Factor VIII replacement prophylaxis in patients with hemophilia A transitioning to adults: a systematic literature review

Abstract

Background Despite the advantages of prophylactic treatment for hemophilia, patients tend to discontinue or not adhere to it because of several challenges such as long-term use, high cost, young patients transitioning to adolescents, and switch to self-infusion or self-care. The goal of this systematic literature review is to emphasize adherence to and efficiency of prophylactic treatment in adults. Methods A literature review was conducted in PubMed, Embase, and Cochrane databases until April 2021 according to PRISMA guidelines, and the protocol was registered with PROSPERO (CRD42020220085). Studies evaluating the efficacy of prophylaxis in enhancing the quality of life were included. Results A total of 31 articles involving 2379 patients with hemophilia were included in this systematic review. Of these, 26 studies were observational, questionnaire-based studies, and 5 were randomized controlled trials. The majority of studies reported lower annualized bleeding rates in patients receiving prophylaxis compared with those receiving on-demand treatment or those who discontinued prophylaxis. Standard-dose prophylaxis was reported to be effective in most of the studies. In developing countries like China, data suggest that low doses were administered because of limited available resources. However, standard dose or individualized prophylaxis should be provided to prevent joint damage in the long term. Compared with adults, greater adherence to treatment was observed in patients aged < 16 years. Conclusion This systematic review emphasizes the importance of adherence to prophylaxis among young adults transitioning from childhood. In countries like China, low-dose prophylaxis can help in preventing joint bleeds in the short term, but in the long term, standard-dose therapy has shown high adherence among young adults and better joint health, in turn improving the quality of life.

Most subjectively affected joints in patients with haemophilia – what has changed after 20 years in Germany?

“…In China, low‐dose prophylaxis also improved the joint situation of PwH 33 . Prophylactic substitution nevertheless shows better long‐term effects on the joint status than low‐dose prophylaxis 33 …”

“…A weekly mean substitution of 30 IU/kg in Tunisia showed a significantly reduced bleeding rate in children with haemophilia compared to on‐demand therapy 36 . In China, low‐dose prophylaxis also improved the joint situation of PwH 33 . Prophylactic substitution nevertheless shows better long‐term effects on the joint status than low‐dose prophylaxis 33 …”

“… 31 A comparison of the countries in Table 4 shows that only the two countries, Germany and Netherlands, predominantly use prophylactic therapy 14,32 . Overall, access to prophylactic therapy, which leads to a better joint situation compared to on‐demand therapy, is not available in all countries 17,33 …”

“…14,32 Overall, access to prophylactic therapy, which leads to a better joint situation compared to on-demand therapy, is not available in all countries. 17,33 It should be noted that different tools were used to determine the most frequently affected joint. As shown in Table 4, the most common diagnostic tool is the clinical joint examination, the bleeding rate and questionnaires about the joint situation.…”

Medication Adherence for Haemophilia Patients: Outcome of Prophylaxis Treatment Intervention

“…The annualised bleeding rate (ABR) is an important variable to measure the effectiveness of prophylactic therapy. More recently, studies on the efficacy of preventive treatment in adolescents and adults have been published [ 11 , 12 , 13 ]. The prophylactic factor regimens have demonstrated clinical advantages in preventing and reducing bleeding episodes [ 13 , 14 ].…”