Objective: To present final results from the post-authorization safety study BETAPAEDIC Background: BETAPAEDIC is the first prospective, international, multicenter, observational study to assess the tolerability and effectiveness of interferon beta-1b (IFNB-1b) in pediatric patients with relapsing-remitting MS (RRMS). Design/Methods: Treatment-naive patients (12–16 years) diagnosed with RRMS who started treatment with IFNB-1b were enrolled. Follow-up visits were planned for 6, 12, 18, and 24 months. Tolerability was evaluated as the proportion of patients with adverse events (AEs). Effectiveness was evaluated by annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS) progression (>=1.0-step increase from baseline), and MRI. Neuropsychological function was measured by WISC-IV, SPM+, Beery VMI, and d2. Fatigue was assessed by the Fatigue Severity Scale (FSS). Results: 68 patients were enrolled (mean age: 14.2 years; 50 females). Mean time since disease onset was 11 months. At baseline, mean (SD) EDSS was 0.6 (1.0) and number of T2 lesions was 18.3 (15.1). Mean ARR in the 2-year observation period was 0.7 (n=57). 49.1% (28/57) had no relapse and 76.9% (40/52) of patients had no EDSS progression while 41.1% (23/56) were relapse- and progression-free to last follow-up visit. New T2 or Gd+ lesions were seen in 43 and 29 patients, respectively, out of 55 with data. 10.7% (6/56) of patients with MRI assessment had NEDA-3 (no relapses, disease progression, or MRI activity). Cognitive performance was within normal ranges at baseline and last follow-up. Mean total FSS score was 3.0 (n=29); 31.6% of patients (18/57) had a total score >4 at some point. 76% of patients (51/67) reported drug-related AEs. The most frequent drug-related AEs were flu-like symptoms (46.3%), headache (19.4%), injection site reactions (16.4%), and abnormal liver function tests (11.9%). Conclusions: Final results from BETAPAEDIC suggest that IFNB-1b is an effective treatment with a favorable tolerability profile for pediatric patients with RRMS. Study Supported by: Bayer Healthcare Disclosure: Dr. Gaertner has received personal compensation from Bayer Vital, Biogen, Merck Serono, Teva, and Novartis as a consultant and for honoraria. Dr. Gaertner has received research support from Novartis and Biogen. Dr. Brueck has received personal compensation for activities with Bayer Vital, Biogen, Merck Serono, Teva Pharma, Genzyme, Sanofi Aventis, and Novartis as a lecturer or member of scientific advisory boards. Dr. Weddige has received personal compensation for activities with Bayer Pharma AG. Dr. Hummel has received personal compensation for activities with Bayer Pharma AG as an speaker. Dr. Norenberg has received personal compensation for activities with Bayer Pharma AG. Dr. Bugge has received personal compensation for activities with Bayer Pharma AG as an employee.
Study evaluating Betaferon(R)'s safety and tolerability in paediatric patients with multiple sclerosis (BETAPAEDIC) is a prospective, open-label observational multicentre study to assess the safety and effectiveness of interferon beta-1b in paediatric patients with relapsing-remitting multiple sclerosis.Treatment-naïve patients (12-16 years) scheduled to start interferon beta-1b were enrolled with follow-up visits every six months for two years. Effectiveness was evaluated by annualised relapse rate, Expanded Disability Status Scale progression, cranial magnetic resonance imaging and cognitive testing. Fatigue was assessed by the Fatigue Severity Scale.Sixty-eight patients were screened and 67 enrolled, with mean (standard deviation) age 14.2 (1.3) years (n=65 in the effectiveness analysis). Mean disease duration was 11 months before study enrolment; at baseline, mean (standard deviation) Expanded Disability Status Scale was 0.6 (1.0); T2 lesion number 18.3 (15.1). Mean annualised relapse rate during the study was 0.7 (n=57), 28/57 patients (49.1%) had no relapses and for 40/52 (76.9%) no Expanded Disability Status Scale progression was observed; 23/56 (41.1%) were relapse- and progression-free to last follow-up. Neuropsychological test and fatigue scores were within normal ranges (baseline and last follow-up). Eighteen patients had fatigue at some point. New T2 and gadolinium-enhancing (Gd+) lesions were seen in 43/55 (66.2%) and 29/55 (52.7%) patients respectively. Most frequent adverse events were influenza-like illness, headache, injection-site reactions and elevated liver enzymes.Interferon beta-1b is an effective treatment with a favourable safety profile for paediatric patients.
Objective: Study aims were to determine the frequency of highly active disease in pediatric multiple sclerosis (MS), the response to natalizumab (NTZ) and fingolimod (FTY) treatment, and the impact of current treatment modalities on the clinical course. Methods: Retrospective single-center study in the German Center for MS in Childhood and Adolescence. Results: Of 144 patients with first MS manifestation between 2011 and 2015, 41.6% fulfilled the criteria for highly active MS. In total, 55 patients treated with NTZ and 23 with FTY demonstrated a significant reduction in relapse rate (NTZ: 95.2%, FTY: 75%), new T2 lesions (NTZ: 97%, FTY: 81%), and contrast-enhancing lesions (NTZ: 97%, FTY: 93%). However, seven patients switched from NTZ to FTY experienced an increase in disease activity. Comparing pediatric MS patients treated in 2005 with those treated in 2015 showed a 46% reduction in relapse rate and a 44% reduction in mean Expanded Disability Status Scale (EDSS). Conclusion: The rate of highly active disease among pediatric MS patients is high; more than 40% in our cohort. Response to NTZ and FTY treatment is similar if not better than observed in adults. Current treatment modalities including earlier treatment initiation and the introduction of NTZ and FTY have significantly improved the clinical course of pediatric MS.
Obesity reportedly increases the risk of pediatric multiple sclerosis (MS), but little is known about its association with disease course.To investigate the association of obesity with pediatric MS risk and with first-line therapy response among children with MS.This single-center retrospective study used the medical records and database at the Center for MS in Childhood and Adolescence, Göttingen, Germany. The study included 453 patients with relapsing-remitting pediatric MS and body mass index (BMI) measurement taken within 6 months of diagnosis. Onset of the disease occurred between April 28, 1990, and June 26, 2016, and the mean disease duration was 38.4 months. Data were collected from July 14, 2016, to December 18, 2017.Data on BMIs were stratified by sex and age using German BMI references and compared with the BMI data of 14 747 controls from a nationwide child health survey for odds ratio (OR) estimates. Baseline magnetic resonance imaging findings, intervals between first and second MS attacks, annualized relapse rates before and during treatment with interferon beta-1a or -1b and glatiramer acetate, frequency of second-line treatment, and Expanded Disability Status Scale (EDSS) scores were compared between nonoverweight (BMI≤90th percentile), overweight (BMI>90th-97th percentile), and obese (BMI>97th percentile) patients.In total, 453 patients with pediatric MS were included, of whom 306 (67.5%) were female, and the mean (SD) age at diagnosis was 13.7 (2.7) years. At diagnosis, 126 patients (27.8%) were overweight or obese, with obesity associated with statistically significant twofold odds of MS in both sexes (girls OR, 2.19; 95% CI, 1.5-3.1; P < .001 vs boys OR, 2.14; 95% CI, 1.3-3.5; P = .003). Obese patients, compared with nonoverweight patients, had statistically significantly more relapses on first-line treatment with interferon beta and glatiramer acetate (ARR, 1.29 vs 0.72; P < .001) and a higher rate of second-line treatment (21 [56.8%] of 37 vs 48 [38.7%] of 124; P = .06). Baseline neuroimaging, interval between first and second MS attacks, pretreatment relapses, and EDSS progression scores were not correlated with BMI.In this study, increased pediatric MS risk appeared to be associated with obesity, and obese patients did not respond well to first-line medications; altered pharmacokinetics appeared to be most likely factors in treatment response, suggesting that achieving healthy weight or adjusting the dose according to BMI could improve therapy response.
Background/Purpose: Current therapy concepts in multiple sclerosis (MS) are based on the early separation of patients with mild/moderate or highly active disease activity. Aim of the study was to determine the effect of this treatment approach on disease progression in pediatric MS.
Background/Purpose: A preponderance of females affected by relapsing remitting multiple sclerosis is well reviewed. Several studies have shown an equal sex distribution before puberty. So far no studies have been performed exploring possible differences in the magnetic resonance imaging (MRI) presentation of multiple sclerosis in boys and girls. Our purpose was to study sex- and age-related differences in pediatric relapsing-remitting multiple sclerosis before and after puberty.
