Management of Still's Disease Refractory to High-Dose Methylprednisolone

Immediate Next Steps

The European League Against Rheumatism (EULAR) recommends adding IL-1 inhibition (anakinra) or IL-6 inhibition (tocilizumab) immediately, with anakinra preferred as first-line biologic therapy due to superior safety profile and efficacy in controlling both systemic and articular manifestations 1, 2
Anakinra is the preferred biologic agent when adding to corticosteroids for refractory Still's disease, with the most reassuring safety profile among biologics and proven efficacy even in critically ill patients 2
Anakinra should be dosed higher than standard (>1-2 mg/kg/day), potentially with repeated intravenous dosing for severe disease 1
IL-6 inhibitors (tocilizumab) are equally effective but carry higher rates of serious adverse events and infections compared to IL-1 inhibition 2

Before escalating therapy, actively assess for MAS, which occurs in 15-20% of Still's disease patients and can develop at any time, including during treatment 1
If MAS is present or impending, continue high-dose methylprednisolone (15-30 mg/kg/day, maximum 1g/infusion) and add Ciclosporin (oral or IV) as first additional agent 1
Anakinra at high doses (intravenous repeated dosing) can be added for severe MAS 1
Emapalumab (anti-IFN-γ antibody) can be considered for severe MAS failing standard therapy, though not yet approved in Europe 1

Anakinra (preferred): Start at doses >2 mg/kg/day, consider IV dosing 1, 2
Tocilizumab (alternative): 8 mg/kg IV every 4 weeks, may increase to every 2 weeks based on response 3
Both agents control systemic manifestations (fever, rash) and articular disease while enabling glucocorticoid tapering 2

Day 7: Resolution of fever, CRP reduction >50% 6
Week 4: No fever, active joint count reduction >50%, normal CRP, physician/patient global assessment <20/100 6
Month 3: Glucocorticoid dose ≤0.1 mg/kg/day (adults) or ≤0.2 mg/kg/day (children) 2
Month 6: Clinically inactive disease on minimal therapy 2

Never maintain high-dose glucocorticoids (10-15 mg/day prednisone) long-term for arthritis control, as this leads to severe joint destruction despite steroid treatment 4, 6
Do not delay biologic therapy: The "window of opportunity" is within 3 months of symptom onset; early biologic initiation prevents persistent chronic course 6
Maintain high suspicion for MAS throughout the disease course, as it can develop abruptly at any time—at onset, during diagnostic workup, during biologic treatment even when disease is well-controlled, or during drug tapering 1

If Tuberculosis history present, Methotrexate + glucocorticoids preferred over biologics due to substantial TB reactivation risk with IL-1/IL-6 inhibitors 5
If Lung disease present, IL-1 or IL-6 inhibitors are not contraindicated in patients with Still's disease-related lung disease 6
Combination of high-dose glucocorticoids + anakinra + methotrexate achieves prolonged remission in refractory cases 7
Multiple agents on background of high-dose glucocorticoids should be considered as initial therapy for severe presentations 1