Concizumab prophylaxis in people with hemophilia A or B without inhibitors: patient-reported outcome results from the phase 3 explorer8 study

Abstract

Background: Patient-reported outcomes (PROs) can provide useful insights into patient perception of concizumab, an anti-tissue factor pathway inhibitor monoclonal antibody intended for once-daily, subcutaneous prophylaxis for hemophilia A (HA) or hemophilia B (HB), with and without inhibitors.

Objectives: To evaluate PROs from the phase 3 explorer8 study (NCT04082429).

Methods: Male patients aged ≥12 years with HA/HB without inhibitors were enrolled and randomized 1:2 to no prophylaxis/on-demand treatment (arm 1) or concizumab prophylaxis (arm 2) or allocated to concizumab prophylaxis (arms 3 and 4). PRO questionnaires included the 36-item short-form health survey version 2, Haemophilia Quality of Life Questionnaire for Adults, Hemophilia Treatment Experience Measure, and Haemophilia Patient Preference Questionnaire.

Results: Estimated treatment difference for change in 36-item short-form health survey version 2 "bodily pain" and "physical functioning" from baseline to week 24 between patients in arms 1 and 2 was 9.5 points (95% CI, 2.4 to 16.7) and 0.3 points (95% CI, -5.1 to 5.6), respectively. Estimated treatment difference at week 24 between patients in arms 1 and 2 was -18.0 points (95% CI, -26.4 to -9.5) for Haemophilia Quality of Life Questionnaire for Adults "total score" and -16.8 points (95% CI, -32.2 to -1.4) for "physical health." Hemophilia Treatment Experience Measure and Haemophilia Patient Preference Questionnaire results favored concizumab prophylaxis over no prophylaxis or previous treatment.

Conclusion: PRO data from the phase 3 explorer8 study provided additional support for concizumab prophylaxis compared with no prophylaxis as a treatment option for patients with HA/HB.

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

Figure 1

explorer8 study design. [24] ^aAdditional patients on on-demand (OD) treatment or patients on prophylaxis (PPX) with factor replacement, patients from explorer5 (phase 2 concizumab study on people with hemophilia A; NCT03196297) [18] enrolled after the restart and patients randomized to arms 1 or 2 before the treatment pause.

Figure 2

Health-related quality of life (36-item short-form health survey version 2.0 [SF-36v2]) in patients with hemophilia A or B without inhibitors receiving no prophylaxis (PPX; arm 1) or concizumab (CZM) PPX (arm 2). Estimated treatment difference (ETD) in SF-36v2 domain scores and component summary scores at week 24 in patients receiving CZM PPX vs no PPX is shown. Change from baseline to week 24 for patients in arms 1 and 2 was analyzed with mixed model for repeated measures, with treatment, type of hemophilia, and bleeding frequency prior to screening as factors and the baseline value as a covariate. Higher scores in the SF-36v2 correspond to better health-related quality of life.

Figure 3

Health-related quality of life (Haemophilia Quality of Life Questionnaire for Adults [Haem-A-QoL]) in patients with hemophilia A or B without inhibitors receiving no prophylaxis (PPX; arm 1) or concizumab (CZM) PPX (arm 2). Estimated treatment difference (ETD) in Haem-A-QoL domain scores and “total score” at week 24 in patients receiving CZM PPX vs no PPX is shown. Change from baseline to week 24 for patients in arms 1 and 2 was analyzed with mixed model for repeated measures, with treatment, type of hemophilia, and bleeding frequency prior to screening as factors and the baseline value as a covariate. Lower scores in the Haem-A-QoL correspond to better health-related quality of life.

Figure 4

Treatment burden (Hemophilia Treatment Experience Measure [Hemo-TEM]) in patients with hemophilia A or B without inhibitors receiving no prophylaxis (PPX; arm 1) or concizumab (CZM) PPX (arm 2). Estimated treatment difference (ETD) in Hemo-TEM “total score” and domain scores at week 24 in patients receiving CZM PPX vs no PPX are shown. Change from baseline to week 24 for patients in arms 1 and 2 was analyzed with analysis of covariance, with treatment, type of hemophilia, and bleeding frequency prior to screening as factors and the baseline value as a covariate. Lower scores in the Hemo-TEM correspond to lower treatment burden.

Figure 5

Treatment preferences (Haemophilia Patient Preference Questionnaire) in patients with hemophilia A or B without inhibitors receiving concizumab prophylaxis (arms 2 to 4). Treatment preference results from the Haemophilia Patient Preference Questionnaire in patients with hemophilia A or B without inhibitors receiving concizumab prophylaxis in arms 2 to 4 who responded to the questionnaire (n = 102 from a total of 127 patients). Patients who preferred their current treatment (ie, concizumab, n = 90) were asked to provide (A) the 2 main reasons for their preference, and (B) indicate the strength of their preference.