The natural history of primary progressive multiple sclerosis: insights from the German NeuroTransData registry.

BACKGROUND: Primary progressive multiple sclerosis (PPMS) is characterised by gradual worsening of disability from symptom onset. Knowledge about the natural course of PPMS remains limited. METHODS: PPMS patients from the German NeuroTransData (NTD) MS registry with data from 56 outpatient practices were employed for retrospective cross-sectional and longitudinal analyses. The cross-sectional analysis included a contemporary PPMS cohort with a documented visit within the last 2 years before index date (1 Jan 2021). The longitudinal analysis included a disease modifying therapy (DMT)-naïve population and focused on the evolution of expanded disability status scale (EDSS) from the first available assessment at or after diagnosis within the NTD registry to index date. Outcome measures were estimated median time from first EDSS assessment to first 24-week confirmed EDSS ≥ 4 and ≥ 7. Besides EDSS change, the proportion of patients on disability pension were described over time. RESULTS: The cross-sectional analysis included 481 PPMS patients (59.9% female, mean [standard deviation, SD] age 60.5 [11.5] years, mean [SD] EDSS 4.9 [2.1]). Estimated median time from first EDSS assessment after diagnosis to reach 24-week confirmed EDSS ≥ 4 for DMT-naïve patients was 6.9 years. Median time to EDSS ≥ 7 was 9.7 years for 25% of the population. Over a decade mean (SD) EDSS scores increased from 4.6 (2.1) to 5.7 (2.0); the proportion of patients on disability pension increased from 18.9% to 33.3%. CONCLUSIONS: This study provides first insights into the German NTD real-world cohort of PPMS patients. Findings confirm the steadily deteriorating course of PPMS accompanied by increasingly limited quality of life.

Comparing the risk of serious infections in patients with and without MS: A German claims data analysis.

BACKGROUND: Research suggests that serious infections (SIs), comorbidities, and advanced disability represent key drivers of early death in people with Multiple Sclerosis (pwMS). Nevertheless, further research is warranted to better characterize and quantify the risk of SI among pwMS compared to the general population. METHODS: Our study consisted of a retrospective analysis of claims data provided by a German statutory health insurance fund, AOK PLUS, covering 3.4 million individuals in Saxony and Thuringia from 01/01/2015-31/12/2019. A propensity score (PS) matching method was used to compare the incidence of SIs among people with and without MS. PwMS were required to have ≥1 inpatient or ≥2 confirmed outpatient diagnoses of MS (ICD-10 G35) from a neurologist from 01/01/2016-31/12/2018, while people from the general population could not have any inpatient/outpatient codes for MS during the entire study period. The index date was defined as the first observed MS diagnosis or, in the case of the non-MS cohort, a randomly assigned date within the inclusion period. For both cohorts a PS was assigned, corresponding with their probabilistic likelihood of having MS based on observable factors including patient characteristics, comorbidities, medication use and other variables. People with and without MS were matched using a 1:1 nearest neighbor strategy. An exhaustive list of ICD-10 codes was created in association with 11 main SI categories. SIs were those recorded as the main diagnosis during an inpatient stay. ICD-10 codes from the 11 main categories were sorted into smaller classification units, used to distinguish between infections. A 60-day threshold for measuring new cases was defined to account for the potential risk of re-infection. Patients were observed until the end of the study period (31/12/2019) or death. Cumulative incidence, incidence rates (IRs) and IR ratios (IRRs) were reported during follow-up and at 1-, 2- and 3-years post-index. RESULTS: A total of 4250 and 2,098,626 patients were included in the unmatched cohorts of people with and without MS. Ultimately, one match was identified for all 4,250 pwMS, corresponding with a final population of 8,500 patients. On average, patients were 52.0/52.2 years in the matched MS/non-MS cohorts; the gender breakdown was 72% female. Overall, IRs of SIs per 100 patient years (PY) were higher in pwMS than in those without MS (1 year: 7.6 vs. 4.3; 2 years: 7.1 vs. 3.8; 3 years: 6.9 vs. 3.9). During follow-up, the most common infection types in pwMS were of a bacterial/parasitic origin (2.3 per 100 PY), followed by respiratory (2.0) and genitourinary (1.9) infections. Respiratory infections were most common in patients without MS (1.5 per 100 PY). Differences in the IRs of SIs were statistically significant (p<0.01) at each measurement window, with IRRs ranging from 1.7-1.9. PwMS had a higher risk of hospitalized genitourinary infections (IRR: 3.3-3.8) and bacterial/parasitic infections (2.0-2.3). CONCLUSIONS: The incidence of SIs is much higher in pwMS, than comparators from the general population in Germany. Differences in hospitalized infection rates were largely driven by higher levels of bacterial/parasitic and genitourinary infections in the MS population.

Clinical outcomes of COVID-19 in patients with multiple sclerosis treated with ocrelizumab in the pre- and post-SARS-CoV-2 vaccination periods: Insights from Israel.

The coronavirus disease 2019 (COVID-19) pandemic caused challenges in the management of patients living with multiple sclerosis (PLwMS). We investigated the occurrence and severity of COVID-19 infection post-vaccination among PLwMS treated with ocrelizumab and enrolled in the Maccabi Health Services (MHS) (n = 289) or followed at the Hadassah Medical Center (HMC) (n = 80) in Israel. Most patients were fully vaccinated (MHS n = 218; HMC n = 76) and confirmed infection post-vaccination was low (3.7% and 2.6%, respectively). MHS: infection was more severe (hospitalization/intensive care unit/death) in non-vaccinated (33.3%) vs vaccinated patients (25%). HMC: one vaccinated patient required hospitalization with COVID-19 vs two unvaccinated patients. These data from two Israel cohorts suggest that occurrence of COVID-19 after mRNA vaccination is low and limited in severity.

Growth in children with pulmonary arterial hypertension: a longitudinal retrospective multiregistry study.

BACKGROUND: To enable adequate interpretation of growth measurements in the management of children with pulmonary arterial hypertension (PAH), we assessed growth and its associated determinants in children with PAH. METHODS: We did a retrospective longitudinal study of height and body-mass index in reference to WHO growth standards by pooling data from four contemporary prospective registries of paediatric PAH representing 53 centres in 19 countries. The main outcome measures were median height for age and body-mass index for age percentiles and longitudinal deviation of height for age and body-mass index for age Z scores from WHO standards. FINDINGS: 601 children were followed up for a median of 2·9 years (IQR 1·5-4·4). Baseline median height for age percentile was 26 (IQR 4-54) and baseline median body-mass index for age percentile was 41 (IQR 12-79). Mean height for age Z score was significantly lower than the reference (-0·81, 95% CI -0·93 to -0·69; p<0·0001), as was body-mass index for age Z score (-0·12, -0·25 to -0·01; p=0·047). Height for age Z score was particularly decreased in young patients (aged ≤5 years) with idiopathic or hereditary PAH and in all patients with PAH associated with congenital heart disease. Although Z scores increased in some patients and decreased in others, we detected no significant trend in height for age Z score (p=0·57) or body-mass index for age Z score (p=0·48) before taking account of covariates. Multivariable linear mixed effects modelling showed that age, cause of PAH, ex-prematurity, WHO functional class, trisomy 21, and time since diagnosis were associated with height for age Z score, whereas age, ethnicity, and trisomy 21 were associated with body-mass index for age Z score. A favourable WHO functional class course was independently associated with increases in height for age Z score. INTERPRETATION: PAH is associated with impaired growth, especially in younger children and those with pulmonary arterial hypertension associated with congenital heart disease. The degree of impairment is independently associated with cause of PAH and comorbidities, but also with disease severity and duration. Because a favourable clinical course was associated with catch-up growth, height for age could serve as an additional and globally available clinical parameter to monitor patients' clinical condition. FUNDING: Actelion Pharmaceuticals.

Workshop on vaccine pressure and Neisseria meningitidis, Annecy, France, 9-11 March 2005.

A 3-day workshop, "Vaccine pressure and Neisseria meningitidis", was held in Annecy, France, 9-11 March 2005, to summarize the current state of knowledge regarding N. meningitidis capsule switching and vaccine pressure from capsular polysaccharide-based N. meningitidis vaccines, including conjugates. Main discussion topics were the host-bacteria relationship and N. meningitidis population, worldwide experience of meningococcal vaccination, and using existing experience to shape the future of meningococcal vaccination strategies. The workshop concluded that there is no current evidence to suggest that serogroup C conjugate vaccine pressure has resulted in meningococcal serogroup switching or replacement.