Matt Hoffman

An original version of this article was published on our sister site, CGTLive.

Single-dose etranacogene dezaparvovec (EtranaDez; Hemgenix) was associated with long-term improvements demonstrating treatment efficacy compared with standard of care factor IX prophylaxis in men with severe or moderately severe hemophilia B, with or without preexisting AAV5 neutralizing antibodies (NAbs), past the 2-year mark, according to new analysis.

In these data, which included 52 patients with factor IX ≤2% who completed 36 months of follow-up, the mean annualized bleeding rate (ABR) for all bleeds from months 7 to 36 post treatment was reduced by 64% (mean ABR, 1.52) compared with the 6-or-more-month lead-in period (mean ABR, 4.17), which was statistically significant (

 = .0004). Additionally, the total bleeds (including all types)—which numbered 136 during the lead-in period—decreased to 55 during year 1, then 48 during year 2, and finally to 37 during year 3.

The median bleeds per participant decreased and remained stable from 2.0 (range, 0-10) during the lead-in period to 0.0 (range, 0-4) in the first year, remaining at 0.0 (range, 0-10) and 0.0 (range, 0-8) in the second and third years, respectively. Of note, at the 3 years post-treatment time point, 51 patients (94%) remained free of continuous factor IX prophylaxis.

The uniQure and CSL Behring gene therapy product—which was the first approved for hemophilia B in the United States—is an adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized, highly active factor IX Padua R338L transgene. Previously, EntranaDez demonstrated a superiority of bleeding protection compared with standard prophylaxis for up to 24 months post-treatment—this long-term follow-up from year 2 post-administration onward is currently ongoing.

The data were presented at the American Society of Hematology (ASH) 2023 Annual Meeting in San Diego this weekend, by Steven W. Pipe, MD, a professor of pediatric hematology/oncology at CS Mott Children’s Hospital, and colleagues. “Long-term follow-up during the HOPE-B trial has shown that a single-dose of etranacogene dezaparvovec resulted in long-term endogenous FIX Padua expression and superior bleeding protection compared to FIX prophylaxis in participants without or with AAV NAb titer [of less than] 1:678, with a favorable safety profile over 3 years post-administration,” Pipe et al wrote.

Overall, the mean endogenous FIX activity level—in the absence of exogenous FIX exposure, Pipe and colleagues noted—of participants was 41.5 IU/dL (±21.7; median, 39.9; range, 5.9-113; n = 50) at year 1. This dropped to 36.7 IU/dL (±19.0; median, 33.9; range, 4.7-99.2; n = 50) at year 2, and was sustained at a level of 38.6 IU/dL (±17.8; median, 36.0; range, 4.8-80.3; n = 48) in year 3. The pharmacodynamic profile was deemed not significantly different among those individuals with undetected AA5 NAb or a titer ≤1:678, as Pipe et al wrote.

A single participant who lacked efficacy—this individual recorded their highest AAV5 NAbs titer of 1:3212—and another who received a 10% partial dose of treatment did not discontinue prophylaxis. One of those participants eventually had factor IX levels decline to a range of 2% to 5%, at which time his bleeding phenotype returned and he resumed prophylaxis per protocol at 30 months after treatment.

During the second and third years post-treatment, 37 patients (70%) and 39 patients (75%) participants received no factor IX infusion, respectively; the overall mean annualized factor IX consumption decreased by 96% (–246,763 IU/kg per participant, including those receiving FIX prophylaxis after administration of EntranaDez) over the 3 years after treatment in comparison with the lead-in period, which was also significant (

At ASH 2022, Pipe presented a similar dataset from HOPE B, out to 24 months of follow-up. At the time, he 

, offering his perspective on the treatment’s resulting stable factor IX expression and lack of new adverse events. “This is confirming what we thought going into the trial based on earlier trial experience, and I think it bodes well for the future. Perhaps from this 1-time treatment, we will be able to achieve sustained FIX expression that is potentially transformative for the patient for bleed control and durable for, hopefully, their lifespan,” he said.

In this new analysis, the safety profile was similar, with no new deaths, no new hepatocellular carcinoma (HCC), nor any late treatment-related alanine transaminase (ALT) elevations or thromboembolic events. All participants experienced at least 1 treatment-emergent AE (AE) in the 3 years post treatment, and of the 709 AEs recorded, 541 (76%) were deemed mild, 137 (19%) moderate, and 31 (4%) severe.

No serious AEs related to treatment were recorded, though a serious AE of HCC and a death were reported previously, prior to year 2, that were deemed unrelated to EntranaDez. In total, 38 of 54 patients (70%) experienced 96 treatment-related, treatment-emergent AEs, 95% of which occurred prior to the 6-month post-treatment time point. The most common AE reported was ALT increase, for which 9 participants (16.7%) received supportive care with reactive corticosteroids (mean duration, 81.4 days; ±28.6; range, 51-130).

Additional data presented at ASH 2023 demonstrated efficacy and safety in a subset of patients with comorbid HIV treated in 2 clinical trials for the gene therapy.2 Between a phase 2b clinical trial (NCT03489291) and the HOPE-B trial, 5 of 57 total participants treated had HIV infections that were considered controlled per study protocol. The data suggest that after 36 months, the overall posttreatment annualized bleeding rate (ABR) for these 5 patients ranged from 0 to 5.0 (median, 0.64), compared with an ABR ranging from 1 to 10.4 (median, 5) prior to treatment. Of note, 2 of the 5 patients had no recorded bleeds at all in the 36 months after receiving EtranaDez. Furthermore, at 3 weeks posttreatment, 4 of the 5 patients (80%) had factor IX activity levels in the mild/normal range that were maintained going forward. Three patients had measurable factor IX levels after 3 years which was uncontaminated by any return to prophylaxis or use of on-demand replacement therapy. Of those, endogenous factor IX ranged from 31.5% to 58% (median, 32.3%).

Pipe S, van der Valk P, Verhamme P, et al. Long-Term Bleeding Protection, Sustained FIX Activity, Reduction of FIX Consumption and Safety of Hemophilia B Gene Therapy: Results from the HOPE-B Trial 3 Years after Administration of a Single Dose of Etranacogene Dezaparvovec in Adult Patients with Severe or Moderately Severe Hemophilia B. Presented at: ASH 2023 Annual Meeting & Exposition. December 9-12; San Diego, CA. Abstract 1055

Pipe S, Gomez E, Hermans CR, et al. HIV comorbid infection and liver-directed AAV-based gene therapy in adults with severe and moderately severe hemophilia B: efficacy and safety results from phase 2b and the pivotal phase 3 HOPE-B trials 3 years after administration of a single dose of etranacogene dezaparvovec. Presented at: ASH 2023 Annual Meeting & Exposition. December 9-12; San Diego, CA. Abstract 801

Articles

Phase 3 data presented at ASH 2023 show the gene therapy significantly reduced annualized bleeding rates and the number of total bleeds.

Etranacogene Dezaparvovec Significantly Improves Hemophilia B Past 2 Years

This article was originally published on 

The FDA has approved Sandoz’s injection treatment natalizumab-sztn (Tyruko; formerly known as PB006), the first biosimilar to the approved formulation of natalizumab (Tysabri; Biogen) for the treatment of adults with relapsing forms of multiple sclerosis (MS).

With this indication, the therapy can be utilized for patients with clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.

Additionally, the biosimilar is indicated for inducing and maintaining clinical response and remission in adults with moderately to severely active Crohn disease (CD) who also have evidence of inflammation and have had an inadequate response or inability to tolerate conventional therapies and inhibitors of tumor necrosis factor.

“Biosimilar medications offer additional effective treatment options that have the potential to increase access for people living with relapsing forms of multiple sclerosis,” Paul R. Lee, MD, PhD, director of the Division of Neurology II in the FDA Center for Drug Evaluation and Research, said in a statement.

“Today’s approval could have a meaningful impact for patients managing their disease.”

According to the agency, the decision to approve was based on evidence showing no clinically meaningful differences between the Sandoz product and the already approved Biogen agent in terms of safety, purity, and potency. The treatment was assessed in the 

, which included 264 participants, of which 131 received the biosimilar and 133 received the reference agent natatlizumab.

 At week 24, the model-based, least squares mean difference in cumulative number of new active lesions between biosimilar and reference treatment groups was 0.17 (biosimilar, 0.34 [SE, 0.34]; reference, 0.45 [SE, 0.28]; 95% CI, –0.61 to 0.94). There were no significant differences between treatment groups observed across secondary efficacy end points, safety, tolerability, or immunogenicity assessments, according to the authors.

Sarah Yim, MD, director of the Office of Therapeutic Biologics and Biosimilars in the FDA’s Center for Drug Evaluation and Research, said in a statement1 that the approval “furthers the FDA’s longstanding commitment to support a competitive marketplace for biological products and ultimately empowers patients by helping to increase access to safe, effective and high-quality medications at potentially lower cost.”

The most common adverse events associated with natalizumab products are headache and fatigue, with other common AEs including arthralgia, urinary tract infection, lower respiratory tract infection, gastroenteritis, vaginitis, depression, pain in extremity, abdominal discomfort, diarrhea, and rash.

Notably, the prescribing information for natalizumab products—which now includes both Tyruko and Tysabri formulations—contains a boxed warning for health care professionals and patients about the increased risk of progressive multifocal leukoencephalopathy (PML). The risk factors for PML include the presence of anti-JCV antibodies, longer duration of therapy, and immunosuppressant use, and the FDA noted that these factors “should be considered in the context of expected benefit” when beginning or choosing to continue treatment with natalizumab products. Because of these PML risks, however, natalizumab products are available only through a restricted drug distribution program, under a risk evaluation and mitigation strategy (REMS). Part of these requirements include 3- and 6-month post first infusion evaluations, continuing every 6 months thereafter, as well as immediately and 6 months after treatment discontinuation.

The therapy’s label also includes information on the risks of herpes infections, thrombocytopenia, immunosuppression, and serious hypersensitivity reactions. The FDA granted approval of Tyruko, the first biosimilar to Tysabri (natalizumab), to Sandoz Inc.

® gathered a number of advanced practice providers together to discuss the who, what, and where of biosimilars, the role of these therapies in MS care, and clinical data on biosimilars currently in development for MS. To get all of their insights into how to incorporate biosimilars into MS clinical practice, check out the full series here:


How Similar are Biosimilars? A look into the Future with Biosimilars in Multiple Sclerosis

In this clip below, Amy Perrin Ross, APN; Patricia Melville, NP-C; Aliza Ben-Zacharia, PhD, DNP, ANP-BC; and John Kramer, PA-C, discuss Sandoz’s natalizumab biosimilar and the phase 3 Antelope study.

1. FDA Approves First Biosimilar to Treat Multiple Sclerosis. News release. FDA. August 24, 2023. Accessed August 24, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-biosimilar-treat-multiple-sclerosis
2. Hemmer B, Wiendl H, Roth K, et al. Efficacy and Safety of Proposed Biosimilar Natalizumab (PB006) in Patients With Relapsing-Remitting Multiple Sclerosis: The Antelope Phase 3 Randomized Clinical Trial. JAMA Neurol. 2023;80(3):298–307. doi:10.1001/jamaneurol.2022.5007

The approval was based on evidence showing no clinically meaningful differences between natalizumab-sztn and the reference drug in terms of safety, purity, and potency.

Natalizumab-sztn Receives FDA Approval as First Biosimilar for Multiple Sclerosis

The FDA has approved the Proclaim XR spinal cord stimulation (SCS) system for the treatment of painful diabetic peripheral neuropathy (DPN), according to an announcement from Abbott.

 The company noted the system offers alternative options for those patients receiving other medications.

The system was previously approved in 2019 for the treatment of chronic pain. After a minimally invasive trial and the device implantation, patients can then control their therapy via an Apple device. Abbott also noted in its announcement that individuals who receive therapy from the Proclaim XR SCS system will have access to the company’s NeuroSphere Virtual Clinic, a connected care app that allows for patient-physician communication and remote treatment adjustments via cellular or Wi-Fi connection.

Notably, the list of available disease-modifying therapeutics for DPN is blank. With only symptomatic and behavioral avenues for disease management, there is great need for more treatment approaches to improve patient care.

 Additionally, the population of individuals with diabetes is large—an estimated 34 million people in the United States—and approximately 50% of adults with diabetes develop peripheral neuropathy, often leading to symptoms including pain and numbness in the extremities.

Jason E Pope, MD, DABPM, FIPP, president of Evolve Restorative Center in Santa Rosa, California, said in a statement,

 "Diabetic peripheral neuropathy has long plagued people affected by type 1 and type 2 diabetes, often adding another area of disease management on top of their ongoing monitoring of their glucose levels to manage this challenging disease. Abbott's Proclaim XR spinal cord stimulation system provides patients with painful diabetic peripheral neuropathy the opportunity to obtain a better quality of life while more seamlessly fitting into their current lifestyles."

In a prospective open-label trial (NCT01162993) conducted by Maastricht University Medical Center, in Maastricht, the Netherlands, trial stimulation was successful in 77% of the SCS patients after they were randomly assigned to SCS in combination with the best medical treatment (BMT) (n = 22) or to BMT only (n = 14).

 Treatment success, defined as at least 50% pain relief during daytime or nighttime or a response of "(very) much improved" for pain and sleep on the patient global impression of change (PGIC) scale at 6 months, was observed in 59% of the SCS group and in 7% of the BMT group (

Daytime pain relief and nighttime pain relief were reported by 41% and 36% of the SCS group, and 0% and 7% of the BMT group, respectively (

 <.05). Likewise, pain and sleep were noted as "(very) much improved" by 55% and 36% of the SCS group, whereas the BMT group reported no changes in either, respectively (pain, 

 <.05). The study authors concluded that, “Treatment success was shown in 59% of patients with PDPN who were treated with SCS over a 6-month period, although this treatment is not without risks.”

In another multicenter trial that also randomly assigned patients with DPN (n = 60) in a 2:1 ratio to SCS with BMT or BMT alone, the average visual analogue scale (VAS) score for pain intensity was 73 in the SCS group and 67 in the BMT group at baseline. After 6 months, the average VAS score was reduced to 31 in the SCS group (

"As a leader in diabetes care, Abbott is intimately familiar with the challenges people with diabetes encounter daily. This new indication for Proclaim XR will drive meaningful change in the treatment of pain associated with diabetic peripheral neuropathy and will be an important tool for physicians and patients in managing this debilitating condition," Pedro Malha, the vice president of neuromodulation at Abbott, said in a statement.

REFERENCES
1. FDA Approves Abbott's Spinal Cord Stimulation for People Living with Painful Diabetic Peripheral Neuropathy. News release. Abbott. January 26, 2023. Accessed January 26, 2023. https://prnmedia.prnewswire.com/news-releases/fda-approves-abbotts-spinal-cord-stimulation-for-people-living-with-painful-diabetic-peripheral-neuropathy-301731127.html
2. Hicks CW, Selvin E. Epidemiology of Peripheral Neuropathy and Lower Extremity Disease in Diabetes. 

.2019;19(10):86. doi:10.1007/s11892-019-1212-8
3. Cernea S, Raz I. Management of diabetic neuropathy. 

. 2021;123:154867. doi:10.1016/j.metabol.2021.154867
4. Feldman EL, Callaghan BC, Pop-Busui R, et al. Diabetic neuropathy. 

. 2019;5(1):42. doi:10.1038/s41572-019-0097-9
5. Slangen R, Schaper NC, Faber CG, et al. Spinal cord stimulation and pain relief in painful diabetic peripheral neuropathy: a prospective two-center randomized controlled trial. 

. 2014;37(11):3016-24. doi:10.2337/dc14-0684?
6. de Vos CC, Meier K, Zaalberg PB, et al. Spinal cord stimulation in patients with painful diabetic neuropathy: a multicentre randomized clinical trial. 

. 2014;155(11):2426-31. doi:10.1016/j.pain.2014.08.031

Abbott's Proclaim XR spinal cord stimulation system allows patients with painful diabetic peripheral neuropathy to improve quality of life using a system that is easily incorporated into their everyday lives.

FDA Approves Proclaim XR Spinal Cord Stimulation for Painful Diabetic Peripheral Neuropathy 

 field have experienced both progress and challenges. The insomnia care paradigm in particular saw treatment advances such aspharmacological therapy with the FDA approval of daridorexant (Quviviq; Idorisa), following the 2019 greenlight of lemborexant (Dayvigo; Eisai), as well as more data on cognitive behavioral therapy (CBT), which has become a recommended treatment for patients.

Challenges, though, persisted. Conversations about the impact of daylight saving time and its effect on patients’ sleep health were ongoing, as were those focused on school start times and pediatric sleep. Another major challenge that has been reported in the literature that needs more research is substance use, which has been shown to have significant effects on sleep. 

Overall, in conversations with NeurologyLive® over the course of this year, sleep medicine physicians indicated that the future of sleep care for conditions like insomnia appears to be moving toward a digital approach with artificial intelligence (AI), digital CBT, and wearable devices. This future holds much hope for those caring for patients, even with the various challenges that lie ahead. Ultimately, a better scientific understanding of sleep’s overall effects on health and an exacerbation of sleep conditions by societal issues has brought sleep health to the forefront of population health conversations.

One of the most recently approved therapies for insomnia is daridorexant, which got the FDA go-ahead on January 7, 2022. Shortly after the approval, Thomas Roth, PhD, the director of the Sleep Disorders and Research Center at Henry Ford Hospital, and an investigator in the clinical development studies of the newly approved Idorsia therapy, offered theclinician perspective on the efficacy and safety profiles from the study as well ashis other takeaways.

On the day of the decision, he noted in a statement that contextually it is important to remember that insomnia “is not only a problem of the night, but affects a patient’s ability to function during the day,” adding that, “elevating the [awareness about the] impact insomnia has on both the night and day remains critical in addressing patients’ needs.”

Martine Clozel, MD, the chief scientific officer at Idorsia, also said in a statement,

 that the companydesigned daridorexantwith the goal of “help[ing] address several issues people with insomnia face. Daridorexant properties include a potent inhibition of both orexin receptors, a rapid absorption for sleep onset, and a pharmacokinetic profile such that around 80% of daridorexant has been eliminated after a night of sleep to help minimize residual effects."

Another therapy that was approved and continues to be beneficial for individuals with insomnia is lembroexant. A recent study from the post-hoc analysis of Study 303 (NCT02952820) demonstrated that those who had clinically meaningful reductions on Insomnia Severity Index (ISI) scores reported greater changes from baseline in several outcome measures. The treatment was approved in 2019 for insomnia and has been used in different analyses studies since then. The Study 303 analysis suggested that most patients on lembroexant experience a positive medication effect.

In recent years, treating sleep disorders including insomnia with CBThas become a recommended approach, but there have been challenges in increasing its use. Yuri Maricich, MD, MBA, an internal medicine physician, and chief medical officer and head of development at Pear Therapeutics, recently published data along with a group of investigators froma real-world cohort of individuals that utilized a digital therapeutic called Somryst (previously known as SHUTi) which evaluates healthcare resource utilization, associated costs, and insomnia severity effects of the therapy.

“There’s been a lot of work looking at the importance of—and what is addressed in the clinical guidelines—cognitive behavioral therapy for insomnia, but unfortunately, the vast majority of patients can’t get access [to it] because there are only 600 clinicians who are trained, and less than 400 who are even certified,” Maricich told NeurologyLive® in an interview where he shared his perspectives on the motivations for the real-world use of CBT interventions. 

Similarly, Michelle Chen, PhD, a neuropsychologist at Rutgers University and core member at the Institute for Health at Rutgers, told NeurologyLive® that CBT is the gold standard for treating insomnia. She noted that its effectiveness lies in part because it teaches patients what the best habits are to promote good sleep—not necessarily changing the brain chemistry of the patient. Additionally, it lacks as many adverse effects as pharmacologic medications.

Additionally, another nonpharmacological approach that has become more widespread recently in clinical care is the incorporation of AI. The use of AI technology in sleep medicine has assisted with improving the labor-intensive acts of monitoring and scoring sleep stages. One such AI effort is being spearheaded by the American Academy of Sleep Medicine (AASM), which has established a 2-year pilot program called the AI/Autoscoring Certification Program that will focus on polysomnograms for sleep stage scoring and whether the software demonstrates equivalent or better accuracy than manual scoring.

Anuja Bandyopadhyay, MD, an assistant professor of clinical pediatrics at Indiana University School of Medicine, and the chair of the AASM’s Artificial Intelligence in Sleep Medicine Committee, spoke with NeurologyLive® about her perspective on the state of understanding insomnia, and how better phenotype-specific treatment can improve care. “We didn’t really realize that there could be different phenotypes, different clinical expressions of the same disease. So, a person with sleep apnea and insomnia is very different from a person with depression and insomnia, not just in the clinical expression, but in how they respond to different medications,” Bandyopadhyay said.

Other types of nonpharmacological interventions for insomnia include listening to music. One example from research this year comes from a review of randomized controlled trials. The updated review showed thatmusic potentially can be an effective approach for the improvement of subjective sleep quality for adults that experience insomnia symptoms.

Listening to music has been known to be used as a sleeping aid and can be an effective nonpharmacological intervention for improving insomnia symptoms in adults, according to the review.

Lead investigator Kira Jespersen, PhD, MSc, an assistant professor in the Center for Music in the Brain and the Department of Clinical Medicine at Aarhus University & The Royal Academy of Music Aarhus/Aalborg, in Aarhus, Denmark, and colleagues wrote, “Listening to music may improve slightly sleep‐onset latency (how quickly a person falls asleep), sleep duration (length of time a person is asleep) and sleep efficiency (amount of a time a person is asleep compared to the total time spent in bed), compared to no treatment or treatment as usual. None of the studies reported any negative effects caused by listening to music.”

School start times have been another hot topic in sleep and have been shown to have an impact on pediatric circadian rhythms. These unhealthy sleep patterns can carry on from childhood into adulthood. And although sleep disorders may be common in some children and adolescents influenced by lifestyle behaviors, others could be from the cause of a neurological condition, making their recognition imperative. Carol Rosen, MD, a professor of pediatrics at Case Western University, has concerns about the transition period before school begins, when children start going to bed earlier and adjusting their internal clock.

"Figure out what the schedule is, how much sleep your child needs, and kind of work backwards. Maybe go back in 15- or 30-minute increments, starting with your wakeup time. Move that back," Rosensaid in an interview with NeurologyLive® where she shared the advice she’s given to parents.

Chris Winter, MD, owner of Charlottesville Neurology and Sleep Medicine clinic and CNSM Consulting, and an author of several books on sleep, also shared his perspective on pediatric sleep on the Mindful Moments® podcast. He summarized the state of pediatric sleep disorders and provided some thoughts on the current system of schooling and how it impacts the sleep health of children along. He also expanded on the current trends in sleep medicine research, and what issues—such as recognition of sleep disorders—need to be addressed.

Children that experience poor sleep may also have their moods impacted as well. "When you’re cranky, it affects emotional regulation," Jodi Mindell, PhD, told NeurologyLive®. “How can you keep it together? Do you get angry much more easily? Do you burst out into tears? Do you start laughing and can’t control it? The kid whose super silly in school may be because they can’t regulate their emotions because they’re not getting enough sleep."Mindell, a psychologist in the Department of Child Adolescent Psychiatry and Behavioral Sciences, and the associate director of the Sleep Center at the Children’s Hospital of Philadelphia (CHOP), explained that there are 5 main domains of sleep-related issues in children and adolescents: mood, cognition, behavior, health, and families.

Seema Khosla, MD, FCCP, FAASM, the medical director of the North Dakota Center for Sleep, was also interviewed by NeurologyLive®, for the Mindful Moments® podcast, about the AASM’s current stance on another societal effect on sleep health—and not just on children, but adults as well—daylight saving time. Kholsa offered insight into the academy’s ongoing initiative to switch to a fixed standard time year-round and provided an expert opinion on how it might help address the impact on circadian rhythm.

Earlier in the year, the Sunshine Protection Act was passed by the US Senate, legislation that would make daylight saving time permanent starting in 2023. In response to the bill, the AASM released a statement further expressing its gratitude to the Senate. Although, the AASM also advised the House of Representatives to take more time in assessing the potential ramifications of establishing this permanent daylight savings time, and plan for the future with health in mind.

Another ongoing point of discussion was the effects of various substances on sleep health, including alcohol and cannabis, among others. Based on recent research this year, the frequency of alcohol and cannabis use may be strongly associated with insomnia-related symptoms from poor sleep quality. Investigator Wendy Troxel, PhD, a senior behavioral scientist at the RAND Corporation,told NeurologyLive®that, according to her observed research, “We found in looking at longitudinal profiles of sleep that having poor sleep quality alone or in combination with other dimensions of disrupted sleep was associated with higher frequency of alcohol use at baseline and greater increases in alcohol use over time, as compared to other sleep profiles with good sleep quality.”

Among these concerns are still some lingering challenges when it comes to the treatment of insomnia. Despite progress, there are a few nonpharmacological interventions available. Other recommendations for patients to improve their sleep health include incorporating positive lifestyle changes that may alleviate symptoms suchas changingthe sleep area or schedule, avoiding big meals and alcohol before bed, and staying active—but implementing behavioral changes often prove difficult in practice. However, if behavioral interventionsare ineffective method for the patient experiencing insomnia, then the pharmacological treatments may provide a better route for patients to take.

Ashgan A. Elshinawy, DO, a pulmonologist at Penn Medicine, believes that from both the clinician and patient perspectives, patience is the most important aspect of care. Elshinawy discussed some of the present challengesin caring for patients with insomniaduring an interview with NeurologyLive®,and mentioned some of the biggest priorities for the future with improving the paradigm.

COVID-19 has been anotherfactor impacting individuals with insomnia as the pandemic has been associated with an increase in symptoms of insomnia based on prior research from this year. Lead author of an investigational analysis on the topic, Maha Meshal Alrasheed, PhD, MSc, an associate professor in the Clinical Pharmacy Department at the College of Pharmacy of King Saud University, wrote that their data, “suggests that the COVID-19 pandemic is associated specifically with a marked increase in the rates of subthreshold insomnia symptoms but not moderate or severe insomnia.”

Alrasheed and colleagues found statistically significant differences between countries for all severities of insomnia symptoms in their assessment. Notably, neither age nor sex appeared to be moderators of the cumulative prevalence of subthreshold insomnia symptoms or of clinically significant insomnia.

“Over the past couple years, in the wake of the COVID-19 pandemic, sleep in general is having a moment.Insomnia specificallydefinitely has grown in the public awareness of what a problem it is. Insomnia rates were rising considerably during the pandemic, particularly during the stay-at home orders, really raising the salience of sleep problems, across the population. From young people to old people, many people, even more so than before, are aware of it,” Troxel told NeurologyLive®. She added that insomnia has been the most common sleep disorder for quite some time, affecting more than 50 million adults in the United States alone.

Troxel noted that the future is bright, though. Growth in awareness often lends itself to progress in research, and Troxel explained that progress has been made in the development of interventions not only at the individual level but the community level. The work of the AASM and other organizations has begun to lead to policy decisions and changes, making sleep health a priority at a population health level. All in all, it points to a growth in understanding about sleep’s impact on general health and comorbidity—and as one improves, so does the other. “I think, resolving any sleep issues or trying to help patients sleep better, for most conditions, usually would lead to better functioning because sleep is so important. If you have poor sleep, it's hard for people to be productive. It can often exacerbate a lot of other conditions and other symptoms such as fatigue, cognition, mood, and so on,” Chen said.

1. Idorsia receives US FDA approval of Quiviviq (daridorexant) 25 and 50 mg for the treatment of adults with insomnia. News release. Idorsia. January 10, 2022. Accessed January 10, 2022. https://www.biospace.com/article/releases/idorsia-receives-us-fda-approval-of-quviviq-daridorexant-25-and-50-mg-for-the-treatment-of-adults-with-insomnia/?s=85
2. Forma F, Knight TG, Thorndike FP, et al. Real-World Evaluation of Clinical Response and Long-Term Healthcare Resource Utilization Patterns Following Treatment with a Digital Therapeutic for Chronic Insomnia. Clinicoecon Outcomes Res. 2022;14:537-546. doi:10.2147/CEOR.S368780
3. Pear Therapeutics Announces Publication of New Analysis of Real-World Data Showing Reduction in Insomnia Severity, Healthcare Resource Utilization and Associated Costs in Adults Using Somryst®. News release. Pear Therapeutics. August 10, 2022. Accessed August 25, 2022. https://peartherapeutics.com/pear-therapeutics-announces-publication-of-new-analysis-of-real-world-data-showing-reduction-in-insomnia-severity-healthcare-resource-utilization-and-associated-costs-in-adults-using-somryst/
4. Jespersen KV, Pando-Naude V, Koenig J, Jennum P, Vuust P. Listening to music for insomnia in adults. Cochrane Database Syst Rev. 2022;8(8):CD010459. Published 2022 Aug 24. doi:10.1002/14651858.CD010459.pub3

The past year has provided great steps forward in sleep science, and coupled with the lingering difficulties in care and the COVID-19 pandemic’s effects, the field is coming to a head to make sleep health a public health priority.