Inhibitor development according to concentrate in severe hemophilia: reporting on 1392 Previously Untreated Patients from Europe and Canada.

Background: Clotting factor concentrates have been the mainstay of severe hemophilia treatment over the last 50 years. Differences in risk of neutralizing antibody (inhibitor) formation according to concentrate used remain clinically relevant. Objectives: To assess inhibitor development according to type of clotting factor concentrate in previously untreated patients (PUPs) with severe hemophilia A and B. Methods: The European Haemophilia Safety Surveillance (EUHASS) and Canadian Bleeding Disorders Registry (CBDR) have been monitoring adverse events overall and according to concentrate for 11 and 8 years, respectively. Inhibitors were reported quarterly, and PUPs completed 50 exposure days without inhibitor development annually. Cumulative inhibitor incidences and 95% confidence intervals (CIs) were compared without adjustment for other risk factors. Results: Fifty-six European and 23 Canadian centers reported inhibitor development in 312 of 1219 (26%; CI, 23%-28%) PUPs with severe hemophilia A and 14 of 173 (8%; CI, 5%-13%) PUPs with severe hemophilia B. Inhibitor development was lower on plasma-derived factor (F)VIII (pdFVIII, 20%; CI, 14%-26%) than on standard half-life recombinant FVIII (SHL-rFVIII, 27%; CI, 24%-30% and odds ratio, 0.67; CI, 0.45%-0.98%; P = .04). Extended half-life recombinant FVIII (EHL-rFVIII, 22%; CI, 12%-36%) showed an intermediate inhibitor rate, while inhibitor rates for Advate (26%; CI, 22%-31%) and Kogenate/Helixate (30%; CI, 24%-36%) overlapped. For other SHL-rFVIII concentrates, inhibitor rates varied from 3% to 43%. Inhibitor development was similar for pdFIX (11%; CI, 3%-25%), SHL-rFIX (8%; CI, 3%-15%), and EHL-rFIX (7%; CI, 1%-22%). Conclusion: While confirming expected rates of inhibitors in PUPs, inhibitor development was lower in pdFVIII than in SHL-rFVIII. Preliminary data suggest variation in inhibitor development among different SHL-rFVIII and EHL-rFVIII concentrates.

Immunoglobulin use in immune deficiency in the UK: a report of the UKPID and National Immunoglobulin Databases.

Supply of immunoglobulin in the UK faces pressures due to increasing demand, cost and variable supply. This paper describes immunoglobulin replacement therapy (IGRT) in primary immunodeficiency (PID) and secondary immunodeficiency (SID) to assist in the ongoing planning of UK immunoglobulin provision. A retrospective analysis of the National Immunoglobulin Database and the UKPID registry was carried out. In total, 3,222 patients are registered as receiving IGRT for immunodeficiencies. Predominately antibody disorders made up the largest diagnostic category (61% of patients). The total cost of IGRT for immunodeficiency for 2015/16 was £40,673,350; an average annual cost of £1,099,254 per centre and £12,124 per PID patient. SCIg accounted for 43.8% and 50.1% of IGRT, with home therapy accounting for 42.7% and 57.5% of place of therapy in the National Immunoglobulin Database and UKPID registry respectively. In 2015/16 use of immunoglobulin in SID increased by 24% over the previous financial year. The overall trends of increasing demand in immunology are mirrored in other specialties, most notably neurology and haematology. These data are the first national overview of IGRT for immunodeficiencies, providing a valuable resource for clinicians and policy makers in the ongoing management of UK immunoglobulin supply.

Immunoglobulin therapy.

Immunoglobulin is an expensive blood product of potentially limited supply used in a wide variety of medical conditions, across a number of specialties. Historically, immunoglobulin has been associated with transmission of blood borne infection (eg hepatitis C). Immunoglobulin use needs to be carefully considered, appropriately prescribed and recorded. The Department of Health, in conjunction with relevant stakeholders, has established a demand management programme to secure immunoglobulin supplies for patients most in need of treatment and to limit use for indications where evidence is lacking.

Developing an automated process of uploading immunoglobulin batch numbers to the UK National Immunoglobulin Database.

OBJECTIVES: To develop a more efficient and robust process for entering patient-specific, immunoglobulin batch number data onto the UK National Immunoglobulin Database. METHODS: A manual method of input, which relied on paper records, was replaced with an automated upload that was developed by linking the pharmacy dispensing system, JAC, with a number of information technology support systems to produce a batch number report. Both systems ran parallel for a period of 7 weeks, and administration time and completeness of data for both were analysed. RESULTS: Over the 7-week period, 550 g of immunoglobulin would not have been entered using the manual method (=4108 g per annum; 4.66% of total immunoglobulin usage). The time taken to enter the data was reduced from 4 h to 30 min per week. CONCLUSIONS: An automated process of uploading batch numbers increases accuracy and completeness of data, reduces administrative time and risk of financial loss; therefore, significantly increasing efficiency.