Investigation of the effect of bevacizumab on cartilage and synovium in hemophilic arthropathy: An experimental animal study

Background/objective: Hemophilic Arthropathy (HA) is an important cause of morbidity that is most commonly seen in patients with hemophilia and can cause serious damage to the synovium and cartilage due to recurrent hemarthrosis. Bevacizumab is a monoclonal vascular endothelial growth factor inhibitor that has been increasingly used in the treatment of certain cancer types in recent years. This study aims to investigate the effect of intra-articular Bevacizumab administration on cartilage and synovium in targeted therapy in patients with HA. Methods: 21 New Zealand rabbits were divided into three groups to form the HA model. To create the HA model, autologous blood from the ears of rabbits was injected into the right and left knee joints twice a week for eight weeks for mild arthropathy and sixteen weeks for severe arthropathy. In the mild arthropathy group, bevacizumab was injected into the right knee once every two weeks. Bevacizumab was injected into the right knee of one of the severe arthropathy groups once every two weeks for 16 weeks, and intra-articular Bevacizumab injections were administered to the right knees of the other group of severe arthropathy once every two weeks after the 8th week. An equal volume of 0.9% saline was injected into the left knee of all arthropathy groups. Eight knee joints of four New Zealand rabbits were determined as the control group and no action was taken. To evaluate the efficacy of bevacizumab, macroscopic, microscopic, and immunohistochemical evaluations were performed on samples, which has taken from cartilage and synovium after Magnetic Resonance (MR) imaging. Results: In the severe arthropathy group, discoloration due to hemosiderin deposition in the cartilage and synovium was higher than in the mild arthropathy group. In severe arthropathy groups, intra-articular bevacizumab applied knee joint diameter was found to be lower than the contralateral knee (p=0.016). In the severe arthropathy group, the OARSI score indicating cartilage damage and the scores indicating synovial damage was lower in the group that received intra-articular bevacizumab treatment from the beginning (p=0.016). Signal intensity change in the dynamic contrast MRI showing perfusion in severe arthropathy groups was observed to be increased compared to the control group knee (p=0.012). Conclusions: It has been shown in our study that Bevacizumab intra-articular injection when treatment is started early during the development of HA, it reduces the damage to the cartilage and synovium. This study supports the view that intra-articular Bevacizumab can be used in targeted therapy to slow down or prevent synovial changes and cartilage destruction secondary to recurrent bleeding in HA.