A multicentre real-world data study to assess the bleeding rate and management of patients with haemophilia A and factor VIII inhibitors in Argentina

Abstract

The development of inhibitors against factor VIII (FVIII) concentrates is a severe complication of treatment for patients with haemophilia. We investigated annualized bleeding rates (ABRs) in patients in Argentina with haemophilia A with inhibitors and analysed potential differences between treatment strategies. This multicentre, retrospective, real-world data, cohort design study comprised ambulatory paediatric and adult patients with congenital haemophilia A and FVIII inhibitors treated according to standard clinical practice, with 12-months follow-up. Of 69 included patients, 39 (56.5%) received on-demand treatment, 13 (18.8%) received prophylactic treatment, and 17 (24.6%) received immune tolerance induction (ITI) therapy. The mean overall ABR was 7.68 ± 8.18, with similar rates for on-demand (8.59 ± 9.69), prophylaxis (5.54 ± 4.71), and ITI (7.24 ± 6.23) subgroups. In the negative binomial regression model, prophylactic treatment [incidence rate ratio (IRR) 0.41, 95% confidence interval (CI): 0.21–0.79, P < 0.01] and ITI (IRR 0.47, 95% CI: 0.27–0.81, P < 0.01) therapy were significantly associated with a decrease in the ABR compared with on-demand treatment. Age (IRR 0.96, 95% CI: 0.94–0.97, P < 0.01), number of target joints (IRR 1.21, 95% CI: 1.11–1.31, P < 0.001), and history of recurring bleeding (IRR 2.3, 95% CI: 1.19–4.57, P = 0.012) were significantly and independently associated with ABR. The ABR in standard clinical practice was lower than that reported in controlled clinical trials. Patients undergoing prophylaxis and ITI therapy showed reduced ABRs compared with on-demand treatment, after controlling for bleeding predictor variables.

Unmet needs for severe hemophilia A cases without inhibitors in Argentina: a cross-sectional study.

“…Although there is no specific data on individuals with HA without inhibitors in Argentina, our findings coincide with a report of a multicenter, retrospective, real-world cohort of Argentinian HA individuals with inhibitors handled according to standard clinical practice published in 2017, that showed that most of them received treatment with bypassing agents either on-demand (56.5%) or as prophylaxis (18.8%) followed by Immune Tolerance Induction (ITI) (24.6%); being the main indication for longterm prophylaxis the failure of ITI (53.8%) and recurrent bleeding (46.2%). Additionally, it exhibited that even when the mean overall ABR was similar for the different strategies, the use of prophylactic treatment was associated with a significant decrease when compared with on-demand treatment (10) . It is interesting to note that in our sample, despite having relatively adequate treatment regimes in terms of dosage and frequency of application, HA individuals without inhibitors still suffer from fairly frequent bleeding episodes, ≥ 2 bleeding episodes in the same joint, mild to severe mobility restrictions and ineligibility for surgery.…”

“…Despite the promising long-term clinical outcomes, there are still some unmet needs for patients both on prophylaxis and on-demand treatment, such as decreased mental health (8) , impaired mobility, and occasional pain or discomfort (9) . In Argentina, there is information on clinical outcomes in HA individuals with inhibitors reporting a mean overall ABR of 7.68 (± 8.18), although the information regarding cases without inhibitors is relatively scarce (10) . In mid-2016, a survey among specialists in Latin America (including Argentina) reported unmet needs such as the importance of a national registry, the absence of a multi-stakeholder decision-making process, the supply barriers of CFCs in some countries, restrictions on the use of prophylaxis (e.g., due to the absence of insurance coverage in Argentina for adults), and the lack of clinical-and health-services research (11) .…”

Interim analyses of the multinational real‐world prospective cohort HEM‐POWR study evaluating the effectiveness and safety of damoctocog alfa pegol in patients with hemophilia A

“…Currently, real‐world studies of prophylactic FVIII use in hemophilia A are limited 7,19–21 . HEM‐POWR is an ongoing, Phase 4, observational, 36‐month study assessing the effectiveness and safety of damoctocog alfa pegol in real‐world PTPs 22 .…”

“…[13][14][15][16][17][18] Currently, real-world studies of prophylactic FVIII use in hemophilia A are limited. 7,[19][20][21] HEM-POWR is an ongoing, Phase 4, observational, 36-month study assessing the effectiveness and safety of damoctocog alfa pegol in real-world PTPs. 22 The first interim analysis of the HEM-POWR real-world study showed that the recombinant FVIII prevented bleeding and was well tolerated, with no study drug-related adverse events (AEs) in a small group of patients.…”