Subcutaneous Immunoglobulin Infusions Research Articles

Cost-minimization analysis of HYQVIA® in the treatment of primary immunodeficiency disease (PID) and secondary immunodeficiency disease (SID) in Italy

Background: Primary (PID) or secondary (SID) immunodeficiencies are diseases caused by quantitative and/or functional alterations of the different mechanisms involved in the innate and adaptive immune response. This economic evaluation was conducted to compare the cost of treatment of HYQVIA® (hyaluronidase-facilitated subcutaneous infusion of immunoglobulin, fSCIG) compared to intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (SCIG), currently reimbursed in Italy, in the treatment of PIDs or SIDs. Methods: A cost-minimisation analysis was carried out, considering the hospital’s perspective. The direct medical costs (cost of immunoglobulins and cost of administration) were assessed. The analysis was conducted considering one year (52 weeks) time horizon. The reference population included adult patients with PID with impaired antibody production or adult patients with SID with severe or recurrent infections, ineffective antimicrobial treatment and documented specific antibody defect (PSAF) or serum IgG level < 4 g/L. Results: In the maintenance treatment of PID, HYQVIA® (€ 20,020.00) was the therapeutic alternative with the lowest mean annual cost compared to HIZENTRA® (€ 22,165.19) and VENITAL® (€ 24,967.68). Moreover, in the maintenance treatment of SIDs, HYQVIA® (€ 17,160.00) was the cost-saving therapeutic alternative compared to VENITAL® (€ 22,107.68). A sensitivity analysis confirmed the base case results. Conclusion: Due to lower costs of administration and different scheme of administration, HYQVIA® was a cost-saving alternative to SCIG e IVIG in the treatment of PID and to IVIG in the treatment of SID

Facilitated subcutaneous immunoglobulin 10% at a target dose of 0.4 g/kg/infusion is well tolerated with accelerated or no dose ramp-up in healthy participants

IntroductionTransitioning to recombinant human hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) infusions from intravenous immunoglobulin therapies in primary immunodeficiency disease (PID) is implemented using a gradual dose ramp-up schedule, whereby infusion volumes are increased over a number of weeks to achieve the target dose level (TDL). This study investigated the tolerability and safety of fSCIG 10% at a TDL of 0.4 g/kg/infusion (i.e. 4 mL/kg/infusion) with accelerated and no dose ramp-up schedules in comparison with conventional dose ramp-up. MethodsThis was a phase 1, open-label, single-center trial (NCT04578535). This analysis compared three fSCIG 10% treatment arms at a TDL of 0.4 g/kg/infusion: (i) conventional dose ramp-up from 0.1 g/kg/infusion at Week 1 increasing to the TDL at Week 8; (ii) accelerated dose ramp-up from 0.2 g/kg/infusion at Week 1 increasing to the TDL at Week 5; (iii) the TDL administered without dose ramp-up. Participants were healthy adults aged 19–50 years. The primary endpoint was the tolerability of fSCIG 10% infusions, assessed as the proportion of participants who completed all initiated infusions without interruptions, stoppages or reductions in infusion rate due to treatment-emergent adverse events (TEAEs). Safety was assessed as a secondary endpoint. ResultsTwenty-four participants (mean [standard deviation] age 35.3 [8.6] years; 62.5% female) were assigned equally to the three treatment arms. All participants completed all initiated infusions except for one participant who experienced a headache resulting in an infusion rate reduction in the conventional dose ramp-up arm. All participants experienced local TEAEs, including infusion site swelling, erythema, pain and pruritus. Systemic TEAEs were experienced by 1/8 (12.5%), 2/8 (25.0%) and 2/8 (25.0%) participants in the conventional, accelerated and no dose ramp-up arms, respectively. All TEAEs were mild in severity. ConclusionsfSCIG 10% at a target dose of 0.4 g/kg/infusion showed a favorable safety and tolerability profile in healthy adults, with comparable tolerability and safety outcomes between the dose ramp-up treatment arms. Accelerated and no dose ramp-up schedules could be considered as potential alternatives to conventional dose ramp-up.Takeda Development Center Americas, Inc. funded this study. Takeda Pharmaceuticals International AG funded writing support.

PAINFUL SKIN LESIONS AFTER STARTING SUBCUTANEOUS IMMUNOGLOBULIN REPLACEMENT

<h3>Introduction</h3> 17-year-old female with history of Behcet's, Sweet's syndrome, Chilblain lupus, inflammatory arthritis and ileitis complains of painful skin lesions of the extremities after initiation of subcutaneous immunoglobulin (SCIg) replacement (Cutaquig). <h3>Case Description</h3> Patient is on multiple immunosuppressants including ustekinumab, canakinumab, and leflunomide managed by Rheumatology. She has received intermittent IVIg at ∼1 g/kg (anti-inflammatory dosing) for joint pain and skin lesions. Due to post-IVIg headaches, SCIg was opted and the patient was started on Cutaquig 15 g weekly. On the 2nd - 3rd Cutaquig infusions, painful red/purplish lesions appeared on fingers and toes bilaterally, which worsened weekly with the infusions. Skin biopsy was considered, but the lesions crusted and resolved over a few weeks shortly after Cutaquig was stopped. Allergy and Immunology (A/I) has been involved in the patient's care for concern for hypogammaglobulinemia with lowest IgG at 469 mg/dL. Past immune evaluation showed normal IgG and appropriate response to Pneumovax two years ago. Genetic testing has been unremarkable so far. Recent evaluation revealed persistently low IgG and gradually down trending IgA at 623 mg/dL and 45 mg/dL, respectively. Additionally, the patient also had a few ear infections; thus, A/I currently trialing Cuvitru at IgG replacement dosing (∼500 mg/kg). <h3>Discussion</h3> Systemic reaction to SCIg infusions are rare and thus well tolerated by patients. In contrast, local reactions with swelling, pain, and bruising on SCIg infusion sites have been well reported. To our knowledge, systemic dermatological adverse reactions due to SCIg have not been reported in the past.

Cost-minimization analysis of immunoglobulin treatment of primary immunodeficiency diseases in Spain

Primary immunodeficiency diseases (PID), which are comprised of over 400 genetic disorders, occur when a component of the immune system is diminished or dysfunctional. Patients with PID who require immunoglobulin (IG) replacement therapy receive intravenous IG (IVIG) or subcutaneous IG (SCIG), each of which provides equivalent efficacy. We developed a cost-minimization model to evaluate costs of IVIG versus SCIG from the Spanish National Healthcare System perspective. The base case modeled the annual cost per patient of IVIG and SCIG for the mean doses (per current expert clinical practice) over 1 year in terms of direct (drug and administration) and indirect (lost productivity for adults and parents/guardians of pediatric patients) costs. It was assumed that all IVIG infusions were administered in a day hospital, and 95% of SCIG infusions were administered at home. Drug costs were calculated from ex-factory prices obtained from local databases minus the mandatory deduction. Costs were valued on 2018 euros. The annual modeled costs were €4,266 lower for patients with PID who received SCIG (total €14,466) compared with those who received IVIG (total €18,732). The two largest contributors were differences in annual IG costs as a function of dosage (– €1,927) and hospital administration costs (– €2,688). However, SCIG incurred training costs for home administration (€695). Sensitivity analyses for two dose-rounding scenarios were consistent with the base case. Our model suggests that SCIG may be a cost-saving alternative to IVIG for patients with PID in Spain.

Treatment of Children with Primary Immunodeficiencies with a Subcutaneous Immunoglobulin 16.5% (Cutaquig ® [Octanorm

Background: Subcutaneous human immunoglobulin (16.5%; octanorm/cutaquig®) was efficacious and well tolerated in patients with primary immunodeficienciesin a Phase IIIstudy. A subanalysis of pediatric data is presented here. Materials & methods: Children (2-16years) previously treated with intravenous human immunoglobulin received weekly subcutaneous human immunoglobulin infusions over 64weeks. The main objective was to assess the efficacy of cutaquigin preventing serious bacterial infections. Results:38children received 2213 infusions of cutaquig. No serious bacterial infections developed during the study. The rate of other infections was 3.1 per person-year and the rate of adverse drug reactions was 0.083 per infusion. Higher immunoglobulin Gtrough levels were achieved with cutaquigcompared with previous intravenous therapy. Conclusion: Once-weekly infusions of cutaquigwere efficacious and well tolerated in children with primary immunodeficiencies.

Primary antibody deficiency: The impact on the quality of life and mental health of affected children and their parents.

To evaluate health-related quality of life, mental health and treatment-related stress responses in children with primary antibody deficiency and both their parents. Children and their parents completed the standardised questionnaires Pediatric Quality of life Inventory, Strength and Difficulties Questionnaire and Impact of Event Scale. Parents also completed standardised questionnaires regarding their own mental health and quality of life. The results were compared to those of healthy children, kidney transplanted children and children in remission from acute lymphoblastic leukaemia. Children with primary antibody deficiency reported a poorer health-related quality of life compared to healthy children and children in remission from acute lymphoblastic leukaemia. They reported poorer mental health compared with healthy children. Mothers of children with primary antibody deficiency reported poorer mental health compared to mothers of healthy children but comparable to mothers of chronically ill children. Parents reported a similar quality of life as the general Norwegian population. Treatment with subcutaneous immunoglobulin infusions at home is generally well tolerated, but some report severe treatment-related stress. Primary antibody deficiency has a significant impact on quality of life and mental health of affected children. Patients and parents with severe treatment-related stress should be identified and helped.

Long-term efficacy, safety, and tolerability of recombinant human hyaluronidase-facilitated subcutaneous infusion of immunoglobulin (Ig) (fSCIG; HyQvia(®)) in immunodeficiency diseases: real-life data from a monocentric experience.

Humoral immunodeficiency diseases represent a heterogeneous group of disorders that require long-term therapies. Thus, the treatment provided must not only be effective but also safe and well tolerated. In this paper, we report our data on the efficacy, safety, and tolerability of recombinant human hyaluronidase-facilitated subcutaneous infusion of immunoglobulin (Ig) (fSCIG; HyQvia(®)) in immunodeficiency patients. We collected retrospective data from 30 patients with primary and secondary immunodeficiency diseases in therapy with fSCIG from September 2014 to December 2019. We evaluated the efficacy of the therapy, taking into account serum IgG values during follow-up and the number of annual infectious events and serious bacterial infections reported by patients. Safety was assessed on the basis of the number and intensity of adverse events (AEs) and local reactions reported. Our real-life data suggest that long-term repeated self-administration of recombinant human hyaluronidase-facilitated subcutaneous infusion of immunoglobulins results in a reduced rate of infectious events if compared to the pre-treatment rate. Both AEs and local reactions are mild to moderate and were never reasons for treatment discontinuation. Therapy with HyQvia shows prolonged efficacy and good tolerability; these aspects, together with the possibility of self-administration at home, minimize the impact the illness has on patients.

Protective Role Immunoglobulin Replacement Therapy in Chronic Lymphocytic Leukemia: FOCUS on Subcutaneous Immunoglobulin Formulations

INTRODUCTION. Secondary antibody deficiency is a common complication in chronic lymphocytic leukemia (CLL) that could be present at diagnosis or can be acquired during the follow-up due to CLL progression, perturbation of non-neoplastic immune system and chemoimmunotherapy. Despite new and active target therapies a significant amount of CLL patients still develops severe and life-threatening infections. Intravenous immunoglobulin (IG) (IVIG) replacement therapy (IGRT) has been proven to be an effective supportive treatment in patients with primary and secondary antibody deficiency such as CLL. Subcutaneous immunoglobulin (SCIG) is a new valid treatment option that allows patients self-administration without access to the clinic which proved to be as effective as IVIG in primary immunodeficiencies. However, the activity SCIG is CLL patients with IG defect has been little investigated.The aim of this study was to retrospectively evaluate IG levels, infection rate and safety of patients treated with SCIG as compared to those managed with IVIG.METHODS. Inclusion criteria were: diagnosis of CLL according to iwCLL guideline, age >18 years, received at least 1 IVIG or SCIG infusion. IGRT was started according to hospital policies in patient with severe symptomatic hypogammaglobulinemia. The physician was responsible for the choice between IGRT formulations (the first patient received SCIG since Nov 2008). IG levels (IgG, IgA and IgM) were recorded within 3 months before starting IGRT (baseline), after 6 months and within three months from the last available follow-up. Continuous variables were compared with Wilcoxon's tests while categorical variables with Fisher's exact or Chi-square tests when appropriate. Time to IGRT discontinuation was calculated from the beginning IGRT to death or discontinuation (event) or last available follow-up /(censored).RESULTS. We gathered data from 116 CLL patients followed in 2 hematology centers who received IGRT: 63% were male, the median age at diagnosis was 58 years, 77 were at Binet A stage, 48% and 16% were unmutated IGHV and harbor TP53 abnormalities, respectively. 91% received at least one therapies, the median numbers of treatments were 3 (range 0-9) and 36% died during the follow-up due to infections in 22 cases, CLL progression in 5, Richter transformation in 6 patients and 9 other causes such as second cancers or major bleedings. Forty-nine patients received IVIG and 88 SCIG (41 the 20% formulation and 47 the 16% drugs).Despite similar basal and +6 months IgG levels, patients treated with SCIG achieved significant higher serum IgG at last available follow-up (3.99, 5.67 and 5.4 g/L vs 3.89, 6.07 and 6.22 g/L for IVIG and SCIG, p=0.0009). Both IgA and IgM levels remained stable during replacement therapy.While the number of grade 3-4 infections remain stable during IVIG (both 80% before and after IVIG), they decrease with SCIG (88% vs 64%, p<0.0019). Furthermore, the incidence of all and grade 3-4 infections decreased to 0.59 and 0.17, and 0.30 and 0.13 events/people/year with IVIG and SCIG, respectively. Incidences of infections was not higher in patients receiving oral inhibitors (i.e. ibrutinib, idelalisib and venetoclax).Adverse events during SCIG infusions occurred in 11% of subjects, most commonly skin reaction and pruritus. They were mild, limited to the site of infusion and easily to manage. Bruising did not increase during concomitant treatment of SCIG and ibrutinib.After a median duration of IGRT of 3.7 years (4.7 for IVIG and 3.1 for SCIG) 71% of subjects managed with IGEV discontinued therapy as compared to 36% of SC formulation (p<0.0001), 16% due to death in the former group as opposite to 9% of the latter. The estimated 3-year time to IGRT discontinuation were 44% vs 29% for IVIG and SCIG, respectively (p=0.2089). 29 patients shit from IVIG to SCIG, while none to opposite. We also observed that patients who shift from IVIG to SCIG were able to achieved higher IgG levels at last follow-up (median IgG 4.76 vs 6.62g/L, p<0.0001).CONCLUSIONS. In this study we described the clinical and biological characteristics of the bigger population with CLL and secondary hypogammaglobulinemia receiving IGRT. We demonstrated that SCIG are well tolerated, non-inferior to IVIG, they also allow to reach higher IgG through levels and to decrease the incidence of severe infections even during continuous CLL therapies. DisclosuresVisentin:janssen: Consultancy, Honoraria. Mauro:abbvie: Other: board member; janssen: Other: board member. Foà:ROCHE: Other: ADVISORY BOARD, Speakers Bureau; AMGEN: Other: ADVISORY BOARD; ABBVIE: Other: ADVISORY BOARD, Speakers Bureau; GILEAD: Speakers Bureau; CELGENE: Other: ADVISORY BOARD, Speakers Bureau; JANSSEN: Other: ADVISORY BOARD, Speakers Bureau; CELTRION: Other: ADVISORY BOARD; INCYTE: Other: ADVISORY BOARD; NOVARTIS: Speakers Bureau. Trentin:Gilead: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria; Janssen: Research Funding.

In-depth interviews of patients with primary immunodeficiency who have experienced pump and rapid push subcutaneous infusions of immunoglobulins reveal new insights on their preference and expectations.

PurposePatients with primary immunodeficiency (PID) often receive immunoglobulin replacement therapy (IgRT). Physicians and patients have the choice between various methods of administration. For subcutaneous immunoglobulin infusions, patients may use an automated pump (P) or push the plunger of a syringe (rapid push [RP]). P infusions are performed once a week and last around 1 hour. RP decreases the duration of administration, but requires more frequent infusions.Patients and methodsEight out of 30 patients (coming from a single center) who had participated in the cross-over, randomized, open-label trial comparing P and RP participated in a focus group or underwent in-depth interviews. Patients had a long history of home-based subcutaneous immunoglobulin using P. The trial suggested that RP had slightly greater interference on daily life than P, but similar efficacy and better cost-effectiveness. When asked about the delivery method they had preferred, around one-third of patients pointed out RP rather than P. In-depth interviews may reveal unforeseen reasons for patients’ preferences.ResultsInterviews underlined the complexity of the relationship that the patients maintain with their disease and IgRT. Even if they recognized the genetic nature of the disease and claimed PID was a part of them, patients tried not to be overwhelmed by the disease. IgRT by P was well integrated in patients’ routine. By contrast, RP too frequently reminded the patients of their disease. In addition, some patients pointed out the difficulty of pushing the plunger due to the viscosity of the product. Coming back too frequently, RP was not perceived as time saving over a week. Long-lasting use of P could partly explain patients’ reasonable reluctance to change to RP.ConclusionIn-depth interviews of PID patients highlighted unforeseen reasons for patients’ preference that the physician needs to explore during the shared medical decision-making process.

Passive blood anaphylaxis: subcutaneous immunoglobulins are a cause of ongoing passive anaphylactic reaction

BackgroundAllergic, especially anaphylactic, reactions during immunoglobulin replacement therapy are rare, but their pathophysiology and classification remain ambiguous. Recent findings show positive results of skin tests with commercially available immunoglobulins, but target antigens and responsible compounds of the tested immunoglobulins have not been strictly identified.Case description and findingsFour adult patients with recently diagnosed common variable immunodeficiency qualified for standard subcutaneous immunoglobulin replacement therapy regimen. They had no history of receiving immunoglobulins, blood or blood product transfusions. Edema, confluent wheals and erythema were observed at the site of subcutaneous immunoglobulin infusion: typical early and late phase reaction. A transient increase in various passively transferred IgG and IgE antibodies was responsible for misleading positive outcome of the serological testing for active humoral response such as type I allergy, anti-Rh, isohemagglutinins and rheumatoid factor (RF). Although the clinical presentation was very unusual and severe, the retrospective analysis showed no isohemagglutinins, RF and IgE in the patients’ serum before but it was positive after the infusion (median IgE = 18 IU/ml, RF = 8 IU/ml). Type I allergic reaction (laryngeal edema, rhinoconjuctivitis) came out at +14 days of replacement therapy when the patient visited countryside. In the second patient anaphylactic reaction was observed 5 days after ScIg administration, and only when the patient consumed peanuts. Therefore, IgE concentration was measured retrospectively in a series of commercial preparations used in the initial subcutaneous immunoglobulin replacement therapy that caused the adverse event (AE) and it was determined between 138 and 232 IU/ml (kU/l), i.e. 690–2100 IU per g of protein. Specific IgE was within a wide range from 198 (mix of food) to 2809 kUA/l (mix of grass) but many of the tested allergen-specific IgE were class 2 or 3 (i.e. 0.71–17.5 kUA/l).ConclusionsThe case resembles passive cutaneous anaphylaxis and Prausnitz–Küstner reaction but clinical significance of the classical phenomena has not yet been described. This observation indicates that anaphylactic reactions during immunoglobulin replacement therapy may result from IgE or pathological IgG content. Such IgE presence was sporadically reported (34.5–105 IU/ml, i.e. 862.5–1450 IU/g of protein) in intravenous immunoglobulins that are used and monitored by healthcare professionals. In clinical practice the definition of adverse events is inadequate since individual batches of immunoglobulins come with different specificity therefore, they should be classified as transfusion products (not bioequivalents). Such new approach implies establishing (1) new control methods and strategies to ensure introduction of the safety regulations for subcutaneous home self-administration of immunoglobulins as well as (2) guidelines for the prevention of anaphylaxis in patients receiving immunoglobulins (for example peanut).

Recombinant human hyaluronidase-facilitated subcutaneous immunoglobulin infusion in primary immunodeficiency diseases.

Most primary immunodeficiency diseases (PIDDs) resulting in antibody deficiency require intravenous or subcutaneous immunoglobulin G (SCIG) replacement therapy. The flow and distribution of SCIG to the vasculature is impeded by the glycosaminoglycan hyaluronan in the extracellular matrix, which limits the infusion rate and volume per site, necessitating frequent infusions and multiple infusion sites. Hyaluronidase depolymerizes hyaluronan and is a spreading factor for injectable biologics. Recombinant human hyaluronidase (rHuPH20) increases SCIG absorption and dispersion. In patients with PIDD, SCIG facilitated with rHuPH20 (IGHy) has been shown to prevent infections, be well-tolerated and reduce infusion frequency and number of infusion sites as compared with conventional SCIG. This article reviews IGHy clinical studies and real-world practice data in patients with PIDD.

The Efficacy and Cost Effectiveness of Subcutaneous Immunoglobulin (SCIG) Replacement in Patients with Immune Deficiency Secondary to Chronic Lymphocytic Leukemia

Introduction:The most common immune defect in chronic lymphocytic leukemia (CLL) is hypogammaglobulinemia, secondary to the underlying malignancy and intensified by chemotherapy. Subcutaneous immunoglobulin (SCIG) infusions have been widely adopted to treat patients with primary immune-deficiency (PID) this approach has not been widely accepted in CLL. The goal of this program was to evaluate SCIG in patients with CLL to determine: a) whether it is possible for the CLL population to manage SCIG; b) whether SCIG is effective in these patients; c) whether using SCIG improves patient quality of life, and d) whether using SCIG produces a cost-saving when compared to IVIG.Methods:We implemented a nurse-led SCIG clinic within the CLL Clinic at CancerCare Manitoba for ambulatory CLL patients with hypogammaglobulinemia experiencing infectious complications (documented IgG <4g/L and > 2 courses of oral antibiotics in a 12 month period, or 1 severe infection IV antibiotics). Patients were screened for eligibility, trained, and transitioned (85% enrollment rate). Patients started replacement therapy at a dose of 12 grams/month with doseescalation based on infections rather than trough IgG levels. Demographic and clinical characteristics were collected, in addition to pre- and post-antibiotic use, treatment satisfaction and quality of life measurements along with cost analysis.Results:In its first 2 years, 53 patients with CLL were referred to the program [n=45(85%) enrolled, n=4(7.5%) ineligible (mean age 71 years), and n=4(7.5%) declined (mean age 77 years)]. Reasons for declining were related to the presence of anxiety and a fear of needles. Only 2 patients (4%) switched back to IVIG within 3 months of starting SCIG but both patients lived outside the city limits and did not have the ability to do repeat training and support with the SCIG nurse.Median duration of participation on program is 16 mos. (range 1-24 mos), male gender 27(60%), median age 69 years (range 48-91), rural dwelling 17(38%), 36 patients (80%) were married with a partner to assist. Median time since CLL diagnosis was 8 years (range 1-26 years). Most (84%) of patients had received prior treatment for CLL & 43% were on chemotherapy concurrent with SCIG.Trough IgG Levels: At Diagnosis: Median IgG 5.5g/L , 65% hypogammaglobulinemiaLowest charted IgG: 2.84g/LEnrolled patients comprised 60% n=27 of the sample with 40% n=18 transitioned from IVIG infusions.Of the subset of patients (n=27) that had no prior IgG replacement:IgG (dx) 3,02; lowest IgG 3.34; 1 month post 4,24; 3months post 5.29; 6 months post 5.79g/L showing a steady rise in levels.Using a low dose approach, our median SCIG dose was 12 grams/month vs. weight-based dosing. (200-400mg/kg, mean weight 81 kg, mean dose 24 grams/infusion). This represented a 50% savings per infusion of donor IgG.Resource Savings: (n=45 patients) In the first 24 months: a total of 597 IVIG infusions were saved, which represents 1791 infusion chair hours. The savings in each subsequent 12 month period is projected to be 540 hours, and 1620 infusion chair hours. SCIG infusions represent an additional 50% savings in supply costs.Donor IgG Savings: (n=45)By not using dosing based on patient weight, our low dose approach reduced infusion doses by 50%. In the first 24 months, the 597 infusions saved 7164 grams of product (equivalent to $358, 200 Canadian funds).Savings in each subsequent 12 month period would be an additional 6480 grams (equivalent to $324,000 Canadian funds).Antibiotics Use:The median number prescriptions/patient decreased 3 fold after the initiation of SCIG. (109 Prescription pre vs. 46 Prescription post SCIG).Treatment Satisfaction & Quality of life data will be presented with patients reporting significant improvements citing multiple benefits. Overall, patients were very satisfied with <4% switchback rate. At 6 months, 94% are satisfied, somewhat or extremely satisfied with SCIG’s ability to prevent infections. 29 patients (81%) reported no side effects, 31(86%) report SCIG being easy to infuse and 60% patients extremely satisfied and 40% satisfied or somewhat satisfied.Conclusions:The implementation SCIG at our cancer center has changed our standard of care for Ig replacement and has resulted in significant cost saving, efficacy and improved quality of life and treatment satisfaction. DisclosuresNo relevant conflicts of interest to declare.

P242 Real world experience of recombinant human hyaluronidase-facilitated subcutaneous infusion of immunoglobulin in common variable immunodeficiency

IGHy (HYQVIA) was approved September 2014 in the US for the treatment of PIDD in adults. Data from a single-practice cohort in Southern Utah was analyzed to understand IGHy treatment adoption.

Practical Considerations for Self-Administration of Subcutaneous Immunoglobulin G Utilizing Recombinant Human Hyaluronidase, an Advanced Method of Subcutaneous Administration: A Nurse's Perspective.

An approved subcutaneous infusion of immunoglobulin G using recombinant human hyaluronidase (IGHy) allows adult patients with primary immunodeficiency disease to self-administer every 3 to 4 weeks using 1 to 2 subcutaneous infusion site(s). This article reviews the practical considerations for nurses to simplify patient education and training. Key considerations include pump choice and parameters, ancillary supplies, and technique. Patient education includes infusion log upkeep and management of potential reactions. Educational initiatives should be designed to meet specific patient needs. Successful IGHy self-administration depends on proper patient training and continuing interaction between the health care team and the patient to optimize the patient experience.

Subcutaneous immunoglobulin for treatment of multifocal motor neuropathy.

Subcutaneous immunoglobulin (SCIg) has been used for treatment of immune neuropathies. We evaluated the safety and efficacy of 1.53:1 SCIg to intravenous immunoglobulin (IVIg) in individuals receiving <2 g/kg IVIg per month and 1:1 in individuals receiving 2 g/kg per month for treatment of multifocal motor neuropathy (MMN) in an open-label, 6-month trial. Medical Research Council sum score, grip strength, modified Guy's Upper Limb Neurological Disability score, Health Utility Index Quality of Life score, and immunoglobulin levels were evaluated at baseline and at 3 and 6 months. Eleven men and 4 women, aged 31-82 years, were enrolled. Eleven patients completed the program with minor localized reactions and high satisfaction. Three of 6 patients receiving less than 1.53:1 replacement developed intolerable weakness by month 3, and 1 exited after developing erythema and elevated transaminase levels. Patients with MMN tolerate SCIg infusion with maintained strength, but some patients may develop increasing weakness and merit close monitoring. Muscle Nerve 54: 856-863, 2016.

Long-Term Tolerability, Safety, and Efficacy of Recombinant Human Hyaluronidase-Facilitated Subcutaneous Infusion of Human Immunoglobulin for Primary Immunodeficiency

PurposeTreatment of primary immunodeficiency diseases (PIDD) with subcutaneous (SC) infusions of IgG preceded by injection of recombinant human hyaluronidase (rHuPH20) (IGHy) to increase SC tissue permeability was evaluated in two consecutive, prospective, non-controlled, multi-center studies.MethodsSubjects >4 years of age received SC IgG replacement at a weekly dose equivalent of 108 % of their previous intravenous (IV) dose, facilitated by prior injection of 75 U/g IgG of rHuPH20. Starting with weekly SC infusions, the interval was increased (ramped-up) to a 3- or 4-week schedule.ResultsEighty-three subjects (24 < 18 years; 59 ≥ 18 years) received 2729 infusions (excluding ramp-up) at a mean dose of 0.155 g/kg/week in the pivotal and 0.156 g/kg/week in the extension study. IGHy exposure exceeded 30 months in 48 subjects.During 187.7 subject-years of IGHy exposure, 2005 adverse events (AEs) (10.68 per subject-year) occurred. The rate of related systemic AEs during consecutive 1-year periods remained low; the rate of related local AEs decreased from 3.68/subject-year in months 1–12 to approximately 1.50/subject-year after 30 months of treatment. Fifteen subjects transiently developed anti-rHuPH20 binding antibody. There was no difference in AE rates in these subjects before and after the first titer increase to ≥1:160.The rate of infections during IGHy exposure was 2.99 per subject-year and did not increase during the studies. Annual infection rates were 3.02 in subjects <18 years and 2.98 in subjects ≥18 years.ConclusionsLong-term replacement therapy with IGHy was safe and effective in 83 pediatric and adult subjects with PIDD.Electronic supplementary materialThe online version of this article (doi:10.1007/s10875-016-0298-x) contains supplementary material, which is available to authorized users.

Efficacy of Recombinant Human Hyaluronidase-Facilitated Subcutaneous Infusion of Immunoglobulin G (IgG) (IGHy) in Patients with Primary Immunodeficiency Disease (PIDD): Infections over Time

Efficacy of Recombinant Human Hyaluronidase-Facilitated Subcutaneous Infusion of Immunoglobulin G (IgG) (IGHy) in Patients with Primary Immunodeficiency Disease (PIDD): Infections over Time

Local Adverse Reaction Rates Decreased over Time during Treatment with Recombinant Human Hyaluronidase-Facilitated Subcutaneous Infusion of Immunoglobulin G (IGHy) in Patients with Primary Immunodeficiency Disorders in the IGHy Phase 3 Studies

Local Adverse Reaction Rates Decreased over Time during Treatment with Recombinant Human Hyaluronidase-Facilitated Subcutaneous Infusion of Immunoglobulin G (IGHy) in Patients with Primary Immunodeficiency Disorders in the IGHy Phase 3 Studies

Real-World Use of Recombinant Human Hyaluronidase-Facilitated Subcutaneous Infusion of Immunoglobulin G (IG) (IGHy) in Patients with Primary Immunodeficiency Disorders (PIDD)

Real-World Use of Recombinant Human Hyaluronidase-Facilitated Subcutaneous Infusion of Immunoglobulin G (IG) (IGHy) in Patients with Primary Immunodeficiency Disorders (PIDD)

Multiple necrotic deep wound infections associated with a subcutaneous immunoglobulin infusion

Multiple necrotic deep wound infections associated with a subcutaneous immunoglobulin infusion