From the Guidelines
Adult-onset Still's disease (AOSD) should be treated with a combination of NSAIDs, corticosteroids, and biologic therapies, with anakinra (100mg subcutaneously daily) being a promising option for refractory cases, as shown in recent studies 1.
Treatment Approach
The treatment of AOSD typically begins with NSAIDs like naproxen (500mg twice daily) or ibuprofen (600-800mg three times daily) for mild cases. For moderate to severe disease, corticosteroids such as prednisone (0.5-1mg/kg/day) are often necessary 1.
Steroid-Sparing Agents
Steroid-sparing agents include methotrexate (starting at 7.5mg weekly, increasing to 15-25mg weekly as needed) and biologic therapies like anakinra (100mg subcutaneously daily), tocilizumab (8mg/kg IV every 4 weeks), or canakinumab (4mg/kg subcutaneously every 4 weeks) 1.
Disease Monitoring
Disease monitoring requires regular blood tests including complete blood count, liver function, and inflammatory markers (ESR, CRP, ferritin) 1.
Complications
AOSD is thought to result from dysregulation of innate immunity with overproduction of pro-inflammatory cytokines like IL-1, IL-6, and TNF-alpha. The disease can follow different patterns: monophasic (single episode), intermittent (recurrent flares with remission), or chronic (persistent symptoms). Complications may include macrophage activation syndrome, requiring prompt intensive immunosuppression, and long-term joint damage if inadequately treated 1.
Key Considerations
- Anakinra has shown promise in treating refractory AOSD cases, with rapid clinical improvement and normalization of laboratory values 1.
- Methotrexate can be used as a steroid-sparing agent, allowing for tapering of prednisone dose and eventual discontinuation in some cases 1.
- Regular monitoring of blood tests and inflammatory markers is crucial to adjust treatment and prevent complications 1.
From the Research
Definition and Clinical Spectrum of Adult Onset Still's Disease
- Adult onset Still's disease (AOSD) is a rare systemic inflammatory condition characterized by episodes of spiking fever, evanescent rash, polyarthritis or diffuse arthralgias, and multiorgan involvement 2, 3.
- The clinical spectrum of AOSD ranges from self-limiting forms with mild symptoms to life-threatening cases 2.
- AOSD is a multisystemic complex disorder with a pathogenesis that is not completely recognized, but the central role of macrophage activation and pro-inflammatory cytokines such as interleukin (IL)-1, IL-6, and IL-18 is well established 3.
Treatment Options for Adult Onset Still's Disease
- Glucocorticoids and non-steroidal anti-inflammatory drugs (NSAIDs) represent the first line of therapy for AOSD, with add-on therapy with second-line drugs reserved for steroid-dependent patients and in life-threatening cases 2.
- Conventional disease modifying anti-rheumatic drugs (DMARDs) can be effective in some severe and steroid-dependent cases of AOSD, but anti-cytokine agents represent an effective and overall more suitable alternative in this specific subset of patients 2.
- IL-1 and IL-6 blockade are effective in treating systemic and articular inflammation of AOSD patients, with IL-1 blockade having an excellent safety profile and representing the first choice of biologic treatment in this clinical scenario 2, 3.
- Biologic DMARDs, such as IL-1 inhibitors (e.g., anakinra and canakinumab) and anti-IL-6 (e.g., tocilizumab), have proven to have high efficacy and an excellent safety profile in the treatment of AOSD 3, 4, 5.
Expert Consensus and Recommendations for Treatment
- A Delphi panel of experts reached consensus on 29 statements, including statements related to diagnosis, diagnostic tests, definition of response and remission, therapy, and the use of methotrexate and tapering of treatment 4.
- The panel consented on reduction of the use of glucocorticoids to avoid side effects and preferred the use of biologics over conventional treatment, with IL-1 and IL-6 blocking agents considered important in the treatment of AOSD 4, 5.
- Expert consensus statements recommend the use of IL-1 inhibitors in addition to glucocorticoids in patients with poor prognostic factors at diagnosis, and a switch to an IL-6 inhibitor may be considered in patients with prevalent joint involvement who are unresponsive or intolerant to IL-1 inhibitors 5.