Introduction

In people with hemophilia A, repeated bleeding may result in joint deterioration leading to joint replacement, chronic pain, impaired physical functioning, and reduced health-related quality of life (QoL). Effective prevention of bleeding has been shown to prevent joint deterioration in people with hemophilia A. In the Phase 3 XTEND-1 study (NCT04161495) in patients assigned to receive weekly prophylaxis with efanesoctocog alfa, joint health improved from baseline to Week 52. Significant improvements were also seen at Week 52 in the Haem-A-QoL Physical Health (PH) score and the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Intensity worst score.

Aim

Using data from the XTEND-1 study, this post-hoc analysis investigated the association, at baseline and after 1 year of efanesoctocog alfa treatment, between joint health (measured by Hemophilia Joint Health Scores [HJHS]) and patient-reported outcomes (PROs) across the following domains: pain, physical functioning, and overall QoL.

Methods

Patients included in the XTEND-1 study were previously treated adults and adolescents aged ≥12 years with severe hemophilia A without inhibitors. This analysis included patients on prior standard-of-care prophylaxis factor VIII who received once-weekly prophylactic efanesoctocog alfa for 52 weeks during the study.

Joint health was measured by HJHS total score (ranging from 0 to 124, with higher scores indicating worse joint health); endpoints were baseline score and change from baseline (CFB) at Week 52. HJHS CFB at Week 52 was categorized into two subgroups (“Maintenance” [-2< CFB <2] or “improvement” [CFB ≤-2] versus “Worsening” [CFB ≥2]).

PRO domains were Pain Intensity (PROMIS Pain Intensity worst score, ranging from 1 [no pain] to 5 [very severe pain], and T-score, ranging from 30.7 to 71.8), overall QoL (Haem-A-QoL total score, ranging from 0 to 100), and Physical Function (Haem-A-QoL PH score and PROMIS Physical Function [PF] T-score, ranging from 21.0 to 59.0). Lower scores represent lower pain and better physical health; except for PROMIS PF, where higher values represent better physical function.

Spearman correlations between HJHS total scores and PRO scores were computed at baseline. The least-squares (LS) means CFB in PRO scores at Week 52 were estimated and compared between HJHS subgroups using analysis of covariance models, with HJHS subgroups, age, baseline HJHS total score, and baseline PRO scores as covariates. All p-values are nominal.

Results

Of the 133 patients in XTEND-1 receiving efanesoctocog alfa prophylactically, 116 patients had a HJHS total score at baseline; of these, 107 also had a change from baseline score at Week 52. At baseline, HJHS total score was strongly correlated (absolute correlations) to Physical Function (Haem-A-QoL PH [0.65] and PROMIS PF T-score [-0.71]), moderately correlated to Haem-A- QoL total score (0.51), and weakly to moderately correlated to Pain Intensity worst score (0.34) and T-score (0.43). “Worsening” and “Maintenance or improvement” HJHS subgroups included 14% and 86% of patients at Week 52, respectively. A greater and significant improvement in QoL PROs was observed in patients with a maintenance or improvement in HJHS subgroup compared with patients who worsened in HJHS. LS mean difference (95% confidence interval) between QoL PROs CFB at Week 52 in “Maintenance or improvement” and “Worsening” HJHS subgroups were: PROMIS Pain Intensity worst score -0.61 (-1.17 to -0.05; p=0.032), PROMIS Pain Intensity T-score -3.79 (-7.56 to -0.02; p=0.049), Haem-A-QoL total score -6.21 (-12.38 to -0.05; p=0.048), Haem-A-QoL PH score -2.65 (-4.63 to -0.67; p=0.009), and PROMIS PF T-score 3.34 (5.99 to 0.69; p=0.014).

Conclusion

Our findings indicate a stronger improvement in PROs across the three domains of pain, physical functioning, and overall QoL, in patients with joint improvement or maintenance compared with patients with joint worsening, thus highlighting the importance of improved or preserved joint health in patients with hemophilia A. Prospective validation is warranted to confirm these data.

Disclosures

Königs:Bayer Vital: Consultancy, Research Funding; CSL Behring: Consultancy, Research Funding; MSD: Consultancy; Novo Nordisk: Consultancy, Research Funding; Roche/Chugai: Consultancy; Sanofi/Sobi: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Biotest: Research Funding; Intersero: Research Funding; Pfizer: Research Funding. Quon:Takeda: Honoraria, Other: Consulting /Advisory Boards; Pfizer: Honoraria, Other: Consulting /Advisory Boards, Speakers Bureau; Novo Nordisk: Honoraria, Other: Consulting /Advisory Boards, Speakers Bureau; Genentech/Roche: Honoraria, Other: Consulting /Advisory Boards; Hemabiologics/LFB: Honoraria, Other: Consulting /Advisory Boards, Speakers Bureau; CSL Behring: Honoraria, Other: CSL Behring, Speakers Bureau; Sanofi: Honoraria, Other: Consulting /Advisory Boards, Speakers Bureau; Bayer: Honoraria, Other: Consulting /Advisory Boards. Hermans:Novo Nordisk: Consultancy, Honoraria; Sobi: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Regeneron: Consultancy, Honoraria; BioMarin: Consultancy, Honoraria; CSL Behring: Consultancy, Honoraria; Octapharma: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; LFB: Consultancy, Honoraria. Kragh:Sobi: Current Employment, Current holder of stock options in a privately-held company. Msihid:Sanofi: Other: Employee of Sanofi and may hold stock/stock options in Sanofi.. Gerard:Sanofi: Current Employment. Bozkaya:Sanofi: Current Employment. Bystrická:Sobi: Current Employment. Le Camus:Sanofi: Current Employment. Santagostino:Sobi: Current Employment. Willemze:Sanofi: Current Employment. von Drygalski:Biomarin: Consultancy, Honoraria; Regeneron: Consultancy, Honoraria; Pfizer: Consultancy, Research Funding; Genentech: Consultancy, Honoraria; Hematherix LLC: Other: Co-founder; Bioverativ/Sanofi: Consultancy, Research Funding; CSL-Behring: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Novo Nordisk: Consultancy, Honoraria; Sparx Therapeutics: Consultancy, Honoraria.

This content is only available as a PDF.
2024
Sign in via your Institution