Anakinra as first‐line disease‐modifying therapy in systemic juvenile idiopathic arthritis: Report of forty‐six patients from an international multicenter series

Abstract

Objective. To examine the safety and efficacy of the interleukin-1 (IL-1) receptor antagonist anakinra as first-line therapy for systemic juvenile idiopathic arthritis (JIA). Methods.Patients with systemic JIA receiving anakinra as part of initial disease-modifying antirheumatic drug (DMARD) therapy were identified from 11 centers in 4 countries. Medical records were abstracted using a standardized instrument, and resulting data were analyzed to characterize concomitant therapies, clinical course, adverse events, and predictors of outcome.Results. Among 46 patients meeting inclusion criteria, anakinra monotherapy was used in 10 patients (22%), while 67% received corticosteroids and 33% received additional DMARDs. Outcomes were evaluated at a median followup interval of 14.5 months. Fever and rash resolved within 1 month in >95% of patients, while C-reactive protein and ferritin normalized within this interval in >80% of patients. Active arthritis persisted at 1 month in 39% of patients, at 3 months in 27%, and at >6 months of followup in 11%. Approximately 60% of patients, including 8 of 10 receiving anakinra monotherapy, attained a complete response without escalation of therapy. Disease characteristics and treatment were similar in partial and complete responders, except that partial responders were markedly younger at onset (median age 5.2 years versus 10.2 years; P ‫؍‬ 0.004).

A Synthetic Mammalian Therapeutic Gene Circuit for Sensing and Suppressing Inflammation

“…31 Anakinra has been previously shown to have a beneficial effect on the disease outcome, when administered early in the disease progression before arthritis has become well established. 18 That is exactly what the described anti-inflammatory device enables and anakinra as a therapeutic output was also validated in this study ( Figures 5B, 5C, and 5E). The activation of the system by the human serum from sIJA patient was lower than in the in vitro titration experiment.…”

“…Early intervention could clearly contribute to beneficial clinical outcomes in Crohn's disease 16,17 or sIJA. 18 As a safety and regulatory feature, implantable therapeutic cellular device aimed at treating inflammation should be amenable to external control and capability to rest into the standby state once the inflammation has been resolved. Additionally, autonomous activation of the device could also serve as a sensor of inflammation, reporting the previous inflammatory episode.…”

Macrophage activation syndrome as part of systemic juvenile idiopathic arthritis: diagnosis, genetics, pathophysiology and treatment

“…13,14 This, along with the similarity of many clinical and laboratory features shared by MAS and sJIA flare, led to the concept that MAS may be an inherent aspect of sJIA pathophysiology in a large percentage of patients. The fact that anakinra was shown to be highly effective for sJIA 114,115 suggested anakinra would also be a valuable treatment for MAS as part of sJIA.…”

“…In a large case series of 46 sJIA patients treated with anakinra at disease onset, anakinra was a potential MAS trigger in five children at doses of 1 --2 mg kg À1 per day. 115 However, dose escalation of anakinra often seemed to help control MAS, and permanent discontinuation of anakinra was unnecessary for any of the children. 115 The overall published experience for the use of IL-1 blockade therapy for the treatment of refractory MAS as part of sJIA has been highly favorable (Table 2).…”

Advances in the pathogenesis and treatment of systemic juvenile idiopathic arthritis

“…An alternative therapy to etoposide is antithymocyte globulin; however, this treatment is also less commonly used in those with MAS (34). More recently, the IL-1 blocking agent, anakinra, has been successfully used to treat MAS (35); however, it should be noted that some patients with s-JIA have developed MAS while being managed with anakinra (36). Immunoglobulin (i.v.)…”