Grifols (United States)

IntroductionPlasma-derived von Willebrand factor containing FVIII concentrates (pdVWF/FVIII-C) are indicated as replacement therapy for patients with von Willebrand disease (VWD). This study assessed safety and efficacy associated with long-term real-world experience of the pdVWF/FVIII-C, Fanhdi®, in patients with VWD.MethodsThis observational, prospective, post-authorization cohort study was conducted at five centers in Spain. Patients with VWD were treated with the pdVWF/FVIII-C to achieve satisfactory hemostasis for on-demand (bleeding episodes and surgical/invasive procedures) and prophylaxis treatment. Clinical efficacy was evaluated as the response to treatment in both settings. Safety parameters were assessed.ResultsFifteen VWD patients received at least one dose of the pdVWF/FVIII-C and were followed for 12 months. Forty-six bleeding episodes were reported for 9 (60.0%) patients, and 6 surgical/invasive procedures for 5 (33.3%) patients. Most frequently reported bleedings were gastrointestinal (3 [33.0%] patients) and gynecological (3 [33.0%] patients). No complications nor bleeding episodes related to surgical/invasive procedures were reported. Overall clinical efficacy of treatment (including on-demand and prophylaxis) achieved 100% excellent and/or good (n = 15 patients), being excellent for 7 (46.7%) patients. There were 27 treatment-emergent adverse events in 8 (53.3%) patients, 11 serious adverse events in 3 (20.0%) patients, but none of them were drug-related. No clinical signs and symptoms of immunogenicity or thromboembolic events were reported.ConclusionsThis real-world evidence study confirmed the efficacy of the pdVWF/FVIII-C as on-demand and/or prophylaxis treatment in patients with bleeding episodes or surgical procedures in VWD. Fanhdi® was well tolerated without any safety concerns.

Prospective, randomized, controlled trials of intravenous immunoglobulin (IVIG) maintenance therapy in myasthenia gravis (MG) are lacking. In this trial, we evaluated the safety and efficacy of caprylate/chromatography-purified IVIG; (IGIV-C) in patients with generalized MG undergoing standard care. Sixty-two patients enrolled in this phase 2, multicenter, international, randomized trial (1:1 IGIV-C [2 g/kg loading dose; 1 g/kg every 3 weeks through week 21] or placebo). Efficacy was assessed by changes in Quantitative MG (QMG) score at week 24 versus baseline (primary endpoint) and percentage of patients with clinical improvement in QMG, MG Composite (MGC), and MG-Activities of Daily Living (MG-ADL) scores (secondary endpoints). Safety assessments reported all adverse events (AEs). The change in QMG at 24 weeks was -5.1 for IGIV-C and -3.1 for placebo (p = .187). Seventy percent of patients in the IGIV-C group had improvement in MG-ADL (≥2-point decrease) versus 40.6% in the placebo group (p = .025). Patients showing clinical improvement in QMG and MGC (≥3-point decrease) were 70.0% for IGIV-C versus 59.4% for placebo (p = .442) and 60.0% for IGIV-C versus 53.1% for placebo (p = .610). IGIV-C was well tolerated; serious AEs were similar between arms. Three of four MG exacerbations requiring hospitalizations occurred in the IGIV-C arm with one death. Several efficacy parameters showed numerical results greater than those seen in the placebo group. This was a small study and may have been underpowered to see significant differences. Additional studies may be warranted to fully determine the efficacy of IVIG maintenance therapy in MG.

The rising prevalence of liver diseases related to obesity and excessive use of alcohol is fuelling an increasing demand for accurate biomarkers aimed at community screening, diagnosis of steatohepatitis and significant fibrosis, monitoring, prognostication and prediction of treatment efficacy. Breakthroughs in omics methodologies and the power of bioinformatics have created an excellent opportunity to apply technological advances to clinical needs, for instance in the development of precision biomarkers for personalised medicine. Via omics technologies, biological processes from the genes to circulating protein, as well as the microbiome - including bacteria, viruses and fungi, can be investigated on an axis. However, there are important barriers to omics-based biomarker discovery and validation, including the use of semi-quantitative measurements from untargeted platforms, which may exhibit high analytical, inter- and intra-individual variance. Standardising methods and the need to validate them across diverse populations presents a challenge, partly due to disease complexity and the dynamic nature of biomarker expression at different disease stages. Lack of validity causes lost opportunities when studies fail to provide the knowledge needed for regulatory approvals, all of which contributes to a delayed translation of these discoveries into clinical practice. While no omics-based biomarkers have matured to clinical implementation, the extent of data generated has enabled the hypothesis-free discovery of a plethora of candidate biomarkers that warrant further validation. To explore the many opportunities of omics technologies, hepatologists need detailed knowledge of commonalities and differences between the various omics layers, and both the barriers to and advantages of these approaches.

A direct antiglobulin test (DAT) is used to evaluate hemolytic transfusion reactions and autoimmune hemolytic anemias. DATs are performed with polyspecific anti-human globulin (AHG, anti-IgG, and anti-C3d), followed by differentiation between IgG and C3d using monospecific anti-IgG and anti-C3d. Evaluating RBCs for surface-bound C3d is traditionally performed using conventional tube test (CTT) methodology. A recently FDA-licensed DAT gel column agglutination card containing monoclonal anti-C3d reagent offers a new, more efficient method of detecting C3d on RBCs. As part of a large study evaluating the sensitivity of a DAT gel card, the data presented here compares the performance of CTT and gel methods in detecting RBC-bound C3d. This IRB-approved study included 141 samples from 29 patients and 112 blood donors. Parallel testing between the gel method and CTT was performed at three sites: two used automated gel and one used manual gel. The FDA-licensed anti-C3 reagents chosen for CTT consisted of two murine monoclonal antibodies, anti-C3b and anti-C3d. Anti-C3d reactivity was considered the most reliable for comparison with the CTT method in a previous comparison study. Discordant sample results were tested by an independent fourth referee site. Of the 141 samples tested, the gel method demonstrated 100% concordance with CTT when tested with both manual and automated methods. The concordance of all test results was calculated by comparing the number of results in agreement (PPA + NPA, where PPA represents positive percent agreement and NPA represents negative percent agreement with the total number of results). Hundred percent was achieved at all 3 test sites for PPA, NPA, and overall percent agreement (OPA). There was one discrepancy where the gel method result was consistent with the referee site. See Table 1. TABLE 1.

Evaluating the effectiveness of Chagas disease treatment poses challenges due to the lack of biomarkers for disease progression and therapeutic response. In this study, we aimed to assess the clearance of Trypanosoma cruzi (T. cruzi) parasites in a group of benznidazole (BNZ)-treated chronic Chagas disease patients using high-sensitivity quantitative PCR (qPCR) and track T. cruzi antibody levels through a semiquantitative chemiluminescent assay. A total of 102 T. cruzi seropositive patients with previous PCR-positive results were enrolled in the study. We collected samples 30 days before treatment (T-30d), on the day before initiating BNZ treatment (T0d), and at follow-up visits 60 days (T60d), 6 months (T6M), 12 months (T12M), and 36 months (T36M) after treatment initiation. Treatment efficacy was assessed by testing of serial samples using a target-capture qPCR assay specific to satellite T. cruzi DNA and the ORTHO T. cruzi ELISA Test System for antibody quantitation. Of the enrolled individuals, 87 completed at least 50% of the treatment course, and 86 had PCR results at follow-up visits T6M, T12M, and T36M. PCR results exhibited fluctuations before and after treatment, but levels were significantly lower post-treatment. Only 15 cases consistently tested PCR-negative across all post-treatment visits. Notably, nearly all participants demonstrated a declining antibody trajectory, with patients who tested PCR-negative at T36M exhibiting an earlier and more pronounced decline compared to PCR-positive cases at the same visit. Our study suggests that serial PCR results pose challenges in interpretation. In contrast, serial antibody levels may serve as an ancillary, or even a more reliable indicator of parasite decline following BNZ treatment. Monitoring antibody levels can provide valuable insights into the efficacy of treatment and the persistence of parasites in Chagas disease patients.

In the United States, source plasma (SP) donors can donate up to 104 times per year. Considering the global need for SP and plasma-derived medicinal products, it is critical to maintain the health of frequent donors. This study explores SP donors' self-reported reasons for a lapse in donating. There were 5608 SP donors from 14 SP centers who enrolled in a longitudinal cohort study to assess self-reported functional health and well-being. Donors were assigned to one of four groups, according to the frequency of SP donation in the 12 months before enrollment. One thousand four hundred forty-eight SP donors who lapsed in donating during 6 months or greater during the study follow-up were asked to complete a survey. There were 545 lapsed SP donors who returned surveys (37.6%); 63% were female. Most responses given for stopping SP donation were categorized as convenience reasons (69.1%). Self-reported health concerns, including being deferred multiple times, which were categorized as possibly related or unable to determine a relationship to plasmapheresis, represented 45.5% of the responses. Primary reasons US SP donors report for a lapse in donation were categorized as convenience (e.g., schedule conflicts/lack of time). Donor responses categorized as health concerns which have a possible or uncertain relationship to plasmapheresis were less frequent but present in all frequency groups. This study adds to the body of evidence that SP donors cease donating for a variety of self-reported reasons with the majority not directly related to a perceived negative impact on their health.

Given the possibility for disease transmission, this study was performed to determine whether there is detectable SARS-CoV-2 viral RNA in the blood of deceased tissue donors. A retrospective analysis of blood samples from eligible deceased tissue donors from Oct 2019 through June 2020 was performed. Plasma aliquots were initially tested with a SARS-CoV-2 NAT Assay; positive samples were further tested using an alternate NAT and an antibody assay. The proportion of donors with confirmed RNAemia and 95% confidence intervals were computed. Of donor samples collected in 2019, 894 yielded valid results, with 6 initially positive, none of which confirmed positive by alternate NAT. Of donor samples collected in 2020, 2562 yielded valid initial NAT results, with 21 (0.8%) initially positive. Among those, 3 were confirmed by alternate NAT, 17 were not confirmed, and 1 had an invalid alternate NAT result. The rate of SARS-CoV-2 RNAemia in deceased tissue donors is approximately 1 per 1000, and it is unknown whether this RNAemia reflects the presence of infectious virus. Given these results, the risk of transmission through tissue is thought likely to be low.