Abstract

Introduction: In patients with hemophilia, the development of inhibitors against exogenous factor VIII (FVIII) or factor IX (FIX) is one of the most serious complications of repeated exposure to replacement therapy and has major clinical and economic consequences. The multicenter, non-interventional, cross-sectional, case-control ESOS study aimed to evaluate the relationship between inhibitor status of patients with hemophilia and their quality of life (QoL) and degree of arthropathy, as well as to compare the orthopedic status of patients with inhibitors with that of patients without inhibitors.

Methods: Overall, 128 patients were enrolled: group A (n=38), males aged 14–35 years, with severe congenital hemophilia A or B (basal FVIII/FIX level <0.01 IU/mL) and inhibitors against FVIII/FIX who were classified as high responders (inhibitor titer >5 BU) and who have had the inhibitors >5 years; group B (n=41), as group A, but aged 36–65 years; and group C (n=49), as group A, but without inhibitors. Key assessments included: socio-demographics; data on replacement therapy, inhibitor characteristics, immune tolerance testing, genotype, and prophylaxis; care management; QoL (EuroQoL questionnaire); and Gilbert’s and Pettersson’s classifications.

Results: A maximum inhibitor titer >50 BU was observed in 71% of patients in group A and 63% in group B. There were significant differences in genotype for patients in groups A and B compared with those in group C (e.g. inversions, large deletions, missense mutations). Prior to enrolling in the study, orthopedic procedures had been performed in 66% of patients in group A compared with 34% in group B and 37% in group C; arthroplasty had been performed only in patients with inhibitors (groups A and B, n=2 in each). During the 12-month study period, patients with inhibitors had more absence from work or school due to orthopedic complications than patients without inhibitors. In groups A and B, 16% and 27% of patients were hospitalized for orthopedic procedures compared with only 4% in group C. Patient mobility was severely reduced in groups A and B, with 24% and 23% of patients using wheelchairs compared with only 4% in group C, and 50% and 51% of patients needing a walking aid compared with only 29% in group C. In terms of orthopedic status, significantly more joint pain was reported by patients in group A compared with those in group C; clinical/radiological orthopedic scores were also worse in group A compared with group C. In terms of bleeding, there was no difference in the incidence of muscle hematomas between the groups; the incidences of hemarthroses were higher in younger patients (groups A and C) than in older ones (group B). For the QoL analysis, patients in group A reported significantly more joint abnormality than those in group C.

Conclusion: Our study confirms that the burden of orthopedic complications and the impact on QoL is more severe in patients with hemophilia who have developed inhibitors compared with those patients without inhibitors.

Disclosures: Consulting fees or other remuneration for sponsor of study, NovoNordisk.

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