HealthDay News — For adults with radiologically isolated syndrome (RIS), teriflunomide is associated with a reduction in the first clinical demyelinating event compared with placebo, according to a study presented at the annual meeting of the American Academy of Neurology, held from April 22 to 27 in Boston.

Christine Lebrun Frenay, MD, from the University Hospital of Nice in France, and colleagues randomly assigned 89 patients with RIS to teriflunomide or placebo in a phase III study. Participants underwent follow-up at weeks 48 and 96.

The researchers detected 28 clinical events during follow-up (20 with placebo; 8 with teriflunomide). The superiority of teriflunomide was demonstrated in unadjusted and adjusted analyses (hazard ratios, 0.38 and 0.34, respectively). The teriflunomide arm had a reduction in the number of patients with gadolinium+ lesions and the cumulative number of new or enlarging T2 lesions, although these results were not statistically significant.

“Our findings suggest that early intervention with teriflunomide may be beneficial to those diagnosed with radiologically isolated syndrome, the presymptomatic phase of multiple sclerosis,” Lebrun Frenay said in a statement. “However, more research is needed in larger groups of people to confirm our findings. Additionally, it is important that medical professionals are cautious when using MRI expertise to diagnose this condition, selecting only patients at risk of developing multiple sclerosis and not increasing MRI misdiagnoses.”

The study was funded by Sanofi, which manufactures teriflunomide.

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HealthDay News — Amygdala and insula retraining (AIR), a neuroplasticity program, may be a viable means of reducing fatigue and increasing energy among patients with long COVID, according to a study published online July 17 in the Evidence-Based Complementary and Alternative Medicine Journal.

Loren L. Toussaint, PhD, from Luther College in Decorah, Iowa, and Alexandra J. Bratty, MBA, PhD, from AB Research Consulting in Las Vegas, randomly assigned 100 participants (aged 21 to 65 years) with postviral symptoms at least 3 months after an acute COVID-19 infection to AIR or control.

The researchers found a significant decrease in participants’ fatigue and a significant increase in their energy after the 3-month AIR intervention. Fatigue reduction was nearly 4 times higher in the AIR group vs the control group, while the absolute reduction in mean scores for the AIR group was more than double that of the control group. Similarly, the effect size in energy enhancement among AIR participants was twice that of the control group, and the absolute increase in energy mean scores for the AIR group was almost double that of the control group.

“These findings are both timely and pertinent, as so little is known about how to treat long COVID and so many patients suffer from it after the acute infection of COVID-19,” the authors write.

Bratty is the CEO of AB Research Consulting, which provides consulting services to The Gupta Program, the commercial version of the AIR intervention; Bratty’s company was compensated for this work by independent donors.

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The Food and Drug Administration (FDA) has approved Austedo^® XR, a new once-daily formulation of deutetrabenazine, for the treatment of adults with tardive dyskinesia and chorea associated with Huntington disease.

Austedo XR is a vesicular monoamine transporter 2 inhibitor. Because the once-daily formulation has been shown to be therapeutically equivalent to the twice-daily formulation, the same total daily dosage can be used when switching between Austedo (twice daily) tablets and Austedo XR (once daily) tablets. Unlike Austedo (twice daily) tablets, which should be administered with food, the new once-daily formulation can be administered with or without food.

“The approval of Austedo XR is a reflection of our ongoing innovation for people living with TD and HD chorea,” said Eric Hughes, MD, PhD, Executive Vice President of R&D and Chief Medical Officer at Teva. “For some patients living with TD and HD, treatment adherence can be a challenge that this new once-daily dosing option can help to address.”

Austedo XR is supplied as 6mg, 12mg, and 24mg strength extended-release tablets. The dose is determined individually for each patient based on reduction of chorea or tardive dyskinesia and tolerability. The product is expected to be available later this year.

References

1. Teva announces FDA approval of Austedo^® XR (deutetrabenazine) extended-release tablets, a new once-daily formulation of Austedo^® (deutetrabenazine) tablets. News release. Teva Pharmaceuticals. Accessed February 21, 2023. https://ir.tevapharm.com/news-and-events/press-releases/press-release-details/2023/Teva-Announces-FDA-Approval-of-AUSTEDO-XR-deutetrabenazine-Extended-Release-Tablets-a-New-Once-Daily-Formulation-of-AUSTEDO-deutetrabenazine-Tablets/default.aspx.
2. Austedo XR. Package insert. Teva Pharmaceuticals; 2023. Accessed February 21, 2023. https://www.austedo.com/globalassets/austedo/prescribing-information.pdf.

Sonia Hernández‑Díaz, MD, Dr PH, from the Harvard TH Chan School of Public Health in Boston, and colleagues identified a population-based cohort of pregnant women and their children within 2 health care utilization databases. Exposure to specific antiseizure medications was defined based on prescription fills from gestational week 19 until delivery.

The researchers found that at 8 years of age, the estimated cumulative incidence of autism spectrum disorder was 1.9% for the 4,199,796 children who had not been exposed to antiseizure medications. On restriction to children born to mothers with epilepsy, the incidence was 4.2, 6.2, 10.5, and 4.1% with no exposure to antiseizure medications, exposure to topiramate, exposure to valproate, and exposure to lamotrigine, respectively. Compared with no exposure to antiseizure medications, propensity score-adjusted hazard ratios were 0.96 (95% CI, 0.56 to 1.65), 2.67 (95% CI, 1.69 to 4.20), and 1.00 (95% CI, 0.69 to 1.46) for exposure to topiramate, valproate, and lamotrigine, respectively.

“After adjustment for indication, the association was substantially attenuated for topiramate and lamotrigine, whereas a dose-dependent increased risk remained for valproate,” the authors write.

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Adam de Havenon, MD, from Yale University in New Haven, Connecticut, and colleagues examined the burden of neurologic health care and incident neurologic diagnoses in the year after hospital-based care for COVID-19 vs influenza in an analysis of data from a large collection of electronic medical records for individuals aged 18 years or older during the index event. The study outcomes were subsequent health care encounters for 6 neurologic diagnoses during the following year. In addition, a composite of the 6 diagnoses was created, termed “incident neurologic diagnoses.”

The cohort included 77,272 individuals with COVID-19 and 77,272 with influenza after propensity score matching. The researchers found that patients with COVID-19 had a lower risk for subsequent care for migraine, epilepsy, neuropathies, movement disorders, stroke, or dementia compared with patients with influenza (hazard ratios, 0.645, 0.783, 0.567, 0.644, 0.904, and 0.931, respectively). In 2.79 and 4.91% of the COVID-19 and influenza cohorts, respectively, postinfection incident neurologic diagnoses were observed.

“While the results were not what we expected to find, they are reassuring in that we found being hospitalized with COVID did not lead to more care for common neurologic conditions when compared to being hospitalized with influenza,” coauthor Brian C. Callaghan, MD, from the University of Michigan in Ann Arbor, said in a statement.

Several authors disclosed ties to the biotechnology industry.

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Anjel Vahratian, PhD, MPH, from the National Center for Health Statistics in Hyattsville, Maryland, and colleagues used data from the 2021 to 2022 National Health Interview Survey to describe the percentage of adults who had ME/CFS by selected demographic and geographic characteristics.

The researchers found that 1.3% of adults had ME/CFS in 2021 to 2022. There was an increase seen in the percentage of adults with ME/CFS with age through ages 60 to 69 years, followed by a decrease among those aged 70 years and older. The likelihood of having ME/CFS was higher for White non-Hispanic adults than Asian non-Hispanic and Hispanic adults (1.5% vs 0.7 and 0.8%, respectively). The likelihood of having ME/CFS was higher for adults with a family income less than 100% of the federal poverty level, followed by those at 100 to 199% and those at or above 200% (2.0, 1.7, and 1.1%, respectively). With increasing rurality of place of residence, the percentage of adults who had ME/CFS increased.

“As the prevalence estimates in this report are based on a doctor’s diagnosis, adults who are undiagnosed are not included in this analysis,” the authors write. “True prevalence estimates may be higher, as previous studies suggest that many people with ME/CFS are undiagnosed.”

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Chirag M. Vyas, MBBS, from Massachusetts General Hospital in Boston, and colleagues compared whether daily supplementation with cocoa extract produces better cognitive change over two years than placebo. Analysis included 492 adults (≥60 years).

The researchers found that daily cocoa extract supplementation had no significant effect on 2-year change in global cognition. Additionally, compared to placebo, cocoa extract had no significant effects on change in episodic memory or executive function/attention over time. However, cocoa extract may have cognitive benefits for participants with poorer baseline diet quality.

“Additional research on the role of cocoa extract supplementation in more diverse populations and among those with lower diet quality is warranted,” the authors write.

Several authors disclosed ties to Mars Edge, which helped fund the study.

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Chirag M. Vyas, MBBS, MPH, from Massachusetts General Hospital in Boston, and colleagues examined the effects of MVM supplementation on cognitive change using in-person, detailed neuropsychological assessments and conducted a meta-analysis to assess the MVM effects on cognition within the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) substudies. A total of 573 participants were included in the clinic subcohort of COSMOS (COSMOS-Clinic) who completed all cognitive tests administered at baseline. Nonoverlapping participants across 3 COSMOS substudies were included in the meta-analysis (COSMOS-Clinic [573 participants], COSMOS-Mind [2158 participants], and COSMOS-Web [2472 participants]).

The researchers found that over 2 years, there was a modest benefit for MVM vs placebo on global cognition in COSMOS-Clinic, with a significantly more favorable change in episodic memory but not in executive function/attention. Clear evidence of the benefits of MVM on global cognition and episodic memory were seen in the meta-analysis of COSMOS substudies. The magnitude of the effect on global cognition was equivalent to a two-year reduction in cognitive aging.

“These findings will garner attention among many older adults who are, understandably, very interested in ways to preserve brain health, as they provide evidence for the role of a daily multivitamin in supporting better cognitive aging,” senior author Olivia Okereke, M.D., also from Massachusetts General Hospital, said in a statement.

The study was partially funded by Mars Edge, Contract Pharmacal Corp., and Pfizer Consumer Healthcare.

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HealthDay News — For patients with chronic subdural hematoma, a 19-day tapering course of dexamethasone therapy is not noninferior to surgery with respect to functional outcomes at 3 months, according to a study published in the June 15 issue of the New England Journal of Medicine.

Ishita P. Miah, MD, PhD, from Amphia Hospital in Breda, Netherlands, and colleagues enrolled 252 symptomatic patients with chronic subdural hematoma who were randomly assigned to a 19-day tapering course of dexamethasone or burr-hole drainage (127 and 125 patients, respectively). Due to safety and outcome concerns in the dexamethasone group, the trial was terminated early by the data and safety monitoring board.

The researchers found that the adjusted common odds ratio for a lower (better) score on the modified Rankin scale at 3 months was 0.55 for dexamethasone vs surgery, which failed to demonstrate noninferiority of dexamethasone. The scores on the Markwalder Grading Scale and Extended Glasgow Outcome Scale were generally supportive of these results. Complications occurred in 59 and 32% of patients in the dexamethasone and surgery groups, respectively; additional surgery was performed in 55 and 6 percent, respectively.

“Dexamethasone therapy was not found to be noninferior to surgery by burr-hole drainage,” the authors write. “Patients who received dexamethasone more frequently underwent additional surgery and had more adverse events than patients who initially had surgical drainage.”

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HealthDay News — Digital cognitive behavioral therapy for insomnia (dCBT-I) is effective for patients with insomnia, with the optimal treatment including a combination of medication and dCBT-I, according to a study published online April 11 in JAMA Network Open.

Menglin Lu, from Zhejiang University in Hangzhou, China, and colleagues conducted a retrospective cohort study to examine the clinical effectiveness, engagement, durability, and adaptability of dCBT-I. A total of 4052 patients were selected for treatment with dCBT-I, medication, or combination therapy (418, 862, and 2722, respectively); outcomes were compared at months 1, 3, and 6.

The researchers found that participants receiving both dCBT-I and combination therapy had significant reductions compared with the change in the Pittsburgh Sleep Quality Index score at 6 months for patients receiving medication alone (from a mean of 13.51 to 7.15 and 12.92 to 6.98, respectively, vs 12.85 to 8.92); the effect of dCBT-I was comparable to that of combination therapy but showed unstable durability. During the first three months, the outcomes of dCBT-I improved steadily and rapidly, then fluctuated. Higher response rates were seen with dCBT-I and combination therapy compared with medication. Significant benefits were seen from dCBT-I and combination therapy in secondary outcomes.

“These positive findings provide clinical evidence that dCBT-I contributes to meaningful sleep improvements,” the authors write. “Given the unstable durability of dCBT-I at six-month follow-up, the design, implementation, and delivery of dCBT-I in the practice setting warrants further investigation.”

One author disclosed financial ties to Hangzhou slan-health.

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The 48-week, randomized, double-blind, placebo-controlled PHOENIX trial (ClinicalTrials.gov Identifier: NCT05021536) included 664 adults with ALS. Study participants were randomly assigned 3:2 to receive either Relyvrio or placebo, in addition to standard of care therapy. Participants were permitted to continue a stable dosing regimen of riluzole and/or edaravone.

Findings showed treatment with Relyvrio was not associated with a statistically significant difference from baseline in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) total score at week 48 compared with placebo (primary endpoint; P =.667). Moreover, statistically significant differences were not observed across secondary endpoints. As for safety, Relyvrio was well tolerated with no new safety signals observed.

In a press statement, Justin Klee and Joshua Cohen, Co-CEOs of Amylyx said they were “surprised and deeply disappointed by the PHOENIX results following the positive data from the CENTAUR trial.” Relyvrio received approval from the Food and Drug Administration (FDA) in 2022 based on data from the phase 2 CENTAUR trial (ClinicalTrials.gov Identifier: NCT03127514). Findings showed a statistically significant difference in the rate of reduction in the ALSFRS-R total score from baseline to week 24 in the Relyvrio group compared with the placebo group.

At this time, the Company has decided to pause promotion of the drug, though it continues to be available in the US for ALS patients. “Over the next 8 weeks, our team will continue to engage with regulatory authorities and the ALS community to discuss the results from PHOENIX,” said Klee and Cohen. These discussions may include potentially withdrawing Relyvrio from the market. 

Additional findings from the PHOENIX trial will be presented at an upcoming medical meeting and will be published in a medical journal later this year.

Compared with patients with DMD who do not receive treatment, those treated with eteplirsen experience a delay in ambulatory and pulmonary decline. For the study, researchers assessed the survival of patients with DMD who received eteplirsen vs those who received no treatment, or natural history control individuals.

The researchers compared survival among patients with DMD treated with eteplirsen as routine care vs those with DMD natural history by utilizing real world data from 2 US-based and 2 European studies.

Via the digitization of Kaplan-Meier curves, the researchers replicated patient data. To compare survival age between the 2 patient groups, they used unadjusted Kaplan-Meier curves, log-rank tests, Cox models, and parametric specifications. With the help of a simulation, the researchers randomly matched each patient who received eteplirsen alive at age of treatment initiation with up to 15 natural history control individuals to compare time from treatment initiation to death. They adjusted for baseline age and age-treatment interaction.

The study included a total of 579 patients (mean age at initiation, 11.9 years; mean exposure, 3.7 years) with DMD who received eteplirsen.

Compared with natural history control individuals, those treated with eteplirsen had a higher median age at death (32.8 vs 27.4 years; P <.0001) and a prolonged median survival rate of 5.4 years. Moreover, survival was 66% higher among patients treated with eteplirsen compared with natural history control individuals (HR, 0.64; 95% CI, 0.23-0.50; P <.001). The researchers noted that younger age at initiation and longer treatment exposure to eteplirsen were both independently associated with prolonged survival.

Across 5-year segments, spanning from 5 to 45 years, mortality rates were lower in patients who received eteplirsen compared with those who received no treatment.

“These real-world data suggest that eteplirsen may prolong survival in patients with DMD across a wide age range,” the researchers concluded.

The study was limited by the inability to perform adjusted comparison controlling for prognostic factors due to data limitations.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Compared with traditional SCS devices, the closed-loop feature of the Inceptiv SCS senses neural responses (50 times per second) and is able to automatically adjust stimulation in real time, providing more consistent therapy. The device is implanted through a minimally invasive procedure and utilizes signals generated by the spinal cord in response to electrical stimuli (evoked compound action potentials), which allows a proprietary algorithm to respond and make adjustments in order to maintain the physician’s prescribed stimulation.

The Inceptiv system also offers full-body 1.5T and 3T MRI access with no power or impedance restrictions.

“For patients dealing with chronic pain, every day is a struggle,” said David Carr, vice president and general manager, Pain Interventions within the Neuromodulation business, which is part of the Neuroscience Portfolio at Medtronic. “They deserve personalized and effective relief, without compromising future access to MRI. They deserve the comfort that the smallest and thinnest device on the market can provide. We are proud to offer the most cutting-edge solution available today with Inceptiv SCS.”

The Inceptiv SCS is expected to be available in the coming weeks.

The Food and Drug Administration (FDA) has cleared Abbott’s Alinity^® i TBI lab test to aid in the evaluation of adults with suspected mild traumatic brain injury (mTBI; Glasgow Coma Scale score 13-15).

The Alinity i TBI test is a laboratory-based test that measures ubiquitin C-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein, 2 biomarkers in the blood correlated to brain injury when present in elevated concentrations. The test provides results with 96.7% sensitivity and 99.4% negative predictive value.

The new test can be used when a patient presents to the hospital with a suspected mTBI within 12 hours of injury. After a blood sample is drawn from the patient’s arm, the test is run on Abbott’s Alinity^® i laboratory instrument, a high throughput instrument widely used in US hospitals and laboratories. Results are available in 18 minutes. Negative results rule out the need for a computed tomography (CT) scan.

The availability of a blood test provides clinicians with an objective method to quickly evaluate patients with mTBIs while eliminating the need for a head CT scan. According to the Company, the test could help reduce the number of unnecessary CT scans by up to 40%, potentially reducing health care costs and minimizing wait times in the emergency department.

“People sometimes minimize a hit to the head, thinking it’s no big deal. Others wonder if a visit to the doctor or emergency room for a possible concussion will provide them with meaningful answers or care,” said Beth McQuiston, MD, medical director in Abbott’s diagnostics business. “Now that this test will be widely available in labs across the country, medical centers will be able to offer an objective blood test than can aid in concussion assessment. That’s great news for both doctors and people who are trying to find out if they have suffered a traumatic brain injury.”

The Alinity i TBI blood test will run on the Alinity^® i laboratory instrument, making TBI testing more widely available across the country. It is the first commercially available lab-based blood test for TBI and complements Abbott’s previously cleared i-STAT TBI Plasma test, the first rapid handheld blood test for TBI.

Reference

Abbott receives FDA clearance for first commercially available lab-based blood test to help evaluate concussion. News release. Abbott. Accessed March 7, 2023. https://prnmedia.prnewswire.com/news-releases/abbott-receives-fda-clearance-for-first-commercially-available-lab-based-blood-test-to-help-evaluate-concussion-301764488.html.

The Food and Drug Administration (FDA) has approved Daybue (trofinetide) for the treatment of Rett syndrome in adults and pediatric patients 2 years of age and older.

Trofinetide is a novel synthetic analogue of glycine-proline-glutamate, the amino-terminal tripeptide of insulin-like growth factor-1. Though the mechanism by which trofinetide exerts its therapeutic effects in patients with Rett syndrome is unknown, it is believed to increase branching of dendrites and synaptic plasticity signals based on animal studies.

The approval was supported by data from the randomized, double-blind, placebo-controlled phase 3 LAVENDER study (ClinicalTrials.gov Identifier: NCT04181723), which evaluated the efficacy and safety of trofinetide in female patients 5 to 20 years of age with Rett syndrome. Patients were randomly assigned to receive trofinetide (n=93) or placebo (n=94) orally or via gastrostomy tube twice daily for 12 weeks. 

The coprimary endpoints were the change from baseline to week 12 in the Rett Syndrome Behaviour Questionnaire (RSBQ) total score (a caregiver assessment) and the Clinical Global Impression-Improvement (CGI-I) score (a physician assessment). Lower scores reflect lesser severity in signs and symptoms of Rett syndrome.

Treatment with trofinetide was associated with a statistically significant improvement on the RSBQ compared with placebo (-4.9 vs -1.7; treatment difference, -3.2 [95% CI, -5.7, -0.6]; P =.018). A statistically significant improvement over placebo was also observed on the CGI-I (3.5 vs 3.8; treatment difference, -0.3 [95% CI, -0.5, -0.1]; P =.003). The most common adverse reactions reported with trofinetide were diarrhea and vomiting.

“Rett syndrome is a profoundly debilitating and complex, rare, neurodevelopmental disorder that presents differently across patients and can lead to an array of unpredictable symptoms throughout the course of a patient’s life,” said Jeffrey L. Neul, MD, PhD, Annette Schaffer Eskind Chair and Director, Vanderbilt Kennedy Center, Professor of Pediatrics, Division of Neurology, Pharmacology, and Special Education, Vanderbilt University Medical Center and Phase 3 LAVENDER study investigator. “Now, for the first time after decades of clinical research, health care providers finally have a treatment option to address a range of core behavioral, communication and physical symptoms for their patients living with Rett syndrome.”

Daybue is supplied as a strawberry-flavored oral solution containing 200mg of trofinetide per mL. The dosage is determined by patient weight and can be administered orally or via gastrostomy tube. The product is expected to be available by the end of April 2023.

References

1. Acadia Pharmaceuticals announces US FDA approval of Daybue (trofinetide) for the treatment of Rett syndrome in adult and pediatric patients two years of age and older. News release. Acadia Pharmaceuticals. March 10, 2023. https://www.businesswire.com/news/home/20230303005382/en/Acadia-Pharmaceuticals-Announces-U.S.-FDA-Approval-of-DAYBUE%E2%84%A2-trofinetide-for-the-Treatment-of-Rett-Syndrome-in-Adult-and-Pediatric-Patients-Two-Years-of-Age-and-Older.
2. Daybue. Package insert. Acadia Pharmaceuticals; 2023. Accessed March 13, 2023. https://acadia.com/wp-content/uploads/2023/03/daybue-prescribing-information.pdf.

The Food and Drug Administration (FDA) has accepted for review the New Drug Application (NDA) for valbenazine oral granules, a new sprinkle formulation for the treatment of adults with tardive dyskinesia and the treatment of chorea associated with Huntington disease.

Valbenazine, a selective vesicular monoamine transporter 2 (VMAT2) inhibitor, is currently available as capsules for oral administration under the brand name Ingrezza. The new sprinkle formulation is intended to be opened for sprinkling on soft foods prior to administration.

The NDA is supported by chemistry, manufacturing, and controls information and data showing the bioequivalence and tolerability of the valbenazine oral granule sprinkle capsules compared with the currently approved Ingrezza capsules.

A Prescription Drug User Fee Act target date of April 30, 2024 has been set for this application.

“Patients with tardive dyskinesia or chorea associated with Huntington’s disease can experience dysphagia that can impact their ability to swallow capsules,” said Eiry W. Roberts, MD, Chief Medical Officer at Neurocrine Biosciences. “We developed this potential new formulation of Ingrezza as an alternative administration option for those patients who have difficulty swallowing or simply prefer not to take whole capsules.”