Halting the intra-articular accumulation of blood is essential to abbreviate these processes, and standard therapy for a joint haemorrhage is to replace clotting factor until evidence of ongoing bleeding has stopped. Nevertheless, achieving haemostasis cannot be expected to arrest inflammation once initiated. Iron deposition, inflammation and neoangiogenesis likely continue for prolonged periods after the cessation of haemorrhage and contribute to increased

risk of recurrent haemorrhage. There is limited data evaluating whether adjunctive therapy with anti-inflammatory agents Maraviroc supplier can augment replacement clotting factor concentrates to improve joint outcomes. To our knowledge, the only prospective, randomized controlled studies in humans with haemophilia that have examined the addition of anti-inflammatory

agents to clotting factor in the treatment of haemarthrosis have used short courses of oral corticosteroids. This approach led to lower amounts of factor replacement needed to achieve return Everolimus ic50 of joint function in one report in which 5 days of prednisolone treatment was used [24]. Another report using only 2 days of oral prednisolone, and conducted exclusively in inhibitor patients, failed to demonstrate a benefit [25]. Several non-controlled series report partial amelioration of chronic synovitis using intra-articular corticosteroids [26–28]. Like corticosteroids, non-steroidal anti-inflammatory agents (NSAIDs) are important in the chronic management of rheumatoid arthritis, which is the archetypal inflammatory arthritis. Bleeding due to NSAID-related platelet dysfunction limits the use of NSAIDs for most individuals with haemophilia to the cyclooxygenase 2 (COX-2) inhibitors. Uncontrolled series report that COX-2 inhibitors

improve patient-reported and subjective symptoms in chronic synovitis [4,29,30]. Our group has examined the addition of a short-course of a TNF-α receptor antagonist (etanercept, given as a course of 10 doses) to factor replacement in both haemophilia A and haemophilia B mice with induced recurrent knee bleeding using a joint capsular puncture model. In each of Tryptophan synthase these haemophilic strains, if the TNF-α antagonist is begun early in the course of developing synovitis, the presence of joint pathology examined 3–4 weeks after the induced haemorrhages was strikingly better than control mice receiving only clotting factor replacement at the time of haemorrhage or clotting factor with dexamethasone [3]. In further proof-of-concept experiments, we investigated combining MR16-1, a rat IgG-blocking antibody directed against mouse IL-6 receptor (anti IL-6R), with factor VIII (FVIII) replacement to protect against inflammatory sequelae of haemarthrosis in haemophilia A mice.