What is the initial treatment for Still's disease?

Initial Treatment for Still's Disease

The initial treatment for Still's disease should be an IL-1 inhibitor (preferably anakinra) or an IL-6 inhibitor (tocilizumab), initiated as early as possible—ideally within 3 months of symptom onset—to control both systemic and articular manifestations while minimizing glucocorticoid exposure. 1, 2

Primary Treatment Approach

IL-1 or IL-6 inhibitors are the treatment of choice and should be started immediately upon diagnosis. 1 The 2024 EULAR/PReS guidelines strongly recommend these biologics based on overwhelming real-world evidence demonstrating their efficacy in controlling all disease aspects—systemic symptoms, joint manifestations, and fever—while limiting glucocorticoid dependence. 1

Choosing Between IL-1 and IL-6 Inhibitors

Among the available options, anakinra (an IL-1 inhibitor) has the most reassuring safety profile. 1 The comparative safety data shows:

• Anakinra: 10.4 serious adverse events per 100 patient-years, 18.1 infectious adverse events per 100 patient-years 1
• Tocilizumab (IL-6 inhibitor): 36.5 serious adverse events per 100 patient-years, 104.6 infectious adverse events per 100 patient-years 1

Anakinra is specifically preferred if macrophage activation syndrome (MAS) is impending or present. 2 IL-6 inhibitors carry higher rates of both serious adverse events and infections compared to IL-1 inhibition. 1

Timing: The Window of Opportunity

Initiate biologic therapy before 3 months from symptom onset. 1 Real-world observational data demonstrates that early initiation of IL-1 or IL-6 inhibitors is associated with:

• Very favorable short-term outcomes with high rates of clinically inactive disease off glucocorticoids 1
• Decreased likelihood of chronic persistent disease course 1
• Prevention of Th17 cell expansion that drives chronic arthritis 1

This therapeutic window of opportunity is supported by translational data from IL-1RN-deficient mice, where early but not late IL-1 inhibition prevented both arthritis development and Th17 cell increases. 1

Role of Glucocorticoids

Glucocorticoids should be used only as bridging therapy at low doses (≤0.1 mg/kg/day prednisone equivalent) while initiating biologics, not as maintenance therapy. 2 The goal is clinically inactive disease off glucocorticoids. 1, 2

• Historical data shows 76-95% response rates to glucocorticoids, but 88% of patients eventually require additional therapy 1
• 46% of patients required maintenance prednisone in older cohorts 1
• Glucocorticoid dependence must be avoided; if present, add other therapies rather than continuing steroids 1

High-dose glucocorticoids should be reserved for life-threatening complications like MAS or severe serositis, limited to 6 months maximum. 1, 2

NSAIDs: Limited Role

NSAIDs should be used only for symptomatic management of fever and arthralgia during diagnostic workup, not as definitive treatment. 1 There is no RCT evidence supporting NSAID efficacy in Still's disease, and monotherapy controls disease in only 7-15% of patients. 1, 2

Conventional DMARDs: Not First-Line

Conventional synthetic DMARDs (particularly methotrexate) should NOT be used as initial therapy. 1 The evidence is clear:

• Methotrexate was not superior to placebo in the only available RCT (failed to achieve even ACR30 response) 1
• Overall response rate to conventional DMARDs is approximately 40% 1
• These agents should be considered only in countries where IL-1 and IL-6 inhibitors are unavailable 1

Treatment Algorithm

1. Establish diagnosis (exclude infections, malignancies, other autoimmune diseases)
2. Initiate IL-1 inhibitor (anakinra preferred) or IL-6 inhibitor (tocilizumab) immediately 1, 2
3. Add low-dose glucocorticoids (≤0.1 mg/kg/day) only if needed for bridging 2
4. Target clinically inactive disease off glucocorticoids 1, 2
5. Maintain remission for 3-6 months before considering biologic tapering 1, 2

Critical Pitfalls to Avoid

Do not delay biologic therapy while attempting NSAID or glucocorticoid monotherapy. 1 This outdated approach:

• Misses the therapeutic window of opportunity 1
• Increases risk of chronic persistent disease 1
• Leads to glucocorticoid dependence and toxicity 1

Do not use methotrexate as first-line therapy. 1 Despite historical use, it lacks efficacy as monotherapy and delays appropriate treatment.

Do not maintain patients on glucocorticoids long-term. 1, 2 Glucocorticoid dependence indicates need for escalation to biologics, not continued steroid use.

Special Considerations

For patients with impending MAS: Use anakinra at high doses (>100 mg twice daily in adults) with high-dose glucocorticoids. 2

For patients with chronic articular pattern: These patients have worse prognosis and may require more aggressive therapy from the outset. 2

If initial biologic fails: Consider rotating between IL-1 and IL-6 inhibitors rather than abandoning biologic therapy. 2