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. 2023 Jul 24:14:20406207231184323.
doi: 10.1177/20406207231184323. eCollection 2023.

Real-world data in patients with congenital hemophilia and inhibitors: final data from the FEIBA Global Outcome (FEIBA GO) study

Carmen Escuriola Ettingshausen  1 , Cedric Hermans  2 , Pål A Holme  3 , Ana R Cid  4 , Kate Khair  5 , Johannes Oldenburg  6 , Claude Négrier  7 , Jaco Botha  8 , Aurelia Lelli  8   9 , Jerzy Windyga  10
Affiliations

Real-world data in patients with congenital hemophilia and inhibitors: final data from the FEIBA Global Outcome (FEIBA GO) study

Carmen Escuriola Ettingshausen et al. Ther Adv Hematol. .

Abstract

Background: The bypassing agent, activated prothrombin complex concentrate [aPCC, FEIBA (factor VIII inhibitor bypass activity); Baxalta US Inc, a Takeda company, Lexington, MA, USA], is indicated for the treatment of bleeding episodes, perioperative management, and routine prophylaxis in patients with hemophilia A or B with inhibitors. In certain countries, aPCC is also indicated for the treatment of bleeding episodes and perioperative management in patients with acquired hemophilia A.

Objectives: To describe long-term, real-world effectiveness, safety, and quality-of-life outcomes for patients with congenital hemophilia A or B and high-responding inhibitors receiving aPCC treatment in routine clinical practice.

Design: FEIBA Global Outcome (FEIBA GO; EUPAS6691) was a prospective, observational study.

Methods: Investigators determined the treatment regimen and clinical monitoring frequency. The planned patient observation period was 4 years. Data are from the safety analysis set (patients who received ⩾1 aPCC infusion).

Results: Overall, 50 patients received either aPCC prophylaxis (n = 37) or on-demand therapy (n = 13) at screening [hemophilia A, n = 49; hemophilia B, n = 1; median (range) age, 16.5 [2-71] years). Mean ± standard deviation overall annualized bleeding rate and annualized joint bleeding rate for patients receiving prophylaxis were 6.82 ± 11.52 and 3.77 ± 5.71, respectively, and for patients receiving on-demand therapy were 10.94 ± 11.27 and 6.94 ± 7.39, respectively. Overall, 177 and 31 adverse events (AEs) were reported in 28 of 40 and 10 of 13 patients receiving prophylaxis or on-demand therapy, respectively. Two serious AEs were considered possibly related to aPCC: acute myocardial infarction due to coronary artery embolism in one patient receiving prophylaxis. No thrombotic microangiopathy was reported. No AEs resulted in death.

Conclusion: This study demonstrated the long-term, real-world effectiveness and consistent safety profile of aPCC as on-demand therapy and prophylactic treatment in patients with hemophilia and high-responding inhibitors.

Trial registry: FEIBA Global Outcome Study; EUPAS6691 https://www.encepp.eu/encepp/viewResource.htm?id=32774.

Keywords: factor VIII inhibitor bypassing activity; hemophilia A; hemophilia B; inhibitors; observational study.

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Conflict of interest statement

The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Carmen Escuriola Ettingshausen: grant/research support [Biotest, CSL Behring, Octapharma, Shire (a Takeda company), Sobi]; honoraria for lectures/advisory boards [Bayer, Biotest, CSL Behring, Grifols, Kedrion, LFB, Novo Nordisk, Octapharma, Pfizer, Roche/Chugai, Shire (a Takeda company), Sobi]; and consultancy [BioMarin, Biotest, CSL Behring, Grifols, Novo Nordisk, Octapharma, Roche/Chugai, Shire (a Takeda company), Sobi]. Cedric Hermans: grant/research support [Bayer, Pfizer, Shire (a Takeda company), Sobi]; honoraria for lectures/advisory boards [Bayer, Biogen, CAF-DCF, CSL Behring, Kedrion, LFB, Novo Nordisk, Octapharma, Pfizer, Roche, Shire (a Takeda company), Sobi]; and consultancy [Bayer, Biogen, CAF-DCF, CSL Behring, LFB, Novo Nordisk, Octapharma, Pfizer, Roche, Shire (a Takeda company), Sobi]. Pål A. Holme: grant/research support [Bayer, Octapharma, Pfizer, Shire (a Takeda company), Sobi]; and honoraria for lectures/advisory boards [Bayer, CSL Behring, Novo Nordisk, Pfizer, Shire (a Takeda company), Sobi]. Ana R. Cid: honoraria for lectures/advisory boards [Novo Nordisk, Roche, Shire (a Takeda company), Sobi]; and consultancy (Roche, Sobi). Kate Khair: grant/research support [Baxalta/Shire (a Takeda company), CSL Behring, Novo Nordisk, Pfizer, Roche, Sobi, uniQure]; honoraria for lectures/advisory boards [Bayer, Novo Nordisk, Pfizer, Roche, Shire (a Takeda company), Sobi]; consultancy [Bayer, Novo Nordisk, Roche, Shire (a Takeda company), Sobi]; support attending meetings and/or travel (Bayer, Novo Nordisk); leadership or fiduciary role in other board, society, committee or advocacy group (Vice President board of Trustees The Haemophilia Society); and stock or stock options (Haemnet Ltd, Medikhair). Johannes Oldenburg: grant/research support [Bayer, Biotest, CSL Behring, Novo Nordisk, Octapharma, Pfizer, Shire (a Takeda company)]; honoraria for lectures/advisory boards [Bayer, Biogen, Biotest, Chugai, CSL Behring, Grifols, Novo Nordisk, Octapharma, Pfizer, Roche, Shire (a Takeda company), Sobi]; and consultancy [Bayer, Biogen, Biotest, Chugai, CSL Behring, Grifols, Novo Nordisk, Octapharma, Pfizer, Roche, Shire (a Takeda company), Sobi]. Claude Négrier: grant/research support [CSL Behring, Octapharma, Shire (a Takeda company), Sobi]; and consultancy [Bayer, BioMarin, CSL Behring, Freeline, LFB, Novo Nordisk, Octapharma, Pfizer, Roche, Sanofi, Shire (a Takeda company), Sobi, Spark]. Jaco Botha: employee of Takeda Pharmaceuticals International AG, and Takeda stock owner. Aurelia Lelli: employee of Takeda Pharmaceuticals International AG, and Takeda stock owner. Jerzy Windyga: grant/research support and honoraria for lectures [Amgen, Alnylam, Baxalta/Shire (a Takeda company), Bayer, CSL Behring, LFB, Novartis, Novo Nordisk, Octapharma, Pfizer, Roche, Sanofi, Siemens, Sobi, Swixx Biopharma].

Figures

Figure 1.
Figure 1.
Patient disposition (all-patients analysis set). The all-patients analysis set included all patients enrolled in the study. The safety analysis set consisted of data for all patients who were enrolled, met all inclusion and exclusion criteria, and received at least one infusion of aPCC. In total, the all-patients analysis set included 51 patients and the safety analysis set included 50 patients. aPCC, activated prothrombin complex concentrate.
Figure 2.
Figure 2.
Overall ABR and AJBR by (a) treatment regimen and (b) categorized (safety analysis set). ABR is the number of all bleeding events standardized to 12 months. AJBR is the number of joint bleeding events standardized to 12 months. ABR and AJBR were only included in the analysis for patients with a regimen duration of ⩾90 days. All patients without confirmed zero bleeding events were set to missing. Bleeding events were counted for the regimen where the event occurred; therefore, patients who switched regimen could appear more than once. Overall AJBR treatment regimen (categorized): one patient in the prophylaxis group was classified as missing. ABR, annualized bleeding rate; AJBR, annualized joint bleeding rate; SD, standard deviation.
Figure 3.
Figure 3.
Overall ABR and AJBR for patients who completed the study by (a) treatment regimen and (b) categorized (safety analysis set). ABR is the number of all bleeding events standardized to 12 months. AJBR is the number of joint bleeding events standardized to 12 months. ABR and AJBR were only included in the analysis for patients with a regimen duration of ⩾90 days. All patients without confirmed zero bleeding events were set to missing. Bleeding events were counted for the regimen where the event occurred; therefore, patients who switched regimen could appear more than once. One patient switched regimen during the study and an ABR was calculated for both regimens. ABR, annualized bleeding rate; AJBR, annualized joint bleeding rate; SD, standard deviation.
Figure 4.
Figure 4.
(a) ABRs and (b) AJBRs for patients with >48 months of follow-up (safety analysis set). ABR is the number of all bleeding events standardized to 12 months. AJBR is the number of joint bleeding events standardized to 12 months. ABR and AJBR were only included in the analysis for patients with a regimen duration of ⩾90 days. All patients without confirmed zero bleeding events were set to missing. Bleeding events were counted for the regimen where the event occurred; therefore, patients who switched regimen could appear more than once. ABR, annualized bleeding rate; AJBR, annualized joint bleeding rate; SD, standard deviation.
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