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SummaryIn the phase 3 B-LONG (Recombinant Factor IX Fc Fusion Protein [rFIXFc] in Subjects With Haemophilia B) study, rFIXFc demonstrated a prolonged half-life compared with recombinant factor IX (rFIX), and safety and efficacy for prophylaxis and treatment of bleeding in subjects with moderately-severe to severe haemophilia B. In this B-LONG sub-analysis, rFIXFc was evaluated for efficacy in subjects requiring major surgery. Dosing was investigator-determined. Assessments included dosing, consumption, bleeding, transfusions and haemostatic response. A population pharmacokinetics model of rFIXFc was used to predict FIX activity. Twelve subjects underwent 14 major surgeries (including 11 orthopaedic surgeries); most subjects (11/12) received rFIXFc prophylaxis before surgery (range, 2 weeks-12 months). Investigators/surgeons rated haemostatic responses as excellent (n = 13) or good (n = 1). In most surgeries (85Á7%), haemostasis from the pre-surgical dose until the end of surgery was maintained with a single rFIXFc infusion. Blood loss was consistent with similar surgeries in subjects without haemophilia. The strong correlation (R 2 = 0Á9586, P < 0Á001) between observed and population pharmacokinetic model-predicted FIX activity suggests surgery did not impact rFIXFc pharmacokinetics. No unique safety concerns or inhibitors were observed. In conclusion, rFIXFc was safe and efficacious, with prolonged dosing intervals and low consumption, when used perioperatively in haemophilia B. Surgery did not appear to alter rFIXFc pharmacokinetics.

Introduction The safety, efficacy and prolonged half‐life of recombinant factor VIII Fc fusion protein (rFVIIIFc) in previously treated patients with severe haemophilia A was demonstrated in the phase 3 A‐LONG and Kids A‐LONG studies. Here, we report interim safety and efficacy data from the rFVIIIFc extension study, ASPIRE (ClinicalTrials.gov #NCT01454739). Methods Eligible subjects could enrol in ASPIRE upon completing A‐LONG or Kids A‐LONG. There were four treatment groups: individualized prophylaxis; weekly prophylaxis; modified prophylaxis (for subjects in whom optimal treatment could not be achieved with individualized or weekly prophylaxis); and episodic treatment. The primary endpoint was development of inhibitors. Results A total of 150 A‐LONG subjects and 61 Kids A‐LONG subjects enrolled in ASPIRE. As of the interim data cut (6 January 2014), the median time on study was 80.9 (A‐LONG) and 23.9 (Kids A‐LONG) weeks. The majority of subjects (A‐LONG, 92.0%; Kids A‐LONG, 57.4%) had ≥100 cumulative rFVIIIFc exposure days. No inhibitors were observed. Adverse events were generally consistent with those expected in the general haemophilia A population. Median annualized bleeding rates (ABRs) were low with individualized [A‐LONG: 0.66; Kids A‐LONG: 0.00 (<6 years old), 1.54 (6 to <12 years old)], weekly (A‐LONG: 2.03) and modified (A‐LONG: 1.97) prophylaxis. There was no change in prophylactic infusion frequency or total weekly prophylactic dose in the majority of subjects from A‐LONG and Kids A‐LONG. Conclusion Interim data from ASPIRE confirm the long‐term safety of rFVIIIFc and the maintenance of a low ABR with extended‐interval prophylactic dosing in patients with severe haemophilia A.

Eradication of Helicobacter pylori (H. pylori ) from the gastric mucosa has been associated with improvement of several systemic diseases, including immune thrombocytopenic purpura (ITP). Over the last 5 years, several studies have reported improved platelet counts in H. pylori-positive ITP patients following standard triple H. pylori eradication therapy. Review of published studies in which eradication of H. pylori has been performed in the ITP population indicates an overall response rate of 52% in 193 subjects in whom H. pylori was eradicated. Cohorts from Japan and Italy report higher response rates. There is no established mechanism to explain how this organism, which does not invade the gastric mucosa, could be implicated in the pathogenesis of this immune-based platelet disorder. Several theories including molecular mimicry, platelet aggregation, and immunomodulatory effects of macrolides have been proposed to explain the platelet response to anti-H. pylori therapy. Large randomized-controlled studies enrolling patients from various ethnic backgrounds will be necessary to determine the response rate and mechanism of response and to gain a better understanding of the pathogenesis of ITP. Am.

The safety and efficacy of treatment options for patients with haemophilia have significantly improved over the last two decades, particularly with greater utilization of prophylactic approaches. Consequently, it is becoming increasingly difficult to differentiate the treatment benefits of available choices based on standard endpoints such as annualized bleeding rates and joint health scores. Patient-reported outcomes (PROs) have shown limited ability to discriminate between treatment outcomes, in part because of their comprehensive nature; i.e. differences in specific outcomes meaningful to individual patients are masked by a global scoring system based on a fixed set of items, many of which may be unimportant for any given patient. There is a clear need for new outcome measures. Initiatives to develop patient-centric outcomes that capture clinically meaningful change are ongoing. One such approach, goal attainment scaling (GAS), allows patients, in collaboration with a trained clinician, to select goals from a medical condition-specific menu of options and subsequently facilitates quantitative assessment of goal realization. Thus, it is fully personalized and sensitive to small, often idiosyncratic, treatment benefits, such as improvements in functional capacity. In this paper, we present the underlying rationale for GAS and one other novel approach to PRO personalization, and discuss their potential to augment current outcome measures by reliably detecting and quantifying treatment effects in individuals with haemophilia on prophylaxis.

GAS-Hēm was feasible and tapped constructs not captured by ABR or QoL measures.

Cardiovascular disease risk factors and events are relatively common in PWH. PWH can be safely treated for CVD events with similar procedures as the non-PWH populations, though specific clotting factor prophylaxis protocols are not well defined.

Severe haemophilia is often managed by prophylactic factor infusions in developed countries. The benefits of secondary prophylaxis in adults are currently being studied and adherence to the prescribed prophylactic factor regimen is vital to decreasing bleeding episodes. The aim of this study was to measure discrepancy between the physicians' prescription for prophylactic factor usage, and the actual factor usage obtained through infusion logs. During this method subjects with severe haemophilia A or B (FVIII or FIX ≤2%), from a single haemophilia clinic with complete medical and infusion records from July 01, 2009 to June 30, 2011, were evaluated. Continuous prophylaxis ≥4 weeks were included in the analysis. A scoring system for adherence to prescribed dosing and frequency was developed. A global scale of adherence was performed by two independent nurses using visual analogue scale. Thirty-one subjects, all with haemophilia A, with a median age of 26 years (range 18-56) were included. Results showed that the median (IQR) adherence rate to prescribed frequency and dosage, respectively, was 76% (67;85) and 93% (73;97). In multivariate analysis, only the length of time on prophylaxis during the study period showed a positive correlation with adherence whereas age, number of co-infections, number of bleeds and number of joints with chronic arthropathy did not. Global nursing assessments were in general agreement with the score. In conclusion, we observed a moderately good level of adherence based on score and by the nurse global assessment. Better adherence was found in subjects with longer exposure to prophylaxis.