Abstract
ObjectiveThe aim was to carry out a retrospective review of the efficacy and safety of anakinra in paediatric patients with undifferentiated autoinflammatory disease (uAID).MethodsWe carried out a retrospective study of children with uAID at a single quaternary centre. The clinical efficacy of anakinra was evaluated using physician global assessment (PGA) and serological response assessed by levels of serum amyloid A and CRP. Safety was assessed by exploring adverse events, including infection and drug reactions.ResultsThis study included 22 patients, 64% females and 36% males of median age 7.1 years (range 0.13–14.11 years), with uAID. The median starting dose of anakinra was 2 mg/kg (range 2–6 mg/kg) and the median duration of treatment 19.6 months (range 0.8–100 months). Before anakinra treatment, the median PGA, on a three-point Likert scale, was 2 (range 1–2), which fell to 1 (range 0–2) within 3 months of treatment. Eight of 22 (36%) patients achieved complete clinical and serological remission; 8/22 (36%) achieved a partial response; and 6/22 (28%) had no response to anakinra. Adverse events included death (3/22, 14%) and allogeneic haematopoietic stem cell transplantation (1/22, 5%). There were no new safety signals, and anakinra was well tolerated overall.ConclusionRetrospectively, 72% of children with uAID responded well to anakinra, with 36% achieving full clinical and serological remission within 3 months. This suggests that empirical trials of IL-1 blockade might be warranted in children with uAID. Clear stopping criteria based on predefined parameters should be considered, because non-responders required alternative therapies, facilitated by a definitive molecular diagnosis where possible.
Highlights
IntroductionAutoinflammatory diseases (AIDs) are characterized by inflammation caused by abnormal dysregulation of the innate immune system that leads to periodic fevers, various inflammatory cutaneous manifestations, arthritis, CNS inflammation, inflammatory eye disease, myalgia, serositis, and, in children, delay of growth and puberty [1]
Retrospectively, 72% of children with undifferentiated autoinflammatory disease (uAID) responded well to anakinra, with 36% achieving full clinical and serological remission within 3 months. This suggests that empirical trials of IL-1 blockade might be warranted in children with uAID
Clear stopping criteria based on predefined parameters should be considered, because non-responders required alternative therapies, facilitated by a definitive molecular diagnosis where possible
Summary
Autoinflammatory diseases (AIDs) are characterized by inflammation caused by abnormal dysregulation of the innate immune system that leads to periodic fevers, various inflammatory cutaneous manifestations, arthritis, CNS inflammation, inflammatory eye disease, myalgia, serositis, and, in children, delay of growth and puberty [1]. Clinical trials have demonstrated that IL-1 blockade with the IL-1 receptor antagonist anakinra or the monoclonal antibody against IL-1b canakinumab are highly effective for cryopyrin-associated periodic syndromes (CAPS) and, more recently, have demonstrated efficacy for TNF receptor-associated periodic fever syndrome (TRAPS), mevalonate kinase deficiency (MKD) and colchicine-resistant FMF (crFMF) [3]. Anakinra has recently been licensed in Europe for systemic JIA and adultonset Still’s disease [4]. These therapeutic advances represent important progress for AID patients, but an important challenge is how to treat patients with unclassified or undifferentiated autoinflammatory disease (uAID), who do not have genetic confirmation of CAPS, TRAPS, MKD or FMF. No studies relate to the use of anakinra for uAID in children. The purpose of this study was to describe retrospectively the use of anakinra for paediatric uAID patients
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