This is Still’s disease
Still’s disease is a systemic autoinflammatory condition associated with IL-1-driven inflammation1
Although previously referred to as Systemic Juvenile Idiopathic Arthritis (sJIA) and Adult-Onset Still’s Disease (AOSD) in children and adults, respectively, it is now recognized that sJIA and AOSD are the same disease, Still's disease, based on shared genetic, clinical, and laboratory features and disease course.2,3
Onset of Still’s disease can be at any age but is often between 18-24 months in children (sJIA) and 16-35 years in adults (AOSD). Among adults, women are more than twice as likely to develop Still’s disease; in contrast, among children, as many boys as girls have sJIA. Patients with persistent, active disease six months after disease onset are at high risk of developing chronic disease. Early initiation of biologic therapy may lead to better disease control.4-10
EULAR/PReS recommendation for the management of Still’s disease – four overarching principles3
Still’s disease
Recognition that sJIA and AOSD are the same disease, Still ́s disease
Diagnosis
The presence of arthritis is no longer required to make a diagnosis in sJIA to avoid potential deleterious diagnostic delays
Treatment
Early use of IL-1 inhibitors, such as Kineret, or IL-6 inhibitors is recommended to achieve high rates of CID and remission
Monitoring
Importance of monitoring and managing MAS and Still’s disease-related lung disease
Common signs and symptoms associated with Still’s disease4-6
A valuable asset for the treatment of Still’s disease
The clinical efficacy of Kineret for the treatment of Still’s disease (sJIA and AOSD) has been evaluated in multiple clinical studies. Kineret has demonstrated superiority vs. placebo with respect to achieving and maintaining clinical response. Kineret has also shown superiority vs. conventional disease-modifying anti-rheumatic drugs (cDMARDs) with respect to achieving clinical remission. Additional published data in Still’s disease indicate that Kineret induces a rapid resolution of systemic features such as fever, rash, and elevation of inflammatory markers. Glucocorticoid doses can in many cases be reduced after initiation of Kineret therapy.1
Treatment with Kineret induced a rapid response as early as day 39
Within 3 days, 90% of patients had normal body temperature and reduction in inflammatory markers9
*The clinical response to treatment was evaluated according to the adapted American College of Rheumatology Petriatic 70 (ACRpedi 70 and ACRpedi 90) criteria for improvement. An adapted ACRpedi 70 response is indicated by the absence of fever and at least 70% improvement from baseline in at least 3 of any of the 6 core set of variables, worsening by>70%; the adapted ACRpedi 90 is similarly defined (indicating 90% improvement).
Early treatment with Kineret is associated with favorable long-term outcomes10
Definition of clinically inactive disease (per modified Wallace criteria) was absence of arthritis, morning stiffness, and systemic features, physician’s global assessment indicating no disease activity (<10 on a scale of 0–100) and normalization of ESR (<20 mm/hour) and CRP level (<10 mg/L)10
Treatment with Kineret induced more beneficial responses than cDMARD in adults11
Efficacy of Kineret versus cDMARDs demonstrated in a published 24-week, multicenter, randomised, open-label study of 22 patients with glucocorticoid-dependent refractory AOSD. The primary endpoint was remission according to specific criteria: afebrile (≤37°C body temperature) in the absence of NSAIDs 24 hours prior to measurement; decrease of CRP and ferritin to reference limits; normal counts for swollen and tender joints.11
Abbreviations
CID, Clinically Inactive Disease; CRP, C-reactive protein; ESR,Erythrocyte sedimentation rate; GC, Glucocorticoids; IL-1, Interleukin-1; IL-6, Interleukin-6; MAS, Macrophage activation syndrome; NSAID, Non-steroidal anti-inflammatory drug.
Kineret Q&A
- Kineret is given in a pre-filled syringe containing 100 mg of anakinra per 0.67 ml (150 mg/ml).1
- Kineret is given as a subcutaneous injection.1
- Dosage depends on indication. In children, the dose is determined depending on body weight. Please refer to current SmPC.
- Kineret should be stored in a refrigerator between 2°C and 8°C.1
- Kineret should not be frozen or shaken.1
- Kineret should be kept in its original carton and away from light.1
References
- Swedish Orphan Biovitrum AB (publ). Kineret summary of product characteristics [SmPC]. Latest version available from: https://www.ema.europa.eu/en/documents/ product-information/kineret-epar-product-information_en.pdf
- Vastert SJ, Jamilloux Y, Quartier P, Ohlman S, Osterling Koskinen L, Kullenberg T, et al. Anakinra in children and adults with Still's disease. Rheumatology. 2019 Nov 1;58(Supplement_6):vi9–22.
- Fautrel B, Mitrovic S, De Matteis A, et al. EULAR/PReS recommendations for the diagnosis and management of Still's disease, comprising systemic juvenile idiopathic arthritis and adult-onset Still's disease. Annals of the Rheumatic Diseases Published Online First: 24 September 2024.
- Woo P. Systemic juvenile idiopathic arthritis: diagnosis, management, and outcome. Nat Clin Pract Rheumatol. 2006;2(1):28–34.
- Jamilloux Y, Gerfaud-Valentin M, Martinon F, Belot A, Henry T, Sève P. Pathogenesis of adult-onset Still's disease: new insights from the juvenile counterpart. Immunol Res. 2015;61(1):53–62.
- Giacomelli R, Ruscitti P, Shoenfeld Y. A comprehensive review on adult onset Still's disease. J Autoimmun. 2018 Sep;93:24–36.
- Gerfaud-Valentin M, Maucort-Boulch D, Hot A, Iwaz J, Ninet J, Durieu I, et al. Adult-Onset Still Disease. Medicine. 2014 Mar;93(2):91–9.
- Spiegel LR, Schneider R, Lang BA, Birdi N, Silverman ED, Laxer RM, et al. Early predictors of poor functional outcome in systemic-onset juvenile rheumatoid arthritis: A multicenter cohort study. Arthritis Rheum. 2000 Nov;43(11):2402–9.
- Vastert SJ, de Jager W, Noordman BJ, Holzinger D, Kuis W, Prakken BJ, et al. Effectiveness of First-Line Treatment With Recombinant Interleukin-1 Receptor Antagonist in Steroid-Naive Patients With New-Onset Systemic Juvenile Idiopathic Arthritis: Results of a Prospective Cohort Study. Arthritis Rheum. 2014 Apr 1;66(4):1034–43.
- ter Haar NM, et al. Treatment to Target Using Recombinant Interleukin-1 Receptor Antagonist as First-Line Monotherapy in New-Onset Systemic Juvenile Idiopathic Arthritis: Results From a Five-Year Follow-Up Study. Arthritis Rheumatol. 2019 Jul;71(7):1163-1173.
- Nordström, D., Knight, A., Luukkainen, R., van Vollenhoven, R., Rantalaiho, V., Kajalainen, A, et al. Beneficial effect of interleukin 1 inhibition with anakinra in adult-onset Still's disease. An open, randomized, multicenter study. J Rheumatol. 2012;39(10):2008-2011.