PMID- 31686823
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220411
IS  - 1176-6328 (Print)
IS  - 1178-2021 (Electronic)
IS  - 1176-6328 (Linking)
VI  - 15
DP  - 2019
TI  - Assessing effectiveness of aripiprazole lauroxil vs placebo for the treatment of 
      schizophrenia using number needed to treat and number needed to harm.
PG  - 2639-2646
LID - 10.2147/NDT.S207910 [doi]
AB  - OBJECTIVE: Schizophrenia clinical trials commonly measure observed changes in 
      Positive and Negative Syndrome Scale (PANSS) total score. However, it is more 
      intuitive to think of response vs nonresponse, a binary outcome. Assessing binary 
      outcomes enables calculation of number needed to treat (NNT) for therapeutic 
      outcomes, number needed to harm (NNH) for adverse outcomes, and likelihood to be 
      helped or harmed (LHH) to demonstrate benefit/risk tradeoffs. Here, NNT, NNH, and 
      LHH were used to evaluate the clinical usefulness of aripiprazole lauroxil in 
      patients with an acute schizophrenia exacerbation. METHODS: Categorical efficacy 
      and tolerability data were taken from the pivotal Phase 3 trial evaluating 
      aripiprazole lauroxil for treatment of an acute exacerbation of schizophrenia. 
      NNT and NNH values, with 95% CIs, were calculated in this post hoc analysis. 
      RESULTS: Using the intent-to-treat population for the pooled doses of 
      aripiprazole lauroxil (441 mg [n=196] and 882 mg [n=204] q4w), responder rates 
      (>/=30% improvement from baseline PANSS total score) were 35.3% for aripiprazole 
      lauroxil arms vs 18.4% for placebo (n=196), yielding a NNT of 6 (95% CI: 5-11). 
      Discontinuation rates due to adverse events (AEs) were higher among patients 
      randomized to placebo than to either aripiprazole lauroxil dose. Akathisia was 
      the only AE with an incidence >/=5% in each aripiprazole lauroxil group and at 
      least twice that of placebo (11.6%, 11.5%, and 4.3% of the patients receiving 
      aripiprazole lauroxil 441 mg, 882 mg, and placebo, respectively), producing a NNH 
      of 14 (95% CI: 9-33) for pooled aripiprazole lauroxil doses vs placebo. 
      Calculating LHH for therapeutic response vs akathisia, aripiprazole lauroxil was 
      2.3 times more likely to result in a therapeutic response than an incident of 
      akathisia. CONCLUSION: Using metrics of NNT, NNH, and LHH, aripiprazole lauroxil 
      was an efficacious and well-tolerated intervention in a pivotal study in patients 
      with an acute schizophrenia exacerbation.
CI  - (c) 2019 Citrome et al.
FAU - Citrome, Leslie
AU  - Citrome L
AD  - Psychiatry and Behavioral Sciences, New York Medical College, Valhalla, NY, USA.
FAU - Du, Yangchun
AU  - Du Y
AD  - Biostatistics, Alkermes, Inc., Waltham, MA, USA.
FAU - Weiden, Peter J
AU  - Weiden PJ
AD  - Medical Affairs, Alkermes, Inc., Waltham, MA, USA.
LA  - eng
PT  - Journal Article
DEP - 20190912
PL  - New Zealand
TA  - Neuropsychiatr Dis Treat
JT  - Neuropsychiatric disease and treatment
JID - 101240304
PMC - PMC6751763
OTO - NOTNLM
OT  - antipsychotic agents
OT  - aripiprazole lauroxil
OT  - effect size
OT  - long-acting injectable
OT  - number needed to treat
OT  - psychotic disorders
COIS- Dr Leslie Citrome reports personal fees from Alkermes, during the conduct of the 
      study. He reports personal fees as a consultant from Acadia, Alkermes, Allergan, 
      Indivior, Intra-Cellular Therapeutics, Janssen, Lundbeck, Merck, Neurocrine, 
      Noven, Osmotica, Otsuka, Pfizer, Shire, Sunovion, Takeda, Teva, Vanda. He also 
      reports personal fees as a speaker from Acadia, Alkermes, Allergan, Janssen, 
      Lundbeck, Merck, Neurocrine, Otsuka, Pfizer, Shire, Sunovion, Takeda, Teva, and 
      Vanda. Dr Citrome owns stocks from Bristol-Myers Squibb, Eli Lilly, Johnson & 
      Johnson, Merck, and Pfizer. He also reports royalties from Wiley 
      (Editor-in-Chief, International Journal of Clinical Practice), UpToDate 
      (reviewer), Springer Healthcare (book), outside the submitted work. Dr Yangchun 
      Du and Peter J Weiden are employees of Alkermes, Inc. The authors report no other 
      conflicts of interest in this work.
EDAT- 2019/11/07 06:00
MHDA- 2019/11/07 06:01
PMCR- 2019/09/12
CRDT- 2019/11/06 06:00
PHST- 2019/03/07 00:00 [received]
PHST- 2019/08/12 00:00 [accepted]
PHST- 2019/11/06 06:00 [entrez]
PHST- 2019/11/07 06:00 [pubmed]
PHST- 2019/11/07 06:01 [medline]
PHST- 2019/09/12 00:00 [pmc-release]
AID - 207910 [pii]
AID - 10.2147/NDT.S207910 [doi]
PST - epublish
SO  - Neuropsychiatr Dis Treat. 2019 Sep 12;15:2639-2646. doi: 10.2147/NDT.S207910. 
      eCollection 2019.