Mandibular advancement splint in obstructive sleep apnea assessed by IQWiG in Germany

On behalf of the Federal Joint Committee (G-BA), the Institute for Quality and Efficiency in Health Care (IQWiG) investigated whether wearing a lower jaw protrusion splint (Unterkieferprotrusionsschiene, UPS) is beneficial for obstructive sleep apnea.

Obstructive sleep apnea occurs when the muscles in the upper respiratory tract relax. As a result, the airway narrows in the throat area or is even completely blocked, causing loud snoring sounds when inhaling and exhaling. Due to this breathing disorder, the body is not sufficiently supplied with oxygen. In addition, pulse and blood pressure drop. As a result, the respiratory center triggers a wake-up stimulus: a person wakes up for a short time, usually without realizing it. As a result, the sleep rhythm is interrupted, the heart rate and the blood pressure rise.

Sleep apnea leads to sleep fragmentation and, thus, often to a not restful sleep. As a result, exhaustion, daytime sleepiness, involuntary falling asleep, loss of cognitive performance, and increased accident frequency occur, among other things. Untreated obstructive sleep apnea is associated with increased blood pressure, cardiovascular events such as heart attack and stroke, and increased mortality.

The treatment of obstructive sleep apnea depends, among other things, on the severity of the disease. For mild sleep apnea, conservative measures such as weight loss, sleep hygiene measures (no alcohol, no smoking), or postural therapy (avoidance of supine sleep) may be sufficient. For a higher severity, positive airway pressure via a mask (PAP therapy) is the standard treatment. In this case, the airways are kept open by positive pressure ventilation.

Mild to moderate obstructive sleep apnea can also be treated with the help of a UPS worn during sleep. The plastic splint in the mouth, adapted by a dentist or an orthodontist, ensures that the lower jaw is held further forward. As a result, the airways are kept mechanically open. This method is usually well-tolerated and often preferred by patients to PAP therapy. It is generally used in severe obstructive sleep apnea only in case of intolerance or intolerance of PAP therapy.

In its preliminary benefit assessment, the IQWiG examined two questions:

1. Does treatment with a UPS provide any benefit or harm compared to no treatment or placebo treatment?
2. Does treatment with a UPS provide any benefit or harm compared to treatment with positive airway pressure via a mask (PAP therapy)?

In research question 1, 21 randomized controlled trials (RCTs) were comprised, 18 outcomes of which were included in the benefit assessment. Of the total of 17 RCTs for research question 2, 16 yielded usable results for the benefit assessment.

The statements on benefit and non-inferiority in the studies refer to all persons with obstructive sleep apnea. This includes persons with mild to moderate obstructive sleep apnea, who are the focus of the benefit assessment in accordance with the G-BA request.

Results (question 1):

• Sleep quality: there was a statistically significant and clinically relevant difference in favor of treatment with UPS compared to no treatment or placebo treatment (OR [95% CI]; p-value: 3.53 [1.37, 9, 9]; 10]; 0.008)
• Paced Auditory Serial Addition Task (PASAT): in the single analysis of the Barnes study 2004 for the PASAT with the interstimulus interval of 1.2 seconds, there was a statistically significant and clinically relevant difference in favor of the UPS (MD [95% CI], p-value: -0.80; 1.01; -0.59]; <0.001; hedges' g [95% CI]: -1.01; [-1.29; -0.74])
• Fatigue: there was a statistically significant and clinically relevant difference (OR [95% CI]; p-value: 8.14 [2.29; 28.90]; <0.001) for the comparison between UPS versus placebo treatment
• Activities of everyday life: statistically significant differences were observed in all 3 individual questions (UPS 1 track: p <0.03 for all 3 questions, UPS 2 monoblock: p <0.001 for all 3 questions)
• There was no statistically significant difference found in the joint evaluation of the studies with moderate and high qualitative reliability of results regarding the effect of the UPS compared to no treatment or placebo treatment in the assessment using the Epworth Sleepiness Scale (ESS), regarding cognitive performance (vigilance, executive functions – except for the PASAT results assessment), symptoms of depression and fear, mental symptoms, somatic symptoms – headache, cardiovascular morbidity, fatigue (according to the Modified Fatigue Impact Scale assessment), health-related quality of life (according to 36-Item Short-Form Health Survey (SF-36) assessment), functional outcomes of sleep questionnaire (FOSQ), participation in professional and social life, serious adverse events and discontinuations due to adverse events, Apnea-Hypopnea Index (AHI) and oxygen desaturation index (ODI)

Results (question 2):

• Daytime sleepiness - Berlin Questionnaire for Sleep Apnea: Single question about daytime tiredness: there was a statistically significant difference in favor of PAP therapy (MWD [95% CI]; p-value: -0.5 [-0.82; -0.18]; 0.003)
• Health-related quality of life: the individual evaluation for Nottingham Health Profile (NHP)-subscore “sleep” revealed a statistically significant difference (MWD [95% CI]; p-value: -10.30 [-19.65; -0.95]; 0.031)
• There was no statistically significant difference found in the joint evaluation of the studies with moderate and high qualitative reliability of results regarding overall mortality or overall survival, daytime sleepiness, the effect of the UPS compared to PAP-therapy in the assessment using the Epworth Sleepiness Scale (ESS), quality of sleep, regarding cognitive performance (vigilance, executive functions), symptoms of depression and fear, mental symptoms, somatic symptoms, cardiovascular morbidity, health-related quality of life (according to 36-Item Short-Form Health Survey (SF-36) assessment), daily life and participation in professional and social life, serious adverse events and discontinuations due to adverse events, AHI and ODI

Therefore, after preliminary evaluation of the study situation, the institute considers the patient-relevant outcome “daytime sleepiness,” the leading symptom of obstructive sleep apnea, as an indication of the benefit of the UPS compared to no treatment. Compared with the airway pressure therapy via sleep mask PAP therapy, the scientists for the daytime sleepiness derive an indication of the non-inferiority of the UPS. There were no disadvantages of the UPS compared to PAP therapy.

Comments on the preliminary report will be accepted by IQWiG until 20.11.2019. Comments on the published preliminary report will be reviewed after the deadline. If they leave questions unanswered, the respondents will be invited to a verbal discussion. The IQWiG then will provide the final report.

The preliminary report in German can be found here.

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