The effect of secondary prophylaxis versus episodic treatment on the range of motion of target joints in patients with haemophilia

The major hallmark of severe haemophilia is spontaneous bleeding into joints and muscles that begins in early childhood and results in inflammation, cartilage destruction and joint space reduction, eventually leading to chronic arthropathy marked by pain, limited joint range of motion (ROM) and life-long disability (Aronstam et al, 1979). Repeated bleeding into a joint, known as target joint development, is known to initiate chronic progressive arthropathy. The Centers for Disease Control and Prevention (CDC) Universal Data Collection (UDC) surveillance of the complications of haemophilia, defines target joint (TJ) bleeding as recurrent bleeding into a joint on four or more occasions in the 6 months prior to evaluation. Treatment approaches to management of joint health in haemophilia have traditionally included coagulation factor replacement therapy at the time of haemorrhage, known as episodic therapy, or regular infusions of coagulation factor replacement to prevent haemorrhages, known as prophylactic therapy. Prophylactic therapy with regular infusions of coagulation factor VIII or IX with maintenance of nadir levels of factor VIII or IX ≥ 1% reduces the risk of spontaneous bleeding (Nilsson et al, 1992). Primary prophylaxis, defined as the initiation of regularly scheduled replacement therapy before the age of 2 years and after no more than one or two joint haemorrhages, has been recommended as the treatment of choice by the World Health Organization (WHO) and the World Federation of Haemophilia (WFH) (Berntorp et al, 1995; Srivastava et al, 2013). In 2007, the USA Joint Outcome Study first demonstrated, in a multicentre randomized controlled trial, a decrease in joint haemorrhages and joint destruction in boys with severe haemophilia A receiving every other day prophylactic therapy compared to on-demand treatment (Manco-Johnson et al, 2007). Secondary prophylaxis, started after 2 years of age or after two or more joint haemorrhages, is administered in order to avoid or delay the progression of joint destruction. Several studies have demonstrated that this therapy reduces the frequency of haemorrhages and hospitalizations, and improves quality of life (Nilsson et al, 1992; Panicker et al, 2002; Collins et al, 2010). However, there is a paucity of evidence regarding the benefits of secondary prophylaxis on the function of a TJ or future progression of arthropathy (Manco-Johnson et al, 1994; Cohen et al, 1997). The primary aim of this study was to evaluate the hypothesis that secondary prophylaxis will result in improved TJ ROM, prevent new TJ development and lower the rate of total haemarthroses, compared to episodic treatment in patients with moderate and severe haemophilia.