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A. Tiede et al.
Figure 3. Kaplan-Meier estimates of the proportion of patients without a spontaneous bleed according to predicted FVIII:C during the pivotal and extension trial phases. FVIII:C: FVIII factor VIII activity.
with active joint disease (particularly target joints and syn- ovitis), and the intensity of prophylaxis may be reduced in those without active joint disease who have not bled for some time. Further prospective studies are needed to eval- uate this approach.
Bleeds are currently used as the main endpoint for stud- ies in hemophilia, both for newly developed factor concen- trates, as well as for non-factor replacement products. Characteristic features of novel factor concentrates include, but are not limited to, longer half-life and improved preser- vation of post-translational modification. It could be tempting to compare ABR across studies of these products, but it should be kept in mind that ABR is a multifactorial outcome. Our analysis illustrates that ABR changes over time and depends on patients’ characteristics.
In conclusion, in patients of all ages with severe hemo- philia A who were treated with turoctocog alfa, ABR for spontaneous bleeds, including joint bleeds, decreased as FVIII:C increased, indicating an exposure-response rela- tionship. The data presented in the current study suggest that patient-related factors and treatment history influ- ence the FVIII:C level needed to protect patients from bleeding. ABR reported in clinical trials not only reflect efficacy of the FVIII product, but also the characteristics of the population under study.7,20 The choice of prophylactic regimens to target certain trough levels should take into account the patient’s age, joint disease activity, and other determinants of bleeding risk.
Disclosures
AT has received research support, honoraria, or consultation fees from Alnylam, Bayer, Biogen Idec, Biotest, Bristol-Myers Squibb, Boehringer Ingelheim, CSL Behring, Leo Pharma, Novo Nordisk, Octapharma, Pfizer, Roche, Shire, and SOBI. VJ-Y has received reimbursement for attending symposia/congresses and/or honoraria for speaking and/or for consulting, and/or funds for research from Takeda, Bayer, CSL-Behring, Grifols, Novo Nordisk, Sobi, Roche, Octapharma and Pfizer. RK has received
support, honoraria, or consultation fees from Bayer, Biogen Idec, Biotest, Bristol-Myers Squibb, Boehringer Ingelheim, CSL Behring, Grifols, Leo Pharma, Novo Nordisk, Octapharma, Pfizer, Roche, Shire, and SOBI. TS has received consultation and speaker fees from Bayer, Bioverativ, Chugai, CSL Behring, IL Japan, JB Pharma, Kaketsuken, Merck Sharp & Dohme, Nihon-Pharma, Novo Nordisk, Pfizer, Sekisui Medical, and Shire. AG is an employee of Novo Nordisk A/S. ES has attended and received funds for Advisory Boards from Bayer, Grifols, Kedrion, Novo Nordisk, Octapharma, Pfizer, Roche, Shire, and SOBI. She attended Speaker Bureaus for, and received funds from, Bayer, Bioverativ, CSL Behring, Grifols, Kedrion, Novo Nordisk, Octapharma, Pfizer, Roche, Shire, and SOBI. FAK and SL have no conflicts of interest to disclose.
Contributions
AG, representing Novo Nordisk A/S, provided the statistical analyses of the data; AT contributed to the study design and interpreted the results; all authors critically wrote or revised the intellectual content of the manuscript, reviewed and/or comment- ed on each draft, and approved the final version for submission.
Acknowledgments
These trials were sponsored by Novo Nordisk A/S (Bagsværd, Denmark). The authors thank the patients with severe hemophil- ia A and their families/caregivers, as well as the investigators, pharmacists, nurses, and trial staff at each center for participating in these trials. The authors would also like to thank Brigitte Brand-Staufer (Novo Nordisk Health Care AG) and Lars Korsholm for their scientific advice and critical review of the man- uscript. Medical writing support was provided by Jo Fetterman, PhD (Parexel, UK).
Funding
This work was funded by Novo Nordisk A/S (Bagsværd, Denmark). Novo Nordisk’s policy on data sharing may be found at https://novonordisk-ctts.app-trialscope.com/how-access-clini- cal-trial-datasets.
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haematologica | 2021; 106(7)