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Introduction: Octanate® is a human, plasma‐derived, von Willebrand factor‐stabilized coagulation factor VIII (FVIII) concentrate with demonstrated haemostatic efficacy in previously treated patients with haemophilia A. Aim: This prospective, open‐label study aimed to assess the immunogenicity of octanate® in previously untreated patients (PUPs). Methods: The study monitored development of FVIII inhibitors in 51 PUPs. Tolerability, viral safety, FVIII recovery and efficacy of octanate® for the prevention and treatment of bleeds and in surgical procedures were also assessed. Results: Five (9.8%) of the 51 patients developed inhibitors during the study, 4 of which (7.8%) were high titre. Three inhibitor cases (5.9%) were considered clinically relevant; 2 were transient inhibitors that disappeared during regular octanate® treatment without a change in dose or treatment frequency. Amongst 45 patients with FVIII:C <1% at baseline and who received ≥20 exposure days (EDs) or had <20 EDs but developed an inhibitor, inhibitor incidence was 11.1% (6.7% clinically relevant). All clinically relevant inhibitors developed within 20 EDs of on‐demand treatment. No inhibitors developed in PUPs receiving prophylaxis. All patients who developed inhibitors had either intron 22 inversions or large deletions. Irrespective of the reason for administration, haemostatic efficacy was rated as “excellent” in 99.6% of all infusions (4700 of 4717 infusions), and no complications were reported in 23 surgical procedures. Mean incremental in vivo recovery was 2.0%/IU/kg (±0.7) and 1.9%/IU/kg (±0.5) for the first and second assessments, respectively. Tolerability was rated “very good” in 99.9% of infusions. Conclusion: In PUPs with severe haemophilia A, octanate® demonstrated haemostatic efficacy with a low rate of inhibitor development. [ABSTRACT FROM AUTHOR]

This European observational chart review assessed the efficacy/safety of recombinant von Willebrand factor (rVWF) for on-demand treatment of spontaneous/traumatic bleeds and prevention and/or treatment of surgery-related bleeding in adults with von Willebrand disease (VWD). Patients (n = 91) were enrolled at first rVWF administration (index). Data were collected for the 12 months before index and until death, loss to follow-up, or end of study (3-12 months after index). Fifteen patients reported an rVWF-treated spontaneous/traumatic bleed at index. Bleed resolution was obtained for 14 patients (unknown status, n = 1), and investigators assessed treatment satisfaction for 13 rVWF prescriptions (2 moderate, 5 good, and 6 excellent). rVWF was used to prevent/treat surgery-related bleeds at index in 76 patients. Bleed resolution was achieved in 25/58 rVWF-treated surgeries; bleed resolution was not applicable for 33 surgeries. In both groups, there were no reports of treatment-emergent adverse events after initiating rVWF, including hypersensitivity reactions, thrombotic events, and VWF inhibitor development. rVWF was shown to be effective for the on-demand treatment of spontaneous/traumatic bleeds, and for the prevention and treatment of surgical bleeds in this real-world VWD population.

Background  Immune tolerance induction (ITI) with repeated factor VIII (FVIII) administration is the only strategy proven to eradicate inhibitors. The observational ITI study is evaluating ITI with a range of FVIII products. Methods  This subgroup analysis reports prospective interim data for patients treated with a plasma-derived, von Willebrand factor-stabilized FVIII concentrate (pdFVIII/VWF, octanate). Complete success (CS) of ITI required achievement of three criteria: inhibitor titer < 0.6 BU/mL; FVIII recovery ≥ 66%; FVIII half-life ≥6 hours. Partial success (PS) required achievement of two criteria and partial response (PR) one. ITI success was defined as CS or PS. Data were analyzed for patients who achieved CS, had 36 months' observation, or failed ITI. Results  One-hundred prospectively enrolled patients were included in the analysis; 91 had poor prognosis factors for ITI success. The mean (standard deviation) daily ITI dose was 116.4 (61.1) IU FVIII/kg in 14 low responders (< 5 BU/mL) and 173.7 (112.0) IU FVIII/kg in 86 high responders (≥ 5 BU/mL). Inhibitor titers < 0.6 BU/mL were achieved in 71% of patients in a median of 4.01 months, accompanied by a 93% reduction in bleeding rate. ITI success was achieved by 70% of patients and 56 of 72 (78%) primary (first-line) ITI patients. PR was achieved by 5 patients; ITI failed in 25 patients. PS and CS were achieved in a median of 5.55 and 11.25 months, respectively. Conclusions  ITI with pdFVIII/VWF led to rapid eradication of FVIII inhibitors, normalization of FVIII pharmacokinetics in the majority of patients, and a significant reduction in bleeding rates., Competing Interests: Conflict of Interest C. Escuriola Ettingshausen has acted as a consultant and received speaker's fees and/or research funding from the following companies: Bayer, Biomarin, Biotest, Chugai, CSL Behring, Grifols, Kedrion, Novo Nordisk Octapharma, Roche, Swedish Orphan Biovitrum and Takeda. V. Vdovin has participated in studies sponsored by Bayer, Generium, Novo Nordisk, Octapharma and Roche. N. Zozulya has acted as a consultant and received speaker's fees and/or research funding from the following companies: CSL Behring, Generium, Novo Nordisk, Octapharma, Roche, SOBI and Takeda. T. Andreeva has received speaker's fees and/or research funding from Bayer, Baxalta, Biomarin, Catalis, CSL Behring, Generium, Grifols, Novo Nordisk, Octapharma and Roche, and has consulted for CSL Behring, Generium, Novo Nordisk, Octapharma, Roche, Shire and Swedish Orphan Biovitrum. V Jiménez-Yuste has acted as a consultant and/or received speaker's fees and/or research funding from the following companies: Bayer, Grifols, Novo Nordisk, Octapharma, Pfizer, Swedish Orphan Biovitrum and Takeda. L. Kitanovski has acted as a consultant and received speaker's fees from the following companies: Bayer, Novo Nordisk, Octapharma, Roche, Takeda and Swedish Orphan Biovitrum. S. Zupančić Šalek has acted as a consultant and/or received speaker's fees and/or research funding from following companies: Bayer, Novo Nordisk, Octapharma, Roche, Swedish Orphan Biovitrum and Takeda. A. Pavlova has participated in studies sponsored by Octapharma AG. A. Bátorová has acted as a consultant and/or received speaker's fees and/or research funding from the following companies: Grifols, Novo Nordisk, Octapharma, Pfizer, Swedish Orphan Biovitrum and Takeda. C. Montaño Mejía has received speaker's fees from Octapharma and Roche; travel support from CSL Behring, Grifols, Novo Nordisk, Octapharma, Pfizer, Roche and Takeda. J. Oldenburg has acted as a consultant and/or received speaker's fees, honoraria and research funding from the following companies: Bayer, Biogen Idec, Biotest, CSL Behring, Grifols, Novo Nordisk, Octapharma, Pfizer, Swedish Orphan Biovitrum and Takeda. S. Knaub, S. Lowndes, L. Belyanskaya and O. Walter are employees of Octapharma AG. M. Jansen is an employee of Octapharma Pharmazeutika Produktionsges.mbH. P. Svirin, M. Benedik-Dolničar and G. Abdilova stated that they had no conflicts of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Background: The adjuvanted recombinant zoster vaccine (RZV) has demonstrated >90% efficacy against herpes zoster in adults ≥50 years of age and 68% efficacy in autologous hematopoietic stem cell transplant recipients ≥18 years of age. We report the immunogenicity and safety of RZV administered to patients with solid tumors (STs) before or at the start of a chemotherapy cycle., Method: In this phase 2/3 observer-blind, multicenter study (NCT01798056), patients with STs who were ≥18 years of age were randomized (1:1) to receive 2 doses of RZV or placebo 1-2 months apart and stratified (4:1) according to the timing of the first dose with respect to the start of a chemotherapy cycle (first vaccination 8-30 days before the start or at the start [±1 day] of a chemotherapy cycle). Anti-glycoprotein E (gE) antibody concentrations, gE-specific CD4 + T cell frequencies, and vaccine response rates (VRRs) were assessed 1 month after dose 1 and 1 and 12 months after dose 2. Reactogenicity and safety were assessed in the total vaccinated cohort through 12 months after dose 2., Results: There were 232 participants in the total vaccinated cohort, 185 participants in the according-to-protocol cohort for humoral immunogenicity, and 58 participants in the according-to-protocol cohort for cell-mediated immunogenicity. Postvaccination anti-gE antibody concentrations, gE-specific CD4 + T cell frequencies and VRRs were higher in RZV recipients than in placebo recipients. Solicited adverse events (AEs) were more frequent among RZV recipients than placebo recipients. Incidence of unsolicited AEs, serious AEs, fatalities, and potential immune-mediated diseases were similar between RZV and placebo recipients., Conclusion: RZV was immunogenic in patients with STs receiving immunosuppressive chemotherapies. Humoral and cell-mediated immune responses persisted 1 year after vaccination. No safety concerns were identified., (© 2019 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.)

Introduction: Octanate ® is a human, plasma-derived, von Willebrand factor-stabilized coagulation factor VIII (FVIII) concentrate with demonstrated haemostatic efficacy in previously treated patients with haemophilia A., Aim: This prospective, open-label study aimed to assess the immunogenicity of octanate ® in previously untreated patients (PUPs)., Methods: The study monitored development of FVIII inhibitors in 51 PUPs. Tolerability, viral safety, FVIII recovery and efficacy of octanate ® for the prevention and treatment of bleeds and in surgical procedures were also assessed., Results: Five (9.8%) of the 51 patients developed inhibitors during the study, 4 of which (7.8%) were high titre. Three inhibitor cases (5.9%) were considered clinically relevant; 2 were transient inhibitors that disappeared during regular octanate ® treatment without a change in dose or treatment frequency. Amongst 45 patients with FVIII:C <1% at baseline and who received ≥20 exposure days (EDs) or had <20 EDs but developed an inhibitor, inhibitor incidence was 11.1% (6.7% clinically relevant). All clinically relevant inhibitors developed within 20 EDs of on-demand treatment. No inhibitors developed in PUPs receiving prophylaxis. All patients who developed inhibitors had either intron 22 inversions or large deletions. Irrespective of the reason for administration, haemostatic efficacy was rated as "excellent" in 99.6% of all infusions (4700 of 4717 infusions), and no complications were reported in 23 surgical procedures. Mean incremental in vivo recovery was 2.0%/IU/kg (±0.7) and 1.9%/IU/kg (±0.5) for the first and second assessments, respectively. Tolerability was rated "very good" in 99.9% of infusions., Conclusion: In PUPs with severe haemophilia A, octanate ® demonstrated haemostatic efficacy with a low rate of inhibitor development., (© 2018 The Authors. Haemophilia published by John Wiley & Sons Ltd.)

Between 1982 and 1989, 200 patients aged 70 or over seen in one Breast Unit, who were considered to have a surgically resectable cancer of the breast were prospectively randomized to primary surgery or tamoxifen 20 mg per day. At a median follow-up of 6 years (range 3-11 years) and at the censoring date there were 61 first events in the tamoxifen group. Fifty three patients developed local relapse or progression of the cancer; three patients had simultaneous local progression or relapse and distant metastases. In addition a further five patients developed distant recurrence only. In the surgical arm there were 50 events. Thirty-six patients developed local recurrence only; eight had simultaneous local and distant recurrence. A further six patients developed distant metastases of which two subsequently developed local recurrence. There were 33 deaths in the tamoxifen group and 28 deaths in the surgical group of which 17 and 15, respectively were directly attributable to breast cancer. The disease-free interval did not differ between the two groups. Following treatment with tamoxifen, at the censoring date which was the date of last clinical examination or arbitrarily, the date of death, 39 patients had no evidence of relapse whereas in the surgical arm there were 50 patients who had no evidence of recurrence. Fifty-three patients in the tamoxifen arm had local relapse only and were available for crossover to surgery, 39 accepted surgery. Eight developed further local recurrence, 10 developed distant metastases and 21 remained free of disease. Thirty-six patients in the surgical group developed local relapse only and were available for crossover to tamoxifen. Thirty one accepted treatment with tamoxifen, 14 had progression of their local recurrence, seven developed distant metastases and 10 had no further recurrence. Thus in the tamoxifen group, 39 had no progression of their disease and a further 21 benefited from subsequent surgery: 60% in all. In the surgical group 50 had no recurrence of their disease and a further 10 benefited from subsequent tamoxifen therapy: 60% in all.