Efficacy and safety of ocrelizumab in patients with relapsing multiple sclerosis: Real-world experience of two Swiss multiple sclerosis centers.

BACKGROUND: Ocrelizumab (OCR) is a humanized monoclonal antibody directed against CD-20 positive lymphocytes, mainly B-lymphocytes. OCR is approved for treatment of primary progressive (PPMS) and relapsing multiple sclerosis (RMS). This study aims to provide real-world safety and efficacy data of people with RMS treated with OCR in two Swiss Multiple Sclerosis (MS) centers. METHODS: We have conducted a retrospective data analysis using the patient cohorts from the Cantonal Hospital Aarau and Bern University Hospital (RMS: n = 235). Statistical analyses were performed with Mann-Whitney U-Test, Chi-squared test and Spearman-Rho-Correlation. Adjustment for multiple testing was performed by Bonferroni procedure. RESULTS: After initiation of OCR, there was a decrease in disease activity in RMS patients. In our study, 152/190 (80.0 %) RMS patients fulfilled the criteria for NEDA-3 12 months and 88/104 (84.6 %) showed NEDA-3 24 months after OCR initiation. The most frequent adverse events (AEs) in our study were infections, taking place in 78/235 (33.2 %) RMS patients. COVID-19 was the most common infection, followed by urinary infections and other respiratory infections and infectious adverse events occurred significantly more frequent in patients with reduced IgG serum concentration. CONCLUSIONS: Our real-world study showed OCR being associated with low rates of any type of MS disease activity as indicated by NEDA-3. The adverse event profile is comparable to the known events especially infections and an association between infections and reduced IgG serum concentration was found.

Hypogammaglobulinemia: A contributing factor to multiple sclerosis fatigue?

OBJECTIVE: Fatigue is one of the most disabling and difficult to treat symptoms of autoimmune diseases and frequently presents in people with multiple sclerosis (PwMS). Hypogammaglobulinemia for immunoglobulin G (IgG) affects approximately 8-25% of PwMS. We performed a retrospective analysis to investigate the association of MS-fatigue and IgG hypogammaglobulinemia. METHODS: PwMS, treated at Eginition University Hospital Athens or at the University Hospital Bern, were included (n = 134 patients (Bern n = 99; Athens n = 35)). Mann Whitney U-test (MWT), ANOVA test, Chi2 test and multivariable linear regression models were run. RESULTS: 97/134 (72.4%) PwMS reported fatigue. In the multivariable linear regression analysis, IgG serum concentration (-1.6, 95%CI -2.7 - -0.5, p = 0.006), daytime sleepiness (0.8, 95%CI 0.2-1.4, p = 0.009), and a depressive mood (1.1, 95%CI 0.8-1.4, p < 0.001) were significantly associated with fatigue. The impact of IgG serum concentration (-2.9 95%CI -4.7 - -1.1, p = 0.002) remained significant also in the subcohort of PwMS without depressive symptoms or daytime sleepiness. CONCLUSIONS: We found an association between IgG hypogammaglobulinemia and fatigue in PwMS (Level of Evidence IV), which might be translated to other autoimmune diseases. It bears a potential therapeutic consequence considering IgG supplementation strategies, if our finding can be validated prospectively.

Ocrelizumab-related neutropenia: Effects of age, sex and bodyweight using the FDA Adverse Event Reporting System (FAERS).

OBJECTIVE: Neutropenia is a rare complication of anti-CD20 treatment, such as Ocrelizumab (OCR) in Multiple Sclerosis (MS). Using FDA´s Adverse Event Reporting System (FAERS), a post-marketing, open access pharmacovigilance database, we aimed to identify risk factors of neutropenia in OCR-treated patients. METHODS: Data were retrieved from FAERS identifying OCR-treated patients with and without neutropenia. Only data with OCR as the single suspected product were considered. Multivariable logistic regression (MLR) analysis was run to study if MS disease course, age, sex and bodyweight were associated with the risk of neutropenia. RESULTS: Of 15,313 initial hits, 3177 complete datasets were included in the analysis. MLR demonstrated that MS disease course was not associated, whereas sex (female sex (reference male sex) 0.356, 95%CI 0.145-0.875, p = 0.0124), age (years, 0.909, 95%CI 0.875-0.944, p = 7.4105 × 10-7) and bodyweight (kilogram, 0.961, 95%CI 0.935-0.988, p = 0.005) were factors associated with OCR-related neutropenia (Nagelkerkes R2=0.17, n = 3177). No deaths were reported for identified neutropenia cases. CONCLUSION: Using FAERS, we identified male sex, younger age and lower bodyweight as factors associated with OCR-related neutropenia. With the limitations inherent to this open data source, our data need prospective validation, but elucidate potential factors for a personalized side effect profiling.

Renin-angiotensin-aldosterone system blockade and urinary albumin excretion in community-based patients with Type 2 diabetes: the Fremantle Diabetes Study.

AIMS: To determine whether the reduction in urinary albumin excretion through renin-angiotensin-aldosterone system blockade found in intervention trials extends to community-based patients with Type 2 diabetes. METHODS: We analysed data from 302 participants in the longitudinal observational Fremantle Diabetes Study who commenced angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy during follow-up and who had an annual assessment on either side of this therapeutic change. RESULTS: At baseline, the patients had a mean age of 63.8 years, a median diabetes duration of 4 years, a median HbA(1c) of 7.6% (60 mmol/mol) and a geometric mean (sd range) urinary albumin:creatinine ratio of 3.3 mg/mmol (0.8-13.1 mg/mmol). The percentages with normo-, micro- and macroalbuminuria were 49.0, 38.4 and 12.6%, respectively. During 6.1 ± 1.7 years of follow-up, initiation of renin-angiotensin-aldosterone system blockade was associated with a larger geometric mean (sd range) absolute albumin:creatinine ratio reduction in the patients with macroalbuminuria compared with those who had either normo- or microalbuminuria [-40.9 (-825.7 to 159.9) mg/mmol) vs. 1.7 (-1.6 to 20.0) mg/mmol and -0.5 (-23.0 to 39.5) mg/mmol, respectively; P < 0.001]. These changes remained significant after adjustment for changes in blood pressure and other potentially confounding variables, including drug dose and angiotensin-converting enzyme genotype. The post-treatment median albumin:creatinine ratios were 35.4 and 27.4% lower than before treatment in those with micro- or macroalbuminuria, respectively. CONCLUSIONS: Usual-care initiation of renin-angiotensin-aldosterone system blockade confers a quantitatively similar renal benefit to that in intervention trials in Type 2 diabetes.

The epidemiology and characteristics of type 2 diabetes in urban, community-based young people.

As little is known about the impact of type 2 diabetes amongst Australian youth despite international increases in childhood obesity, we aimed to identify and characterize people aged<25 years with type 2 diabetes in an urban community with 60,000 people aged 10-24 years. The estimated maximum prevalence (59/100,000 persons) was lower than US estimates but higher than in Asia and Europe. In eight patients assessed in detail, obesity and related comorbidities were common, and quality of life was low.

Prevalence and predictors of osteopenia and osteoporosis in adults with Type 1 diabetes.

AIMS: To determine the prevalence and biochemical/hormonal determinants of osteopenia and osteoporosis in adults with Type 1 diabetes. METHODS: One hundred and two patients (52 female, 50 male) with Type 1 diabetes aged 20-71 years underwent cross-sectional assessment of biochemical/hormonal markers of bone metabolism, and bone mineral density (BMD) measurement at forearm, hip and spine using dual energy x-ray absorptiometry. BMD data were available for 102 age- and gender-matched population-based control subjects. RESULTS: After adjusting for age and body mass index (BMI), osteopenia and osteoporosis were more common at the spine in males with Type 1 diabetes than in control subjects (P = 0.030). In Type 1 males, after adjustment for age and BMI, BMD, T- and Z-scores at the hip, femoral neck and spine were lower compared with age-matched control subjects (P < or = 0.048). Female Type 1 patients and control subjects had similar BMDs and T- and Z-scores at all sites. On multiple linear regression analysis, which adjusted for the natural logarithm of the sex hormone binding globulin concentration, smoking status and alcohol consumption, and (for women) menopausal status, each of BMI, serum ionized calcium and serum alkaline phosphatase (negatively) were independently associated with BMD at the hip and femoral neck in Type 1 diabetic subjects. CONCLUSIONS: Adult males with Type 1 diabetes have reduced bone density at the hip, femoral neck and spine when compared with age-matched control subjects. Impaired bone formation may occur in Type 1 diabetes.

How important is malnutrition? A prospective study in internal medicine.

BACKGROUND/OBJECTIVE: Data about the prevalence of malnutrition on hospital admission vary and follow-up data are scarce. We assessed the nutritional status of unselected patients on admission and discharge. SUBJECTS/METHODS: A total of 430 consecutively admitted patients were assessed and 168 patients hospitalized > or =6 days were reassessed on discharge. Assessment was carried out by the Mini Nutritional Assessment (MNA), weight and anthropometric measurements, bioelectrical impedance analysis, biochemical markers and a subjective clinical assessment by the physicians in charge. RESULTS: On admission, 47% of all patients were overweight (body mass index, BMI >25 kg m(-2)) and 8% underweight (BMI<18.5 kg m(-2)). In terms of the MNA 70% were adequately nourished, 20% were at risk for malnutrition and 10% were malnourished. By clinical judgment alone 18 (4.3%) malnourished patients according to MNA were missed. The 44 malnourished patients according to the MNA had significantly lower values for BMI, fat-free mass, fat mass, waist circumference, triceps skinfold thickness, hemoglobin, albumin, prealbumin, total cholesterol but higher values for C-reactive protein. Of the 168 patients staying > or =6 days in hospital, 57% lost and 39% gained weight. Only 1.9% of all patients (8 of 430) were malnourished and lost further weight during hospitalization. CONCLUSIONS: We found a low prevalence (10%) of malnourished patients on admission. Clinical judgment and to some extent anthropometrical measurement were helpful for assessing the nutritional status, laboratory values were not.