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Sativex® as add-on therapy vs. further optimized first-line ANTispastics (SAVANT) in resistant multiple sclerosis spasticity: a double-blind, placebo-controlled randomised clinical trial.

Abstract

Purpose/aim: To evaluate the efficacy of tetrahydrocannabinol (THC):cannabidiol (CBD) oromucosal spray (Sativex®) as add-on therapy to optimised standard antispasticity treatment in patients with moderate to severe multiple sclerosis (MS) spasticity.

METHODS

Sativex® as add-on therapy vs. further optimised first-line ANTispastics (SAVANT) was a two-phase trial. In Phase A, eligible patients received add-on THC:CBD spray for 4 weeks to identify initial responders [≥20% improvement from baseline in spasticity 0-10 numerical rating scale (NRS) score]. Following washout, eligible initial responders were randomised to receive THC:CBD spray or placebo for 12 weeks (double-blinded, Phase B). Optimisation of underlying antispasticity medications was permitted in both groups across all study periods.

RESULTS

Of 191 patients who entered Phase A, 106 were randomised in Phase B to receive add-on THC:CBD spray (n = 53) or placebo (n = 53). The proportion of clinically relevant responders after 12 weeks (≥30% NRS improvement; primary efficacy endpoint) was significantly greater with THC:CBD spray than placebo (77.4 vs. 32.1%; p < 0.0001). Compared with placebo, THC:CBD spray also significantly improved key secondary endpoints: changes in mean spasticity NRS (p < 0.0001), mean pain NRS (p = 0.0013), and mean modified Ashworth's scale (p = 0.0007) scores from Phase B baseline to week 12. Adverse events, when present, were mild/moderate and without new safety concerns.

CONCLUSIONS

Add-on THC:CBD oromucosal spray provided better and clinically relevant improvement of resistant MS spasticity compared with adjusting first-line antispasticity medication alone.

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  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    a Neurology Department , Thomayer's Hospital , Praha , Czechia.

    ,

    b O. Meany Consultancy GmbH , Hamburg , Germany.

    ,

    c Market Access Manager , Almirall Hermal GmbH , Reinbek , Germany.

    ,

    d Clinical Statistics , Almirall S.A. , Barcelona , Spain.

    ,

    e International Clinical Trial Managers , Almirall Hermal GmbH , Reinbek , Germany.

    ,

    e International Clinical Trial Managers , Almirall Hermal GmbH , Reinbek , Germany.

    f Neurology Medical Manager , Global Medical Affairs, Almirall S.A. , Barcelona , Spain.

    Source

    MeSH

    Cannabidiol
    Double-Blind Method
    Dronabinol
    Drug Combinations
    Drug Therapy, Combination
    Female
    Humans
    Male
    Middle Aged
    Multiple Sclerosis
    Muscle Spasticity
    Parasympatholytics
    Prospective Studies
    Treatment Outcome

    Pub Type(s)

    Journal Article
    Randomized Controlled Trial

    Language

    eng

    PubMed ID

    29792372

    Citation

    Markovà, Jolana, et al. "Sativex® as Add-on Therapy Vs. Further Optimized First-line ANTispastics (SAVANT) in Resistant Multiple Sclerosis Spasticity: a Double-blind, Placebo-controlled Randomised Clinical Trial." The International Journal of Neuroscience, vol. 129, no. 2, 2019, pp. 119-128.
    Markovà J, Essner U, Akmaz B, et al. Sativex® as add-on therapy vs. further optimized first-line ANTispastics (SAVANT) in resistant multiple sclerosis spasticity: a double-blind, placebo-controlled randomised clinical trial. Int J Neurosci. 2019;129(2):119-128.
    Markovà, J., Essner, U., Akmaz, B., Marinelli, M., Trompke, C., Lentschat, A., & Vila, C. (2019). Sativex® as add-on therapy vs. further optimized first-line ANTispastics (SAVANT) in resistant multiple sclerosis spasticity: a double-blind, placebo-controlled randomised clinical trial. The International Journal of Neuroscience, 129(2), pp. 119-128. doi:10.1080/00207454.2018.1481066.
    Markovà J, et al. Sativex® as Add-on Therapy Vs. Further Optimized First-line ANTispastics (SAVANT) in Resistant Multiple Sclerosis Spasticity: a Double-blind, Placebo-controlled Randomised Clinical Trial. Int J Neurosci. 2019;129(2):119-128. PubMed PMID: 29792372.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Sativex® as add-on therapy vs. further optimized first-line ANTispastics (SAVANT) in resistant multiple sclerosis spasticity: a double-blind, placebo-controlled randomised clinical trial. AU - Markovà,Jolana, AU - Essner,Ute, AU - Akmaz,Bülent, AU - Marinelli,Marcella, AU - Trompke,Christiane, AU - Lentschat,Arnd, AU - Vila,Carlos, Y1 - 2018/09/13/ PY - 2018/5/25/pubmed PY - 2019/4/23/medline PY - 2018/5/25/entrez KW - Multiple sclerosis KW - Sativex KW - THC:CBD KW - nabiximols KW - spasticity SP - 119 EP - 128 JF - The International journal of neuroscience JO - Int. J. Neurosci. VL - 129 IS - 2 N2 - : Purpose/aim: To evaluate the efficacy of tetrahydrocannabinol (THC):cannabidiol (CBD) oromucosal spray (Sativex®) as add-on therapy to optimised standard antispasticity treatment in patients with moderate to severe multiple sclerosis (MS) spasticity. METHODS: Sativex® as add-on therapy vs. further optimised first-line ANTispastics (SAVANT) was a two-phase trial. In Phase A, eligible patients received add-on THC:CBD spray for 4 weeks to identify initial responders [≥20% improvement from baseline in spasticity 0-10 numerical rating scale (NRS) score]. Following washout, eligible initial responders were randomised to receive THC:CBD spray or placebo for 12 weeks (double-blinded, Phase B). Optimisation of underlying antispasticity medications was permitted in both groups across all study periods. RESULTS: Of 191 patients who entered Phase A, 106 were randomised in Phase B to receive add-on THC:CBD spray (n = 53) or placebo (n = 53). The proportion of clinically relevant responders after 12 weeks (≥30% NRS improvement; primary efficacy endpoint) was significantly greater with THC:CBD spray than placebo (77.4 vs. 32.1%; p < 0.0001). Compared with placebo, THC:CBD spray also significantly improved key secondary endpoints: changes in mean spasticity NRS (p < 0.0001), mean pain NRS (p = 0.0013), and mean modified Ashworth's scale (p = 0.0007) scores from Phase B baseline to week 12. Adverse events, when present, were mild/moderate and without new safety concerns. CONCLUSIONS: Add-on THC:CBD oromucosal spray provided better and clinically relevant improvement of resistant MS spasticity compared with adjusting first-line antispasticity medication alone. SN - 1563-5279 UR - https://www.unboundmedicine.com/medline/citation/29792372/Sativex®_as_add_on_therapy_vs__further_optimized_first_line_ANTispastics__SAVANT__in_resistant_multiple_sclerosis_spasticity:_a_double_blind_placebo_controlled_randomised_clinical_trial_ L2 - http://www.tandfonline.com/doi/full/10.1080/00207454.2018.1481066 DB - PRIME DP - Unbound Medicine ER -