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Meta-Analysis
. 2021 Dec 1;17(12):2543-2555.
doi: 10.5664/jcsm.9610.

Indirect treatment comparison of solriamfetol, modafinil, and armodafinil for excessive daytime sleepiness in obstructive sleep apnea

Sarah Ronnebaum  1 , Morgan Bron  2 , Dipen Patel  1 , Diane Menno  2 , Shay Bujanover  2 , David Kratochvil  1 , Eleanor Lucas  1 , Carl Stepnowsky  3
Affiliations
Meta-Analysis

Indirect treatment comparison of solriamfetol, modafinil, and armodafinil for excessive daytime sleepiness in obstructive sleep apnea

Sarah Ronnebaum et al. J Clin Sleep Med. .

Abstract

Study objectives: Excessive daytime sleepiness associated with obstructive sleep apnea affects 9%-22% of continuous positive airway pressure-treated patients. An indirect treatment comparison meta-analysis was performed to compare efficacy and safety of medications (solriamfetol, modafinil, and armodafinil) approved to treat excessive daytime sleepiness associated with obstructive sleep apnea.

Methods: Efficacy and safety measures assessed in this indirect treatment comparison included Epworth Sleepiness Scale (ESS), 20-minute Maintenance of Wakefulness Test (MWT20), Clinical Global Impression of Change (CGI-C), Functional Outcomes of Sleep Questionnaire (FOSQ), and incidence of treatment-emergent adverse events (any, serious, or leading to discontinuation).

Results: A systematic literature review identified 6 parallel-arm, placebo-controlled randomized controlled trials that randomized 1,714 total participants to placebo, solriamfetol, modafinil, or armodafinil. In this indirect treatment comparison, all comparators were associated with greater improvements than placebo on the ESS, MWT20, and CGI-C after 4, 8, and 12 weeks of treatment. Relative to comparators and placebo at 12 weeks, solriamfetol at 150 mg or 300 mg had the highest probabilities of improvement in the ESS, MWT20, and CGI-C. Modafinil (200 or 400 mg) and solriamfetol (150 or 300 mg) were associated with greater improvement on the FOSQ than placebo at 12 weeks. Less than 2% of patients using placebo or comparators experienced serious or discontinuation-related treatment-emergent adverse events.

Conclusions: The results of this indirect treatment comparison show 12 weeks of treatment with solriamfetol, modafinil, and armodafinil resulted in varying levels of improvement on the ESS, MWT20, and CGI-C and similar safety risks in participants with excessive daytime sleepiness associated with obstructive sleep apnea.

Citation: Ronnebaum S, Bron M, Patel D, et al. Indirect treatment comparison of solriamfetol, modafinil, and armodafinil for excessive daytime sleepiness in obstructive sleep apnea. J Clin Sleep Med. 2021;17(12):2543-2555.

Keywords: Epworth Sleepiness Scale; armodafinil; modafinil; obstructive sleep apnea; solriamfetol.

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Conflict of interest statement

All authors have seen and approved the manuscript. Work for this study was performed at Jazz Pharmaceuticals and OPEN Health. This study was funded by Jazz Pharmaceuticals. Sarah Ronnebaum, Eleanor Lucas, David Kratochvil, and Dipen Patel are employees of OPEN Health, which received funding from Jazz Pharmaceuticals to conduct the analysis. Morgan Bron, Diane Menno, and Shay Bujanover are current or former employees of Jazz Pharmaceuticals who, in the course of their employment, have received stock options exercisable for, and other stock awards of, ordinary shares of Jazz Pharmaceuticals plc. Carl Stepnowsky reports no conflicts of interest.

Figures

Figure 1
Figure 1. Forest plots of ESS outcomes relative to placebo at 4, 8, and 12 weeks.
CrI = credible interval, ESS = Epworth Sleepiness Scale, qd = daily.
Figure 2
Figure 2. Forest plots of MWT20 outcomes relative to placebo at 4 and 12 weeks.
CrI = credible interval, MWT20 = Maintenance of Wakefulness Test at 20 minutes, qd = daily.
Figure 3
Figure 3. Forest plots of CGI-C outcomes relative to placebo at 4, 8, and 12 weeks.
CGI-C = Clinical Global Impression of Change, CrI = credible interval, qd = daily.
Figure 4
Figure 4. Forest plots of FOSQ outcomes relative to placebo at 12 weeks.
Bold formatting indicates that the 95% CrI does not cross the line of no effect. CrI = credible interval, FOSQ = Functional Outcomes of Sleep Questionnaire, qd = daily.
Figure 5
Figure 5. Forest plots of cumulative safety events relative to placebo at end of treatment.
Bold formatting indicates that the 95% CrI does not cross the line of no effect. CrI = credible interval, NR = not reported, qd = daily, TEAE = treatment-emergent adverse event.
Figure 6
Figure 6. Forest plots of individual safety events relative to placebo at end of treatment.
Bold formatting indicates that the 95% CrI does not cross the line of no effect. CrI = credible interval, NR = not reported, qd = daily.
See this image and copyright information in PMC

References

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