Pridgencarpenter5386

Second-line treatment for immune thrombocytopenia (ITP) is not well reported for patients treated in real-world clinical settings.

The purpose of this study was to compare outcomes of four second-line treatments for ITP.

Included adult patients had at least two medical records containing ITP diagnoses and second-line eltrombopag, romiplostim, rituximab, or splenectomy. Date of treatment initiation or splenectomy was set as index date, between July 1, 2008, and March 31, 2017. Patients had first-line corticosteroid or intravenous immune globulin treatment and continuous database activity from 6months before to 12months after index. Patient characteristics, treatment patterns, platelet counts, bleeding-related episodes (BREs), and thrombotic events (TEs) were compared by second-line treatment cohort.

The sample included 3332 patients (mean age, 60.5years; 52.3% female) eltrombopag (5.8%), romiplostim (9.9%), rituximab (73.3%), and splenectomy (11.0%). Patients having splenectomy were younger, more likely female and commercially insured, and less likely to require a third line of treatment than medical regimen cohorts. Proportions of patients having treatment-free (≥180days with no second-line index or rescue agent) periods varied significantly (

=.01) by regimen 33% for eltrombopag, 23% for romiplostim, 26% for rituximab, and 17% for splenectomy. All regimens significantly improved platelet counts, while TE and BRE rates differed significantly (

=.03 and

=.01, respectively) when all treatment groups were compared.

Over an average 7-year follow-up, all second-line regimens improved platelet counts, but eltrombopag yielded the highest proportion of patients with completely treatment-free periods of at least 180days.

Over an average 7-year follow-up, all second-line regimens improved platelet counts, but eltrombopag yielded the highest proportion of patients with completely treatment-free periods of at least 180 days.

The occurrence of mosaicism in hemophilia A (HA) has been investigated in several studies using different detection methods.

To characterize and compare the ability of AmpliSeq/Ion Torrent sequencing and droplet digital polymerase chain reaction (ddPCR) for mosaic detection in HA.

Ion Torrent sequencing and ddPCR were used to analyze 20 healthy males and 16 mothers of sporadic HA patients.

An error-rate map over all coding positions and all positions reported as mutated in the

-specific mutation database was produced. The sequencing produced a mean read depth of >1500X where >97% of positions were covered by >100 reads. Higher error frequencies were observed in positions with A or T as reference allele and in positions surrounded on both sides with C or G. Seventeen of 9319 positions had a mean substitution error frequency >1%. The ability to identify low-level mosaicism was determined primarily by read depth and error rate of each specific position. Limit of detection (LOD) was <1% for 97% of positions with substitutions and 90% of indel positions. The positions with LOD >1% require repeated testing and mononucleotide repeats with more than four repeat units need an alternative analysis strategy. Mosaicism was detected in 1 of 16 mothers and confirmed using ddPCR.

Deep sequencing using an AmpliSeq/Ion Torrent strategy allows for simultaneous identification of disease-causing mutations in patients and mosaicism in mothers. ddPCR has high sensitivity but is hampered by the need for mutation-specific design.

Deep sequencing using an AmpliSeq/Ion Torrent strategy allows for simultaneous identification of disease-causing mutations in patients and mosaicism in mothers. ddPCR has high sensitivity but is hampered by the need for mutation-specific design.

Monitoring hemophilia treatment with extended half-life products is challenging for coagulation laboratories since factor assays may show substantial differences between results obtained with the one-stage assay (OSA) and the chromogenic substrate assay (CSA).

The aim of this study was to evaluate and compare different factor assays and global coagulation methods.

Factor VIII (FVIII) and IX (FIX) activities and global assay parameters were analyzed in pre- and postinfusion samples (5 patients 2 samples/product/method).

Samples containing FVIII products (NovoEight, Elocta, and Nuwiq) gave higher levels when measured with CSA compared to OSA. The correlation was excellent (



≥.97) while biases of 42%-72% of mean (CSA-OSA) were obtained. With FVIII (OSA) as independent variable, the correlations to kaolin clot time (CT) and thrombin generation assay (TGA) peak were modest (

=.71-.72 and .64-.65, respectively), except for Nuwiq for which there was a poor correlation to TGA peak (



=.08). Belumosudil Samples conrrelations to factor activities.

We report the first analysis of an extended half-life recombinant factor IX, nonacog beta pegol (N9-GP), in previously untreated patients (PUPs) and minimally treated patients with hemophilia B.

Paradigm 6 (Safety and Efficacy of Nonacog Beta Pegol [N9-GP] in Previously Untreated Patients With Haemophilia B) is a multicenter, open-label, single-arm, phase 3 trial. Main inclusion criteria were males aged<6years, with hemophilia B with factor IX (FIX) activity≤2%, who were previously untreated or with≤3 exposure days (EDs) to FIX-containing products. Patients received N9-GP 40IU/kg once weekly (prophylaxis) or individualized dosing (preprophylaxis). Bleeds were treated with N9-GP 40IU/kg (80IU/kg if severe). The primary end point was incidence of anti-FIX inhibitory antibodies (inhibitors). Secondary end points included safety outcomes and annualized bleeding rate (ABR).

At data cutoff (August 31, 2018), 38 patients had been screened, and 37 had received N9-GP (median age, 1.0years [range, 0-4]). Total in-trial EDs amounted to 2833, representing~65 patient-years. Two (6.1%) of 33 "at-risk" patients (patients with≥10 EDs plus patients who developed inhibitors) developed high-titer inhibitors and were withdrawn. No other safety concerns, including thromboembolic events, were identified. In the prophylaxis group (n=28), 67.9% were bleed free; all bleeds (n=15) were treated with one N9-GP injection; and overall, spontaneous, and traumatic ABRs were low (median ABRs of 0.0, 0.0, and 0.0, respectively; modeled mean ABRs of 0.31, 0.08, and 0.23, respectively). Estimated mean FIX trough activity was 15.0%.

We report an inhibitor incidence of 6.1%, which is within the expected range for PUPs with hemophilia B. No other safety concerns were identified; moreover, N9-GP provided effective hemostatic coverage.

We report an inhibitor incidence of 6.1%, which is within the expected range for PUPs with hemophilia B. No other safety concerns were identified; moreover, N9-GP provided effective hemostatic coverage.