RT Journal Article
SR Electronic
T1 Combination leflunomide and methotrexate (MTX) therapy for patients with active rheumatoid arthritis failing MTX monotherapy: open-label extension of a randomized, double-blind, placebo controlled trial.
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 1521
OP 1531
VO 31
IS 8
A1 Joel Kremer
A1 Mark Genovese
A1 Grant W Cannon
A1 Jacques Caldwell
A1 John Cush
A1 Daniel E Furst
A1 Michael Luggen
A1 Ed Keystone
A1 Joan Bathon
A1 Arthur Kavanaugh
A1 Eric Ruderman
A1 Patricia Coleman
A1 David Curtis
A1 Elliott Kopp
A1 Seth Kantor
A1 Michael Weisman
A1 Jonathan Waltuck
A1 Herbert B Lindsley
A1 Joseph Markenson
A1 Bruce Crawford
A1 Indra Fernando
A1 Karen Simpson
A1 Vibeke Strand
YR 2004
UL http://www.jrheum.org/content/31/8/1521.abstract
AB OBJECTIVE: To obtain additional safety and efficacy data on leflunomide (LEF) treatment in combination with methotrexate (MTX) therapy in an open-label extension study in patients with rheumatoid arthritis (RA). METHODS: Following a 24 week, randomized, double-blind trial of adding placebo (PLA) or LEF to stable MTX therapy, patients could enter a 24 week extension. Subjects randomized to LEF and MTX continued treatment [(LEF/LEF) + MTX]. Subjects randomized to PLA and MTX switched to LEF (10 mg/day, no loading dose) and MTX [(PLA/LEF) + MTX]. The double-blind regarding initial randomization was maintained. RESULTS: For subjects in the extension phase, American College of Rheumatology 20% (ACR20) responder rates for the (LEF/LEF) + MTX group were maintained from Week 24 (57/96, 59.4%) to Week 48 (53/96, 55.2%). ACR20 responder rates improved in patients switched to LEF from PLA at Week 24 [(PLA/LEF) + MTX] from 25.0% (24/96) at Week 24 to 57.3% (55/96) at Week 48. Patients in the extension who switched from PLA to LEF without a loading dose exhibited a lower incidence of elevated transaminases compared to patients initially randomized to LEF. Diarrhea and nausea were less frequent during the open-label extension in patients who did not receive a LEF loading dose. CONCLUSION: Response to therapy was maintained to 48 weeks of treatment in patients who continued to receive LEF and MTX during the extension. Importantly, ACR20 response rates after 24 weeks of LEF therapy were similar between patients switched from PLA to LEF without loading dose, and those who received a loading does of LEF (100 mg/day x 2 days) at randomization. Fewer adverse events were reported in patients switched to LEF without a loading dose.