Controlled, cross-sectional MRI evaluation of joint status in severe haemophilia A patients treated with prophylaxis vs. on demand (original) (raw)
Related papers
Haemophilia, 2004
X-ray Scale (WFH XR Scale) were inadequately sensitive to detect early changes in joints. New scales were developed based on suggested modifications of the existing scales and called the Haemophilia Joint Health Score (HJHS) and the International MRI Scales. The new scales were piloted. Concordance was measured by the intra-class correlation coefficient of variation. Reliability of the HJHS was excellent with an inter-observer co-efficient of 0.83 and a test-retest value of 0.89. The MRI study was conducted using both Denver and European scoring approaches; inter-reader reliability using the two approaches was 0.88 and 0.87; test-retest reliability was 0.92 and 0.93. These new PT and MRI scales promise to improve outcome assessment in children on early preventive treatment regimens.
Effect of late prophylaxis in hemophilia on joint status: a randomized trial
Journal of Thrombosis and Haemostasis, 2017
High-quality data are lacking on use of prophylaxis in adults with hemophilia and arthropathy. SPINART was a 3-year randomized clinical trial of late/tertiary prophylaxis vs on-demand therapy. Prophylaxis improved function, quality of life, activity and pain but not joint structure by MRI. Prophylaxis improves function but must start before joint bleeding onset to prevent arthropath.y ABSTRACT Background: Limited data exist on the impact of prophylaxis on adults with severe hemophilia A and pre-existing joint disease. Objectives: This analysis describes 3-year bleeding, joint, health-related quality-of-life (HRQoL), and other outcomes from the open-label, randomized, multinational SPINART study. Patients/Methods: Males aged 12-50 years with severe hemophilia A, ≥150 FVIII exposure days, no inhibitors, and no prophylaxis for >12 consecutive months in the past 5 years were randomized to sucrose-formulated recombinant FVIII (rFVIII-FS) prophylaxis or on-demand therapy (OD). Data collected included total and joint bleeding events (BEs), joint structure (magnetic resonance imaging [MRI]), joint health (Colorado Adult Joint Assessment Scale [CAJAS]), HRQoL, pain, healthcare resource utilization (HRU), activity, and treatment satisfaction. Results: Following 3 years of prophylaxis, adults maintained excellent adherence with 94% reduction in BEs despite severe pre-existing arthropathy; 35.7% and 76.2% of prophylaxis participants were bleed-free or had <2 BEs/year, respectively. Compared with OD, prophylaxis was associated with improved CAJAS (least squares [LS] mean,-0.31 [n=42] vs +0.63 [n=42]) and HAEMO-QoL-A scores (LS mean, +3.98 [n=41] vs-6.00 [n=42]), less chronic pain (50% decrease), and ~2-fold less HRU; activity, EQ-5D-3L, and satisfaction scores also favored prophylaxis. However, MRI score changes were not different for prophylaxis versus OD (LS mean, +0.79 [n=41] vs +0.96 [n=38]). Conclusions: Over 3 years, prophylaxis versus OD in adults with severe hemophilia A and arthropathy led to decreased bleeding, pain, and HRU, better joint health, activity, satisfaction, and HRQoL, but no reduction in structural arthropathy progression, suggesting pre-existing joint arthropathy may be irreversible.
Haemophilia, 2020
Bleeding into joint spaces (haemarthrosis) is a common complication in children with haemophilia. Repeated haemarthrosis leads to joint degradation and haemophilic arthropathy (HA). One goal of treating patients with haemophilia with prophylaxis (regular replacement therapy) is to decrease the frequency of joint bleeds and ultimately limit end organ damage. Observational and randomized controlled trials have demonstrated the effectiveness of prophylaxis. 1-3 However, validated and responsive clinical indices are still needed to monitor patient disease status and evaluate treatment regimens in longitudinal studies. Additionally, it is unclear how novel nonfactor therapeutics such as FVIII-mimetics and gene therapy affect joint health. If effective, a measure of early-stage HA could be instrumental to guide decisions between different prophylaxis regimens.
Long‐term joint outcomes in adolescents with moderate or severe haemophilia A
Haemophilia
Introduction: Favourable joint outcomes are expected with modern haemophilia A (HA) management. Evaluation of long-term treatment outcomes is hampered by the delay between bleeding episodes during childhood and resulting joint outcomes in adulthood. Aim: To measure the long-term joint health of adolescents with moderate and severe HA, according to severity and inhibitor status. Methods: Pilot cross-sectional study of five European PedNet centres in moderate and severe HA patients aged 10-19 years. Structured assessment of joint status by physical examination (HJHS) and ultrasound (HEAD-US). Results: In total, 141 HA patients were evaluable, 100 without inhibitors (81 severe, 19 moderate HA), and 41 severe HA with current/past inhibitors. On physical examination, 12/81 (15%) of severe HA without inhibitors, 3/19 (16%) of moderate HA, and 13/41 (32%) of severe HA patients with inhibitors exhibited joint abnormalities. Inhibitor persistence, longer inhibitor duration, and a high peak inhibitor level were associated with impaired joint health. Ultrasound showed joint damage (bone or cartilage) in 13/49 (27%) of severe HA without inhibitors, 1/12 (8%) of moderate HA, and 10/28 (36%) of severe HA patients with inhibitors. A discordant ankle evaluation by ultrasound versus physical examination was present in 53/169 joints (31%). Conclusions: Most adolescents with severe or moderate HA show favourable joint health. Future research with combined ultrasound and/or MRI is needed to better understand joint outcomes in the remaining patients. Patents with inhibitors showed a twofold increased proportion with joint deterioration. Ultrasound paired with physical examination increases sensitivity for detection of joint damage.
Haemophilia, 2013
Magnetic resonance imaging (MRI) and ultrasonography (US) are increasingly used in haemophilia A (HA) to detect early joint changes. A total of 40 clinically asymptomatic joints, never involved by bleeding events ["healthy joints" (HJ)], were evaluated by MRI and, in parallel, by US in 20 young subjects with severe HA (22.45 AE 2.72 years old; no history of arthritides, of viral infections or of inhibitors against factor VIII). The same joints were evaluated in 20 matched non-haemophilic (no-HA) subjects (mean age 23.90 AE 2.31 years, P = 0.078 vs. HA subjects). US images were obtained with specific probe positions according to validated procedures. A validated US score and progressive (P-MRI) and additive (A-MRI) MRI scores were employed for data collection and analysis. The US score was higher in HA than in no-HA subjects (3.40 AE 1.72 vs. 0.80 AE 1.10, P < 0.001). Taking into account only moderate/severe alterations, joint effusion was found in 55% of HA and in 5% of no-HA joints (P < 0.001); synovial hypertrophy was found in 20% of HA and in none of the no-HA joints; cartilage erosion was found in 30% of HA and in none of no-HA joints. MRI examinations confirmed these findings and the US score correlated with the A-MRI (r = 0.732, P < 0.001) and with the P-MRI (r = 0.598, P < 0.001) scores. MRI and US data significantly correlated as to effusion (r = 0.819, P = 0.002), synovial hypertrophy (r = 0.633, P = 0.036) and cartilage erosion (r = 0.734, P = 0.010). Despite inherent limitations, joint US examination identified subclinical abnormalities of HJ in young subjects with severe HA.
Haemophilia, 2020
IntroductionThe prevalence of arthropathy in moderate haemophilia A (MHA) and B (MHB) is not well known.AimWe evaluated joint health in Nordic patients in relation to their treatment modality.MethodsA cross‐sectional, multicentre study covering MHA and MHB in Sweden, Finland and Norway. Arthropathy was evaluated by ultrasound (HEAD‐US) and Haemophilia Joint Health Score (HJHS).ResultsWe report on 145 patients: median age 28 years (IQR 13‐52) and 61% MHA. Baseline factor VIII/factor IX activity (FVIII/FIX:C) was 2 IU/dL (median) (IQR 2‐4): lower for MHB (2 IU/dL, IQR 1‐2) than MHA (3 IU/dL, IQR 2‐4) (P < .01). Eighty‐five per cent of MHA and 73% MHB had a history of haemarthrosis (P = .07). Age at first joint bleed was lower for MHA (5 years [median], IQR 3‐7) than MHB (7 years, IQR 5‐12) (P = .01). Thirty‐eight per cent received prophylaxis, started at median 10 years of age (IQR 4‐24). Median joint bleeds and serious other bleeds during the last 12 months were both zero (IQR 0‐1...
Various regimens for prophylactic treatment of patients with haemophilia
European Journal of Haematology, 2015
Haemophilia prophylaxis is superior to on-demand treatment to prevent joint damage. 'High-dose prophylaxis' as used in Sweden is more effective in preventing arthropathy than an 'intermediate-dose regimen' (the Netherlands) and the Canadian tailored primary prophylaxis. Prophylaxis may reduce the risk of developing inhibitors. There is no difference in inhibitor risk between plasma derived and recombinant factor VIII (rFVIII) products but the Rodin study showed increased risk with second-generation rFVIII products. MRI is a new and very sensitive tool to detect the symptoms of early arthropathy but some results (soft tissue changes in 'bleed-free joints') still need to be investigated. Ultrasound is a very helpful method to aid diagnosis especially during the acute phase of a bleed. The risk of infection with central venous access remains a matter of debate. A fully implanted central venous access device (CVAD) has a significant lower risk of infection compared to external CVADs. Patient's age under 6 yr and inhibitor presence are additional risk factors for infections. The role of arteriovenous fistulae needs to be investigated because significant complications have been reported. Disease-specific quality of life instruments are complementary to generic instruments evaluating QoL in patients with haemophilia and have become important health outcome measures.
Results of an orthopaedic survey in young patients with severe haemophilia in Spain
Haemophilia, 2002
Summary. This paper outlines the results obtained in a cross-sectional study of a group of young patients with severe haemophilia A and B. The primary aim of the study was to ascertain the level of orthopaedic complications in the group, the effects that these complications have on quality of life, and the medical resources used on these patients. The secondary aim was to relate their current orthopaedic state to the type of treatment received before the study. The study was carried out in 11 hospitals in Spain, where 70 severe haemophilia patients (factor VIII [FVIII] < 2%), with an average age of 21.6 and a median age of 22, and no inhibitors, were monitored. The percentage of patients suffering from articular complaints was 84.3% and 85.7% according to the Gilbert and Petterson scales, respectively. Furthermore, pain was reported in 16.1% of joints, most frequently in ankles. Using the SF-36 Health Survey, patients were observed to have a poorer quality of life relative to healthy controls. Despite high levels of both the coagulant factor given to patients and the financial resources dedicated to their treatment, the type of treatment (on demand and/or as secondary prophylaxis) provided to the young adults was found to be incapable of preventing haemophilic arthropathy and subsequent negative quality of life consequences.
Musculoskeletal evaluation in severe haemophilia A patients from Latin America
Haemophilia, 2014
There is a paucity of literature on haemophilia treatment in Latin American countries, a region characterized by rapidly improving systems of care, but with substantial disparities in treatment between countries. The aim of this study was to evaluate the musculoskeletal status of haemophilia patients from Latin America and to examine the relationship between musculoskeletal status and treatment practices across countries. The Committee of Latin America on the Therapeutics of Inhibitor Groups conducted a survey of its member country representatives on key aspects of haemophilia treatment in 10 countries. Musculoskeletal status of patients was obtained during routine comprehensive evaluations between March 2009 and March 2011. Eligible patients had severe haemophilia A (factor VIII <1%) without inhibitors (<0.6 BU mL À1) and were ≥5 years of age. Musculoskeletal status was compared between three groups of countries, based primarily on differences in the availability of long-term prophylaxis. Overall, 143 patients (5-66 years of age) were enrolled from nine countries. In countries where long-term prophylaxis had been available for at least 10 years (Group A), patients aged 5-10 years had significantly better mean World Federation of Hemophilia clinical scores, fewer target joints and fewer affected joints than patients from countries where longterm prophylaxis has been available for about 5 years (Group B) or was not available (Group C). In Latin America, the musculoskeletal status of patients with severe haemophilia without inhibitors has improved significantly in association with the provision of longterm prophylaxis. As more countries in Latin America institute this practice, further improvements are anticipated.