In the Joint Outcome Study (JOS; ClinicalTrials.gov Identifier: NCT00207597), children with severe hemophilia A who received prophylactic treatment with factor VIII (FVIII) showed greater joint health compared with participants who received episodic FVIII treatment for bleeding.

Results of the original JOS analysis varied within treatment arms, and reasons for variation were explored in a recent secondary analysis of the JOS, with results reported in the journal Haemophilia.

In this secondary analysis, multiple plasma components from participants of the JOS were evaluated in conjunction with treatment characteristics and joint outcomes. Sixty-five toddlers had been randomly assigned to be given either prophylactic FVIII (32 patients) or enhanced episodic FVIII for bleeding (33 patients).

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Based on magnetic resonance imaging results upon study exit at age 6 years, the episodic treatment arm showed 10.5 (95% CI, 2.1-51.9; P =.004) times the odds of joint failure compared with the prophylaxis arm.

Treatment arm and FVIII trough level were the only examined features that were shown to significantly affect joint failure in univariate logistic regression analysis. In univariate analysis, the odds of joint failure decreased by 0.18 (95% CI, 0.05-0.68; P =.012) with each 1% rise in FVIII trough level.

The significance of the relationship between FVIII trough level and joint failure disappeared in multivariate analysis when adjusted for treatment group (P =.12). FVIII trough level itself significantly covaried with prophylactic treatment (P <.0001).

Treatment group was the most influential parameter in multivariate analysis of joint failure, with analysis adjusted for treatment adherence. In this analysis, episodic treatment gave an odds ratio of 18.59 (95% CI, 2.50-138.1; P =.0043) for joint failure in comparison with prophylactic treatment.

Though the study did not determine reasons for variation within each treatment arm of the JOS, it reinforced the effect of prophylaxis on joint outcomes. “Prophylaxis remains the most important treatment regimen for maintaining joint health in patients with severe hemophilia A,” stated the study authors.

Reference

  1. Warren BB, Jacobson L, Kempton C, et al. Factor VIII prophylaxis effects outweigh other hemostasis contributors in predicting severe haemophilia A joint outcomes [published online May 21, 2019]. Haemophilia. doi: 10.1111/hae.13778