Concizumab prophylaxis in persons with hemophilia A or B with inhibitors: patient-reported outcome results from the phase 3 explorer7 study

Abstract

Background: Patient-reported outcomes (PROs) reflect patient perceptions of disease and treatment and are important for evaluating new therapies.

Objectives: Evaluate the effects of once-daily concizumab prophylaxis on health-related quality of life (HRQoL), treatment burden, and treatment preference in males aged ≥12 years with hemophilia A/B with inhibitors.

Methods: Patients enrolled in the multicenter, open-label explorer7 phase 3 study (ClinicalTrials.gov identifier: NCT04083781) were randomized to receive no prophylaxis (arm 1) or concizumab prophylaxis (arm 2) or were nonrandomly allocated to concizumab prophylaxis (arms 3 and 4). The study included questionnaires to assess patients' perception of HRQoL (Haemophilia Quality of Life Questionnaire for Adults), treatment burden (Hemophilia Treatment Experience Measure), and treatment preference (Haemophilia Patient Preference Questionnaire).

Results: The estimated treatment difference between patients receiving concizumab prophylaxis vs no prophylaxis at week 24 for Haemophilia Quality of Life Questionnaire for Adults "total score" was -22.6 points (95% CI, -42.5; -2.7), directionally favoring patients receiving concizumab prophylaxis. For Hemophilia Treatment Experience Measure "total score," the estimated treatment difference was -19.9 points (95% CI, -34.3, -5.6) in favor of concizumab vs no prophylaxis. The majority of patients receiving concizumab expressed a preference for concizumab over their previous treatment, the main reasons being "fewer bleeds," "require less time," and "less painful to inject." Across all PROs, there were less responses collected than anticipated, limiting interpretations.

Conclusion: PROs collected during the explorer7 study showed improvements in some domains of HRQoL, treatment burden, and patient treatment preference in persons with hemophilia A or B with inhibitors receiving concizumab prophylaxis compared with no prophylaxis.

Keywords: concizumab; health-related quality of life; hemophilia A; hemophilia B; patient preference; patient-reported outcomes.

Graphical abstract

Figure 1

Health-related quality of life measured with Haemophilia Quality of Life Questionnaire for Adults in persons with hemophilia A/B with inhibitors receiving no prophylaxis (arm 1) or concizumab prophylaxis (arm 2). Estimated treatment difference (ETD) in Haemophilia Quality of Life Questionnaire for Adults “total score” (shaded) and domain scores at week 24 in patients receiving concizumab prophylaxis vs no prophylaxis are shown. The ETD was analyzed using a mixed model for repeated measures and based on patients with data at baseline and ≥1 visits postbaseline in arm 1 (n = 4) and arm 2 (n = 13); in some domains, fewer patients responded (“sport and leisure” [arm 1, n = 3; arm 2, n = 9] and “work and studies” [arm 1, n = 4; arm 2, n = 9]). Analysis for the domain “family planning” was not performed due to insufficient data.

Figure 2

Patient-reported treatment burden measured with Hemophilia Treatment Experience Measure in persons with hemophilia A/B with inhibitors receiving no prophylaxis (arm 1) or concizumab prophylaxis (arm 2). Estimated treatment difference (ETD) in Hemophilia Treatment Experience Measure “total score” (shaded) and domain scores at week 24 in patients receiving concizumab prophylaxis vs no prophylaxis are shown. The ETD was analyzed using analysis of covariance and based on patients with responses at baseline and ≥1 visits postbaseline in arm 1 (n = 6) and arm 2 (n = 19).

Figure 3

Patient-reported treatment preferences evaluated with Haemophilia Patient Preference Questionnaire in persons with hemophilia A/B with inhibitors receiving concizumab prophylaxis (arms 2-4) who responded to the questionnaire (n = 83 from a total of 99 patients). Patients who preferred their current treatment (ie, concizumab, n = 77) were asked to provide the 2 main reasons for their preference (A) and the strength of their preference (B).