Results from an open-label extension study of etanercept in ankylosing spondylitis
Article first published online: 5 APR 2004
Copyright © 2004 by the American College of Rheumatology
Arthritis Care & Research
Volume 51, Issue 2, pages 302–304, 15 April 2004
How to Cite
Davis, J., Webb, A., Lund, S. and Sack, K. (2004), Results from an open-label extension study of etanercept in ankylosing spondylitis. Arthritis & Rheumatism, 51: 302–304. doi: 10.1002/art.20241
- Issue published online: 5 APR 2004
- Article first published online: 5 APR 2004
- Immunex Corp., Seattle WA
- NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases. Grant Number: N01-AR-9-2244
- The Rosalind Russell Medical Research Center for Arthritis
To the Editor:
The efficacy and safety of etanercept in the treatment of ankylosing spondylitis (AS) in a 4-month randomized, double-blind, placebo-controlled trial has been previously described by our group (1). After participation in the initial 4-month trial, patients could enroll in a 6-month open-label extension period. We now provide the results of the open-label study as well as a description of the effects of a total of 10 months of etanercept treatment in patients with AS.
Thirty-eight of the original 40 patients in the study enrolled in the 6-month extension trial and received open-label etanercept (Enbrel; Immunex, Seattle, WA) at a dose of 25 mg subcutaneously twice weekly; 36 patients completed the open-label extension. Patients in the original etanercept group continued to demonstrate sustained benefit with continued therapy, and patients in the original placebo group achieved similar improvements once they began receiving etanercept. After 4 months in the original study, 14 of 19 etanercept patients (74%) had achieved an Assessments in Ankylosing Spondylitis 20% response (ASAS20) (2), and after an additional 6 months of etanercept, 16 of 17 patients (94%) had achieved this end point. In comparison, 5 of 19 original placebo patients (26%) achieved the ASAS20 at the end of the 4-month study, but after 6 months of open-label etanercept, 16 of 19 patients (84%) achieved the end point.
Additionally, with extended therapy with etanercept, many patients achieved the more stringent ASAS50 and ASAS70 responses, representing 50% and 70% improvements from baseline, respectively. At the end of the 10-month study, a total of 29 of 36 patients (81%) achieved the ASAS50, and 15 of 36 (42%) achieved the ASAS70. Of particular note, at the end of the original 4-month study, only 3 of 19 patients (16%) in the original placebo group achieved the ASAS50, and only 2 of 19 (11%) achieved the ASAS70. After 6 months of open-label etanercept, however, 16 of 19 patients (84%) achieved the ASAS50, and 9 of 19 patients (47%) achieved the ASAS70.
Five primary outcome measures (duration of morning stiffness, nocturnal spinal pain, the Bath Ankylosing Spondylitis Functional Index , patient global assessment, and swollen joint count) were assessed independently over the 10-month period. Mean values of these measures were similar at baseline in both of the original treatment groups. At 10 months, patients in both treatment groups showed significant percent improvements from baseline in the primary outcome measures, indicating that etanercept has a sustained effect on these aspects of AS (data not shown).
Measures of spinal mobility (chest expansion, modified Schober's test, and occiput-to-wall measurement) also showed significant improvement with etanercept therapy. Of the patients who received placebo in the original 4-month study period and received etanercept during the 6-month extension, the mean percent improvement from baseline at 10 months was 48.8% for the chest expansion measurement, 7.8% for the modified Schober's test, and 24.8% for the occiput-to-wall measurement. In the group that received etanercept throughout both periods, the mean percent improvement from baseline was 59.6% for chest expansion, 26.2% for the modified Schober's test, and the 48.1% for the occiput-to-wall measurement. The 3-fold improvement in the modified Schober's test in the group that received continuous etanercept treatment suggests that some aspects of spinal mobility in AS patients may benefit from a longer etanercept treatment period. Recent studies have shown significant improvement in a composite measure of spinal mobility (Bath Ankylosing Spondylitis Metrology Index) (4) with infliximab (5) and pamidronate (6). Additionally, spinal mobility improvements have been reported in a phase III clinical trial with etanercept (7).
Etanercept continued to be well tolerated during the 6-month extension of the study. Adverse events occurred with similar frequencies during the blinded and open-label phases of the trial. There were no deaths, no serious adverse events or infections, and no safety-related discontinuations during the extension period. We observed no cases of tuberculosis or malignancies.
Of interest, during the controlled phase of the study, patients could continue preexisting AS therapies such as nonsteroidal antiinflammatory drugs (NSAIDs), methotrexate (≤20 mg/week), sulfasalazine (≤3 gm/day), and/or oral corticosteroids (≤10 mg/day). During the open-label extension, thus, they could modify their treatment regimens. At baseline of the original study, 84% of patients were receiving NSAIDs, 39% were receiving disease-modifying antirheumatic drugs (DMARDs), and 16% were being treated with corticosteroids. Approximately 40% of patients were receiving 2 or more medications for treatment of their AS. By the end of the open-label extension, 66% of all patients discontinued or decreased at least one of their AS therapies (Figure 1). A total of 14 patients (42%) discontinued NSAID therapy, and 5 patients (15%) decreased the dosage. One patient, who had not been receiving an NSAID, added a selective cyclooxygenase-2 inhibitor after discontinuing methotrexate and prednisone. A total of 8 patients (53%) discontinued at least one DMARD by the end of the open-label study: 5 patients (63%) discontinued sulfasalazine, 2 patients (25%) discontinued methotrexate, and 3 patients (38%) decreased the dosage of methotrexate. Corticosteroid use also was decreased or discontinued.
Etanercept represents an important advancement in the treatment of AS. In addition to successfully modifying the characteristic axial manifestations of disease, etanercept appears to be well tolerated. More extended observations will be important in assessing the long-term safety and impact of etanercept on disease progression.
Supported by Immunex Corp., Seattle WA, a wholly owned subsidiary of Amgen Inc., Thousand Oaks CA, NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases grant N01-AR-9-2244, and The Rosalind Russell Medical Research Center for Arthritis. The authors are indebted to Jennifer Gorman, MD, Maureen Fitzpatrick, MPH, Anne-Marie Duhme, BSN, RN, Melanie Vose, BS, Alan Bostrom, PhD, Jeffrey Kishiyama, MD, Scott Fields, PharmD, Désirée van der Heijde, MD, PhD, and David Wofsy, MD.
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John Davis Jr. MD, MPH*, Allison Webb BS*, Steven Lund MS*, Kenneth Sack MD*, * University of California San Francisco.