Any Role Left for Sulfasalazine in Ankylosing Spondylitis?

Janis C. Kelly

June 17, 2011

June 17, 2011 — A new study has confirmed etanercept efficacy in early, active ankylosing spondylitis (AS) but did not quite knock sulfasalazine out of contention. Juergen Braun, MD, from Rheumatology Medical Center, Ruhr District, Herne, Germany, led the multinational study, which was published in the June issue of Arthritis & Rheumatism.

An accompanying editorial by Michael M. Ward, MD, from the National Institute of Arthritis and Musculoskeletal and Skin Disease at the National Institutes of Health in Bethesda, Maryland, notes that although the researchers recruited patients with early, active disease generally considered likely to respond to sulfasalazine, the dosing and adequacy of time on treatment are questionable.

"Sulfasalazine was started at a dosage of 500 mg daily, which, appropriately, was escalated slowly so that the full dosage of 3 gm daily was not reached until week 6. Given that the study end points were assessed 10 weeks later, one can question whether the duration of treatment with sulfasalazine at full dose was sufficiently long to judge its potential effect. Many would consider 4-6 months of treatment with sulfasalazine at 3 gm daily to be an adequate trial," Dr. Ward wrote.

In the Wyeth/Pfizer-sponsored Ankylosing Spondylitis Study Comparing Enbrel With Sulfasalazine Dosed Weekly (ASCEND) study, Braun et al randomly assigned 379 patients to receive etanercept 50 mg once weekly and 187 patients to receive sulfasalazine titrated to 3 g/day, both for 16 weeks. The primary end point was the Assessment of SpondyloArthritis International Society criteria for 20% improvement (ASAS20) at week 16. Inclusion criteria included active AS, having failed at least 1 nonsteroidal anti-inflammatory drug, and being candidates for either sulfasalazine (eg, having swollen or tender peripheral joints) or etanercept. Exclusions included prior tumor necrosis factor (TNF) inhibitors, receiving sulfasalazine within 6 months before study entry, or failure to respond to more than 1 disease-modifying antirheumatic drug.

ASAS20 responses were observed in 76% of patients treated with etanercept vs 53% treated with sulfasalazine (P < .0001).

In addition to short study duration and slow titration of sulfasalazine, other study limitations pointed out by the authors include lack of placebo control and no imaging to monitor disease progression.

The researchers concluded: "In this population of patients with AS, etanercept was significantly more effective than sulfasalazine in improving the signs and symptoms of AS in the axial skeleton and peripheral joints."

However, Dr. Ward said that this is essentially an answer to a question nobody is asking, as the superiority of TNF inhibitors for patients with AS with axial involvement, but not peripheral involvement, is not in doubt. About 73% of the participants had peripheral joint symptoms, but only 31% had peripheral synovitis at study entry.

Dr. Ward said that one more "clinically relevant" question would be whether sulfasalazine or a TNF inhibitor would be better treatment for patients with AS with active peripheral joint manifestations but axial symptoms too mild to warrant anti-TNF treatment. Another would be whether starting patients who have both axial and peripheral joint manifestations on sulfasalazine, then switching to a TNF inhibitor if response is not adequate, would be better than starting with a TNF inhibitor. Moreover, given the chronic nature of AS, symptom control, toxicities, and costs would need to be examined over the course of several years, he added.

Dr. Braun and coauthor Ruben Burgos-Vargas, MD, have received consulting fees, speaking fees, grant funding, and/or honoraria from Wyeth/Pfizer, Centocor, Abbott, Schering-Plough, Merck, Bristol Meyers-Squibb, and/or Amgen. Coauthors Bonnie Vlahos, RN, Andrew S. Koenig, DO, and Bruce Freundlich, MD, were employees of Wyeth and own stock or stock options in Wyeth/Pfizer. Dr. Ward has disclosed no relevant financial relationships.

Arthritis Rheum. 2011;63:1543-1551. Abstract

Arthritis Rheum. 2011;63:1472-1474. Abstract


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