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Assessing effectiveness of aripiprazole lauroxil vs placebo for the treatment of schizophrenia using number needed to treat and number needed to harm

Authors Citrome L, Du Y, Weiden PJ

Received 7 March 2019

Accepted for publication 12 August 2019

Published 12 September 2019 Volume 2019:15 Pages 2639—2646


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Roger Pinder

Leslie Citrome,1 Yangchun Du,2 Peter J Weiden3

1Psychiatry and Behavioral Sciences, New York Medical College, Valhalla, NY, USA; 2Biostatistics, Alkermes, Inc., Waltham, MA, USA; 3Medical Affairs, Alkermes, Inc., Waltham, MA, USA

Correspondence: Leslie Citrome 11 Medical Park Drive, Suite 106, Pomona, NY 10970, USA
Tel +1 845 362 2081
Email [email protected]

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.

Keywords: aripiprazole lauroxil, long-acting injectable, psychotic disorders, antipsychotic agents, number needed to treat, effect size

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