Cost-minimization Analysis of IgPro20, a Subcutaneous Immunoglobulin, in Japanese Patients With Primary Immunodeficiency

AbstractPurposeIgPro20, Hizentra® an L-proline−stabilized 20% human subcutaneous immunoglobulin (SCIG), has been shown in a Phase III pivotal study to be well tolerated and efficacious in adult and pediatric Japanese patients with primary immunodeficiency. Economic aspects of SCIG treatment in comparison with previous intravenous immunoglobulin (IVIG) therapy were analyzed in this Phase III study in Japan.MethodsTwenty-four Japanese patients with primary immunodeficiency on IVIG treatment were switched to IgPro20 at an equivalent dose (full analysis set). The study consisted of a screening period, an IVIG treatment period with 3 planned infusions every 3 or 4 weeks, a 12-week SCIG wash-in and wash-out period, and a 12-week SCIG efficacy period. The difference in medical cost and productivity loss resulting from changes in hospital frequency between the SCIG and IVIG treatment was evaluated. Information about treatment cost was collected as part of the Life Quality Index questionnaire. In addition, productivity loss and hospital-related absenteeism were evaluated.FindingsLife Quality Index scores for all domains were higher with SCIG than with IVIG in this patient population. In the full analysis set, the mean (SD) Life Quality Index score of the Costs domain increased from 45.1 (26.34) at Week 1 (IVIG period) to 71.9 (18.52) at Week 24 (end of the SCIG efficacy period), representing a mean change of 26.74 and a large score improvement effect size (1.01). Median productivity loss was reduced by 60% from baseline to Weeks 12 and 24. This resulted in a reduction in costs of JPY 10,875 per patient per month at Weeks 12 and 24. Subcutaneous treatment with IgPro20 also reduced hospital-related absenteeism. The number of patients, parents, or guardians who were not absent from work or housework duties and had no reduction in working time increased from 4 (17.4%) at Week 1 to 9 (39.1%) at Week 24. Similar results were obtained in the per-protocol set (n = 21).ImplicationsSwitching from IVIG to SCIG reduced markedly productivity loss and hospital-related absenteeism. The reduction in hospital visit frequency due to the use of home-based IgG therapy enabled by the change in administration route is expected to produce an important pharmacoeconomic benefit in Japan. Study Code: ZLB06_002CR, ClinicalTrials.gov identifier: NCT01199705

IL-12の抗腫瘍効果におけるCXCケモカイン,IP-10およびMigの関与について

取得学位 : 博士（医学）, 学位授与番号 : 医博乙第1493号，学位授与年月日：平成11年6月16日,学位授与年：199

新生児期のインターロイキン2レセプタ-α鎖陽性ナイーブCD4[+]T細胞の機能とCD45抗原ファミリーの発現に関する研究

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第993号, 学位授与年月日：平成3年3月25日,学位授与年：199

Long-term efficacy and safety of Hizentra® in patients with primary immunodeficiency in Japan, Europe, and the United States: a Review of 7 Phase 3 Trials

Many patients with primary immunodeficiency (PID) require immunoglobulin G (IgG) replacement therapy, delivered as intravenous IgG (IVIG) or subcutaneous IgG (SCIG). We aim to identify trends in efficacy and safety that would not be evident in individual studies of small patient numbers. Seven open-label, Phase 3, prospective, multicenter studies of the efficacy and safety of Hizentra® (a SCIG), conducted in Japan, Europe, and the US were summarized. Overall, 125 unique patients received 15,013 weekly infusions during a total observation period of 250.9 patient-years. Mean weekly doses of Hizentra® were 83.22–221.3 mg/kg body weight; infusion rates per patient (total body rate) were 25.2–49.3 mL/h across studies. The rates of infections and serious bacterial infections were 3.10 and 0.03 events per patient/year, respectively. Annualized rates of days hospitalized due to infection, out of work/school, and prophylactic antibiotic use were 0.95, 5.14, and 36.78 per patient, respectively. For the equivalent monthly dose, weekly Hizentra® SCIG administration resulted in expectedly-increased serum IgG trough levels in patients switching from IVIG, and maintained levels in patients switching from previous SCIG. Adverse events (AEs) totaled 5039 (events/infusion 0.094–0.773), almost all of which were mild/moderate. Three thousand one hundred ninety-seven were considered treatment-related, the most common of which were injection site reactions (2919 events; 0.001–0.592 AEs per infusion). Systemic AEs were very uncommon. The results from these seven studies indicate that Hizentra® therapy was both efficacious and well tolerated during long-term treatment. This is particularly important in patients with PID, who may require lifelong IgG replacement therapy

A sporadic case of CTLA4 haploinsufficiency manifesting as Epstein–Barr virus-positive diffuse large B-cell lymphoma

Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) is a coinhibitory receptor that plays an essential role in maintaining immune system homeostasis by suppressing T-cell activation. We report a sporadic case of CTLA4 haploinsufficiency in a patient with Epstein-Barr virus-positive diffuse large B-cell lymphoma and subsequent benign lymphadenopathy. A missense mutation in exon 2 of the CTLA4 gene (c.251T>C, p.V84A) was found in the patient's peripheral blood and buccal cell DNA, but not in her parents' DNA. CTLA4 expression decreased in the peripheral regulatory T cells upon stimulation, whereas CTLA4 and PD-1-positive T cell subsets increased, possibly to compensate for the defective CTLA4 function. This case suggests that some adult lymphoma patients with no remarkable medical history have primary immune disorder. As immune-targeted therapies are now widely used for the treatment of malignancies, it is increasingly important to recognize the underlying primary immune disorders to properly manage the disease and avoid unexpected complications of immunotherapies

Ansiedade ao tratamento odontológico em atendimento de urgência

OBJECTIVE: The purpose of the study was to assess the frequency of dental anxiety and/or fear among patients in an emergency dental service. METHODS: Research was based on interviews with 252 patients, aged 18 years old and over, attended at an emergency dentistry service of São Paulo, Brazil, from August to November, 2001. Two methods were used to measure dental anxiety: the Modified Dental Anxiety Scale (MDAS) and the Gatchel Fear Scale. The study group answered questions concerning major complaint, how much time had elapsed since their last visit to the dentist and since the initial symptoms leading to the current visit to the emergency service, level of education, family income and previous traumas. Statistical analysis (chi2 and Fisher exact test) was performed to evaluate these characteristics. RESULTS: It was found that 28.17% of this sample was dentally anxious, according to the MDAS, and 14.29%, felt fear related to dental treatment according to the Gatchel Fear Scale. Women were more anxious than men at a statistically significant rate (MDAS). The time elapsed since the onset of initial symptoms was more than 7 days for 44.44% of the participants. A large proportion of anxious women returned to treatment during the last year. A previous traumatic experience with dental was identified in 46.48% of the dentally anxious patients. No significant relation between level of education or income and dental anxiety was found. CONCLUSIONS: Dentally anxious patients frequent attend emergency care. Females are more likely to report high dental anxiety than males. Previous experience seems to be an important factor contributing to avoidance of dental care.OBJETIVO: Avaliar a freqüência de pacientes com ansiedade ou medo do tratamento odontológico em um setor de urgência. MÉTODOS: Participaram do estudo 252 pacientes, com 18 anos ou mais, que compareceram ao setor de urgência de uma faculdade de odontologia, de São Paulo, SP, entre agosto e novembro de 2001. Para avaliar a ansiedade, foram utilizadas a Modified Dental Anxiety Scale (MDAS), e a Escala de Medo de Gatchel. O grupo estudado respondeu a questões sobre: tempo decorrido desde a última visita ao dentista e desde o início dos sintomas, escolaridade, renda familiar e história prévia de trauma. Os resultados foram analisados pelos testes estatísticos (chi2 e Teste Exato de Fisher). RESULTADOS: Foram identificados 28,2% de indivíduos com algum grau de ansiedade, segundo a MDAS, na qual as mulheres foram consideradas mais ansiosas que os homens (chi2=0,01); e 14,3% de pacientes com alto grau de medo segundo a Escala de Medo de Gatchel. Em 44,4% da amostra a demora para procura de alívio dos sintomas foi >; sete dias. Mulheres ansiosas procuraram atendimento mais rapidamente e em maior número. Experiência traumática anterior ocorreu em 46,5% dos pacientes ansiosos. Não foi possível relacionar escolaridade e renda familiar com ansiedade e/ou medo. CONCLUSÕES: Pacientes ansiosos, com destaque para as mulheres, são freqüentes no atendimento odontológico de urgência. Experiência prévia traumática mostrou-se importante para o desenvolvimento da ansiedade em relação ao atendimento odontológico

Treatment satisfaction with subcutaneous immunoglobulin replacement therapy in patients with primary immunodeficiency: a pooled analysis of six Hizentra® studies

Purpose Primary immunodeficiency diseases (PIDDs) are a heterogenous group of disorders characterized by intrinsic impairment in the immune system. Most patients with PIDD require life-long immunoglobulin G replacement therapy, which has been shown to reduce the rate of infections and, related hospitalizations and reduce health-related quality of life (HRQOL). Here, treatment satisfaction and HRQOL in patients with PIDD was evaluated upon switching from intravenous (IVIG) or subcutaneous immunoglobulins (SCIGs) to 20% SCIG (Hizentra®), and during long-term steady-state Hizentra® treatment. Methods Analyses were based on two pivotal (switch) and four extension/follow-up (maintenance) Phase III studies of Hizentra® conducted in Europe (EU), Japan (JP), and the United States (US). Two validated questionnaires were used: Life Quality Index (LQI) for assessment of IgG-specific perceptions of HRQOL and Short Form 36 version 2 (SF-36v2). Results In the EU and JP switch studies, there was significant and meaningful improvement from Screening in LQI domain scores at all time points, largely driven by patients switching from IVIG to SCIG. In the EU switch study, there were also significant increases in mean SF-36v2 domain scores for Physical Function and General Health from Screening to Week 12. These improvements were observed also at Week 24. Overall, LQI and SF-36v2 domain scores were generally sustained in the maintenance studies. Conclusions These results showed that switching patients from IVIG to SCIG improves patient self-reported health status and IgG-specific HRQOL perception. The maintenance studies generally showed no deterioration of this improved health status over a long follow-up period

Severe Chronic Active EBV Infection in an Adult Patient: Case Report

Severe chronic active Epstein-Barr virus (EBV) infection is a rare and life-threatening illness. Although the criteria for diagnosis include chronic or recurrent infectious mononucleosis-like symptoms lasting more than 6 months and high titers of anti-EBV antibodies, clinical and laboratory findings may be heterogeneous and flexible application of those criteria is necessary in cases showing typical clinical and pathologic findings. We report a case of severe chronic active EBV infection in a 62-yr-old female patient who showed classical clinical findings with infiltration of EBV-infected T lymphocytes in the bone marrow, spleen, and lymph nodes, and died four months after presentation