resistant MS spasticity [Citation6]. The preliminary 4-week, single-blind phase identified 272 patients (47% of the enrolled population) with an initial response to THC:CBD oromucosal spray, defined as ≥20% reduction from baseline in the spasticity 0–10 Numerical Rating Scale (NRS) score; 241 of these patients (42%) entered the double-blind treatment phase. After 12 weeks, the mean MS spasticity 0–10 NRS score was maintained in the group randomized to active treatment but worsened in the group allocated to placebo. The result in favor of THC:CBD oromucosal spray was highly statistically significant (p = 0.0002).
Over the past several years, considerable additional supporting evidence for THC:CBD oromucosal spray has been generated in observational studies and randomized clinical trials. At the 34th Congress of the European Committee for Treatment and Research in Multiple Sclerosis in Berlin, Germany, a symposium was held entitled “THC:CBD oromucosal spray for treating symptoms of multiple sclerosis spasticity: newest evidence confirming effectiveness and safety’, which I had the honor to chair. During the symposium, myself, Dr Francesco Patti (Catania, Italy) and Dr Jolana Marková (Prague, Czechia) reviewed the latest evidence for THC:CBD oromucosal spray with a focus on three key studies (one pragmatic study and two new randomized controlled trials) that confirm its effectiveness and tolerability in the treatment of resistant MS spasticity. These proceedings summarize and interpret the new evidence in order to provide practical recommendations for managing patients with MS spasticity with THC:CBD oromucosal spray in daily clinical practice.
Acknowledgments
The article is based on a symposium presented at European Committee for Treatment and Research in Multiple Sclerosis 2018 in Berlin, Germany.
Financial & competing interests disclosure
T Ziemssen has received personal compensation for participating in advisory boards, trial steering committees and data and safety monitoring committees, scientific talks and project support from: Almirall, Bayer, Biogen, Merck, Novartis, Roche, Sanofi and Teva. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Writing assistance was provided by Content Ed Net (Madrid, Spain) with funding from Almirall SA (Barcelona, Spain).
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