PMID- 30886530
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220408
IS  - 1179-5735 (Print)
IS  - 1179-5735 (Electronic)
IS  - 1179-5735 (Linking)
VI  - 11
DP  - 2019
TI  - Daily Practice Managing Resistant Multiple Sclerosis Spasticity With 
      Delta-9-Tetrahydrocannabinol: Cannabidiol Oromucosal Spray: A Systematic Review 
      of Observational Studies.
PG  - 1179573519831997
LID - 10.1177/1179573519831997 [doi]
LID - 1179573519831997
AB  - BACKGROUND/PURPOSE: Spasticity is one of the most common symptoms in people with 
      multiple sclerosis (MS). Conventional anti-spasticity agents have limitations in 
      their efficacy and tolerability. Delta-9-tetrahydrocannabinol: cannabidiol 
      (THC:CBD) spray, a cannabinoid-based medicine, is approved as an add-on therapy 
      for MS spasticity not adequately controlled by other anti-spasticity medications. 
      The results from randomized controlled trials (RCTs) have demonstrated a 
      reduction in the severity of spasticity and associated symptoms. However, RCTs do 
      not always reflect real-life outcomes. We systematically reviewed the 
      complementary evidence from non-interventional real-world studies. METHODS: A 
      systematic literature review was conducted to identify all non-RCT publications 
      on THC:CBD spray between 2011 and 2017. Data on study design, patient 
      characteristics, effectiveness, and safety outcomes were extracted from those 
      publications meeting our inclusion criteria. RESULTS: In total, we reviewed 14 
      real-world publications including observational studies and treatment registries. 
      The proportion of patients reaching the threshold of minimal clinical important 
      difference (MCID), with at least a 20% reduction of the spasticity Numeric Rating 
      Scale (NRS) score after 4 weeks ranged from 41.9% to 82.9%. The reduction in the 
      mean NRS spasticity score after 4 weeks was maintained over 6-12 months. The 
      average daily dose was five to six sprays. Delta-9-tetrahydrocannabinol: 
      cannabidiol was well tolerated in the evaluated studies in the same way as in the 
      RCTs. No new or unexpected adverse events or safety signals were reported in 
      everyday clinical practice. CONCLUSIONS: The data evaluated in this systematic 
      review provide evidence for the efficacy and safety of THC:CBD in clinical 
      practice and confirm results obtained in RCTs.
FAU - Akgun, Katja
AU  - Akgun K
AD  - Department of Neurology, Center of Clinical Neuroscience, University Hospital 
      Dresden, Dresden, Germany.
FAU - Essner, Ute
AU  - Essner U
AUID- ORCID: 0000-0003-4502-0948
AD  - O.MEANY Consultancy GmbH, Hamburg, Germany.
FAU - Seydel, Cordula
AU  - Seydel C
AD  - Almirall Hermal GmbH, Reinbek, Germany.
FAU - Ziemssen, Tjalf
AU  - Ziemssen T
AD  - Department of Neurology, Center of Clinical Neuroscience, University Hospital 
      Dresden, Dresden, Germany.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20190311
PL  - United States
TA  - J Cent Nerv Syst Dis
JT  - Journal of central nervous system disease
JID - 101595026
PMC - PMC6413425
OTO - NOTNLM
OT  - Central nervous system
OT  - cannabinoids
OT  - multiple sclerosis
OT  - real-world data
OT  - spasticity
COIS- Declaration of conflicting interests:The author(s) declared following potential 
      conflicts of interest with respect to the research, authorship, and/or 
      publication of this article: CS is an employee of Almirall Hermal and UE works as 
      a consultant for Almirall Hermal.
EDAT- 2019/03/20 06:00
MHDA- 2019/03/20 06:01
PMCR- 2019/03/11
CRDT- 2019/03/20 06:00
PHST- 2018/10/23 00:00 [received]
PHST- 2019/01/21 00:00 [accepted]
PHST- 2019/03/20 06:00 [entrez]
PHST- 2019/03/20 06:00 [pubmed]
PHST- 2019/03/20 06:01 [medline]
PHST- 2019/03/11 00:00 [pmc-release]
AID - 10.1177_1179573519831997 [pii]
AID - 10.1177/1179573519831997 [doi]
PST - epublish
SO  - J Cent Nerv Syst Dis. 2019 Mar 11;11:1179573519831997. doi: 
      10.1177/1179573519831997. eCollection 2019.