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.

Long-term safety of hyaluronidase-facilitated subcutaneous immunoglobulin 10%: a European post-authorization study.

Aim: To assess the long-term safety of hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) 10% in European routine clinical practice.Materials & methods: This prospective, noninterventional, open-label, post-authorization safety study (EUPAS5812) sourced data on adverse events, immunogenicity, treatment regimens and product administration for 106 adult patients prescribed fSCIG 10% across 17 sites in six European countries from July 2014 to February 2020.Results: In total, 1171 treatment-emergent adverse events were reported in 94 patients (88.7%); 25.5% of these events were considered related to fSCIG 10%. Positive binding antibody titers developed in three patients; no neutralizing antibodies to recombinant human hyaluronidase were detected.Conclusion: This real-world study of fSCIG 10% is the longest to date and confirms its long-term safety and tolerability in adults with antibody deficiency diseases.

One way that the immune system fights infection is by making proteins known as antibodies, also called immunoglobulins. In conditions known as primary immunodeficiency diseases or secondary immunodeficiency diseases, the immune system may not work properly and so treatment with immunoglobulins might be needed. This study looked at the use of an antibody treatment called hyaluronidase-facilitated subcutaneous immunoglobulin (or fSCIG) in European adults mostly with primary immunodeficiency diseases in the real world. Details of adverse events and how fSCIG was used was taken from patient medical records and other documents, and information provided by patients. Of 106 patients, 94 (88.7%) reported 1171 adverse events which started during fSCIG treatment, and 25.5% of these events were considered related to patients receiving fSCIG. For the 105 patients who had information available, 66 patients (62.9%) were treated with fSCIG every 4 weeks. The study results support that fSCIG has a beneficial safety profile in adults with primary or secondary immunodeficiency diseases.

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.

Use of immunoglobulin replacement therapy in patients with secondary antibody deficiency in daily practice: a European expert Q&A-based review.

INTRODUCTION: Secondary antibody deficiencies (SAD) are often a side effect of specific therapies that target B cells directly or affect the antibody response indirectly. Treatment of immunodeficiency by immunoglobulin replacement therapy (IgRT) is well established in primary antibody deficiencies, although the evidence for its use in SAD is less well established. To fill the gap and provide opinion and advice for daily practice, a group of experts met to discuss current issues and share best practical experience. AREAS COVERED: A total of 16 questions were considered that covered use of a tailored approach, definition of severe infections, measurement of IgG levels and specific antibodies, indications for IgRT, dosage, monitoring, discontinuation of IgRT, and Covid-19. EXPERT OPINION: Key points for better management SID should include characterization of the immunological deficiency, determination of the severity and degree of impairment of antibody production, distinguish between primary and secondary deficiency, and design a tailored treatment protocol that should include dose, route, and frequency of Ig replacement. There remains the need to carry out well-designed clinical studies to develop clear guidelines for the use of IgRT in patients with SAD.

In-line warming reduces in-line pressure of subcutaneous infusion of concentrated immunoglobulins.

Immunoglobulin replacement therapy is a life-saving treatment in patients with immunodeficiency and effective in the management of autoimmune disorders. Immunoglobulins are administered intravenously or subcutaneously, with the latter route reducing systemic reactions and providing an option for self-infusion, increasing patient convenience, while decreasing patient burden, healthcare utilization, and costs. A major limitation with subcutaneous administrations is the frequency of infusion due to limited volumes administrable into subcutaneous space, necessitating increased drug concentration, absorption, and dispersion. Increasing the concentration of immunoglobulins from 10 to 20% halves the required volume, but leads to higher dynamic viscosity, limiting infusion rate. Recombinant human hyaluronidase increases dispersion and absorption of immunoglobulins allowing administration of ≤ 600 mL per site, but does not change viscosity. Since the viscosity of fluids depends on temperature, we tested the feasibility of in-line warming of immunoglobulin formulations to physiological temperatures. In vitro analysis showed no negative impact of in-line warming to 38 °C on product quality. Subcutaneous infusion studies in pigs confirmed the feasibility of infusion rates of up to 7.5 mL/min with in-line warmed TAK-881, an immunoglobulin 20% facilitated with recombinant human hyaluronidase. In-line pressures were reduced compared with conventional immunoglobulin 20%, and local tolerance was not altered. Reduction of in-line pressures was more pronounced with thinner needle sets, indicating a potential benefit for patients. In summary, an in in-line warming device can circumvent the limitation of high viscosity, while product quality and local tolerance are maintained. The results of the presented studies warrant further testing in a phase 1 clinical study.

Intravenous and subcutaneous immunoglobulins-associated eczematous reactions occur with a broad range of immunoglobulin types: A French national multicenter study.

BACKGROUND: Human immunoglobulins are used for treating diverse inflammatory and autoimmune disorders. Eczema is an adverse event reported but poorly described. OBJECTIVES: To describe the clinical presentation, severity, outcome, and therapeutic management of immunoglobulin-associated eczema. METHODS: This retrospective and descriptive study included a query of the French national pharmacovigilance database, together with a national call for cases among dermatologists. RESULTS: We included 322 patients. Eczema occurred preferentially in men (78.9%) and in patients treated for neurological pathologies (76%). The clinical presentation consisted mainly of dyshidrosis (32.7%) and dry palmoplantar eczema (32.6%); 5% of cases exhibited erythroderma. Sixty-two percent of the eczema flares occurred after the first immunoglobulin course. Eczema was observed with 13 intravenous or subcutaneous immunoglobulin types and recurred in 84% of patients who maintained the same treatment and in 68% who switched the immunoglobulin type. After immunoglobulin discontinuation, 30% of patients still had persistent eczema. LIMITATIONS: Retrospective study, with possible missing data or memory bias. CONCLUSION: Immunoglobulin-associated eczema occurred with all immunoglobulin types, preferentially in patients with neurologic diseases who required prolonged immunoglobulin treatment. Recurrence was frequent, even after switching the immunoglobulin type, which can lead to a challenging therapeutic situation when immunoglobulin maintenance is required.

Serum Sickness like Reaction Postequine Rabies Immunoglobulins.

A 30-year-old, previously healthy adult male received equine rabies immunoglobulins (Ig) (ERIG) along with anti-rabies vaccinations as per protocol for postexposure prophylaxis after an unprovoked rabid dog bite of grade three wound over the shin of the left lower limb. On the 8th day, he developed urticarial rashes beginning from the site of the wound, which gradually became a widespread maculopapular rash. Development of the rash was followed by low-grade fever, nonspecific arthralgias and soreness in the throat. A diagnosis of serum sickness-like illness was made based on history, temporal correlation of administration of ERIG and development of symptoms. He responded well to antihistaminic and a short course of injectable steroids. The purpose of this article is to increase awareness regarding the clinical presentation and management of this rare yet potentially curable adverse event if identified timely.

Eficacia y seguridad de romiplostim en pacientes pediátricos con trombocitopenia inmune primaria crónica, respuesta inadecuada o intolerancia a inmunoglobulina, corticoesteroides e intolerancia a eltrombopag, no candidatos a esplenectomía / Efficacy and safety of romiplostim in pediatric patients with chronic primary immune thrombocytopenia, inadequate response or intolerance to immunoglobulin, corticosteroids and intolerance to eltrombopag, not candidates for splenectomy

ANTECEDENTES: El presente dictamen expone la evaluación de la eficacia y seguridad de romiplostim en pacientes pediátricos con trombocitopenia inmune primaria crónica, respuesta inadecuada o intolerancia a inmunoglobulina, corticoesteroides y eltrombopag, no candidatos a esplenectomia. ASPECTOS GENERALES: La trombocitopenia inmunitaria (TPI), anteriormente conocida como púrpura trombocitopénica idiopática o púrpura trombocitopénica inmunitaria, es una enfermedad autoinmune caracterizada por la disminución de plaquetas (conteo de plaquetas menor de 100 x 109/L con conteo normal de células blancas y hemoglobina) (Bussel 2020). La TPI es considerada primaria cuando no existen causas o desórdenes que puedan estar asociados a la trombocitopenia, y crónica cuando tiene una duración mayor a 12 meses (Bussel 2020). En Estados Unidos, entre el 2011 y el 2016, la TPI crónica en niños menores de 18 años representó el 15.9 % de los casos de TPI (Shaw et al. 2019). En Perú no se han reportado datos epidemiológicos de la TPI en niños. La TPI es una enfermedad infrecuente cuyas estimaciones más robustas de su incidencia anual están en el rango de 1.9 a 6.4 casos por cada 100,000 niños (Terrell et al. 2010). Dada la poca frecuencia de la enfermedad, los estimados de mortalidad son escasos; pero se señala que la mortalidad en pacientes pediátricos con TPI es muy rara. La mortalidad en los pacientes recién diagnosticados se debe principalmente a las complicaciones del sangrado (e.g. hemorragia intracraneal); pero en los pacientes con TPI crónica puede ocurrir por complicaciones del tratamiento inmunosupresor de largo plazo (Bussel 2022). La incidencia de hemorragia intracraneal también es infrecuente (menor al 1 %); sin embargo, sería ligeramente mayor en los pacientes con TPI crónica (Psaila et al. 2009). TECNOLOGÍA SANITARIA DE INTERÉS: Romiplostim (NPLATE ®, AMGEN) es un TPO-RA que pertenece a la clase de agonistas miméticos (FDA 2020). Romiplostim es una proteína de fusión que media y activa las vías de transcripción intracelular a través del receptor de TPO para aumentar la producción de plaquetas (Tecnofarma 2020). Este medicamento se obtiene por tecnología de ácido desoxirribonucleico recombinante en E. coli (Tecnofarma 2020). METODOLOGÍA: La búsqueda de la literatura se realizó con el objetivo de identificar evidencia sobre la eficacia y seguridad de romiplostim, comparado con la mejor terapia de soporte (corticoesteroides e inmunoglobulina), en pacientes pediátricos con trombocitopenia inmune primaria crónica, respuesta inadecuada o intolerancia a inmunoglobulina, corticoesteroides e intolerancia a eltrombopag, no candidatos a esplenectomía. La búsqueda de la evidencia se realizó en las bases de datos bibliográficas: PubMed, LILACS y The Cochrane Library. Adicionalmente, se amplió la búsqueda revisando la evidencia generada por grupos internacionales que realizan revisiones sistemáticas, evaluaciones de tecnologías sanitarias y guías de práctica clínica, tales como The National Institute for Health and Care Excellence (NICE), The Canadian Agency for Drugs and Technologies in Health (CADTH), Centro Nacional de Excelencia Tecnológica en Salud (CENETEC), Scottish Intercollegiate Guidelines Network (SIGN), Institute for Quality and Efficiency in Health Care (IQWiG), Scottish Medicines Consortium (SMC), Agency for Healthcare Research and Quality's (AHRQ), National Health and Medical Research Council (NHMRC), New Zealand Guidelines Group (NZGG), Haute Autorité de Santé (HAS), Institute for Clinical and Economic Review (ICER), y Comissáo nacional de incorpornáo de tecnologías no sus (CONITEC), Canadian Medical Association (CMA), American College of Physicians Clinical Practice Guidelines, American Society of Hematology (ASH), y Registered Nurses Association of Ontario (RNAO). Adicionalmente, se realizó una búsqueda manual en las bases The Guidelines International Network (G-I-N), el portal de la Base Regional de Informes de Evaluación de Tecnologías en Salud de las Américas (BRISA), y el repositorio institucional de la Dirección General de Medicamentos, Insumos y Drogas (DIGEMID). Asimismo, se colectó información sobre el medicamento de interés del presente dictamen en las páginas web de la European Medicines Agency (EMA), y Food and Drug Administration (FDA). Finalmente, se realizó una búsqueda manual en el portal ClinicalTrials.govdel National Institutes of Health (NIH) para identificar ensayos clínicos en desarrollo o que aún no hayan sido publicados. RESULTADOS: Guías de práctica clínica (GPC) Publicaciones incluidas en la sección de descripción y evaluación: Neunert et al., 2021. "American Society of Hematology 2019 guidelines for immune thrombocytopenia" (Cindy Neunert et al. 2019). Provan et al., 2019. "Updated international consensus report on the investigation and management of primary immune thrombocytopenia" (Provan et al. 2019). Publicaciones No incluidas en la sección de descripción y evaluación: La siguiente GPC no fue incluida dentro de la evidencia del presente dictamen porque no brinda recomendaciones para la población objetivo del presente dictamen (pacientes con intolerancia a un primer TPO-RA y no candidatos a esplenectomía). Centro Nacional de Excelencia Tecnológica en Salud (CENETEC). "Diagnóstico y Tratamiento de Trombocitopenia Inmune Primaria" (CENETEC 2019). La siguiente GPC no fue incluida en la evidencia del presente dictamen porque los autores no realizaron una búsqueda sistemática de la evidencia para formular sus recomendaciones. Matzdorff et al., 2018. "Immune Thrombocytopenia - Current Diagnostics and Therapy: Recommendations of a Joint Working Group of DGHO, OGHO, SGH, GPOH, and DGTI" (Matzdorff et al. 2018). La siguiente GPC no fue incluida dentro de la evidencia del presente dictamen porque se encuentra disponible una versión más actualizada de la guía. Neunert et al., 2011. "The American Society of Hematology 2011 evidencebased practice guideline for immune thrombocytopenia" (Cindy Neunert et al. 2011). CONCLUSIONES: En el presente dictamen, se evaluó la mejor evidencia científica, disponible hasta la actualidad, en relación con la eficacia y seguridad de romiplostim en pacientes pediátricos con trombocitopenia inmune primaria crónica, respuesta inadecuada o intolerancia a inmunoglobulina, corticoesteroides e intolerancia a eltrombopag, no candidatos a esplenectomía. La búsqueda sistemática de la evidencia culminó con la selección de una GPC (Provan et al. 2019). También, se analizó la GPC de la ASH, que fue sugerida por los especialistas de EsSalud (Cindy Neunert et al. 2019). Además, debido a que no se encontraron estudios que evaluaran el uso de romiplostim versus corticoesteroides o inmunoglobulina, se analizaron los resultados del ECA de fase III, pivotal de romiplostim (Tarantino et al. 2016). La GPC de la ASH no brinda recomendaciones para pacientes que hayan recibido previamente un TPO-RA, característica de la población de interés para el presente dictamen. El reporte de consenso de Provan et al. recomienda, basada en la experiencia/opinión de expertos, cambiar a un TPO-RA alternativo y/o considerar combinarlo con inmunosupresores, en pacientes en los que no hay respuesta a un TPO-RA o se pierde la respuesta. El ECA de Tarantino et al., pivotal de romiplostim, que compara el uso de romiplostim versus placebo, muestra que romiplostim generaría un beneficio en términos de la respuesta plaquetaria duradera y respuesta plaquetaria general. No se observaron diferencias en la incidencia de episodios de sangrado serio y EA serios, calidad de vida y el uso de medicamentos de rescate. Los especialistas de EsSalud señalan que los pacientes pediátricos con TPI y conteo de plaquetas menores de 10 x 109/L tienen un mayor riesgo de sangrado serio (i.e hemorragias intracraneales). En línea con esto, en la literatura se indica que un conteo plaquetas menor de 10 x 109/L o 20 x 109/L es un predictor de sangrado serio. En el ECA de Tarantino et al., pivotal de romiplostim, la mitad de los participantes que recibieron romiplostim tuvieron un conteo basal de plaquetas menor de 20 x 109/L; por lo que es plausible que la respuesta plaquetaria producida con el uso de romiplostim sí reduzca el riesgo de sangrado serio en aquellos pacientes cuyo conteo de plaquetas es menor de 10 x 109/L o de 20 x 109/L. Por todo lo expuesto, el 'ETS' aprueba el uso de romiplostim en pacientes pediátricos con trombocitopenia inmune primaria crónica; respuesta inadecuada o intolerancia a inmunoglobulina, corticoesteroides; intolerancia a eltrombopag; no candidatos a esplenectomía, y conteo de plaquetas menor de 20 x 109/L a pesar del tratamiento, según lo establecido en el Anexo N°1. Debido a la incertidumbre sobre el balance riesgo-beneficio, no se aprueba el uso de romiplostim en los pacientes con conteo de plaquetas mayor o igual a 20 x 109/L. La vigencia del presente dictamen preliminar es de un año a partir de la fecha de publicación. Así, la continuación de dicha aprobación estará sujeta a la evaluación de los resultados obtenidos y de mayor evidencia que pueda surgir en el tiempo.

Subcutaneous immunoglobulins replacement therapy in secondary antibody deficiencies: Real life evidence as compared to primary antibody deficiencies.

Secondary antibody deficiencies (SAD) may require immunoglobulin replacement therapy (IgRT). While the intravenous route (IVIG) is broadly considered effective in SAD, the use of subcutaneous immunoglobulins (SCIG) is mainly adopted from the experience in primary antibody deficiencies (PAD), where SCIG have been shown to perform as effective as IVIG. However, evidence-based data on SCIG administration in SAD patients are still insufficient. Herein we retrospectively evaluated the efficacy and safety profile of SCIG treatment in 131 SAD patients as compared to a group of 102 PAD patients. We found SCIG being equally effective in reducing annual infectious rate both in SAD and PAD patients. However, SAD patients required lower SCIG dosage and lower IgG through level to achieve similar biological effect in terms of infection burden, at the steady state. SAD patients also showed better correlation between SCIG dose and serum IgG achieved value. Furthermore, within SAD, SCIG were found to work irrespective of the underlying disease. Especially in Non-Hodgkin Lymphoma patients, whose indication to IgRT is still not included in all guidelines and for whom evidence-based data are still lacking, SCIG were as effective as in Chronic Lymphocytic Leukemia or Multiple Myeloma patients, and SCIG discontinuation, without evidence of B cell recovery, led to IgG decline and relapsed infections. Finally, treatment tolerance in SAD patients was comparable to the PAD cohort. Globally, our data suggest that SCIG, as already appreciated in PAD, represent a valuable option in SAD patients, independent on the disease leading to antibody deficiency.

Is Lutikizumab, an Anti-Interleukin-1α/ß Dual Variable Domain Immunoglobulin, efficacious for Osteoarthritis? Results from a bayesian network meta-analysis.

OBJECTIVE: Most guidelines recommend the use of nonsteroidal anti-inflammatory drugs (NSAIDs), duloxetine, and tramadol for the nonoperative treatment of osteoarthritis (OA), but the use of them is limited by the tolerability and safety concerns. Lutikizumab is a novel anti-IL-1α/ß dual variable domain immunoglobulin that can simultaneously bind and inhibit IL-1α and IL-1ß to relieve the pain and dysfunction symptoms. We conducted this network meta-analysis to comprehensively compare the clinical efficacy and safety of lutikizumab with other drugs recommended by guidelines. METHODS: We conducted a Bayesian network and conventional meta-analyses to compare the efficacy and safety of lutikizumab with other traditional drugs. All eligible randomized clinical trials, in PubMed, CNKI, EMBASE, and Web of Science databases, from January 2000 to January 2020, were included. The Cochrane risk of the bias assessment tool was used for quality assessment. Pain relief, function improvement, and risk of adverse effects (AEs) were compared in this study. RESULTS: 24 articles with 11858 patients were included. Duloxetine (DUL) had the largest effect for pain relief (4.76, 95% CI [2.35 to 7.17]), and selective cox-2 inhibitors (SCI) were the most efficacious treatment for physical function improvement (SMD 3.94, 95% CI [2.48 to 5.40]). Lutikizumab showed no benefit compared with placebo for both pain relief (SMD 1.11, 95% CI [-2.29 to 4.52]) and function improvement (SMD 0.992, 95% CI [-0.433 to 4.25]). Lutikizumab and all other drugs are of favorable tolerance for patients in the treatment of OA compared with placebo. CONCLUSIONS: Lutikizumab, the new anti-Interleukin-1α/ß dual variable domain immunoglobulin, showed no improvement in pain or function when compared with placebo. Selective cox-2 inhibitors and duloxetine remain the most effective and safest treatment for OA. More high-quality trials are still needed to reconfirm the findings of this study.

Facilitated Subcutaneous Immunoglobulin Replacement Therapy in Clinical Practice: A Two Center, Long-Term Retrospective Observation in Adults With Primary Immunodeficiencies.

Facilitated subcutaneous immunoglobulin (fSCIG) replacement therapy is the latest method of IgG administration; however, real-life data are limited. We retrospectively analyzed the everyday experience of fSCIG administration, particularly, the method used to switch from intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (SCIG) to fSCIG and the dosing modifications required. Of the 39 adult patients with primary immunodeficiency (PID) who received fSCIG, 34 remained on the therapy at the end of the study. The median observation time was 18 (range, 3-24) months. Two patients were IgG-treatment-naïve; 23 had previously received IVIG and 14 had received SCIG. In 25 cases, a non-ramp-up dosing mode was used to switch to fSCIG (including two half-monthly doses given biweekly in 14 cases, and full monthly doses given in 11 cases), a ramp-up mode was used in six cases; other methods were used in eight cases. The median IgG trough level at baseline was 7.9 g/L (n = 38), 7.9 g/L (n = 32) at Month 6, 9.0 g/L (n = 30) at Month 12, 8.6 g/L (n = 22) at Month 18, and 9.0 g/L (n = 11) at Month 24. No serious bacterial infections or hospitalizations due to PID complications occurred. At the end of the study, 24 patients (71%) received fSCIG every 4 weeks, six (18%) received fSCIG every 3 weeks, and four (12%) received fSCIG biweekly. In conclusion, our study provides real-life evidence of clinical efficacy of personalized fSCIG treatment when switching from prior immunoglobulin replacement using various switching modes and dosing frequencies.

Nuts and Bolts of Subcutaneous Therapy.

Immunoglobulin replacement therapy is standard of care in treatment of many primary immunodeficiency diseases. The goal of replacement therapy is to reduce infections in individuals with primary immune deficiency and improve their quality of life. Immunoglobulin replacement therapy is most often lifelong, therefore ease of administration is vital for adherence to treatment. Self-infusion via subcutaneous intravenous immunoglobulin (SCIG) allows patient input to design an individualized and optimal treatment plan. Because SCIG regimens are flexible and allow for increased autonomy, patients receiving SCIG report improved quality of life. This article summarizes the dosing, administration, and adverse event management of SCIG infusions.

Switch from intravenous or intramuscular to subcutaneous hepatitis B immunoglobulin: effect on quality of life after liver transplantation.

BACKGROUND: Hepatitis B immunoglobulin (HBIG) therapy is available in intravenous (IV) or intra-muscular (IM) formulations. Recently, a subcutaneous (SC) formulation was introduced. This study evaluated changes in quality of life when liver transplant (LT) recipients were switched from IV or IM HBIG to the SC formulation. METHODS: This multicentre, observational study involved adults who had undergone LT at least 1 year prior to study entry. Quality of life was evaluated using the ITaLi-Q questionnaire, assessing the impact of HBIG therapy on daily activities and patient satisfaction, and the SF-36 Health Survey. Patients completed the questionnaires prior to switching from IV or IM HBIG to SC HBIG and 6 months later. RESULTS: Eighty-six patients were enrolled; before the switch, 68.6% were receiving IM HBIG and 31.4% IV HBIG. After 6 months, significant improvements in 7 of the 8 ITaLi-Q domains were found, particularly side effects, need for support to adhere to the therapy and satisfaction with the HBIG therapy. Significant improvements in several SF-36 domains were documented, including physical functioning, physical and emotional role limitations, pain, social functioning, physical and mental summary scores. CONCLUSIONS: The SC route of administration reduces side effects and their interference with daily life, ameliorates negative feelings, and increases patient autonomy.

Efficacy and tolerability of subcutaneously administered immunoglobulin in myasthenia gravis: A systematic review.

Subcutaneous immunoglobulin (SCIg) is an emerging therapeutic alternative in the management of myasthenia gravis (MG) due to its potential efficacy, safety, cost effectiveness and ease of administration. At present, there are no systematic reviews that summarized the effects of SCIg in patients with MG. The objective of this study is to determine the efficacy and safety of SCIg in the treatment of adult patients with myasthenia gravis. Relevant records were identified from August 2018 to January 2019 systematic search. Five relevant articles with a total of 34 patients with MG were included in this review. Data on functional disability score and adverse events were obtained. Based on the included uncontrolled studies, the functional disability scores of adult MG patients after SCIg administration showed consistent improvement. Headache and local site injection reactions were the most common adverse events reported. The evidence from limited uncontrolled studies gathered in this review showed that SCIg may improve functional disability in patients with MG. Local and mild adverse events were reported with its administration, but no systemic and serious adverse events were noted.

Keep the cat, change the care pathway: A transformational approach to managing Fel d 1, the major cat allergen.

BACKGROUND: Allergies to cats are the most common animal-origin allergy, and affect approximately 1 in 5 adults worldwide. The prevalence of allergy to furry animals has been increasing, and allergy to cats is a major risk factor for the development of asthma and rhinitis. The diagnosis of cat allergy is now well established. The exact significance of component-resolved diagnosis in the diagnosis of cat allergy remains to be fully understood. Allergen avoidance is effective but often has a psychologic impact. Allergen immunotherapy is not well demonstrated. There is a need for innovative approaches to better manage cat allergens. Next-generation care pathways for asthma and rhinitis will define the place of cat allergen avoidance. METHODS AND RESULTS: This manuscript, based on content presented at the European Academy of Allergy and Clinical Immunology Congress 2019, provides information on the prevalence and impact of cat allergies and the molecular biology of Fel d 1, the major cat allergen. DISCUSSION: The authors present the scientific basis of a novel care pathway that utilizes anti-Fel d 1 IgY antibodies to safely and effectively neutralize Fel d 1 after its production by the cat but before human exposure. CONCLUSION: Efficacy of a feline diet with an egg product ingredient containing anti-Fel d 1 IgY antibodies was demonstrated in vitro, ex vivo, and in vivo, and further validated by a pilot exposure study involving cat-allergic human participants.

Romiplostim for the management of pediatric immune thrombocytopenia: drug development and current practice.

Since successful cloning of thrombopoietin (TPO) in 1994, significant advances have been made in the development of recombinant TPO receptor agonists. The US Food and Drug Administration (FDA) has approved 2 agents for use in patients with immune thrombocytopenia (ITP): eltrombopag and romiplostim. Romiplostim is a once-weekly subcutaneous injection that has been shown to increase the platelet count, lessen bleeding, and reduce concurrent medication use in adults with ITP. In December 2018, the US FDA approved romiplostim for use in pediatric patients ≥1 year of age with ITP of >6 months' duration and insufficient response to corticosteroids, immunoglobulins, or splenectomy, based on similarly favorable clinical trial data. In addition, romiplostim is well tolerated, making it an attractive option for the treatment of children. Expansion of off-label romiplostim use is being reported in children for ITP <6 months, neonatal thrombocytopenia, hereditary thrombocytopenias, and chemotherapy- and bone marrow transplant-associated thrombocytopenia. We review here the development of romiplostim with a focus on pediatric use.

Switching immunoglobulin products, what are the implications? Result of 2018 census of immunology centres.

The use of regular infusions of immunoglobulin is well established as a treatment for patients with antibody deficiency and for patients requiring immunomodulation. Although efficacy is believed to be equivalent for the different immunoglobulin products, it is generally regarded as best practice not to switch from one product to another unless there is a clinical reason to change. Changes in commissioning guidance and issues with the supply of some immunoglobulin products to the UK resulted in a requirement for a significant number of patients to switch between immunoglobulin products in 2017-2018. Data from the 2018 UK Primary Immunodeficiency census has been used to evaluate the clinical results of switching. Results from 30 immunology centres reported a total of 802 immunoglobulin product switches. Twelve reactions were recorded, none of which required admission to hospital, one patient was treated with oral corticosteroids, the others required either no treatment or treatment with oral antihistamines. This review of immunoglobulin product switch reactions gives a clearer indication regarding the safety of product switching than has previously been published.