Rheumatology Advance Access originally published online on March 5, 2008
Rheumatology 2008 47(4):555-556; doi:10.1093/rheumatology/ken030
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Anakinra treatment for systemic onset juvenile idiopathic arthritis (SOJIA)
1Department of Paediatric Rheumatology, Bristol Royal Hospital for Children and Royal National Hospital for Rheumatic Diseases, Bath, 2Department of Paediatric Rheumatology, Royal Liverpool Children's Hospital, Liverpool and 3Paediatric Rheumatology, Newcastle University and Newcastle Hospitals NHS Trust, UK.
Correspondence to: A. V. Ramanan, Department of Paediatric Rheumatology, Bristol Royal Hospital for Children, King David Building, Upper Maudlin Street, Bristol BS2 8BJ, UK. E-mail: avramanan{at}hotmail.com
SIR, Systemic onset juvenile idiopathic arthritis (SOJIA) accounts for 
10–20% of all patients with JIA, but it accounts for increased morbidity and mortality compared with other forms of JIA [1]. A significant number of patients have ongoing disease activity despite aggressive treatment. A follow-up study found that the probability of disease remission 10 yrs after onset was only 37% [2]. Despite a variety of treatments some children with SOJIA have a refractory course with significant morbidity. Pasqual et al. [3] have published data indicating that IL-1 is a major mediator of the inflammatory cascade that underlies SOJIA, and that this cytokine represents a target for therapy in this disease. Anakinra is a recombinant form of human IL-1 receptor antagonist that inhibits activity of IL-1. Recently, case reports using anakinra have suggested efficacy in refractory SOJIA [4, 5]. We report our experience with anakinra in three centres in the UK.
Data were collected from three tertiary paediatric rheumatology centers in the UK on all their patients with SOJIA who had received anakinra. Seven patients were identified. ILAR classification was used to establish SOJIA diagnosis in all centers [6]. Data were retrospectively collected by case notes review of the seven patients using data collection sheets. Age at diagnosis, age at starting anakinra and all previously failed medications were recorded. Core set, clinical and laboratory findings were recorded prior to starting anakinra and at 1, 3, 6 and 12 months after starting anakinra. Serious infections, adverse events and injection site reactions were also recorded.
The median age at diagnosis of SOJIA was 5.3 yrs (range 2.1–14 yrs). The median age at starting anakinra was 8.5 yrs (range 5.2–15 yrs). The median follow-up time from starting anakinra was 1 yr (range 0.75–2.3 yrs). Previous failed treatments included methotrexate (n = 6), cyclosporin (n = 4), immunoglobulin (n = 5), etanercept (n = 2) and infliximab (n = 2). Four patients had active disease despite receiving at least three different medications in addition to steroids. All patients at the start of anakinra treatment were receiving oral prednisolone with a median daily dose of 1 mg/kg (range 0.4–2 mg/kg), being steroid dependent and unable to wean further.
Six patients had excellent response to anakinra with resolution of both systemic and joint disease. Five patients achieved disease remission with 1 mg/kg anakinra, one patient required 2 mg/kg to achieve disease remission. One patient had continued disease activity despite 2 mg/kg anakinra. The laboratory markers also normalized rapidly in those six patients as shown in Table 1. Using the Core Set Criteria as an assessment tool, all variables were much improved after starting anakinra in six patients [7]. The prednisolone dose also reduced once anakinra was started to a median value of 0.75 mg/kg/day at 1 month after starting anakinra and to a median value of 0 mg/kg/day at 6 months after starting anakinra. One patient had macrophage activation syndrome at presentation, also with a pericardial effusion and hepatosplenomegaly. Her systemic features failed to respond to immunoglobulin and cyclosporin but she had a rapid and dramatic response to anakinra. After 1 month on anakinra all her symptoms resolved and laboratory parameters had normalized. The patient who did not respond to anakinra had persistence of active arthritis despite increasing the dose to 2 mg/kg; she also had persistently raised inflammatory markers but no rash, fever, lymphadenopathy or other extra-articular manifestations of the disease.
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One patient developed gastroenteritis with pre-renal failure requiring inotropic support 1 month after starting anakinra. One patient developed a chronic cough with clubbing 1 yr after starting anakinra. A lung biopsy showed resolving inflammatory changes secondary to adenovirus infection. She also developed varicella pneumonitis requiring hospital admission 2 yrs after starting anakinra. Three patients developed itch and/or erythema around the injection sites with one patient developing severe pain at the injection site requiring her to stop anakinra after 3 months. On stopping anakinra she subsequently had a flare of her disease with both systemic features and arthritis requiring further pulses of methylprednisolone.
In six out of seven patients with severe SOJIA, there was a rapid early improvement in systemic symptoms and joint disease. There were three serious infections but anakinra was continued in these patients. One patient stopped anakinra due to severe injection site pain. Irigoyen et al. [4] have demonstrated a good response to anakinra without serious side-effects in a case series of 14 patients. The results obtained in this case series support the use of anakinra as second-line therapy in children with SOJIA who have failed to respond to standard therapy. The small number of patients and the retrospective quality of the data collected limits our case series. We believe that in refractory cases of SOJIA, especially those with active systemic features, anakinra could prove a valuable addition to the therapeutic armamentarium.
Disclosure statement: The authors have declared no conflicts of interest.
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