[Long-term efficacy analysis of the individualized prophylaxis regimen in children with moderate or severe haemophilia A].

Objective: To analyze the long-term clinical efficacy and cost-effectiveness of the Chinese haemophilia individualized prophylaxis study (CHIPS) low-dose escalation regimen in children with moderate or severe haemophilia A. Methods: A dual-center retrospective cohort study was conducted, including 70 children with moderate or severe haemophilia A from Beijing Children's Hospital and Chengdu Women's and Children's Central Hospital between August 2018 and July 2021. All children were treated with the CHIPS regimen, categorized into four escalating dose levels. Treatment was adjusted every 6 months based on bleeding frequency, joint ultrasound (hemophilic early arthropathy detection with ultrasound, HEAD-US) scores, and health assessment scores, if insufficient, escalate to the next dosage. Annualized bleeding rate (ABR), annualized joint bleeding rate (AJBR), HEAD-US scores were compared between baseline and month 6, 12, 18, 24. Zero bleeding rate, target joint resolution rate, and quality of life (Canadian hemophilia outcomes-kid's life assessment tool, CHO-KLAT) scores were compared between baseline and month 24. Annual factor Ⅷ consumption was compared between baseline and months 12 or 24. Paired Wilcoxon signed-rank tests were used for group comparisons. Results: A total of 70 children were included, with the age of 5.3 (3.8, 6.9) years. ABR values at months 6, 12, 18, and 24 were 2.5 (0, 6.0), 1.0 (0, 4.0), 0 (0, 2.0), and 0 (0, 2.0) respectively, all significantly lower than the baseline value of 4.0 (2.0, 8.8) (all P<0.05). AJBR values at the corresponding time points were 0 (0, 2.0), 0 (0, 2.0), 0 (0, 2.0), and 0 (0, 1.0), all showing statistically significant decreases from the baseline value of 2.0 (0, 4.0) (all P<0.05). Of the 15 cases with target joints present at enrollment, 11 cases resolved. Joint HEAD-US scores remained stable throughout the follow-up period (all time points vs.baseline, P>0.05). The CHO-KLAT parent score improved from 69 (61, 78) to 75 (67, 82) (P=0.018). A total of 58 dose escalations occurred, with 31 (53%) attributed to joint bleeding. By the time of study's end, 22 children (31%) used high-dose steps dose. Annual factor Ⅷ consumption increased from 2 819 (1 856, 3 898) U/kg at baseline to 3 194 (2 302, 4 886) U/kg at 24 months (P=0.006). Conclusion: The CHIPS regimen can significantly reduce bleeding frequency, improve joint health status, and halt the progression of joint damage in children with moderate or severe haemophilia A.