Long-Term Safety of Facilitated Subcutaneous Immunoglobulin 10% Treatment in US Clinical Practice in Patients with Primary Immunodeficiency Diseases: Results from a Post-Authorization Safety Study.

Facilitated subcutaneous immunoglobulin (fSCIG) 10% is an immunoglobulin replacement therapy that utilizes recombinant human hyaluronidase (rHuPH20) to enhance immunoglobulin dispersion and absorption, allowing for longer treatment intervals similar to intravenous immunoglobulin (up to once monthly). fSCIG 10% is indicated in the USA for treating adults and children aged ≥ 2 years with primary immunodeficiency diseases (PIDs). This prospective, non-interventional, open-label, multicenter, post-authorization safety study (NCT02593188) was conducted in the USA from November 2015 to October 2021 to assess the long-term safety of fSCIG 10% in routine clinical practice. Patients with PIDs aged ≥ 16 years who were prescribed and/or had started fSCIG 10% treatment were enrolled. In total, 253 patients were enrolled and included (full analysis set). Participants received fSCIG 10% treatment for a median (interquartile range) of 10.0 (3.5-11.8) months, with the majority of infusions administered every 4 weeks (54.4% [1197/2201 infusions]) and at home (62.6% [1395/2230 infusions]). Overall, 98.5% of infusions were administered without rate reduction, interruption, or discontinuation due to adverse events (AEs). Treatment-related, non-serious AEs were experienced by 52 patients (20.6%, 284 events). Two patients (0.8%) each experienced one treatment-related serious AE (aseptic meningitis and deep vein thrombosis). Development of antibodies against rHuPH20 was uncommon; 14/196 patients (7.1%) tested positive for binding antibodies (titer ≥ 1:160) with no neutralizing antibodies detected. There was no relationship between anti-rHuPH20 antibody positivity and the occurrence of treatment-related serious or non-serious AEs. Long-term, repeated self-administration of fSCIG 10% was well tolerated in US clinical practice by patients with PIDs.

Insights into Patient Experiences with Facilitated Subcutaneous Immunoglobulin Therapy in Primary Immune Deficiency: A Prospective Observational Cohort.

BACKGROUND: Immunoglobulin G replacement therapy (IgRT), intravenous (IV) and subcutaneous (SC) routes, is pivotal in treatment of primary immunodeficiencies (PID). In recent years, facilitated subcutaneous immunoglobulin (fSCIG), a combination of rHuPH20 and 10% IgG has emerged as a delivery method to combine advantages of both IV and SC. METHOD: In an observational prospective cohort, we investigated patient experience with fSCIG in PID patients from 5 PID centers for up to 12 months. We assessed the efficacy and safety of this treatment with patient/caregiver- and physician-reported indicators. Additionally, we analyzed patient treatment satisfaction (TSQM-9) and quality of life (QoL). RESULTS: We enrolled 29 patients (22 pediatric and 7 adults; 14 females and 15 males; (median: 15, min-max: 2-40.9 years) who initiated fSCIG as IgRT-naive (n = 1), switched from conventional rapid-push 10% SCIG (n = 6) or IVIG (n = 22). Among the participants, 19 (65%) exhibited antibody deficiencies, 8 (27%) combined immunodeficiencies, and 2 (7%) immune dysregulations. Remarkably, targeted trough immunoglobulin G levels were achieved under all previous IgRTs as well as fSCIG. No severe systemic adverse drug reactions were documented, despite prevalent local (%86.45) and mild systemic (%26.45) adverse reactions were noted with fSCIG. Due to mild systemic symptoms, 2 patients switched from fSCIG to 10% SCIG. The patient satisfaction survey revealed a notable increase at 2-4th (p = 0.102); 5-8th (p = 0.006) and 9-12th (p < 0.001) months compared to the baseline. No significant trends were observed in QoL surveys. CONCLUSION: fSCIG demonstrates admissable tolerability and efficacy in managing PIDs in addition to notable increase of patients' drug satisfaction with IgRT. The identified benefits support the continuation of this therapy despite the local reactions.

Tolerability and Safety of Large-Volume Hyaluronidase-Facilitated Subcutaneous Immunoglobulin 10% Administered with or without Dose Ramp-Up: A Phase 1 Study in Healthy Participants.

PURPOSE: Facilitated subcutaneous immunoglobulin (fSCIG; immune globulin infusion 10% [human] with recombinant human hyaluronidase [rHuPH20]) permits high-volume subcutaneous immunoglobulin (SCIG) infusion, shorter infusion times and reduced dosing frequency relative to conventional SCIG. It is initiated by gradually increasing infusion volumes over time (dose ramp-up) to achieve target dose level (TDL). Whether ramp-up strategies have tolerability or safety advantages over direct initiation at full TDL has not been evaluated clinically. METHODS: This phase 1 open-label study assessed tolerability and safety of fSCIG 10% with accelerated or no ramp-up compared with conventional ramp-up in healthy adults (NCT04578535). Participants were assigned to one of the three ramp-up arms to achieve TDLs of 0.4 or 1.0 g/kg/infusion. The primary endpoint was the proportion of infusions completed without interruption or infusion rate reduction owing to treatment-emergent adverse events (TEAEs). Safety was assessed as a secondary endpoint. RESULTS: Of 51 participants enrolled, 50 (98.0%) tolerated all fSCIG 10% infusions initiated (n = 174). Infusion rate was reduced in one participant owing to headache in the 0.4 g/kg/infusion conventional ramp-up arm. Study discontinuations were higher in the no ramp-up arm (70%) versus the conventional (0%) and accelerated (22%) arms at the 1.0 g/kg/infusion TDL. Safety outcomes did not substantially differ between treatment arms. CONCLUSION: The favorable tolerability and safety profiles of fSCIG 10% in healthy participants support initiating treatment with fSCIG 10% with accelerated ramp-up at TDLs up to 1.0 g/kg. Data support no ramp-up at TDLs close to 0.4 g/kg but additional data are needed for higher doses.

Levodopa infusion therapies for Parkinson disease.

PURPOSE OF REVIEW: to review recent progress in the development and use of continuous levodopa therapies in Parkinson disease (PD). RECENT FINDINGS: Levodopa/Carbidopa intestinal gel (LCIG) is a continuous levodopa therapy which is widely used in the United States, Europe and other countries and is effective at reducing 'off' time. Recent work has shown that LCIG can be useful in managing dyskinesias and can improve nonmotor symptoms and quality of life. Several studies have shown good long-term effectiveness of LCIG. Recent data support the cost-effectiveness of this treatment strategy. Subcutaneous (SC) delivery of levodopa is a newer strategy that avoids the need for a surgically placed gastric tube. Two different products enabling SC delivery of levodopa are in development: ND0612 and foslevodopa/foscarbidopa. Both have recently been shown to reduce 'off' time in randomized, double-blind trials. Adverse effects of SC levodopa are primarily related to skin reactions at the infusion site. SUMMARY: Continuous levodopa therapies can be used to treat Parkinson disease motor fluctuations that cannot be managed with standard oral therapies. They may also improve nonmotor symptoms, and improve overall quality of life in patients with advanced PD.

Lidocaine Infusion: An Analgesic Option for Checkpoint Inhibitor Arthritis: A Case Report.

This report describes the use of subcutaneous lidocaine infusion to manage complex pain associated with checkpoint inhibitor inflammatory arthritis. In addition, the safe administration of lidocaine in the home setting is described. A 49-year-old man with metastatic melanoma to lung, right axilla and posterior chest wall on regular pembrolizumab developed checkpoint inhibitor inflammatory arthritis. Pain associated with this was unresponsive to simple analgesia, escalating opioids and adjuvant analgesics. Lidocaine infusion was used on separate occasions (inpatient unit and home setting) to gain rapid and sustained control of inflammatory pain. Inflammatory pain responded well to 2 mg/kg/h lidocaine infusion over 4 days with sustained response between infusions of up to 6 wk. Resulting in improved mobility, functional status, and overall quality of life. Lidocaine infusion should be considered as an option for analgesic management of checkpoint inhibitor inflammatory arthritis in patients for whom usual treatment is ineffective, and as an opioid-sparing intervention.

Continuous subcutaneous insulin infusion versus multiple daily injection therapy in pregnant women with type 1 diabetes.

INTRODUCTION: The study aimed to compare glycemic control and pregnancy outcomes in women with type 1 diabetes mellitus (T1DM) using multiple daily injection therapy (MDI) and continuous subcutaneous insulin infusion (CSII) and to compare outcomes of women treated with long-acting insulin or neutral protamine Hagedorn (NPH). METHODS: This multicenter prospective cohort study involved women with pregestational T1DM treated with MDI and CSII. Primary outcome was glycated hemoglobin (HbA1c) before and during pregnancy. Secondary outcomes included maternal and neonatal outcomes and quality of life. RESULTS: Of the 121 studied women, the average age was 28.48 years, and the average body mass index was 21.29 kg/m2 at conception and 26.32 kg/m2 at delivery. Of the studied women, 78.51% had planned pregnancy. Women treated with MDI and CSII had comparable HbA1c before pregnancy or in the first and second trimesters. In the third trimester, women on CSII therapy had significantly lower HbA1c (6.07 ± 0.62 vs 6.20 ± 0.88%, p = .017), higher HbA1c on-target rate (71.43% vs 64.62%, p = .030), and greater decline of HbA1c from preconception to the third trimester (-0.65 vs -0.30%, p = .047). Fewer daily insulin requirements were observed in those used CSII compared with MDI-treated women (0.60 ± 0.22 vs 0.73 ± 0.25 U/kg/day, p = .004). Newborns born of mothers treated with the CSII method were more likely to have neonatal jaundice (adjusted odds ratio [OR] 2.76, 95% confidence interval [CI] 1.16-6.57) and neonatal intensive care unit (adjusted OR 3.73, 95%CI 1.24-11.16), and women on CSII had lower scores in patient-reported quality of life (p = .045). In the MDI group, those receiving long-acting insulin had nonsignificant lower HbA1c and higher HbA1c on-target rate in the second and third trimesters, compared with those treated with NPH. CONCLUSIONS: Insulin pump users may achieve better glycemic control than multiple daily insulin injections, which did not substantially improve pregnancy outcome.

Safety and efficacy of continuous subcutaneous levodopa-carbidopa infusion (ND0612) for Parkinson's disease with motor fluctuations (BouNDless): a phase 3, randomised, double-blind, double-dummy, multicentre trial.

BACKGROUND: Conventional oral levodopa therapy for the treatment of Parkinson's disease can be associated with variations in plasma concentrations. Levodopa infusion strategies might provide more consistent drug delivery and fewer motor fluctuations. We aimed to assess the safety and efficacy of a continuous 24 h/day subcutaneous infusion of ND0612 (a levodopa-carbidopa solution) compared with oral immediate-release levodopa-carbidopa for the treatment of motor fluctuations in people with Parkinson's disease. METHODS: We conducted a phase 3, randomised, double-blind, double-dummy, active-controlled, multicentre trial at 117 academic and community neurology sites in 16 countries, including in Europe, Israel, and the USA. Eligible participants were men and women aged 30 years or older with a diagnosis of Parkinson's disease (Hoehn and Yahr stage ≤3 in the on state) who experienced at least 2·5 h/day of off time. Participants underwent an open-label run-in phase (<12 weeks), during which time optimal regimens were established for both oral immediate-release levodopa-carbidopa and for 24 h/day subcutaneous ND0612 infusion (levodopa-carbidopa 60·0/7·5 mg/mL), with supplemental oral levodopa-carbidopa if needed. Participants were then randomly assigned (1:1) to 12 weeks of double-blind treatment with their optimised regimen of either subcutaneous ND0612 or oral levodopa-carbidopa, with matching oral or subcutaneous placebo given as required to maintain blinding. Randomisation was done via an interactive web response system, stratified by region, using a permuted block schedule. Participants, study partners, treating investigators, study site personnel, and the sponsor were masked to treatment group allocation. The primary efficacy endpoint was the change from baseline (ie, time of randomisation, when all patients were receiving an optimised open-label ND0612 regimen) to end of the double-blind phase in total daily on time without troublesome dyskinesia, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, NCT04006210, and is complete. FINDINGS: Between Sept 30, 2019, and April 8, 2022, 381 participants were enrolled, of whom 259 (68%) were randomly assigned, 128 (49%) to subcutaneous ND0612 and 131 (51%) to oral levodopa-carbidopa. 243 (94%) participants completed the study. Treatment with subcutaneous ND0612 provided an additional 1·72 h (95% CI 1·08 to 2·36) of on time without troublesome dyskinesia compared with oral levodopa-carbidopa (change from baseline of -0·48 h [-0·94 to -0·02] with subcutaneous ND0612 vs -2·20 h [-2·65 to -1·74] with oral levodopa-carbidopa; p<0·0001). Significant treatment differences favouring subcutaneous ND0612 were also found in the first four of nine prespecified hierarchical outcomes of daily off time (-1·40 h [95% CI -1·99 to -0·80]), Movement Disorders Society-Unified Parkinson's Disease Rating Scale part II scores (-3·05 [-4·28 to -1·81]), Patients Global Impression of Change (odds ratio [OR] 5·31 [2·67 to 10·58]), and Clinical Global Impression of Improvement (OR 7·23 [3·57 to 14·64]). Hierarchical testing ended after the fourth secondary endpoint. Adverse events were reported by 287 (89%) of 322 participants during open-label ND0612 optimisation, and by 103 (80%) of 128 in the ND0612 group and 97 (74%) of 131 in the oral levodopa-carbidopa group during the double-blind phase. The most common adverse events were infusion-site reactions (266 [83%] participants during open-label ND0612, and 73 [57%] in the ND0612 group vs 56 [43%] in the oral levodopa-carbidopa group during the double-blind phase), most of which were mild. Serious adverse events in four participants in the ND0612 group were related to study treatment (infusion-site cellulitis [n=2], infusion-site abscess and infusion-site ulcer [n=1]; and paraesthesia and peripheral sensorimotor neuropathy [n=1]). One participant in the ND0612 group died during the double-blind phase, but the death was not related to study treatment (fall leading to traumatic brain injury). INTERPRETATION: Results of this phase 3 study showed that subcutaneous ND0612 used in combination with oral immediate-release levodopa-carbidopa increased on time without troublesome dyskinesia and reduced off time, with a favourable benefit-risk profile. ND0612 might offer a safe and efficacious subcutaneous levodopa infusion approach to managing motor fluctuations in people with Parkinson's disease. The ongoing open-label extension phase will provide further information on the long-term efficacy and safety of treatment. FUNDING: NeuroDerm.

Could late-latent syphilis be treated with a single subcutaneous infusion of long-acting penicillin?

Syphilis is an important global health threat and little has changed in its treatment since the mid-20th century. For late-latent or syphilis infection of unknown duration, the standard treatment of multiple intramuscular injections of benzathine penicillin G (BPG) are associated with significant pain and distress to clients and caregivers, negatively impacting on treatment completion. Based on pharmacokinetic modelling from a Phase I study of subcutaneous infusion of high dose BPG (SCIP), we present its feasibility, safety and tolerability for treatment of syphilis in a single infusion. SCIP leads to more sustained penicillin concentrations above the desired target with less reported pain and reduced clinic visits.

Facilitated subcutaneous immunoglobulin treatment patterns in pediatric patients with primary immunodeficiency diseases.

Aim: This retrospective study investigated real-world hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) treatment patterns in pediatric patients with primary immunodeficiency diseases (PIDs) in Poland. Methods: Clinical and demographic information, fSCIG treatment parameters and clinical outcomes were extracted from medical records of 28 participants (aged ≤18 years) with PIDs who received fSCIG. Results: 18 participants (64.3%) started fSCIG with a ramp-up (median duration: 35.5 days). 27 patients (96.4%) were administered fSCIG every 4 weeks and one patient every 3 weeks. 25 patients (89.3%) used one infusion site. No serious bacterial infections occurred. Conclusion: Data support the feasibility of administering fSCIG to children and adolescents with PIDs every 3-4 weeks using a single infusion site and indicate flexibility in modifying fSCIG infusion parameters. Clinical Trial Registration: NCT04636502 (ClinicalTrials.gov).

Antibodies, also known as immunoglobulins, are proteins that are made by the immune system to help fight infections. In primary immunodeficiency diseases (PIDs), part of the immune system may be missing or not working properly. This study looked at the use of an antibody treatment called hyaluronidase-facilitated subcutaneous immunoglobulin (or fSCIG) in Polish children aged 18 years or younger with PIDs. Information on patients, their disease, how fSCIG was being used and how patients responded to treatment was taken from medical records. Out of 28 patients, 18/28 (64.3%) had their fSCIG dose slowly increased, which took an average of 35.5 days. Overall, 27/28 patients were treated with fSCIG every 4 weeks (96.4%), and 25/28 patients used one place to inject fSCIG (89.3%). No serious infections caused by bacteria happened during the study. The study results suggest that children with PIDs could be treated every 3 to 4 weeks with fSCIG, and that flexibility in how fSCIG is injected may offer options suited to individual patients.

Subcutaneous immunoglobulin replacement therapy in patients with immunodeficiencies - impact of drug packaging and administration method on patient reported outcomes.

BACKGROUND: Here, the perspective of patients with primary and secondary immunodeficiency receiving subcutaneous immunoglobulin (SCIg) via introductory smaller size pre-filled syringes (PFS) or vials were compared. METHODS: An online survey was conducted in Canada by the Association des Patients Immunodéficients du Québec (APIQ) (10/2020-03/2021). Survey questions included: reasons for choosing SCIg packaging and administration methods, training experiences, infusion characteristics, and switching methods. The survey captured structured patient-reported outcomes: treatment satisfaction and its sub-domains, symptom state, general health perception, and physical and mental function. Respondents using PFS were compared with vial users, overall and stratified by their administration method (pump or manual push). RESULTS: Of the 132 total respondents, 66 respondents used vials, with 38 using a pump and 28 using manual push. PFS (5 and 10 mL sizes) were being used by 120 respondents, with 38 using a pump and 82 using manual push. PFS users were associated with a 17% lower median (interquartile range) SCIg dose (10 [8, 12] vs. 12 [9, 16] g/week, respectively), a significantly shorter infusion preparation time (15 [10, 20] vs. 15 [10, 30] mins, respectively), and a trend for shorter length of infusion (60 [35, 90] vs. 70 [48, 90] mins, respectively) compared with those on vials. Patient-reported treatment satisfaction scores were overall similar between vial and PFS users (including on the domains of effectiveness and convenience), except for a higher score for vials over PFS on the domain of global satisfaction (p=0.02). CONCLUSIONS: Consistent with prescribing that reflects a recognition of less wastage, PFS users were associated with a significantly lower SCIg dose compared with vial users. PFS users were also associated with shorter pre-infusion times, reflecting simpler administration mechanics compared with vial users. Higher global satisfaction with treatment among vial users compared with PFS users was consistent with users being limited to smaller PFS size options in Canada during the study period. Patient experience on PFS is expected to improve with the introduction of larger PFS sizes. Overall, treatment satisfaction for SCIg remains consistently high with the introduction of PFS packaging compared with vials.

Subcutaneous Bolus Infusions of Undiluted Levetiracetam for End-of-Life Patients: Two Cases.

We present two cases, in which end-of-life patients were inadvertently treated with bolus infusions of undiluted subcutaneous levetiracetam. The patients were treated for three and four days respectively. In both cases, the course of treatment was uneventful. Especially, no seizures, nor local irritation was observed. Administration of undiluted subcutaneous levetiracetam as intermittent bolus infusions by hand holds alluring properties for end-of-life patients. Amongst others reducing patient discomfort, increasing freedom of movement, and accessibility to essential seizure prophylaxis by eliminating the need for a syringe driver, thereby helping accommodate many patients wish to die in their own home. However, pharmacokinetics, efficacy, and safety, including the optimum dilution and administration time of the subcutaneous preparation remains to be determined in clinically controlled trials.

Facilitated Subcutaneous Immunoglobulin Treatment Increases the Quality of Life and Decreases the Number of Infections and Hospitalizations in Children with Primary Immunodeficiencies.

INTRODUCTION: Immunoglobulin replacement therapy is an effective lifelong treatment modality used in patients with primary immunodeficiency to prevent and/or reduce the incidence of serious infections. Facilitated subcutaneous immunoglobulin (fSCIG) was developed to combine the advantages of intravenous immunoglobulin (IVIG) and subcutaneous immunoglobulin (SCIG) and is the latest method of immunoglobulin G (IgG) administration. In this study, switching to fSCIG administration in primary immunodeficiency patients receiving regular IVIG or SCIG therapy was evaluated, and serum IgG trough levels, frequency of infections, frequency and duration of hospitalizations, duration of absence from school/work, and quality of life were determined. METHODS: In this study, fifteen patients with primary immunodeficiency who were previously receiving IVIG or SCIG treatment, followed by fSCIG, were evaluated retrospectively. Age, diagnosis, current complications, mean IgG value, frequency of infection, frequency of hospitalization, and duration of absenteeism from school and work were recorded during and before fSCIG treatment. At the beginning of fSCIG treatment, at 6th and 12th months, "The Quality of Life Scale" was also evaluated in patients and parents. RESULTS: The most common indications for initiation of fSCIG treatment were the difficulty of access to the hospital and the long transfusion periods. No systemic adverse reactions were reported except for redness, swelling, and mild pain on the injection site. The median IgG values for the last 1 year were 529.6 mg/dL for IVIG (n = 9), 876.2 mg/dL for SCIG (n = 6) and 856.7 mg/dL for fSCIG (n = 15, all patients) treatment. The frequency of infections and the number of hospitalizations decreased significantly in the fSCIG group compared to both previous treatment modalities. There was a significant increase in the quality of life score of the patients and their families when compared with previous treatment modalities. CONCLUSION: fSCIG is an effective treatment method and is well tolerated in patients with immunodeficiency. It provides stable immunoglobulin levels and excellent protection against infections and offers the patients the possibility of home-based therapy.

Population pharmacokinetics of immunoglobulin G after intravenous, subcutaneous, or hyaluronidase-facilitated subcutaneous administration in immunoglobulin-naive patients with primary immunodeficiencies.

Immunoglobulin G (IgG) replacement therapy is the standard of care for patients with primary immunodeficiencies with antibody deficiencies. Intravenous (IVIG), subcutaneous (SCIG), and hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) therapies differ in their pharmacokinetic (PK) profiles, administration routes, and dosing regimens. Information on use of subcutaneous therapy in IgG treatment-naive patients is limited. This study used population pharmacokinetic (popPK) model-based simulations to characterize IgG PKs in IgG-naive patients with varying disease severity across several IVIG, SCIG, and fSCIG dosing regimens. An integrated popPK model, developed and validated using data from eight clinical trials, was utilized to simulate scenarios that varied by therapy, loading regimen, maintenance dose (equivalent to 400, 600, or 800 mg/kg every 4 weeks [Q4W]), and baseline endogenous total IgG concentration (1.5 or 4.0 g/L). Simulations were performed for age groups of 2-<6, 6-<12, 12-<18, and ≥18 years. Steady-state serum trough IgG concentrations (Cmin,ss), proportion of patients achieving Cmin,ss ≥ 7 g/L, and days taken to reach this threshold were summarized. SCIG provided greater mean Cmin,ss values than IVIG and fSCIG for any scenario. Across all therapies, Cmin,ss tended to increase with age, dose, and endogenous concentration. Although the findings are model-based and not a summarization of real-world observations, doses ≥ 800 mg/kg Q4W with corresponding loading regimens are likely to be clinically appropriate for achieving target IgG concentrations in treatment-naive patients in a timely manner, especially at low endogenous starting concentrations. Therapy-specific dose adjustment based on baseline endogenous IgG concentration, clinical status, and patient characteristics may be warranted.

A Phase 1 Open-Label Study to Assess the Tolerability, Safety, and Immunogenicity of Hyaluronidase-Facilitated Subcutaneous Immunoglobulin 20% in Healthy Adults.

PURPOSE: Hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) 20% will allow reduced infusion volumes and frequency versus existing subcutaneous therapies such as fSCIG 10% and conventional subcutaneous immunoglobulin 20%, respectively. We assessed the tolerability, safety, and immunogenicity of warmed and unwarmed fSCIG 20%. METHODS: This phase 1, single-dose, open-label, three-arm study enrolled healthy adults aged 19-50 years (inclusive) at a single US center (NCT05059977). Post-screening, participants received a single fSCIG 20% dose comprising recombinant human hyaluronidase and varying doses of in-line warmed or unwarmed immunoglobulin G (IgG) during a 4-day treatment period in a sentinel and sequential dosing design (treatment arm 1, warmed IgG 20% 0.4 g/kg; treatment arm 2, warmed IgG 20% 1.0 g/kg; treatment arm 3, unwarmed IgG 20% 1.0 g/kg). Participants were followed for 12 (± 1) weeks post-infusion. The primary endpoint was tolerability ("tolerable" infusions were not interrupted, stopped, or reduced in rate owing to fSCIG 20%-related treatment-emergent adverse events (TEAEs)). Secondary endpoints included occurrence of TEAEs. RESULTS: Overall, 24 participants were included, 8 per treatment arm (mean age 39.0 years, 54.2% men). All participants tolerated the infusions. All TEAEs were mild (107 events, in all participants), and all participants experienced fSCIG 20%-related (105 events) and local (102 events) TEAEs. Infusion site erythema and infusion site swelling were most frequently reported. No serious TEAEs occurred, and no participants discontinued the study owing to TEAEs. CONCLUSION: fSCIG 20% was well-tolerated with a favorable safety profile in healthy adults. Future studies will evaluate fSCIG 20% in primary immunodeficiency diseases. Trial registration number (ClinicalTrials.gov): NCT05059977 (registered 28 September 2021).

Inibidor da C1 esterase derivado de plasma via subcutânea para profilaxia de crises de angioedema hereditário / Plasma-derived C1 esterase inhibitor subcutaneously for prophylaxis of hereditary angioedema crises

INTRODUÇÃO: O angioedema hereditário (AEH) é uma imunodeficiência primária do sistema complemento, e foi classificado como um erro inato da imunidade em decorrência da deficiência de inibidor de C1 esterase, proteína que controla as vias de ativação do complemento. Trata-se de doença com herança autossômica dominante, heterogeneidade de lócus e expressividade variável. A classificação mais atualizada do AEH agrupa os pacientes naqueles com deficiência do inibidor da C1- esterase (C1-INH), codificado pelo gene SERPING1 e naqueles C1-INH normal (anteriormente denominado de tipo III). O diagnóstico é realizado através do exame clínico (anamnese, exame físico e quadro clínico) e laboratorial (dosagem de C4 e de C1-INH), além de teste genético (presença de mutação patogênica em SERPING1) para confirmação. Embora AEH não tenha cura, há tratamento para a profilaxia e controle das crises. Atualmente, para o tratamento de profilaxia, o Protocolo Clínico e Diretrizes Terapêuticas (PCDT) do angioedema associado a deficiência de C1 esterase (C1-INH) do Ministério da Saúde, recomenda o uso de andrógenos atenuados, sendo o mais utilizado o danazol, e plasma fresco congelado para o tratamento de crises. PERGUNTA 1: O inibidor de C1 esterase via subcutânea é uma alternativa na

Responsabilidades de autocuidado acordes a la edad en población pediátrica con diabetes tratada con ISCI / Age-appropriate self-care responsibilities in the pediatric population with diabetes treated with CSII

Objetivo: Determinar en población infantil con Diabetes tipo 1 (DT1) en tratamiento con infusión subcutánea continua de insulina (ISCI), si asumir responsabilidades de autocuidado tras recibir un programa estructurado de educación terapéutica (PEET) se relaciona con el control metabólico y la calidad de vida (CV). Métodos: Estudio observacional, transversal. Se realizó un sub-análisis retrospectivo. Se incluyeron sujetos con DT1 (edad 9-17 años) en terapia ISCI (>1año) que habían recibido el mismo PEET al inicio de ISCI. Se registraron: grado en que asumían responsabilidades de autocuidado acordes a su edad, control metabólico, CV, nivel de conocimientos sobre diabetes y uso de funciones específicas del dispositivo. Resultados: Se incluyeron 44 pacientes. Los niños que asumieron responsabilidades de autocuidado acordes a su edad presentaron valores de hemoglobina glicada (HbA1c) significativamente menores que los niños que no las asumieron (8,0±0,7% vs. 9,2±1,1%, respectivamente, p<0,001), así como una mayor puntuación en los cuestionarios de CV y de conocimientos (CV 84,3±9,3 vs. 79,4±10,6, p<0,01; conocimientos 27,9±4,2 vs. 26,5±4,3, respectivamente, n.s). El uso de las funciones específicas de la bomba se observó principalmente en aquellos que asumieron esas responsabilidades de autocuidado presentando valores más bajos de HbA1c que aquellos niños que no las utilizaron (7,9±1,0% vs. 8,4±0,8%, p<0,05). Conclusiones: Los pacientes con DT1 en tratamiento con ISCI que asumieron responsabilidades de autocuidado de su diabetes acorde a su edad, mostraron mejor control de HbA1c y mejor CV que aquellos que no lo hicieron. Se necesitan más estudios para profundizar en el conocimiento de estos aspectos. (AU)

Objective: The aim of this study was to determine if children and adolescents with type 1 diabetes (DT1) managed with continuous subcutaneous insulin infusion (ISCI) who assume self-care responsibilities tailored to the age after a specific structured education program (PEET), present better metabolic control and quality of life (CV). Methods: A observational, cross-sectional study was conducted. A retrospective sub-analysis was performed. Subjects with DT1 (aged 9-17 years) who have been using ISCI (>1year) were included. All patients received the same structured PEET when initiating ISCI treatment. The degree of self-care age-appropriate responsibilities assumed by children was registered. Data related to metabolic control, diabetes knowledge, use of different pump features, and quality of life were also collected. Results: Forty-four patients were included. Children assuming age-appropriate self-care responsibilities had a significantly lower glycated hemoglobin (HbA1c) value compared to those children who did not take on these responsibilities (8,0±0,7% vs. 9,2±1,1%, p<0,001). as well as higher scores in the CV and knowledge questionnaires (84,3±9,3 vs. 79,4±10,6 respectively, p<0,01; knowledge 27,9±4,2 vs. 26,5±4,3, respectively, n.s). The use of specific pump features was mainly observed in those who assumed age-appropriate self-care responsibilities and showed lower HbA1c values than those children who did not take on these responsibilities (7,9±1,0% vs. 8,4±0,8%, p<0,05). Conclusion: Patients with DT1 managed with ISCI, who assumed age-appropriate responsibilities on disease self- management, showed better HbAc1 and better CV than those who did not. More studies are needed to deepen the knowledge of these topics. (AU)