Background/Purpose: To demonstrate the efficacy of methotrexate (MTX) and leflunomide (LEF) combination therapy in refractory chronic adult onset Still¡¯s disease (AOSD).

Methods: This is a retrospective case series of five consecutive patients with AOSD who were treated with MTX and LEF. Medical records were reviewed and laboratory findings and clinical features were assessed. Literature search was conducted.

Results: All five patients met the Yamaguchi criteria for AOSD and were treated with corticosteroid (CS) after the diagnosis of AOSD. Systemic inflammation deteriorated in one patient and one patient developed acute respiratory failure despite initial high-dose CS treatment. Tocilizumab was briefly given with prompt control of inflammation and respiratory failure. All five patients flared when PD was tapered to 0 – 20 mg/day. Along with a short-term increase in CS, MTX 15-25 mg/week was added. During further attempt to taper CS, patients flared again and LEF 10-20 mg/day was added. With MTX-LEF combination, all patients reached and remained in remission. CS was tapered off except in one patient who required 5 mg of prednisolone.

Conclusion: To the best of our knowledge, this is the first case series of chronic refractory AOSD that was successfully treated with the combination of MTX and LEF after initial MTX failure. Further prospective studies are warranted to definitively evaluate the efficacy and safety of MTX-LEF combination in AOSD.

Table 1. Summary of the treamtent and clinical outcome of the five patients

Figure 2. Clinical course after the diagnosis of AOSD of patient 1 (A), patient 2 (B), patient 3 (C) and patient 4 (D)