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Analysis of number needed to treat for droxidopa in patients with symptomatic neurogenic orthostatic hypotension.

ABSTRACT: Droxidopa is an orally active prodrug that significantly improved dizziness/lightheadedness measured using the Orthostatic Hypotension Symptom Assessment (OHSA) Item 1 in patients with neurogenic orthostatic hypotension (nOH) caused by primary autonomic failure (Parkinson disease, multiple system atrophy, and pure autonomic failure), dopamine ?-hydroxylase deficiency, or nondiabetic autonomic neuropathy. The efficacy and safety of droxidopa were assessed by determining the number needed to treat (NNT) and the number needed to harm (NNH).Data collected in randomized, placebo-controlled clinical studies in adults with a clinical diagnosis of symptomatic nOH were pooled for efficacy and safety analyses. NNT and NNH were calculated as reciprocals of the risk difference (difference in event rates) for droxidopa versus placebo.The NNT for droxidopa for improvement in OHSA Item 1 was <10. The NNH for adverse events (AEs) leading to discontinuation in the pooled studies was 81. The likelihood of being helped or harmed (LHH) calculated from pooled analysis of the NNT for ?2 units of improvement in OHSA Item 1 score and the NNH for discontinuations due to AEs were 7.8, 8.8, 3.1, and 3.5 for weeks 1, 2, 4, and 8 after randomization, respectively.Droxidopa is efficacious for treatment of nOH, with an NNT below 10 and an acceptable tolerability profile with NNH ranging from 23 to 302 in the pooled analysis of frequently occurring AEs. Based on the LHH for the pooled analysis at week 1, droxidopa is 7.8 times more likely than placebo to show a clinical benefit than result in discontinuation because of an AE.ClinicalTrials.gov identifiers: NCT00782340 , first received October 29, 2008; NCT00633880 , first received March 5, 2008; and NCT01176240 , first received July 30, 2010.

SUBMITTER: Francois C

PROVIDER: S-EPMC4990877 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Analysis of number needed to treat for droxidopa in patients with symptomatic neurogenic orthostatic hypotension.

François Clément C Rowse Gerald J GJ Hewitt L Arthur LA Vo Pamela P Hauser Robert A RA

BMC neurology 20160818 1

<h4>Background</h4>Droxidopa is an orally active prodrug that significantly improved dizziness/lightheadedness measured using the Orthostatic Hypotension Symptom Assessment (OHSA) Item 1 in patients with neurogenic orthostatic hypotension (nOH) caused by primary autonomic failure (Parkinson disease, multiple system atrophy, and pure autonomic failure), dopamine β-hydroxylase deficiency, or nondiabetic autonomic neuropathy. The efficacy and safety of droxidopa were assessed by determining the num ...[more]

PMID: 27538531

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Project description:BackgroundDroxidopa, a prodrug of norepinephrine, was approved for treatment of neurogenic orthostatic hypotension (nOH) due to primary autonomic disorders based on 3 randomized double-blind studies. We performed safety and efficacy analyses of this pooled dataset (n = 460).MethodsEfficacy was assessed using Orthostatic Hypotension Questionnaire (OHQ) scores (composite and individual items). Safety and tolerability were also examined.ResultsDroxidopa improved virtually all nOH symptom scores compared with placebo, significantly reducing OHQ composite score (-2.68 ± 2.20 vs -1.82 ± 2.34 units; P < 0.001), dizziness/lightheadedness score (-3.0 ± 2.9 vs -1.8 ± 3.1 units; P < 0.001), and 3 of 5 other symptom assessments (visual disturbances, weakness, and fatigue [P ≤ 0.010]). Droxidopa significantly improved 3 of 4 measures of activities of daily living (standing a long time, walking a short time, and walking a long time [P ≤ 0.003]) and significantly increased upright systolic blood pressure (11.5 ± 20.5 vs 4.8 ± 21.0 mmHg for placebo; P < 0.001). Droxidopa was effective in patients using inhibitors of dopa decarboxylase (DDCI; the enzyme that converts droxidopa to norepinephrine), but its efficacy was numerically greater in non-DDCI users. Droxidopa was well-tolerated. Rates of most adverse events were similar between groups. Supine hypertension rates were low, but slightly higher in patients receiving droxidopa (≤7.9% vs ≤4.6% for placebo); patients with severe hypertension at screening were excluded from these studies.ConclusionsDroxidopa is effective for the treatment of nOH in patients with primary autonomic disorders and is generally well-tolerated. A longer trial is underway to confirm efficacy beyond the ≤2 to 10 - week period assessed in the current trials.Trial registrationClinicalTrials.gov identifiers: NCT00782340 , first received October 29, 2008; NCT00633880 , first received March 5, 2008; and NCT01176240 , first received July 30, 2010.

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Analysis of number needed to treat for droxidopa in patients with symptomatic neurogenic orthostatic hypotension.

Publications

Analysis of number needed to treat for droxidopa in patients with symptomatic neurogenic orthostatic hypotension.

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