Utilization of Ocrelizumab within Different Treatment Strategies for Multiple Sclerosis: A 5-Year Population-Based Study.

BACKGROUND: We aim to provide up-to-date real-world evidence on the persistence, adherence, healthcare resource utilization, and costs of multiple sclerosis (MS) by comparing ocrelizumab to other disease-modifying treatments (DMTs) and within different DMT sequences. METHODS: We included 3371 people with MS who first received or switched DMT prescriptions from January 2018 to December 2022; they were identified through hospital discharge records, drug prescriptions, and exemption codes from the Campania Region (South Italy). We calculated persistence (time from the first prescription to discontinuation or switching to another DMT), adherence (proportion of days covered (PDC)), DMT costs, and MS hospital admissions and related costs. RESULTS: The most frequently prescribed DMT was dimethyl fumarate (n = 815; age 38.90 ± 11.91 years; 69.5% females), followed by ocrelizumab (n = 682; age 46.46 ± 11.29 years; 56.3%); 28.8% of the patients treated with ocrelizumab were naïve to DMTs. Using ocrelizumab as a statistical reference, the risk of discontinuation was higher for other highly active (HR = 6.32; 95%CI = 3.16, 12.63; p < 0.01) and low-/medium-efficacy DMTs (HR = 10.10; 95%CI = 5.10, 19.77; p < 0.01); adherence was lower for other highly active DMTs (Coeff = -0.07; 95%CI = -0.10, -0.04; p < 0.01) and low-/medium-efficacy DMTs (Coeff = -0.16; 95%CI = -0.19, -0.14; p < 0.01). monthly DMT costs were higher for other highly active DMTs (Coeff = 77.45; 95%CI = 29.36, 125.53; p < 0.01) but lower for low-/medium-efficacy DMTs (Coeff = -772.31; 95%CI = -816.95, -727.66; p < 0.01). The hospital admissions and related costs of MS were similar between ocrelizumab, other highly active DMTs, and other low-/medium-efficacy DMTs, and with ocrelizumab as the first-line DMT after other highly active DMTs and after low-/medium-efficacy DMTs, which was possibly due to the low number of observations. CONCLUSIONS: From 2018 to 2022, ocrelizumab was among the most frequently prescribed DMTs, with 28.8% prescriptions to incident MS patients, confirming its relevance in clinical practice. Ocrelizumab was associated with the highest persistence and adherence, pointing towards its favorable benefit-risk profile. The costs of ocrelizumab were lower than those of other highly active DMTs.

The Cost of Patients with Chronic Kidney Failure Before Dialysis: Results from the IRIDE Observational Study.

BACKGROUND: Chronic kidney disease (CKD) is an important public health problem. Most of the evidence on its costs relates to patients receiving dialysis or kidney transplants, which shows that, in these phases, CKD poses a high burden to payers. Less evidence is available on the costs of the predialytic phase. OBJECTIVE: The aim of this study was to estimate the annual cost of patients with CKD not receiving dialysis treatment, using the Italian healthcare system perspective and a prospective approach. METHODS: A 3-year observational study (December 2010-September 2014) was carried out to collect data on resource consumption for 864 patients with CKD. Costs were estimated for both patients who completed the follow-up and dropouts. RESULTS: The mean annual total (healthcare) cost per patient equalled €2723 (95% confidence interval 2463.0-2983.3). Disease severity (higher CKD stage), multiple comorbidities, dropout status and belonging to the southern region are predictive of higher costs. Pharmaceuticals, hospitalisation, and outpatient services account for 71.5, 18.8 and 9.7% of total healthcare expenditure, respectively. Recent estimates of Italian costs of patients receiving dialysis are nine times the unit costs of CKD for patients estimated in this study. Unit costs at stage 5 CKD (the highest level of severity) equals 4.7 times the costs for patients at stage 1 CKD. CONCLUSION: Despite its limitations, this study provides further evidence on the opportunity to invest in the first phases of CKD to avoid progression and an increase in healthcare costs.

Current pipelines for neglected diseases.

This paper scrutinises pipelines for Neglected Diseases (NDs), through freely accessible and at-least-weekly updated trials databases. It updates to 2012 data provided by recent publications, and integrates these analyses with information on location of trials coordinators and patients recruitment status. Additionally, it provides (i) disease-specific information to better understand the rational of investments in NDs, (ii) yearly data, to understand the investment trends. The search identified 650 clinical studies. Leishmaniasis, Arbovirus infection, and Dengue are the top three diseases by number of clinical studies. Disease diffusion risk seems to be the most important driver of the clinical trials target choice, whereas the role played by disease prevalence and unmet need is controversial. Number of trials is stable between 2005 and 2010, with an increase in the last two years. Patient recruitment was completed for most studies (57.6%), and Phases II and III account for 35% and 28% of trials, respectively. The primary purpose of clinical investigations is prevention (49.3%), especially for infectious diseases with mosquitoes and sand flies as the vector, and treatment (43.2%), which is the primary target for parasitic diseases Research centres and public organisations are the most important clinical studies sponsors (58.9%), followed by the pharmaceutical industry (24.1%), foundations and non-governmental organisations (9.3%). Many coordinator centres are located in less affluent countries (43.7%), whereas OECD countries and BRICS account for 34.7% and 17.5% of trials, respectively. Information was partially missing for some parameters. Notwithstanding, and despite its descriptive nature, this research has enhanced the evidence of the literature on pipelines for NDs. Future contributions may further investigate whether trials metrics are consistent with the characteristics of the interested countries and the explicative variables of trials location, target (disease) choice, and the object of the trials.

Arginine-specific mono ADP-ribosylation in vitro of antimicrobial peptides by ADP-ribosylating toxins.

Among the several toxins used by pathogenic bacteria to target eukaryotic host cells, proteins that exert ADP-ribosylation activity represent a large and studied family of dangerous and potentially lethal toxins. These proteins alter cell physiology catalyzing the transfer of the ADP-ribose unit from NAD to cellular proteins involved in key metabolic pathways. In the present study, we tested the capability of four of these toxins, to ADP-ribosylate α- and ß- defensins. Cholera toxin (CT) from Vibrio cholerae and heat labile enterotoxin (LT) from Escherichia coli both modified the human α-defensin (HNP-1) and ß- defensin-1 (HBD1), as efficiently as the mammalian mono-ADP-ribosyltransferase-1. Pseudomonas aeruginosa exoenzyme S was inactive on both HNP-1 and HBD1. Neisseria meningitidis NarE poorly recognized HNP-1 as a substrate but it was completely inactive on HBD1. On the other hand, HNP-1 strongly influenced NarE inhibiting its transferase activity while enhancing auto-ADP-ribosylation. We conclude that only some arginine-specific ADP-ribosylating toxins recognize defensins as substrates in vitro. Modifications that alter the biological activities of antimicrobial peptides may be relevant for the innate immune response. In particular, ADP-ribosylation of antimicrobial peptides may represent a novel escape mechanism adopted by pathogens to facilitate colonization of host tissues.