Young adult outcomes of childhood prophylaxis for severe hemophilia A: results of the Joint Outcome Continuation Study.

The Joint Outcome Study (JOS), a randomized controlled trial, demonstrated that children with severe hemophilia A (HA) initiating prophylactic factor VIII (FVIII) prior to age 2.5 years had reduced joint damage at age 6 years compared with those treated with episodic FVIII for bleeding. The Joint Outcome Continuation Study (JOS-C) evaluated early vs delayed prophylaxis effects on long-term joint health, following JOS participants to age 18 years in an observational, partially retrospective study. Index joint magnetic resonance imaging (MRI) scores of osteochondral (OC) damage (primary outcome), joint physical examination scores, and annualized rates of joint/other bleeding episodes (secondary outcomes) were collected. Thirty-seven of 65 JOS participants enrolled in JOS-C, including 15 randomized to prophylaxis at mean age 1.3 years ("early prophylaxis"); 18 initially randomized to episodic treatment, starting "delayed prophylaxis" at mean age 7.5 years; and 4 with high-titer inhibitors. At JOS-C exit, MRI OC damage was found in 77% of those on delayed and 35% of those on early prophylaxis for an odds ratio of OC damage, in the delayed vs early prophylaxis group, of 6.3 (95% confidence interval, 1.3, 29.9; P = .02). Annualized bleeding rates were higher with delayed prophylaxis (mean plus or minus standard deviation, 10.6 ± 6.6 vs 3.5 ± 2.1; P < .001), including when only comparing time periods on prophylaxis (6.2 ± 5.3 vs 3.3 ± 1.9; P < .05). In severe HA, early initiation of prophylaxis provided continued protection against joint damage throughout childhood compared with delayed initiation, but early prophylaxis was not sufficient to fully prevent damage. This trial was registered at www.clinicaltrials.gov as #NCT01000844.

Validity and reliability of the Colorado Adult Joint Assessment Scale in adults with moderate-severe hemophilia A.

BACKGROUND: The Colorado Adult Joint Assessment Scale (CAJAS) is designed to assess joint health in adults with hemophilia. The CAJAS comprises nine items (swelling, muscle atrophy, axial deformity, crepitus, range of motion, contracture, instability, strength, gait) and assesses six joints. OBJECTIVE: To assess CAJAS content validity and psychometric properties. PATIENTS/METHODS: Data were obtained from the Trial to Evaluate the Effect of Secondary Prophylaxis With rFVIII Therapy in Severe Hemophilia A Adult and/or Adolescent Subjects Compared to That of Episodic Treatment (SPINART) study and a separate CAJAS validation study. CAJAS assessments in SPINART were performed by physical therapists (PTs) from the United States, Romania, Bulgaria, and Argentina. In the validation study, content validity was assessed from interviews with six PTs at three US hemophilia centers; cultural equivalence was assessed with seven non-US PTs from SPINART. Reliability data were collected from 30 subjects at four US centers. Test-retest reliability was evaluated by having the same PT perform CAJAS examinations at two visits, 7-10 days apart. Inter-rater reliability was assessed by comparing CAJAS scores of two different PTs performing separate examinations of the same patient several hours apart at the same visit. Psychometric properties were assessed using SPINART and validation study data. RESULTS: The CAJAS demonstrated good content validity. Test-retest reliability was high (intraclass correlation coefficient, 0.98), as was inter-rater reliability (intraclass correlation coefficient, 0.88). Internal consistency reliability was strong (α = .90). The CAJAS demonstrated good convergent/divergent validity, known-groups validity, and ability to detect change. CONCLUSIONS: The CAJAS is a valid and reliable measure of joint health in adults with moderate-severe hemophilia and is appropriate for use in clinical practice.