Search

Background Record keeping is integral to home treatment for haemophilia. Issues with paper diaries include questionable compliance, data validity and quality. Implementation of electronic diaries (e-diaries) in haemophilia patients could improve documentation of home treatment. Aim This article evaluates the effects of an e-diary, Haemoassist, on recording and patient compliance with therapy. Patients and Methods An explorative study was used to assess the sequential use of paper diaries and e-diaries by 99 patients with severe haemophilia A or B and 1 with severe factor VII deficiency. Median age was 41 years. Information was obtained from paper records for 3 years preceding the introduction of an electronic record system and the first 6 to 12 months of Haemoassist use. Data from the 3-year period were averaged. Missing data for rounded 12 months of e-diary use were extrapolated to correspond to a full year. Results Enhancement of 23% in record delivery was observed for the period of Haemoassist use (p = 0.013). Twenty-one percent increase in patients’ compliance for data reporting (from 65% 35 to 86% 22, p = 0.003) and 16% increase for documentation of bleedings (from 68 to 84% of patients, p = 0.01) were detected. Compliance to prescribed therapy of patients for the whole studied period improved by 6% (from 82% ± 29 to 88% ± 25, p = 0.05). Major advances were demonstrated predominantly in the age groups of between 13 and 20 and 21 and 40 years. Conclusion e-Diaries' use enables improved recording of information about patients' home treatment and bleeding episodes. Enhanced compliance with therapy may be a further benefit.

SummaryTuroctocog alfa (NovoEight®) is a new recombinant factor VIII (rFVIII) with a truncated B domain and a high degree of tyrosine sulphation, similar to plasma-derived FVIII products. The manufacturing process includes double nanofiltration with a 20-nm pore size and immunoaffinity chromatography with monoclonal F25 anti-FVIII antibodies. Treatment with turoctocog alfa can be monitored with both one-stage and chromogenic substrate assays without a product-specific laboratory standard. In total, 213 previouslytreated patients with severe haemophilia A participated in the pivotal part of the clinical trial programme guardianTM. The median annualised bleeding rate during turoctocog alfa prophylaxis was 3.7 and 3.0 in adolescents/adults and children, respectively, with marked differences between participating countries. The success rate for the treatment of breakthrough bleeds was 85% (adults/ adolescents) and 94% (children). A total of 41 surgical procedures (15 major, 26 minor) were performed in 33 patients, with a successful haemostatic response reported in all cases. No patient developed confirmed inhibitors in any of the trials.

SummaryThe aim of this study was to develop a complex strength measurement method and to apply this new method for the first time in patients with haemophilia (PwH). 20 PwH with severe haemophilia A and 20 controls were included into the study. All subjects completed ten measurements of maximum isometric strength. Furthermore, the 20 control subjects completed re-test-measurements to evaluate the method.As a result, the method showed a high reliability (ICC 0.764 to 0.934). Between the two groups significant reductions in PwH between –(19–35%) were detected, regarding the relative force of the M. triceps brachii (–19%; p = 0.008), M. biceps brachii (–19%; p = 0.031), M. latissimus dorsi (–17%; p = 0.019), M. biceps femoris right (–20%; p = 0.036) and M. quadriceps femoris (right: –29%; p = 0.004; left: –35%; p = 0.002). No differences were found for M. rectus abdominis and in the hand strength. Thus, there is no general deficit in the muscle strength in PwH. The most obvious deficits exist in the upper and lower extremities and in the back muscles.PwH should carry out complex muscle strength training and integrate it early into a comprehensive treatment concept.

ZusammenfassungProphylaxe kann bei Erwachsenen mit schwerer Hämophilie A klinisch notwendig sein. Ziel war es, die prophylaktische Faktor-VIII-Substitution bei erwachsenen Patienten mit Hämophilie in Deutschland ökonomisch zu bewerten. Patienten, Methoden: Für die Analysen wurde ein Entscheidungsmodell erstellt: Zeithorizont ein Jahr; Perspektive gesetzliche Krankenkassen; Referenzpatient (RP) und zwei Patientenprofile. Die Berech-nungen basieren auf Daten aus einer struktu-rierten Literatursuche, -analyse und einer Pharmakovigilanzstudie mit Patienten zu Therapiewechsel On-demand/Prophylaxe (OD/Proph). Ergebnisse: RP: 45 Jahre, 20 Blutungen p.a. OD, 16 vermiedene Blutungen mit 8,5 I.U./kg/d Proph, Zusatzkosten 141 113 Euro p.a.; Profil 1: 50 Jahre, 55 Blutungen p.a. OD, Faktorverbrauch pro Blutung 20 I.U./kg höher als bei R P, 39 vermiedene Blutungen mit 8,5 I.U./kg/d Proph, Zusatzkosten 19 134 Euro p.a.; Profil 2: 60 Jahre, 35 Blutungen p.a. OD, Faktorverbrauch pro Blutung 40–80 I.U./kg höher als bei R P, 34 vermiedene Blutungen mit 11 I.U./kg/d Proph, Einsparung 660 Euro p.a. Schlussfolgerung: In der indivi-duellen Situation kann eine prophylaktische Faktorsubstitution bei erwachsenen Patienten auch ökonomisch sinnvoll sein. Um künftig diesen Effekt umfassend zu bewerten, werden longitudinale Daten aus dem Versorgungsalltag inklusive klinischer Outcomes, Lebensqua-lität und Adhärenz benötigt.

SummaryWhile prophylaxis with factor VIII (FVIII) is considered the first choice therapy for patients with severe haemophilia A the optimal prophylaxis regimen is still under scientific debate. A recent study demonstrated efficacy and safety of a PK-tailored prophylaxis regimen with rFVIII (ADVATE) aimed to maintain FVIII trough levels of ≥1% (19). The annual bleed rate (ABR) could be significantly reduced compared to the previous on-demand treatment period (p < 0.0001) and bodily pain, a health-related quality of life dimension of the SF-36v1 questionnaire also significantly improved (p = 0.0007). Thus PKtailored prophylaxis with ADVATE might offer a valid alternative to standard prophylaxis. Open issues to be considered for implementation of PK-tailored prophylaxis are: What FVIII trough level is needed to prevent any bleed? Do patients with target joints need higher FVIII trough levels to stay bleed-free? Are there user-friendly tools available to calculate individualized PK-driven prophylaxis doses and frequency without the need for a full 9-sample PK curve?Current knowledge on these aspects as well as some considerations about the future of PK-tailored prophylaxis is discussed.

SummaryPrimary prophylaxis has been proven as the gold standard for preserving joint function in severe haemophilia. Secondary prophylaxis in children has also been shown to have a more beneficial effect on joint protection as on-demand treatment. The outcome of delayed secondary prophylaxis started in adulthood is rarely studied. The case of a man (age: 47 years) with severe haemophilia A demonstrates the successful switch from on-demand therapy to prophylaxis with sub-sequent reduction of annual bleeding rate and number of days of work lost. The small increase of factor VIII consumption (16%) and the decrease of bleeding rate are compared with data from two recently published prospective studies.An optimal dosing schedule needs to be discussed and larger and longer prospective studies targeting the benefits of secondary prophylaxis with factor VIII started in adulthood are necessary.

Altersabhangiger Faktor-VIII-Verbrauch von Patienten mit schwerer Hamophilie A in den neuen Bundeslandern

Charakterisierung von Deletionsbruchstellen bei zwei Patienten mit schwerer Hamophilie A, grosen Deletionen und Inhibitoren

Hochtitriger, transienter Inhibitor unter Therapie mit rekombinantem Faktor VIII bei einem Jungen mit schwerer Hamophilie A