What is the treatment plan for a patient with Still's disease, a rare autoimmune disorder?

Treatment of Still's Disease

IL-1 or IL-6 inhibitors should be initiated as early as possible once the diagnosis of Still's disease is established, as these biologics demonstrate the highest level of evidence for efficacy and safety while enabling rapid achievement of glucocorticoid-free remission. 1

Treatment Goals and Targets

The ultimate goal is drug-free remission, achieved through a treat-to-target approach with sequential therapeutic milestones 1, 2:

• Day 7: Resolution of fever and CRP reduction >50% 1
• Week 4: No fever, >50% reduction in active joint count, normal CRP, and physician/patient global assessment <20/100 1
• Month 3: Clinically inactive disease (CID) with glucocorticoids <0.1-0.2 mg/kg/day 1
• Month 6: CID without glucocorticoids 1
• Long-term: Maintain CID for 3-6 months before tapering biologics 1

First-Line Treatment Strategy

Biologic DMARDs (Priority Treatment)

IL-1 inhibitors (anakinra, canakinumab, rilonacept) or IL-6 receptor inhibitors (tocilizumab) should be started immediately upon diagnosis 1, 3. These agents:

• Show the highest level of evidence for efficacy and acceptable risk-benefit ratio 1
• Lead to substantial improvement in quality of life and long-term outcomes 1
• Enable rapid achievement of glucocorticoid-free remission 1
• Should NOT be delayed while attempting conventional therapies 1

Glucocorticoids (Bridging Therapy)

Use glucocorticoids as bridging therapy only while biologics take effect 1:

• Minimize dose and duration to avoid prolonged systemic use 1
• Taper aggressively once biologic therapy demonstrates efficacy 1
• Target complete discontinuation by month 6 1

Conventional Synthetic DMARDs

Methotrexate, ciclosporin A, and other csDMARDs show marginal efficacy compared to biologics 1:

• May be considered in combination with biologics in difficult-to-treat cases 1
• Should NOT replace or delay biologic therapy 1
• TNF inhibitors demonstrate limited efficacy and are not recommended as first-line 1

Management of Life-Threatening Complications

Macrophage Activation Syndrome (MAS)

MAS requires immediate recognition and aggressive treatment 1, 4:

Suspect MAS when: Persistent fever, splenomegaly, elevated/rising ferritin, inappropriate cytopenias, abnormal liver function tests, elevated triglycerides, intravascular coagulation activation 1, 4, 3

Treatment protocol:

• High-dose glucocorticoids (mandatory) 1
• Plus anakinra, ciclosporin, and/or IFNγ inhibitors (emapalumab) as part of initial therapy 1
• Consider these agents at MAS onset for severe/life-threatening presentations 1

Critical pitfall: Do NOT withdraw IL-1 or IL-6 inhibitors during MAS, as this increases risk of severe flares and fatalities 1

Still's Lung Disease

Active surveillance is mandatory for all patients 1, 4:

• Clinical assessment: clubbing, persistent cough, shortness of breath 1
• Pulmonary function tests: pulse oximetry, DLCO measurement 1, 4
• High-resolution CT scan for any patient with concerning symptoms 1, 4
• Echocardiography to screen for pulmonary hypertension or myocarditis 1, 4

Management approach:

• Do NOT withdraw IL-1 or IL-6 inhibitors even if lung disease develops 1
• Withdrawal is not associated with improvement and risks severe flares with MAS 1
• Consider adding T cell-directed immunosuppression (though evidence is limited) 1
• JAK inhibitors reported beneficial in isolated cases 1

Difficult-to-Treat Patients

For patients failing IL-1 and IL-6 inhibitors, or with severe/recurrent MAS or lung disease 1:

• Consult Still's disease expert centers (mandatory) 1
• Consider: repeated intra-articular glucocorticoid injections, periodic glucocorticoid pulses, JAK inhibitors, combination csDMARDs + bDMARDs, novel IL-18 or IFNγ inhibitors 1
• Accept less ambitious intermediate targets 1

Monitoring Protocol

Regular assessments at scheduled intervals 1, 4:

• Each visit: CRP (primary marker), ESR, complete blood count, serum ferritin, liver function tests 4
• If available: IL-18 and S100 proteins (calprotectin) 1, 4, 3
• MAS surveillance: Monitor for persistent fever, splenomegaly, rising ferritin, cytopenias, elevated triglycerides 4, 3
• Pulmonary surveillance: Clinical symptoms, pulse oximetry, DLCO at each visit 4

Critical Pitfalls to Avoid

1. Delaying biologic therapy: Starting with NSAIDs/glucocorticoids alone wastes the "window of opportunity" for achieving drug-free remission 1, 5

2. Withdrawing IL-1/IL-6 inhibitors for lung disease: This exposes patients to severe flares, MAS, and fatalities without improving lung disease 1

3. Missing MAS: Maintain high vigilance with adequate laboratory monitoring, as MAS can occur at any time, even during remission 2, 6

4. Inadequate monitoring: Failure to actively screen for pulmonary disease and MAS leads to delayed recognition of life-threatening complications 1, 4

5. Prolonged glucocorticoid use: Avoid using glucocorticoids as maintenance therapy when effective biologics are available 1