ARTHRITIS & RHEUMATISM Vol. 48, No. 11, November 2003, pp 3230–3236 DOI 10.1002/art.11325 © 2003, American College of Rheumatology Recombinant Human Tumor Necrosis Factor Receptor (Etanercept) for Treating Ankylosing Spondylitis A Randomized, Controlled Trial John C. Davis, Jr., 1 De ´sire ´e van der Heijde, 2 Jurgen Braun, 3 Maxime Dougados, 4 John Cush, 5 Daniel O. Clegg, 6 Alan Kivitz, 7 Roy Fleischmann, 8 Robert Inman, 9 and Wayne Tsuji 10 for the Enbrel Ankylosing Spondylitis Study Group Objective. To determine the safety and efficacy of etanercept in a multicenter, randomized, placebo- controlled, double-blind trial of adults with moderate to severe active ankylosing spondylitis (AS). Methods. Patients (n  277) were treated with either etanercept 25 mg (n  138) or placebo (n  139) subcutaneously twice weekly for 24 weeks. The primary outcome measures were the percentages of patients achieving the Assessments in Ankylosing Spondylitis 20% response (ASAS20) at weeks 12 and 24. Other outcome measures included the percentage of patients achieving higher ASAS responses, and the safety of etanercept in patients with AS. All outcome measures were assessed at 2, 4, 8, 12, and 24 weeks. Results. Treatment with etanercept resulted in dramatic improvement. The ASAS20 was achieved by 59% of patients in the etanercept group and by 28% of patients in the placebo group (P < 0.0001) at week 12, and by 57% and 22% of patients, respectively, at week 24 (P < 0.0001). All individual ASAS components, acute- phase reactant levels, and spinal mobility measures were also significantly improved. The safety profile of etanercept was similar to that reported in studies of patients with rheumatoid arthritis or psoriatic arthritis. The only adverse events that occurred significantly more often in the etanercept group were injection-site reac- tions, accidental injuries, and upper respiratory tract infections. Conclusion. Etanercept is a highly effective and well tolerated treatment in patients with active AS. Ankylosing spondylitis (AS) is an inflammatory arthritis and enthesitis involving the spine and peri- Supported by Immunex Corporation, Seattle, Washington, a wholly owned subsidiary of Amgen Inc., Thousand Oaks, California. 1 John C. Davis, Jr., MD, MPH: University of California, San Francisco; 2 De ´sire ´e van der Heijde, MD, PhD: University Hospital, Maastricht, The Netherlands; 3 Jurgen Braun, MD: Herne, Germany; 4 Maxime Dougados, MD: Hopital Cochin, Paris, France; 5 John Cush, MD: Presbyterian Hospital of Dallas, Dallas, Texas; 6 Daniel O. Clegg, MD: University of Utah Medical Center, Salt Lake City; 7 Alan Kivitz, MD: Altoona Center for Clinical Research, Duncansville, Pennsylva- nia; 8 Roy Fleischmann, MD: Radiant Research, Dallas, Texas; 9 Rob- ert Inman, MD: Toronto Western Hospital, Toronto, Ontario, Can- ada; 10 Wayne Tsuji, MD: Amgen Inc., Thousand Oaks, California. Additional members of the Enbrel Ankylosing Spondylitis Study Group are as follows: Scott Baumgartner, MD: Physicians Clinic of Spokane, Spokane, Washington; Ken Bulpitt, MD: University of California Los Angeles Medical Center; Mark Genovese, MD: Stan- ford University Medical Center, Palo Alto, California; Christopher Jackson, MD: University of Utah Medical Center, Salt Lake City; Richard Jimenez, MD: Evergreen Clinical Research Associates, Ed- monds, Washington; Arthur Kavanaugh, MD: University of California San Diego Medical Center, and Thornton Hospital, La Jolla, Califor- nia; Edward Keystone, MD: Mt. Sinai Hospital, Toronto, Ontario, Canada; Joel Kremer, MD: The Center for Rheumatology, Albany, New York; James Louie, MD: Harbor–University of California, Los Angeles Medical Center, Torrance; Maren Mahowald, MD: Veterans Affairs Medical Center, Minneapolis, Minnesota; Philip Mease, MD: Seattle Rheumatology Associates, Seattle, Washington; Jerry Molitor, MD, PhD: Benaroya Research Institute at Virginia Mason, Seattle, Washington; Larry Moreland, MD: University of Alabama at Birming- ham; Eric Ruderman, MD: Northwestern University, Chicago, Illinois; Michael Schiff, MD: Denver Arthritis Clinic, Denver, Colorado; H. Ralph Schumacher, MD: University of Pennsylvania, and Veterans Affairs Medical Center, Philadelphia, Pennsylvania; Jon Stevenson, MD: Arthritis Northwest, Spokane, Washington; James Taborn, MD: Midwest Arthritis Center, Kalamazoo, Michigan; Robert Valente, MD: Arthritis Center of Nebraska, Lincoln; Daniel J. Wallace, MD: Cedars-Sinai Medical Center, Los Angeles, California; Michael H. Weisman, MD: Cedars-Sinai Medical Center, Los Angeles, California. Address correspondence and reprint requests to John C. Davis, Jr., MD, MPH, Division of Rheumatology, University of California San Francisco, 533 Parnassus Avenue, Room U383, Box 0633, San Francisco, CA 94143. E-mail: jdavis@medicine.ucsf.edu. Submitted for publication March 26, 2003; accepted in revised form July 28, 2003. 3230