What is the treatment for Still's disease?

Treatment of Still's Disease

IL-1 inhibitors (anakinra, canakinumab, rilonacept) or IL-6 inhibitors (tocilizumab) should be initiated as early as possible—ideally within 3 months of symptom onset—as first-line disease-modifying therapy to achieve clinically inactive disease and minimize glucocorticoid exposure. 1, 2

Initial Treatment Approach

Biologic Therapy as First-Line Treatment

• IL-1 and IL-6 inhibitors are the preferred first-line disease-modifying agents based on overwhelming real-world evidence demonstrating efficacy in controlling both systemic and articular manifestations while limiting glucocorticoid exposure. 1

• Among IL-1 inhibitors, anakinra has the most reassuring safety profile with the lowest rates of serious adverse events (10.4 per 100 patient-years) and infectious adverse events (18.1 per 100 patient-years) compared to canakinumab or rilonacept. 1

• IL-6 inhibition with tocilizumab is effective but carries higher rates of serious adverse events (36.5 per 100 patient-years) and infectious complications (104.6 per 100 patient-years) compared to IL-1 inhibition. 1

• Early initiation before 3 months from symptom onset is critical as this therapeutic window of opportunity is associated with higher rates of clinically inactive disease off glucocorticoids and may prevent chronic persistent disease patterns. 1

Role of Glucocorticoids

• Glucocorticoids may be used initially for severe systemic manifestations (persistent anemia, pericarditis, serositis, elevated liver enzymes), particularly at disease onset or with impending macrophage activation syndrome. 1

• Glucocorticoid dependence must be avoided—if disease control cannot be maintained without glucocorticoids, biologic therapy should be added or escalated rather than continuing long-term steroids. 1

• Some patients may not require glucocorticoids at all if IL-1 or IL-6 inhibitors can be initiated promptly. 1

Limited Role of Other Agents

• NSAIDs should only be used as symptomatic treatment during diagnostic workup to manage fever and arthralgia, as monotherapy is effective in only 7-15% of patients. 1, 2

• Conventional synthetic DMARDs (methotrexate) are NOT recommended as first-line therapy as methotrexate was not superior to placebo in the only available RCT. 1

• Methotrexate may be considered as a glucocorticoid-sparing agent in countries where IL-1 and IL-6 inhibitors are unavailable, particularly for prominent joint involvement. 1

Treatment Targets and Monitoring

Sequential Therapeutic Goals

• Day 7 target: Resolution of fever and reduction of CRP by >50%. 1

• Week 4 target: No fever, reduction of active joint count by >50%, normal CRP, and physician/patient global assessment <20 on 0-100 scale. 1

• Month 3 target: Clinically inactive disease with glucocorticoids <0.1-0.2 mg/kg/day. 1

• Month 6 target: Clinically inactive disease without glucocorticoids. 1

• Ultimate goal: Drug-free remission (clinically inactive disease for ≥6 months off all therapy). 1

Treatment-to-Target Approach

• Disease activity must be assessed regularly with dynamic adjustment of therapy (step-up or step-down) based on achievement of targets. 1

• Maintain clinically inactive disease for 3-6 months without glucocorticoids before initiating biologic tapering. 1

Management of Refractory Disease

• If no response to initial biologic therapy, switching between IL-1 and IL-6 inhibitors should be considered. 2

• Difficult-to-treat patients should be managed in collaboration with Still's disease expert centers. 1

• JAK inhibitors or IFN-γ inhibitors may be considered for refractory cases as experimental therapies. 2

Management of Life-Threatening Complications

Macrophage Activation Syndrome (MAS)

• MAS requires immediate treatment with high-dose glucocorticoids PLUS anakinra (>4 mg/kg/day in children or 100 mg twice daily in adults), ciclosporin, and/or IFN-γ inhibitors. 1, 2

• Screen for MAS with persistent fever, splenomegaly, elevated/rising ferritin, inappropriately low cell counts, abnormal liver function tests, intravascular coagulation activation, and elevated/rising triglycerides. 1

• Anakinra is preferred for patients with impending MAS given its safety profile in critically ill patients. 1, 2

Lung Disease

• Actively screen for lung disease with clinical symptoms (clubbing, persistent cough, shortness of breath), pulse oximetry, DLCO measurement, and high-resolution CT scan when symptomatic. 1

• IL-1 or IL-6 inhibitors are NOT contraindicated in patients with lung disease based on available data. 1, 2

Common Pitfalls to Avoid

• Do not rely on NSAIDs or glucocorticoids as long-term monotherapy—most patients require biologic disease-modifying therapy for disease control. 1, 2

• Do not delay biologic therapy initiation—the therapeutic window of opportunity closes after 3 months, potentially leading to chronic persistent disease patterns. 1

• Do not maintain patients on glucocorticoids to achieve disease control—add or escalate biologic therapy instead to avoid long-term steroid toxicity. 1

• Do not miss MAS—this is the most life-threatening complication requiring immediate recognition and aggressive treatment. 1, 2

• Do not use methotrexate as first-line therapy—it lacks RCT evidence of efficacy and delays optimal treatment. 1