Still’s disease

Still’s disease is a systemic inflammatory condition associated with activation of interleukin-1 (IL-1), a proinflammatory cytokine, with severely debilitating disease- and treatment-related morbidity that may significantly impair quality of life and lead to long-term disability, if not controlled.^1-3

The following sections include further background information on this condition, introduce the proven efficacy and safety of Kineret in patients with Still’s disease, and provide appropriate guidance on dosing and administration of Kineret.

Disease background

Still's disease is a systemic inflammatory condition associated with activation of the proinflammatory cytokine interleukin-1 (IL-1), and characterised by severely debilitating disease- and treatment-related morbidity.^{1, 4, 5}

In children, Still's disease is also often referred to as Systemic-onset Juvenile Idiopathic Arthritis (SJIA). Both SJIA and Adult-Onset Still's disease (AOSD) belong to the autoinflammatory Still's disease continuum and share a similar genetic aetiology, clinical presentation, and disease course.^{5, 6}

Common symptoms^4,8,10

• Spiking fever, often on a daily basis
• Arthralgia or arthritis
• Salmon-coloured, evanescent skin rash
• Enlarged liver and/or spleen
• Serositis (organ-lining inflammation)
• Lymphadenopathy
• Sore throat (increased frequency in patients with AOSD)
• Laboratory abnormalities, e.g. an increase in acute phase reactants (ESR, CRP, serum ferritin)

Efficacy

Early treatment with Kineret can provide long-term remission in patients with sJIA.¹³

A single-centre prospective study evaluated a treat-to-target approach in new onset sJIA patients using Kineret as first-line monotherapy to achieve early inactive disease and prevent damage. Patients were also monitored for adverse events.¹³

Kineret provided a quick and sustained response in a substantial proportion of the new onset sJIA patients.¹³ 

• At 1 month, 60% (n=25/42) of patients had inactive disease. 
• At 1 year, 76 % (n=32/42) of patients had inactive disease. 
• At 5 years, 96% (n=24/25) of patients had inactive disease.

In the study, patients were also monitored for adverse events. No patient stopped Kineret due to infections or other serious adverse events. In total, four patients developed MAS during their disease course. One of these, with severe disease refractory to Kineret, MTX, tocilizumab, canakinumab, and glucocorticoids, died due to macrophage activation syndrome 2 years after the start of therapy.¹³

Early treatment of sJIA with Kineret can help reduce patients’ long-term exposure to glucocorticoids.¹³ 

In the same study, 57% of patients (n=24/42) did not require glucocorticoids to sustain inactive disease during follow-up.¹³

Early treatment with Kineret shows numeric differences in efficacy vs DMARDs in AOSD symptoms.¹⁴ 

An open-label, randomised, multicentre study investigated the efficacy of Kineret versus DMARDs in AOSD patients that were refractory to corticosteroid treatment.¹⁴

In the study, three patients experienced serious adverse events, defined as worsening of AOSD (lack of efficacy) in one on Kineret and two on DMARDs. Seven patients receiving Kineret reported grade 1 ISRs and one patient reported a grade 2 ISR. During an open-label extension, four additional patients reported a grade 1 ISR. No subject withdrew from the study due to ISRs.¹⁴

Early treatment of AOSD with Kineret can help reduce patients’ long-term exposure to glucocorticoids.¹⁵

One study assessed the efficacy and safety of Kineret treatment in sJIA and AOSD patients. Please note that this study was not randomised or controlled.¹⁵

Two patients with AOSD stopped taking glucocorticoids and 8 patients reduced their glucocorticoids intake by 45–95% with Kineret.¹⁵ 

Two sJIA patients stopped anakinra treatment during the first 3 months, and three patients stopped treatment between the months 3 and 6. Treatment withdrawal, in these five patients, was either due to intolerance (one case) or a lack of efficacy (four cases).

Four AOSD patients stopped anakinra because of side-effects (n=2) or a lack of efficacy (n=2). A single serious adverse event occurred in a child who developed a visceral Leishmania infection during the month 6 of anakinra treatment.¹⁵

ACR, American College of Rheumatology; AOSD, Adult-Onset Still's disease; AZA, azathioprine; CAPS, Cryopyrin-Associated Periodic Syndromes; CRP, C-reactive protein; DMARD, disease-modifying antirheumatic drugs; ESR, erythrocyte sedimentation rate; FMF, Familial Mediterranean fever; GC, glucocorticoid; IL, interleukin; ISR, injection site reaction; IVIG, intravenous immunoglobulins; LEF, leflunomide; MAS, macrophage activation syndrome; MTX, methotrexate; NSAID, non-steroidal anti-inflammatory drug; RA, Rheumatoid Arthritis; sJIA, Systemic-onset Juvenile Idiopathic Arthritis; TNF, tumour necrosis factor.

References:

1. Kineret Summary of Product Characteristics. https://www.medicines.org.uk/emc/product/559/smpc (Accessed May 2025).
2. Consolaro A, et al. Pediatric Rheumatol . 2016;14:23.
3. Pascual V, et al. J Exp Med. 2005;201(9):1479–86.
4. Giacomelli R, et al. J Autoimmun. 2018;93:24–36.
5. Vastert SJ, et al.Rheumatology. 2019;58(Suppl 6):vi9–vi22.
6. Nigrovic PA, et al. R Arthritis Rheumatol. 2018;70:7–17.
7. McGonagle D, McDermott MF. PLos Med . 2006;3(8):e297.
8. Woo, P. Nat Clin Pract. 2006;2:28–34.
9. Efthimiou P,et al. Ann Rheum Dis. 2006;65(5):564–72.
10. Jamilloux Y, et al. Immunol Res. 2015;61(1–2):53–62.
11. Spiegel LR, et al. Arthritis Rheum. 2000;43(11):2402–9.
12. Vastert SJ, et al. Arthritis Rheumatol. 2014;66(4):1034–43.
13. ter Haar NM, et al. Arthritis Rheumatol. 2019;71(7):1163–1173.
14. Nordström D, et al. J Rheumatol. 2012;39(10):2008–2011.
15. Lequerré T, et al. Ann Rheum Dise. 2008;67(3):302–318.