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[This corrects the article DOI: 10.3389/fimmu.2019.00040.].

Introduction: Subcutaneously administered immunoglobulin (SCIG) is increasingly used to treat patients with primary immunodeficiencies (PIDs). Octanorm (marketed as cutaquig® in USA and Canada) is a new 16.5% solution of human SCIG, manufactured by a process based on that of the intravenous preparation (IVIG) octagam®. Objectives: To investigate the efficacy, safety and tolerability of octanorm in a prospective, open-label, single-arm phase 3 study involving adult and pediatric patients with PIDs (NCT01888484; clinicaltrials.gov/ct2/show/NCT01888484). Methods: Patients who were previously treated with IVIG received a total of 64 weekly SCIG infusions, including 12 weekly infusions during the wash-in/wash-out period, followed by 52 weekly infusions during the evaluation period. Results: A total of 61 patients aged 2-73 years received 3,497 infusions of octanorm. The mean dose per patient was 0.175 g/kg/infusion. The mean calculated dose conversion factor from the patients' previous IVIG dose for octanorm was 1.37. No serious bacterial infections developed during the study. The rate of other infections per person-year during the primary observation period was 3.43 (upper 95% CI 4.57). All but one non-bacterial infection were mild or moderate in intensity. IgG trough levels were constant during the course of the study. Eleven patients (18.0%) experienced 14 mild or moderate systemic adverse events (AEs) related to octanorm. The rate of related AEs per infusion was 0.004. In 76.7% of infusions, no infusion site reactions were observed and only two (0.3%) reactions were deemed severe. The incidence of site reactions decreased with successive infusions. Conclusion: The new 16.5% SCIG octanorm was shown to be efficacious in preventing infections in PIDs, and was well tolerated.

PurposeTo assess the efficacy and safety of panzyga® (intravenous immunoglobulin 10%) in preventing serious bacterial infections (SBIs) in patients with primary immunodeficiency diseases (PIDs), a prospective, open-label, multicenter, phase 3 study and an open-label extension study were undertaken.MethodsInitially, the study drug (infusion rate ≤0.08 mL/kg/min) was administered at intervals of 3 or 4 weeks for 12 months, followed by 3 months of panzyga® at infusion rates increasing from 0.08 to 0.14 mL/kg/min. The primary endpoint in the main study was the rate of SBIs per patient-year on treatment. Secondary outcomes included non-serious infections, work/school absence, episodes of fever, quality of life, and adverse events (AEs).ResultsThe main study enrolled 51 patients (35% female, mean age 26.8 years), with 21 participating in the extension study. The rate of SBIs per patient-year was 0.08 in the total population; there were four SBIs in the 4-weekly treatment group (2/30 patients) and none in the 3-weekly group (n = 21). Compared with 4-weekly treatment, 3-weekly treatment was associated with a higher rate of upper respiratory tract infections (RTIs), ear infections, and work/school absences, but a lower rate of lower RTIs and fever. Treatment was generally well tolerated; no AE led to treatment withdrawal or death.ConclusionsOverall, the use of panzyga® in patients with antibody-deficient PID was associated with a low rate of AEs and was effective in preventing SBIs, exceeding US FDA and European Medicines Agency recommendations for efficacy.

A prospective study and its long-term extension examined whether weekly treatment of patients with primary immunodeficiencies (PIDs) with a 16.5% subcutaneous immunoglobulin (SCIg; cutaquig®) confers acceptable efficacy, safety, and tolerability over a follow-up of up to 238 weeks (>4 years). Seventy-five patients received 4462 infusions during up to 70 weeks of follow-up in the main study and 27 patients received 2777 infusions during up to 168 weeks of follow-up in the extension. In the main study, there were no serious bacterial infections (SBIs), and the annual rate of other infections was 3.3 (95% CI 2.4, 4.5). One SBI was recorded in the extension, for an SBI rate of 0.02 (upper 99% CI 0.19). The annual rate of all infections over the duration of the extension study was 2.2 (95% CI 1.2, 3.9). Only 15.0% (1085) of 7239 infusions were associated with infusion site reactions (ISRs), leaving 85.0% (6153) of infusions without reactions. The majority of ISRs were mild and transient. ISR incidence decreased over time, from 36.9% to 16% during the main study and from 9% to 2.3% during the extension. The incidence of related systemic adverse events was 14.7% in the main study and 7.4% in the extension. In conclusion, this prospective, long-term study with cutaquig showed maintained efficacy and low rates of local and systemic adverse reactions in PID patients over up to 238 weeks of follow-up. Over the whole main study period, 77.7% of the 4,462 infusions resulted in no infusion site reactions (ISRs). In the extension study, most of the 2,777 infusions (96.5%) induced no ISRs. In both adult and pediatric patients, mild ISRs were by far the most common, and in children mild ISRs made up 96% of local reactions. [ABSTRACT FROM AUTHOR]

Alpha 7 subunits of nicotinic acetylcholine receptors (nAChRs) are expressed in microglia and are involved in the suppression of neuroinflammation. Over the past decade, many reports show beneficial effects of nicotine, though little is known about the mechanism. Here we show that nicotine inhibits lipopolysaccharide (LPS)-induced proton (H.sup.+) currents and morphological change by using primary cultured microglia. The H.sup.+ channel currents were measured by whole-cell patch clamp method under voltage-clamp condition. Increased H.sup.+ current in activated microglia was attenuated by blocking NADPH oxidase. The inhibitory effect of nicotine was due to the activation of [alpha]7 nAChR, not a direct action on the H.sup.+ channels, because the effects of nicotine was cancelled by [alpha]7 nAChR antagonists. Neurotoxic effect of LPS-activated microglia due to inflammatory cytokines was also attenuated by pre-treatment of microglia with nicotine. These results suggest that [alpha]7 nAChRs in microglia may be a therapeutic target in neuroinflammatory diseases. Keywords: Microglia, Nicotine, [alpha]7 nAChRs, Lipopolysaccharide, NADPH oxidase, Proton currents, Author(s): Mami Noda[sup.1] and AI Kobayashi[sup.1] Introduction Nicotine, like several other abused drugs, is known to act on the reward system in the brain. It was shown that cues related [...]