Subcutaneous Immunoglobulin 16.5% (Cutaquig®) in Primary Immunodeficiency Disease: Safety, Tolerability, Efficacy, and Patient Experience with Enhanced Infusion Regimens.

PURPOSE: To achieve reductions in infusion time, infusion sites, and frequency, a prospective, open-label, multicenter, Phase 3 study evaluated the safety, efficacy, and tolerability of subcutaneous immunoglobulin (SCIG) 16.5% (Cutaquig®, Octapharma) at enhanced infusion regimens. METHODS: Three separate cohorts received SCIG 16.5% evaluating volume, rate, and frequency: Cohort 1) volume assessment/site: up to a maximum 100 mL/site; Cohort 2) infusion flow rate/site: up to a maximum of 100 mL/hr/site or the maximum flow rate achievable by the tubing; Cohort 3) infusion frequency: every other week at twice the patient's weekly dose. RESULTS: For Cohort 1 (n = 15), the maximum realized volume per site was 108 mL/site, exceeding the currently labeled (US) maximum (up to 40 mL/site for adults). In Cohort 2 (n = 15), the maximum realized infusion flow rate was 67.5 mL/hr/site which is also higher than the labeled (US) maximum (up to 52 mL/hr/site). In Cohort 3 (n = 34), the mean total trough levels for every other week dosing demonstrated equivalency to weekly dosing (p value = 0.0017). All regimens were well tolerated. There were no serious bacterial infections (SBIs). Most patients had mild (23.4%) or moderate (56.3%) adverse events. The majority of patients found the new infusion regimens to be better or somewhat better than their previous regimens and reported that switching to SCIG 16.5% was easy. CONCLUSIONS: SCIG 16.5% (Cutaquig®), infusions are efficacious, safe, and well tolerated with reduced infusion time, fewer infusion sites, and reduced frequency. Further, the majority of patients found the new infusion regimens to be better or somewhat better than their previous regimens.

Subcutaneous immunoglobulin 16.5% for the treatment of pediatric patients with primary antibody immunodeficiency.

INTRODUCTION: Human immunoglobulin (IG) administered intravenously (IVIG) or subcutaneously (SCIG) is used to prevent infections in patients with primary immunodeficiency diseases (PIDDs) such as primary antibody immunodeficiencies. AREAS COVERED: This review provides an overview of PIDD with a focus on SCIG treatment, including the properties and clinical trial results of a new SCIG 16.5% (Cutaquig, Octapharma) in pediatric patients. We also discuss the various benefits of SCIG including stable serum immunoglobulin G levels, high tolerability with fewer systemic side effects, and the flexibility of self-administration. EXPERT OPINION: Individualized treatment for PIDD in children is necessary given the different factors that affect administration of SCIG. Variables such as the dose, dosing interval, administration sites, and ancillary equipment can be adjusted to impact the long-term satisfaction with SCIG administration in pediatric patients. The successful work that has been conducted by both professional and patient organizations to increase awareness of PIDD, especially in pediatric patients, is substantial and ongoing. The importance of early diagnosis and treatment in the pediatric patient population cannot be overstated. The safety, efficacy, and tolerability of SCIG 16.5% have been demonstrated in pediatric patients with PIDDs providing an additional therapeutic option in this vulnerable population.

Human immunoglobulin (IG) is extracted from the plasma of donors as a sterile, purified blood product that is administered intravenously (via a vein [IVIG]) or subcutaneously (under the skin [SCIG]) and is used for a variety of disorders, including the prevention of infections in patients with primary immunodeficiency diseases (PIDDs) such as primary antibody immunodeficiencies. This review provides an overview of PIDD with a focus on SCIG treatment, including the properties and clinical trial results of a new SCIG 16.5% (Cutaquig, Octapharma) in pediatric patients. We also discuss the various benefits of SCIG including stable serum immunoglobulin G levels, high tolerability with fewer systemic side effects, and the flexibility of self-administration. The importance of early identification of PIDD, especially in pediatric patients, cannot be overstated to ensure prompt treatment. The safety, efficacy, and tolerability of SCIG 16.5% have been demonstrated in pediatric patients with PIDDs providing an additional therapeutic option in this vulnerable population.

Overview of subcutaneous immunoglobulin 16.5% in primary and secondary immunodeficiency diseases.

Most primary immunodeficiency diseases, and select secondary immunodeficiency diseases, are treated with immunoglobulin (IG) therapy, administered intravenously or subcutaneously (SCIG). The first instance of IG replacement for primary immunodeficiency disease was a 16.5% formulation administered subcutaneously in 1952. While most SCIG products are now a 10 or 20% concentration, this review will focus on SCIG 16.5% products with a historical overview of development, including the early pioneers who initiated and refined IG replacement therapy, as well as key characteristics, manufacturing and clinical studies. In determining an appropriate IG regimen, one must consider specific patient needs, characteristics and preferences. There are advantages to SCIG, such as stable serum immunoglobulin G levels, high tolerability and the flexibility of self-administered home treatment.

Plain language summary Primary immunodeficiency diseases, and select secondary immunodeficiency diseases, weaken the immune system, allowing infections and other health problems to occur more easily. Some patients require treatments to boost their immune system, such as immunoglobulin (IG) therapy, which can be either injected via a needle into a vein (intravenously) or inserted underneath the skin (subcutaneously; SCIG). The first instance of IG treatment for primary immunodeficiency disease was a 16.5% SCIG product given in 1952. While most SCIG products are now a 10 or 20% concentration, this review will focus on SCIG 16.5% products with a historical overview of development, including the early pioneers who initiated and refined IG therapy, as well as key characteristics, manufacturing and clinical studies. In determining an appropriate IG regimen, one must consider specific patient needs, characteristics and preferences. There are advantages to SCIG, such as stable serum immunoglobulin G levels, high tolerability and the flexibility of self-administered home treatment.

A prospective, open label, multicenter, postmarket study evaluating Princess VOLUME Lidocaine for the correction of nasolabial folds.

The aim of this study was to investigate the safety and performance of Princess VOLUME Lidocaine in nasolabial fold correction. In this prospective, open label, multicenter, postmarket study subjects received injections of Princess VOLUME Lidocaine into both NLF at Baseline (Day 0) and if considered necessary by the investigator, at Week 2 (touch-up treatment). This study was conducted in Austria at the Department of Dermatology and Venereology, Medical University of Graz, at the medical aesthetic center MÄZ WIEN, and at the medical aesthetic center Ordination Dr. Bartsch, Vienna. The 62 mainly female (95.2%) subjects had a median age of 52 years with two fully visible, approximately symmetrical NLFs, each scoring grade 2 or 3 on the nasolabial fold severity rating scale (NLF-SRS) developed by Croma-Pharma. The nasolabial fold severity was assessed by NLF-SRS and Global Aesthetic Improvement Scale (GAIS) 4, 24, and 36 weeks later. Adverse events (AEs) were recorded throughout the investigation. With 95.1% of subjects showing an improvement of at least 1 grade of the NLF-SRS at 24 weeks after the treatment, the primary endpoint was achieved, and clinical performance was demonstrated. Princess VOLUME Lidocaine was well tolerated, with only mild AEs, mainly injection site reactions, reported. Subject satisfaction (≥93.5%) and GAIS scores (≥93.5% improvement) were high. Princess VOLUME Lidocaine was effective in reducing NLFs as shown by an improvement in the severity of NLFs by at least one grade in 95.1% of subjects at Weeks 4 and 24.

Management of moderate-to-severe dry eye disease using chitosan-N-acetylcysteine (Lacrimera®) eye drops: a retrospective case series.

PURPOSE: Dry eye disease is a highly prevalent condition that causes tear film instability, ocular discomfort, and visual disturbance. Lacrimera eye drops are approved for the short-term treatment of dry eye disease. We aimed to evaluate the clinical outcome of patients with moderate-to-severe dry eye disease treated with Lacrimera up to 1 month during routine clinical practice. METHODS: We retrospectively collected data from 25 patients with dry eye disease from the start of Lacrimera treatment up to 1 month of follow-up period. We analyzed standard clinical parameters to follow the course of the patients' dry eye signs and symptoms. RESULTS: Based on corneal staining data, we found that the percentage of patients with intact corneas raised from 12 to 64% after 1 month of Lacrimera treatment. During this period, we also observed an increase in both tear breakup time (p < 0.05) and Schirmer's score (p < 0.001), with lower values indicating severer signs. Lacrimera eye drops were judged by 29% of the patients to be effective at relieving eye symptoms. CONCLUSIONS: Lacrimera appears to be safe and effective in the treatment of dry eye disease, as assessed by corneal staining, tear breakup time, and Schirmer's analyses. Our data suggest that the regenerative effect of Lacrimera eye drops peaks at 2 weeks and is sustained for at least 1 month when administered for a longer period of time.

Safety and effectiveness of hyaluronic acid dermal filler in correction of moderate-to-severe nasolabial folds in Chinese subjects.

BACKGROUND: Modified sodium hyaluronate gel for injection, Princess® VOLUME (PV), has been on the European market since 2009 to correct deeper wrinkles and folds, increasing or restoring volume of the face, and remodeling facial contours. OBJECTIVE: To evaluate the safety and effectiveness of PV in correction of moderate-to-severe nasolabial folds (NLF) in Chinese subjects. METHODS: In this prospective, split-face, randomized, evaluator and subject-blinded, multicenter, noninferiority trial, 120 subjects were randomized to bilateral NLF treatment with PV administered in one NLF and Restylane® (RL) administered in the other NLF. NLFs were evaluated using the validated 5-point Wrinkle Severity Rating Scale with scores ranging from 1= none (no visible NLF) to 5= very severe (extremely deep and long NLF). Response was defined as ≥1 point improvement at Week 24 assessed by the blinded independent review committee (IRC) and the reduction of NLF severity, assessed by subjects and IRC based on the Global Aesthetic Improvement Scale. RESULTS: Among the 115 subjects who completed the study, median initial and touch-up volumes (mL) were 1.00 for both groups with a maximum dosage per NLF of 2.00 and a minimum of 0.30 for PV and 0.60 for RL. At week 24, the Wrinkle Severity Rating Scale improvement rate, as assessed by the IRC, reached 68.70% for PV and 52.17% for RL. The results indicate that PV is noninferior to RL (p<0.001). Most frequently reported adverse events for both devices were injection site swelling and procedural pain. The severity of the majority of the adverse events was mild. CONCLUSION: This study confirms that PV is a safe and effective treatment for the correction of moderate-to-severe NLFs in Chinese subjects.

Analysis of skin penetration of phytosphingosine by fluorescence detection and influence of the thermotropic behaviour of DPPC liposomes.

Phytosphingosine (PS) is a promising compound in skin formulations, considering its application in the treatment of acne and different inflammations as well as in the 'anti age' cosmetics. PS, as an active substance was incorporated in DPPC liposomes intended to standard diffusion experiments, where dermatomed porcine skin was mounted in FRANZ cells. The proved skin retention was about 5.5% (w/w) after 24h and about 6.8% (w/w) after 48 h of the applied PS amount, whereas only about 0.05% (w/w) and about 0.07% (w/w) PS, respectively, could be observed in the acceptor medium. To increase analytical sensitivity PS was derivatised by o-phtalaldehyde (OPA) reagent and analysed by HPLC with fluorescence detection. The higher amount of PS within the skin symbolised an interaction with lipid structures in skin. Further evaluation of this interaction was accomplished by applying microDSC studies of PS with DPPC as a model membrane. For this purpose liposomes were prepared by increasing PS content. The characteristic endothermic peak observed for the single system was shifted to a slightly higher temperature and broadened as the mole fraction of PS increased. This might be the effect of mixing of PS with DPPC. An addition of 10 mol% PS resulted in more than double sized particles pointing to a possible change in the liposomal shape.

Multinuclear NMR characterisation and dermal delivery of fluorinated drugs in soybean-microemulsion systems.

The present study evaluated the effect of different commercially available soybean lecithins in microemulsion systems in terms of microstructure transformation, physicochemical properties and transport of selected entrapped fluorinated drugs through skin. Physicochemical characterisations by particle size and polydispersity index (PDI) measurements were performed and a direct correlation with NMR self-diffusion coefficients of the individual components was found. An increase of lysophosphatidylcholine (LPC), phosphatidylethanolamine (PE) and lysophosphatidylethanolamine (LPE) in the phospholipid mixtures increased the mean particle sizes and PDI. Bicontinous microemulsion structures were proven by 1H and 31P NMR in the placebo microemulsions. Reasonable permeation of the lipophilic drugs of all microemulsions systems was confirmed in standard diffusion studies using porcine skin. This could be due to the incorporation of the drugs in the surfactant structure of the lecithin based bicontinous micro textures, as proven by 19F NMR self-diffusion studies.

Lecithin based nanoemulsions: A comparative study of the influence of non-ionic surfactants and the cationic phytosphingosine on physicochemical behaviour and skin permeation.

Charged drug delivery systems are interesting candidates for the delivery of drugs through skin. In the present study, it was possible to create negatively and positively charged oil/water nanoemulsions by using sucrose laureate and polysorbate 80 as non-ionic surfactants. The positively charged nanoemulsions were generated by adding cationic phytosphingosine (PS). The relationship between the physicochemical properties of the nanoemulsions was shown by particle size and zeta potential measurements. These properties were dependent on the type of non-ionic surfactant and the concentration of PS. Furthermore the cationic PS had a positive impact on the skin permeation rates (flux) of the incorporated model drugs fludrocortisone acetate and flumethasone pivalate. An enhancement factor between 1.1 and 1.5 was obtained in relation to the control. The interaction of pre-impregnated porcine skin with positively and negatively charged nanoemulsions was confirmed by DSC analysis. The generated DSC-curves showed a slight difference in the phase transition temperature assigned to the characteristic lipid transition. However, it was not possible to assign the effect to one of the ingredients in the multicomponent system.

Skin-compatible lecithin drug delivery systems for fluconazole: effect of phosphatidylethanolamine and oleic acid on skin permeation.

The purpose of the present study was to evaluate skin-compatible drug delivery systems for fluconazole. Pseudoternary phase diagrams were constructed, composed of different soybean lecithins/oil/isopropanol and water. The role of the various lecithin compositions was expressed in the different resulting isotropic areas. Based on these phase diagrams, two systems were chosen as drug delivery systems for fluconazole. The influence of phosphatidylethanolamine and of the oil component on the skin permeation of fluconazole was investigated. The more phosphatidylethanolamine, the greater was the fluconazole skin permeation, independent of the hydrophilicity of the system. The influence of oleic acid and isopropylmyristate as the oil component was compared and a greater penetration enhancing effect was found for the microemulsion containing oleic acid.