NEW YORK (Reuters Health) – Results of a large randomized, double-blind study suggest that the TNF inhibitor etanercept (Enbrel; Pfizer) may be more efficacious than sulfasalazine in the treatment of patients with early active ankylosing spondylitis (AS).
“Earlier initiation of anti-TNF therapy may warrant consideration, specifically in place of treatment with sulfasalazine, in patients with active axial and peripheral AS,” the study team concludes in the January 1 issue of the journal Arthritis & Rheumatism.
Sulfasalazine is often tried first, before anti-TNF agents, in patients with both axial and peripheral symptoms of AS, Dr. Juergen Braun of the Rheumatology Medical Center, Ruhrgebeit, Herne, Ruhr-University, Bochum, Germany and colleagues note in their report.
The ASCEND trial (short for AS Study Comparing Enbrel with Sulfasalazine Dosed Weekly) is the first head-to-head comparison of the safety and efficacy of a TNF blocker (etanercept) with sulfasalazine for treatment of AS.
Most patients enrolled in the study had relatively early and active AS; 73% had peripheral joint symptoms, although only 31% had peripheral synovitis at entry.
Study subjects had a Bath AS Disease Activity Index of 30 or higher (on a 0 to 100 scale) despite treatment with nonsteroidal antiinflammatory medication. They also had similarly rated levels of morning stiffness, global assessment, back pain or functional limitations and all were judged to be suitable candidates for treatment with either sulfasalazine or etanercept.
A total of 379 subjects received etanercept 50 milligrams weekly and 187 received sulfasalazine titrated over the first 4 to 6 study weeks to a maximum dose of 3 grams daily.
The primary outcome was the proportion of subjects in each group who achieved a 20% improvement by the Assessment in AS criteria (ASAS20) at 16 weeks. The ASAS20 assess spinal pain, morning stiffness, functioning and patient global assessment.
According to the investigators, significantly more patients treated with etanercept than sulfasalazine achieved the ASAS20 goal (76% vs 53%; p < 0.0001). Etanercept was more effective than sulfasalazine as early as study week 2 for both axial and peripheral AS symptoms, the investigators note.
A number of secondary endpoints also favored etanercept, including decreases in number of tender and swollen joints, physical functional limitations and serum C-reactive protein levels.
Both medications were well tolerated; serious adverse events were rare and did not differ between treatments.
The ASCEND trial was supported by Wyeth Pharmaceuticals, which was acquired by Pfizer Inc in October 2009. Three of the authors were employees of, served as consultants to, or received research support from Wyeth.
In a commentary published with the study, Dr. Michael M. Ward, of the National Institute of Arthritis, Musculoskeletal and Skin Diseases, says the most notable aspect of this study is that it enrolled patients with AS who were most apt to respond to sulfasalazine, “thereby providing a more rigorous challenge to etanercept.”
However, certain aspects of the trial temper the strength of the conclusions that can be drawn from it, Dr. Ward points out. One aspect is the length of the study – only 16 weeks, 6 of which were spent getting sulfasalazine patients up to the full dose.
Dr. Ward questions whether the duration of treatment with full-dose sulfasalazine (10 weeks) is sufficiently long to judge its potential effect. “Many would consider 4 to 6 months of treatment with sulfasalazine at 3 grams daily to be an adequate trial,” he writes.
He also notes that 18% of subjects had previously been on sulfasalazine. “Although prior ineffectiveness of sulfasalazine was an exclusion criterion, the comparisons would have been cleaner if subjects had been required to be naïve to both active treatments.”
Arthritis & Rheumatism 2011.