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Intravenous immunoglobulin (IVIg) has an established role in the treatment of immune thrombocytopenia (ITP). The safety and efficacy of a new ready-to-use IVIg 10% formulation (octagam(®) 10%) were investigated in a prospective phase III study in 116 adult patients with ITP (platelet count ≤20×10(9)/l). Sixty-six patients had chronic ITP and 49 were newly diagnosed. Patients received octagam 10% 1 g/kg/day on two consecutive days; infusion rate was adjusted according to tolerability to a maximum of 0·12 ml/kg/minute. Eighty per cent of patients attained the primary efficacy endpoint of clinical response (platelet count ≥50×10(9)/l within 6 days of dosing). The median time to response was 2 days and the median duration of response was 12 days; mean response duration was 24·1 days. octagam 10% was well tolerated and effective in this population representative of adult patients with ITP, even at the maximum infusion rate of 0·12 ml/kg/minute, without unexpected safety issues.

Mutations in the BRCA1 gene result in an elevated risk of breast cancer (BC) and ovarian cancer (OC). However, risk estimates vary depending on the study population and statistical methodology used, and there are indications that the birth cohort and location of the mutation influence cancer risk. We investigated the risks for BC and OC associated with BRCA1 mutations in a young cohort of female mutation carriers who were identified by molecular genetic testing and belonged to a genetically heterogeneous Central European population. The study included 106 healthy and 158 affected carriers identified at an Austrian risk evaluation center. Risk estimation employed the product limit method. The log rank test was used to compare different strata. The risk of developing cancer to age 70 was found to be 85% for BC (95% CI 75-97%) and 53% for OC (95% CI 37-68%). Female mutation carriers born in 1958 or later were subject to a significantly higher risk of BC (P=0.005; 27% vs. 46% to age 40) and OC (P=0.006; 2% vs. 8% to age 40) than those born earlier. Mutations in exon 11 were associated with lower BC risk than mutations in exons 1-10 (P=0.008) and exons 12-24 (P=0.0006). OC risk was not influenced by mutation location (P=0.86). We conclude that female BRCA1 mutation carriers should be counseled about their cohort-dependent cancer risk. Further research into variables that affect cancer risk and are amenable to modification (e.g., lifestyle-related factors) should be considered a priority., (Copyright 2005 Wiley-Liss, Inc.)

Introduction: The absence of high quality evidence for basic clinical dilemmas in immune thrombocytopenic purpura (ITP) underlines the need for contemporary guidelines relevant to the local treatment context. ITP is diagnosed by exclusions, with a hallmark laboratory finding of isolated thrombocytopenia. Main recommendations: Bleeding, family and medication histories and a review of historical investigations are required to gauge the bleeding risk and possible hereditary syndromes. Beyond the platelet count, the decision to treat is affected by individual bleeding risk, disease stage, side effects of treatment, concomitant medications, and patient preference. Treatment is aimed at achieving a platelet count > 20 × 109/L, and avoidance of severe bleeding. Steroids are the standard first line treatment, with either 6‐week courses of tapering prednisone or repeated courses of high dose dexamethasone providing equivalent efficacy. Intravenous immunoglobulin can be used periprocedurally or as first line therapy in combination with steroids. Changes in management as a result of this statement: There is no consensus on choice of second line treatments. Options with the most robust evidence include splenectomy, rituximab and thrombopoietin receptor agonists. Other therapies include azathioprine, mycophenolate mofetil, dapsone and vinca alkaloids. Given that up to one‐third of patients achieve a satisfactory haemostatic response, splenectomy should be delayed for at least 12 months if possible. In life‐threatening bleeding, we recommend platelet transfusions to achieve haemostasis, along with intravenous immunoglobulin and high dose steroids. [ABSTRACT FROM AUTHOR]

Background: Immune thrombocytopenia (ITP) is a diagnosis of exclusion that can resemble other thrombocytopenic disorders., Objectives: To develop a clinical prediction model (CPM) for the diagnosis of ITP to aid hematogists in investigating patients presenting with undifferentiated thrombocytopenia., Methods: We designed a CPM for ITP diagnosis at the time of the initial hematology consultation using penalized logistic regression based on data from patients with thrombocytopenia enrolled in the McMaster ITP registry (n = 523) called the Predict-ITP Tool. The case definition for ITP was a platelet count less than 100 × 10 9 /L and a platelet count response after high-dose corticosteroids or intravenous immune globulin, defined as the achievement of a platelet count above 50 × 10 9 /L and at least a doubling of baseline. Internal validation was done using bootstrap resampling. Model discrimination was assessed by the c-statistic, and calibration was assessed by the calibration slope, calibration-in-the-large, and calibration plot., Results: The final model included the following variables: (1) platelet count variability (based on three or more platelet count values), (2) lowest platelet count value, (3) maximum mean platelet volume, and (4) history of major bleeding (defined by the ITP bleeding scale). The optimism-corrected c-statistic was 0.83, the calibration slope was 0.88, and calibration-in-the-large for all performance measures was <0.001 with standard error <0.001, indicating good discrimination and excellent calibration., Conclusions: The Predict-ITP Tool can estimate the likelihood of ITP for a given patient with thrombocytopenia at the time of the initial hematology consultation. The tool had high predictive accuracy for the diagnosis of ITP., (© 2022 International Society on Thrombosis and Haemostasis.)

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by platelet destruction and reduced platelet production resulting in decreased platelet level and an increased risk of bleeding. Based on the immunologic mechanism of ITP, front‐line standard therapy consists of corticosteroids and intravenous immunoglobulins (IVIG). If patients do not respond to the first‐line treatment, or if continuous therapy is required, the disorder is called refractory ITP, and second‐line therapy is indicated. This treatment may consist of rituximab, thrombopoietin receptor agonists, splenectomy, or cytotoxic drugs. Despite significant advances, many patients do not respond to any the treatments listed below, and new treatment options need to be developed for this relapsed and refractory group. Recent clinical studies have indicated promising outcomes for novel drugs, either as single agents or in combination with traditional drugs. This review discusses the latest and the most promising novel drugs for ITP in adults. [ABSTRACT FROM AUTHOR]

Summary: Objectives: To assess the efficacy and safety of intravenous immunoglobulin (IVIG) 10% (Panzyga®), a novel human normal IVIG 10%, in patients with chronic immune thrombocytopenia (ITP). Background: First‐line treatment options in ITP include IVIGs. Methods: In this prospective, open‐label, non‐controlled, multicentre, phase III study, patients received a daily dose of IVIG 10% (1 g kg−1 body weight) for two consecutive days. The primary end point was clinical response rate; secondary end points included alternate response definitions, time to response, response duration, platelet counts, regression of bleeding and safety. Results: Forty patients were enrolled (57·5% male, mean age 36·7 years); the full analysis set comprised 36 patients. A clinical response was seen for 29 of 36 patients (80·6%). Median time to response and response duration was 2 days and 14 days, respectively. IVIG 10% was well tolerated at a maximum infusion rate of 8 mg (kg min)−1 in all but one patient; adverse events were mainly mild to moderate in severity, and the most frequent was headache (42·5%). Conclusion: IVIG 10% is well tolerated even at a high infusion speed and induces a rapid platelet count increase, thus decreasing the bleeding rate and the severity of bleeding events. Trial registry: ClinicalTrials.gov record: NCT01349790. [ABSTRACT FROM AUTHOR]

Objectives: To provide detailed data on the tolerability and safety of octagam® 10%, a ready-to-use intravenous immunoglobulin, in a subgroup of patients with immune thrombocytopenia (ITP) involved in an integrated analysis of post-authorisation safety surveillance (PASS) studies. Methods: A subgroup analysis was conducted using data collected from two non-interventional studies that included patients with ITP treated with octagam® 10%. Patients were observed and monitored for possible adverse drug reactions (ADRs) during or after administration of octagam® 10%, with a particular focus on thromboembolic events (TEEs). ADRs were analysed at the case and event level. Results: In this analysis of 112 patients receiving octagam® 10% (mean dose 0.4 g/kg/infusion), there were five cases with at least one adverse drug reaction (ADR) associated with 626 infusions of octagam® 10% (case incidence of 0.8% per infusion). ADRs were of mild or moderate severity. There were a total of 10 events, most commonly back pain (n = 3) and headache (n = 2). Nausea, dizziness and a sensation of heaviness were also reported. The remaining two events involved drug exposure during pregnancy. There were no TEEs or other serious ADRs. Discussion: In this subgroup analysis of patients who received octagam® 10% (manufactured using an amended process) in two PASS studies, the overall ADR rate was low, with ADRs occurring in only 0.8% of all infusions. No TEEs or other serious ADRs were reported. Conclusions: Routine clinical use of octagam® 10% was safe and well tolerated, with no unexpected safety issues, in patients with ITP. The two studies from which data were taken are registered with the International Standard Randomised Controlled Trial Number Registry, numbers ISRCTN58800347 and ISRCTN02245668. [ABSTRACT FROM AUTHOR]

Direct comparisons of tolerability and safety of concentrated intravenous immunoglobulin ( IVIG) versus less concentrated products are scarce. In this postauthorization, prospective, observational, multicenter study, a systematic comparison of 10% and 5% concentrations of Flebogamma® DIF IVIG was performed in both adult and pediatric patients treated with the studied IVIG products according to the approved indications under routine conditions. Dose of product administered, adverse events ( AEs), physical assessments, laboratory tests, and concomitant therapy were analyzed. Patient recruitment in the 10% and 5% product groups was, respectively, 34 (32 analyzed, 13 of them children, receiving 130 IVIG infusions) and 35 (34 analyzed, receiving 135 IVIG infusions). Twenty-four infusions (18.5%; 95% CI: 11.8, 25.1) with the 10% product and 3 (2.2%; 95% CI: −0.3, 4.7) with the 5% product were associated with potentially treatment-related AEs ( P < 0.0001). Nine patients (28.1%) infused with the 10% product and 3 (8.8%) infused with the 5% product presented, respectively, 33 and 8 treatment-related AEs (of which 7 and 6, respectively, were serious AEs, experienced by only three hypersensitive patients). The profile of AEs occurring with the infusion of 10% and 5% products were comparable. The most frequent treatment-related AEs were headache ( n = 17, 3 patients; 15 episodes, 1 patient) and pyrexia ( n = 6, 4 patients). In conclusion, no unpredictable risk was detected for both Flebogamma DIF 10% and 5% concentrations, which were therefore deemed as safe and well-tolerated IVIG in the studied population. The frequency of infusions associated with treatment-related AEs was lower with the 5% concentration. [ABSTRACT FROM AUTHOR]

Background and Objectives The clinical significance of autoimmune thrombocytopenia ( ITP) is reflected by bleeding and/or an increased bleeding risk due to low platelet counts. In most cases, treatment with high-dose (1-2 g/kg body weight) intravenous immunoglobulin has been demonstrated to result in an increase in platelet counts after one day of treatment. Until now, there is little information on the true beginning of therapy effect in patients treated with high-dose intravenous immunoglobulin. In this study, we focused on the kinetic of platelet counts and cessation of bleeding within the first 24 h of treatment. Materials and methods Nineteen patients with chronic ITP were treated with high-dose intravenous immunoglobulin due to clinically relevant bleeding and/or for increased bleeding risk. Results Although the response was variable in treated patients, cessation of bleeding was observed within 12 h in all such affected patients ( n = 7), even in patients with platelet counts that were not increased ( n = 3). Furthermore, platelet counts were observed to increase already within 1 h in 10 (53%) patients and within 8 h in 12 (63%) patients. Conclusions From a clinical perspective, the onset of therapeutic effects of intravenous immunoglobulin in patients with ITP may occur at an earlier stage and be superior to that previously expected. Failure to measure an increase in platelets in the circulation of 'non-responders' may be explained by an increased consumption of platelets due to recognizable or unrecognizable bleeding in such affected patients. [ABSTRACT FROM AUTHOR]

Biologics are a group of drugs that precisely affect certain specific steps in the immune response and are an extremely useful group when used in an appropriate setting. However, their use can often be a double-edged sword. Careful patient selection and thorough knowledge of adverse effects is a key to their successful use in various disorders. The initial enthusiasm has gradually given way to a more cautious approach wherein a balance is sought between clinical usefulness and expected side effects. The adverse effects of the biologics most commonly used in dermatology have been carefully listed for ready reference. The plausible causes of the adverse reactions are succinctly outlined along with their incriminating factor(s). Besides, in brief, the attention has been focused on their management. The content should provide an essential didactic content for educating the practitioner. [ABSTRACT FROM AUTHOR]

Background and Objectives Pharmacokinetics, safety and tolerability of escalating infusion rates of BT090, a 10% intravenous immunoglobulin ( IVIg), were studied in patients with primary immunodeficiency disease. Materials and Methods In Part A, patients ( n = 30) received 3 infusions of BT090 at their pretrial dose and dosing interval; the infusion rate of BT090 was increased from 0·3 to 1·4 to 2·0 ml/kg/h for each infusion in each patient initially at 30-min intervals. Pharmacokinetics was evaluated at the 3rd infusion ( n = 24). At the 4th infusion, infusion rates were to be gradually escalated from 0·3 to 1·4 to 4·0 to a maximum of 8·0 ml/kg/h initially at 30-min intervals to establish the maximum tolerated infusion rate per patient. Results The pharmacokinetic characteristics and safety profile of BT090 were comparable with those of other IVIgs, including Intratect®. Escalation of infusion rates was well tolerated, allowing identification of individual patient's maximum tolerated infusion rate. At subsequent infusions, all patients tolerated their individually defined maximum infusion rate: 17 patients (68·0%) tolerated infusion rates of 6·0 or 8·0 ml/kg/h and four patients (16%) had maximum tolerated infusion rates of <4·0 ml/kg/h at subsequent infusions. Escalation of infusion rates shortened infusion time from a median of around 2·5 h to around 1·6 h. SAEs were reported in three patients, but none was related to BT090 treatment. Conclusions Shortening infusion time may reduce overall healthcare spending, for example nursing time needed, and also minimize disruption of patients' daily routine, especially for those patients in work or school settings. [ABSTRACT FROM AUTHOR]

Over the past several decades, the use of intravenous human normal immunoglobulin (IVIg) products in a diverse range of immunodeficiency, inflammatory and infectious disorders has increased significantly. Newer manufacturing processes have increased the yield of intact IVIg molecules and have also improved the tolerability and safety of these products, including reducing the transmission risk of blood-borne diseases. While there are no appreciable differences between the numerous commercially available IVIg products in terms of efficacy, different manufacturing processes and the final composition of IVIg products have resulted in different safety and tolerability profiles. The tolerability profile of different IVIg products may be idiosyncratic for individual patients and may not be predictable, based on product characteristics. Consequently, patients receiving an IVIg product should be carefully monitored at initial exposure, and switching of products should be avoided. To achieve the best outcomes in patients requiring IVIg therapy, treatment should be tailored to the patient's needs. The risk/benefit profile of an IVIg in relation to patient risk factors and the underlying immune deficiency, or autoimmune or inflammatory disorder should be considered when deciding on the most appropriate therapy. [ABSTRACT FROM AUTHOR]

Mutations in the BRCA1 or BRCA2 genes result in a significantly increased risk of breast and ovarian cancer. Austrian women who carry a BRCA1 mutation have a risk of 85% for breast cancer and 53% for ovarian cancer up to 70 years of age. At-risk women have 2 medical options: closely monitored early detection using mammography, breast ultrasound, and MRI, as well as tumor markers and vaginal ultrasound, or real risk reduction through prophylactic removal of the breast tissue and/or the ovaries. As awareness of such a high risk of disease may cause a great deal of distress, and because prophylactic surgeries offer only very drastic measures for risk reduction, a special multidisciplinary care concept is of particular importance. This care starts with comprehensive genetic counseling before performing molecular genetic analysis and must be continued after a genetic predisposition for breast and ovarian cancer has been identified. Right from the start, special schooling in Austria has ensured that patients in all cooperating genetic counseling centers are counseled, selected, and followed- up according to the same criteria. [ABSTRACT FROM AUTHOR]