Sex differences in mandibular repositioning device therapy effectiveness in patients with obstructive sleep apnea syndrome

Marie-Françoise Vecchierini, Valérie Attali, Jean-Marc Collet, Marie-Pia d'Ortho, Frederic Goutorbe, Jean-Baptiste Kerbrat, Damien Leger, Florent Lavergne, Christelle Monaca, Pierre-Jean Monteyrol, Laurent Morin, Eric Mullens, Bernard Pigearias, Francis Martin, Hauria Khemliche, Lionel Lerousseau, Jean-Claude Meurice, ORCADES investigators, Darius Abedipour, Aurélie Allard-Redon, Alexandre Aranda, Valérie Attali, Frédérique Bavozet, Martine Becu, Wally Beruben, Jerome Bessard, Isabelle Bonafe, Mohammed Boukhana, Bruno Chabrol, Gérard Chatte, Chauvel Lebret, Jean-Marc Collet, Olivier Coste, Nathalie Dumont, Sophie Durand-Amat, Marie-Pia D'ortho, Jean Marc Elbaum, Olivier Gallet De Santerre, Frédéric Goutorbes, Thierry Grandjean, Wilma Guyot, Doniphan Hammer, Carmen Havasi, Pascal Huet, Jean Baptiste Kerbrat, Hauria Khemliche, Christian Koltes, Damien Leger, Laurent Lacassagne, Xavier Laur, Lionel Lerousseau, Olivier Liard, Christophe Loisel, Matthieu Longuet, Anne Mallart, Francis Martin, Frédéric Merle Beral, Jean Claude Meurice, Zoubida Mokhtari, Christelle Monaca, Pierre Jean Monteyrol, Jean-François Muir, Eric Mullens, Dominique Muller, Charles Paoli, François Xavier Petit, Bernard Pigearias, Marc Pradines, Arnauld Prigent, Gil Putterman, Marc Rey, Mickael Samama, Renaud Tamisier, Michel Tiberge, Cyrille Tison, Fabienne Tordjman, Bernard Triolet, Christian Vacher, Marie-Françoise Vecchierini, Alain Verain, Marie-Françoise Vecchierini, Valérie Attali, Jean-Marc Collet, Marie-Pia d'Ortho, Frederic Goutorbe, Jean-Baptiste Kerbrat, Damien Leger, Florent Lavergne, Christelle Monaca, Pierre-Jean Monteyrol, Laurent Morin, Eric Mullens, Bernard Pigearias, Francis Martin, Hauria Khemliche, Lionel Lerousseau, Jean-Claude Meurice, ORCADES investigators, Darius Abedipour, Aurélie Allard-Redon, Alexandre Aranda, Valérie Attali, Frédérique Bavozet, Martine Becu, Wally Beruben, Jerome Bessard, Isabelle Bonafe, Mohammed Boukhana, Bruno Chabrol, Gérard Chatte, Chauvel Lebret, Jean-Marc Collet, Olivier Coste, Nathalie Dumont, Sophie Durand-Amat, Marie-Pia D'ortho, Jean Marc Elbaum, Olivier Gallet De Santerre, Frédéric Goutorbes, Thierry Grandjean, Wilma Guyot, Doniphan Hammer, Carmen Havasi, Pascal Huet, Jean Baptiste Kerbrat, Hauria Khemliche, Christian Koltes, Damien Leger, Laurent Lacassagne, Xavier Laur, Lionel Lerousseau, Olivier Liard, Christophe Loisel, Matthieu Longuet, Anne Mallart, Francis Martin, Frédéric Merle Beral, Jean Claude Meurice, Zoubida Mokhtari, Christelle Monaca, Pierre Jean Monteyrol, Jean-François Muir, Eric Mullens, Dominique Muller, Charles Paoli, François Xavier Petit, Bernard Pigearias, Marc Pradines, Arnauld Prigent, Gil Putterman, Marc Rey, Mickael Samama, Renaud Tamisier, Michel Tiberge, Cyrille Tison, Fabienne Tordjman, Bernard Triolet, Christian Vacher, Marie-Françoise Vecchierini, Alain Verain

Abstract

Purpose: Mandibular repositioning devices (MRDs) are an effective treatment option for obstructive sleep apnea syndrome (OSAS), particularly in patients who refuse or cannot tolerate continuous positive airway pressure (CPAP). However, sex differences in the response to therapy and predictors of response are not clearly defined. This analysis of data from the long-term prospective ORCADES trial compared MRD efficacy in men and women with OSAS.

Methods: The ORCADES study included patients with newly diagnosed mild-to-moderate or severe OSAS who refused or were non-compliant with CPAP. MRD therapy was titrated over 3-6 months. The primary endpoint was treatment success (≥ 50% decrease in apnea-hypopnea index (AHI)). Complete response was defined using a range of AHI cut-off values (< 5/h, < 10/h, < 15/h).

Results: Overall treatment success rates were 89% in women and 76% in men (p = 0.019); corresponding rates in those with severe OSAS (AHI > 30/h) were 100% and 68% (p = 0.0015). In women vs. men, overall complete response rates at AHI cut-off values of < 5/h, <10/h, and < 15/h were 49 vs. 34% (p = 0.0052), 78 vs. 62% (p = 0.016), and 92 vs. 76% (p = 0.0032). On multivariate analysis, significant predictors of MRD treatment success were overbite and baseline apnea index in men, and neck circumference and no previous CPAP therapy in women. There were sex differences in the occurrence of side effects. Temporomandibular joint pain was the most common reason for stopping MRD therapy.

Conclusions: MRD therapy was effective in women with OSA of any severity, with significantly higher response rates compared with men especially in severe OSAS.

Trial registration: www.clinicaltrials.gov (NCT01326143).

Keywords: Apnea-hypopnea index; Mandibular repositioning device; Obstructive sleep apnea; Sex differences.

Conflict of interest statement

Marie-Francoise Vecchierini has received fees for serving on advisory boards and lecture fees from ResMed and Fisher & Paykel Healthcare. Valérie Attali has received fees for serving on advisory boards from Somnomed, and lecture fees and unrestricted grant support from ResMed. Marie-Pia d’Ortho has received fees for serving on advisory boards from ResMed and IP Santé; lecture fees from ResMed, Philips, IP Santé, and VitalAire; grant support from Fisher and Paykel Healthcare, ResMed, Philips, ADEP-Assistance, and IP Santé; and small material donations from VitalAire. Damien Léger has been a primary investigator for studies sponsored by Vitalair and Philips over the last 5 years and declares no other conflicts of interest regarding this publication. Florent Lavergne is an employee of ResMed. Christelle Monaca has received fees for serving on advisory boards from ResMed, Philips and UCB Pharma, and lecture fees from UCB Pharma and Orkyn. Laurent Morin is an employee of ResMed. Francis Martin has received lecture fees from ResMed, Philips, ADEP-ASSISTANCE; grant support from ResMed, Philips, ADEP Assistance, Orkyn and France-Oxygène; and small material donations from ADEP-ASSISTANCE. Jean-Claude Meurice has received fees for serving on advisory boards, lectures, and training sessions from ResMed, Philips, Orkin, and Novartis. For the remaining authors, none were declared.

Figures

Fig. 1
Fig. 1
ORCADES study flow chart. CAD/CAM computer-aided design/computer-aided manufacturing, FU follow-up, m men, MRD mandibular repositioning device, w women
Fig. 2
Fig. 2
Mandibular repositioning device efficacy in men and women at 3- to 6-month follow-up. AHI apnea-hypopnea index, Success rate percentage of patients with a ≥ 50% decrease in AHI from baseline to follow-up

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