ARTHRITIS & RHEUMATISM Vol. 52, No. 2, February 2005, pp 554–562 DOI 10.1002/art.20861 © 2005, American College of Rheumatology Long-Term Open-Label Preliminary Study of the Safety and Efficacy of Leflunomide in Patients With Polyarticular-Course Juvenile Rheumatoid Arthritis Earl Silverman, 1 Lynn Spiegel, 1 David Hawkins, 2 Ross Petty, 3 Donald Goldsmith, 4 Laura Schanberg, 5 Ciaran Duffy, 6 Paul Howard, 7 and Vibeke Strand 8 Objective. To obtain preliminary data regarding the efficacy and long-term safety of leflunomide in patients with refractory polyarticular-course juvenile rheumatoid arthritis (JRA). Methods. Twenty-seven patients were entered into the initial 26-week open-label study of leflunomide therapy; 17 entered the extension phase (maximum 107 weeks). Mean disease duration at study entry was 7.0 years. All patients had >5 joints with active arthritis and had received methotrexate for a mean of 36.0 months. Following a loading dose, patients initially received leflunomide at a dosage of 10 mg/1.73 m 2 /day, which could be increased to 20 mg/1.73 m 2 /day (maxi- mum 20 mg/day) beginning at week 8. The primary efficacy outcome was the American College of Rheuma- tology (ACR) Pediatric 30 (Pedi 30) criteria for im- provement. Last observation carried forward (LOCF) analysis was used, and all patients were entered into an intent-to-treat analysis. Intraarticular corticosteroids (maximum of 2 in the initial 26 weeks) were allowed, but no new disease-modifying antirheumatic drug or change in nonsteroidal antiinflammatory drug was allowed throughout the study. Results. Seventeen of the 27 patients (63%) com- pleted the initial 26-week study. Fourteen patients (52%) met the ACR Pedi 30 response criteria at week 26. Seventeen patients entered into the extension phase (13 who met response criteria and 4 who failed to meet response criteria but decided to continue). Nine of the 17 patients (53%) who entered the extension phase either completed all 30 months of study or the study ended prior to the month 30 visit. Five patients with- drew because of failure to maintain efficacy, 2 withdrew their consent, and 1 withdrew because of an adverse event. Using LOCF analysis, 65% of patients met ACR Pedi 30 response criteria at 1 year and 2 years (weeks 50 and 106, respectively) and 53% at the end of the study. Good response rates were also seen using ACR Pedi 50 and ACR Pedi 70 criteria (47% and 24% at week 106, respectively). Conclusion. In this open-label study of JRA pa- tients who either failed to respond to, or were intolerant of, methotrexate, the majority met the ACR Pedi 30 response criteria at week 26. The response was durable, since 53% of patients who entered into the extension phase (maximum 30 months) responded at the end of this phase. Our findings support the further study of the role of leflunomide in the treatment of polyarticular- course JRA. Juvenile rheumatoid arthritis (JRA), a disease that begins before the age of 16 years, is classified according to the number of joints affected within the 1 Earl Silverman, MD, FRCPC, Lynn Spiegel, MD, FRCPC: Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada; 2 David Hawkins, MD: Children’s Hospital of Eastern On- tario, Ottawa, Ontario, Canada; 3 Ross Petty, MD: British Columbia Children’s Hospital, Vancouver, British Columbia, Canada; 4 Donald Goldsmith, MD: St. Christopher’s Hospital for Children, Philadelphia, Pennsylvania; 5 Laura Schanberg, MD: Duke University, Durham, North Carolina; 6 Ciaran Duffy, MD: Montreal Children’s Hospital, Montreal, Quebec, Canada; 7 Paul Howard, MD: Arthritis Health, Scottsdale, Arizona; 8 Vibeke Strand, MD: Stanford University, Palo Alto, California. Dr. Silverman has received consulting fees ($10,000) from Aventis. Dr. Strand has received consulting fees from Abbott Immu- nology, Abgenix, Amgen, Aventis, BiogenIdec, Celltech, Centocor, Enzon, Genelabs, Genentech, Hoffman-La Roche, Incyte, La Jolla Pharmaceuticals, Millennium, Novartis, Omeros, Organon, Pfizer Re- search, Scios, Serono, SKK, and Sumitomo, and is a member of the speakers’ bureaus for Abbott, Amgen, Aventis, and Pfizer. Address correspondence and reprint requests to Earl Silver- man, MD, FRCPC, Division of Rheumatology, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G 1X8, Can- ada. E-mail: earl.silverman@sickkids.ca. Submitted for publication July 30, 2004; accepted in revised form November 4, 2004. 554