Pitolisant safe, lowers daytime sleepiness in OSA over 1 year
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Key takeaways:
- At the 1-year mark of pitolisant treatment, the Epworth Sleepiness Scale score dropped by 8 points from baseline.
- A little over one-third of patients experienced a treatment-emergent adverse event.
Among adults with obstructive sleep apnea, excessive daytime sleepiness decreased with 1 year of pitolisant treatment, according to results published in CHEST.
“Our data support the long-term maintenance of efficacy of pitolisant in the treatment of [residual excessive daytime sleepiness] in individuals with OSA,” Jean-Louis Pépin, MD, professor at Grenoble Alpes University in France, and colleagues wrote. “The good safety profile was consistent with the prior short-term [randomized controlled trials] of pitolisant and long-term follow-up in narcolepsy.”
Using data from the HAROSA 1 and HAROSA 2 randomized controlled trials, Pépin and colleagues evaluated 512 adults with OSA, with or without CPAP treatment, to determine the impact of 1-year pitolisant (Wakix, Harmony Biosciences) on baseline Epworth Sleepiness Scale (ESS) scores, as well as long-term drug safety.
As Healio previously reported, treatment with pitolisant vs. placebo for 12 weeks reduced excessive daytime sleepiness and improved several other outcomes among patients with OSA who refuse CPAP in the HAROSA 2 trial.
The maximum dose of pitolisant given per day was 20 mg, researchers noted.
Of the total cohort, 128 patients initially received placebo for 12 weeks in a HAROSA trial followed by pitolisant until week 52, whereas 384 patients initially received pitolisant and continued to receive it for a total of 52 weeks.
Researchers had 1-year data for 376 patients, which included 88 treated with placebo until week 12 and 288 treated with pitolisant from baseline.
Efficacy
At baseline, 15.2 was the mean ESS score among those receiving placebo until week 12, and this dropped by 8.5 points (95% CI, –9.3 to –7.7) at week 52.
Switching to the group receiving pitolisant since baseline, researchers observed a 7.8 point reduction in ESS score at week 52 from baseline.
Between baseline and 1 year, the ESS score decreased by an average of 8 points (95% CI, –8.3 to –7.5) in the total cohort.
Researchers also found that from baseline to 1 year, the total cohort demonstrated significant improvement (P < .05) in:
- Oxford Sleep Resistance Test (mean change, 11.9);
- EQ-5D questionnaire (mean change 8.2);
- Leeds Sleep Evaluation Questionnaire (LSEQ)-getting to sleep (mean change, 7.5);
- LSEQ-quality of sleep (mean change, 17.9);
- LSEQ-ease of awakening from sleep (mean change, 18.8);
- LSEQ-alertness and behavior following wakefulness (mean change, 24.1);
- LSEQ total (mean change, 17.1);
- Trail Making Test A (mean change, –9.3);
- Trail Making Test B (mean change, –23.9);
- Clinical Global Impression of Improvement (mean change, –1.4);
- Patient’s Global Opinion of the Effect (mean change, –2); and
- Pichot Fatigue Scale (mean change, –4.9).
Safety
The cohort used to assess long-term drug safety included 435 patients, of whom 103 received placebo until week 12 and 332 received 20 mg pitolisant per day from baseline.
A little over one-third of patients (35.1%) experienced a treatment-emergent adverse event in the total safety cohort. When divided based on initial placebo and initial pitolisant treatment, researchers observed a similar proportion of patients with a treatment-emergent adverse event (39.8% vs. 40.7%).
Of the 11 patients who reported a serious treatment-emergent adverse event, nine came from the pitolisant group in the HAROSA 1 trial (with CPAP). The remaining patients belonged to the placebo groups of the HAROSA 1 (n = 1) and HAROSA 2 (n = 1) trials.
One patient from the HAROSA 2 trial receiving pitolisant passed away, but researchers said, “it was considered unlikely to be related to the study treatment.”
In terms of treatment-emergent adverse events of special interest, a larger proportion of patients initially receiving placebo vs. pitolisant reported these events (14.6%; n = 15 vs. 9.6%; n = 32).
Broken down by HAROSA trial, nonsevere insomnia was a common event in both the initial placebo group (n = 4; 8.3%) and the initial pitolisant group (n = 11; 7.3%) in HAROSA 1.
Other treatment-emergent adverse events of special interest in this trial cohort included severe anxiety, severe depressed mood and severe depression found in the initial pitolisant group, as well as severe upper abdominal pain found in the initial placebo group.
In the HAROSA 2 cohort, insomnia was also common among those initially receiving placebo (mild or moderate, n = 4; 7.3%) and those initially receiving pitolisant (mild or moderate, n = 6; 3.9%; severe, n =1).
Patients receiving pitolisant did not report cardiovascular safety issues, according to researchers.
“Although 376 patients completed the study with 1 year of follow-up, the study was not powered to assess impact on long-term cardiovascular outcomes,” Pépin and colleagues wrote. “Such an effect is unlikely because of the compound’s mechanism of action. However, data on long-term hard outcomes are lacking, and future collaborative studies between sleep specialists and cardiologists are required.”