Takeda (Denmark)

This study aimed to assess the performance of the Nelli seizure monitoring system in detecting and classifying seizures during sleep or while at rest in bed in patients with Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS). We conducted a non-interventional, single-center feasibility study from August 2023 to March 2024, involving 20 patients aged ≥2 years diagnosed with DS or LGS. Participants used Nelli for home-based seizure monitoring during sleep or while at rest in bed for 4 weeks. Seizures were detected and classified by Nelli, and results were compared to epileptologist reviews and seizure diaries. Of 20 enrolled patients, 14 (70%) who experienced seizures at rest were included in the analyses. Among them, Nelli detected 368 seizures, with an accuracy of 97.8%, as confirmed by independent reviewers. Eight seizures (2.2%) detected by Nelli were false positives, identified as part of a single seizure episode. Of the 14 patients, only 35.7% reported experiencing seizures in their diaries, and only 26.1% of the seizures were documented. Seizure durations ranged from 6 to 396 s, with considerable variation. Nelli demonstrated high accuracy in seizure classification (Gwet agreement coefficient [AC1] = .81-1.00) in nine of 14 cases. However, in three of 14 patients, moderate accuracy (AC1 = .41-.60) was observed due to challenges in classifying seizures in patients with high seizure frequency or suboptimal device positioning. The average classification accuracy of Nelli for tonic-clonic seizures was .99 (150/152 seizures), tonic seizures .55 (102/186), clonic seizures 1.00 (3/3), focal motor seizures .89 (16/18), and myoclonic seizures 1.00 (1/1). Nelli demonstrated high sensitivity and classification accuracy for detecting and categorizing seizures in bed in patients with DS and LGS, outperforming seizure diaries and providing a reliable tool for seizure monitoring in home settings.

We agree with the commentary that distinguishing between incident and prevalent patients with CeD is important for understanding the disease’s economic implications. However, the limited timeframe of the available data restricts our ability to accurately identify adult CeD patients who are genuinely newly diagnosed, since most individuals with CeD are diagnosed during childhood or adolescence. The available observation period for patients with CeD is not long enough to follow patients from childhood diagnosis until adulthood. Thus, there is a risk of misclassifying incident patients as prevalent cases, but it should be acceptable regarding the overall evaluation, since the probability of incident patients at older age groups is lower.Given our interest in incident patients, we are currently preparing another publication focused specifically on newly diagnosed children with CeD.

Data on the prevalence of perianal fistulas in Crohn’s disease (pCF) and the associated healthcare costs remain sparse. This study aimed to determine the prevalence of pCF in a nationwide cohort. Secondary outcomes included the use of biologicals, number of surgical interventions, and direct healthcare costs related to pCF. All patients registered in the Danish National Patient Registry as having Crohn’s disease (CD) between 2010 and 2016 were identified of whom the subpopulation with a pCF diagnosis (complex and simple) or a pCF-related surgical procedure were included. Data on in- and out-patient services were retrieved from the National Patient Registry, which includes data on all patient contacts, including diagnoses as well as diagnostic and treatment procedures. The database uses international classification systems, for instance, the ICD-10. Data were linked with the Danish Case Mix System (Diagnose-Related Groups) to assign costs to outpatient and inpatient services in pCF cases. In total, 17789 patients were identified as having CD in the study period. The prevalence of pCF ranged from 612 (5.1 fistula patients per 100 patients with CD) to 544 (3.1 fistula patients per 100 patients with CD) during the study period. Furthermore, the number of incident perianal fistula cases decreased from 303 cases in 2010 to 144 cases in 2016. In total, 1773 (10%) patients were identified with an incident pCF in the study period of whom 49% were female. Mean age was 33.4 years and mean duration of CD prior to pCF was 366 days. Biological treatment was administered to 46.9% of the patients; of whom, 25.9% were in biological treatment prior to the diagnosis of pCF. In total, 35% were subjected to surgical intervention. The mean number of pCF-related surgical procedures per year was 1.4 per patient. During the study period 17 (0.096%) patients had a stoma performed, whereas 8 (0.045%) had reversal of their stoma. Mean cost from 2010 to 2015 was €21708 per patient (IQR: €2501–28930). In 2016, the total hospital-associated costs for diagnosis and treatment of pCF was €2.3 million, with biologicals being the major expenditure (€911200) followed by surgical interventions (€723600). Healthcare costs for treatment of pCF decreased during the study period mainly due to lowered prices on biologicals. In a Danish nationwide cohort of patients with CD, the prevalence of perianal fistulas decreased in the period from 2010 to 2016. The reason for this needs further elucidation. Only half of the incident cases received biologicals, yet biological treatment was the main expenditure for the entire study population. Healthcare costs for pCF decreased during the study period, but are still high compared with non-pCF IBD patients.

The purpose of this study is to examine the effect of PTH(1-84) treatment over 24 months followed by 12 months discontinuation on BMD, bone turnover markers, fractures and the impact of adherence on efficacy. There is limited information about the effect of PTH(1-84) after 18 months and limited data about the impact of compliance on response to anabolic therapy. Seven hundred and eighty-one subjects who received active PTH(1-84) in the Treatment of Osteoporosis with Parathyroid hormone trial for approximately 18 months were entered into a 6-month open-label extension. Thereafter, they were followed for 12 additional months after discontinuation of treatment. Endpoints examined included changes in BMD and biochemical markers. PTH(1-84) treatment over 24 months increased BMD at the lumbar spine by 6.8% above baseline (p<0.05).The total corresponding BMD increases at the hip and femoral neck were 1.1 and 2.2% above baseline. Larger increases in spine BMD were observed in participants with ≥80% adherence to daily injections of PTH(1-84) (8.3% in adherent vs 4.9% in poorly adherent patients). Total hip BMD gains were 1.7% in adherent vs 0.6% in poorly adherent participants. Markers of bone turnover (BSAP and NTx) peaked 6 months after starting PTH(1-84) treatment and declined slowly but remained above baseline at 24 months. After discontinuation of PTH(1-84) treatment (at 24 months), bone turnover markers returned to near baseline levels by 30 months. The adherent group sustained significantly fewer fractures than the poorly adherent group. PTH(1-84) treatment over 24 months results in continued increases in lumbar spine BMD. Adherence to treatment with PTH(1-84) for up to 24 months is also associated with greater efficacy.