Objective: To compare the efficacy, pharmacokinetics and safety of etanercept 50 mg once weekly with 25 mg twice weekly and placebo in patients with ankylosing spondylitis.
Methods: A 12-week, double-blind, placebo-controlled study compared the effects of etanercept 50 mg once weekly, etanercept 25 mg twice weekly and placebo in 356 patients with active ankylosing spondylitis (3:3:1 randomisation, respectively). The primary end point was the proportion of patients achieving a response at week 12 based on the Assessment in Ankylosing Spondylitis Working Group criteria (ASAS 20). The pharmacokinetics of etanercept 50 mg once weekly and 25 mg twice weekly were analysed.
Results: Baseline characteristics and disease activity were similar among the three groups: etanercept 50 mg once weekly, etanercept 25 mg twice weekly and placebo. The percentage of patients discontinuing therapy was 9.0%, 9.3% and 13.7% for the three respective groups. ASAS 20 response at 12 weeks was achieved by 74.2% of patients with etanercept 50 mg once weekly and 71.3% of those with etanercept 25 mg twice weekly, both significantly higher than the percentage of patients taking placebo (37.3%, p<0.001). Percentages of patients with ASAS 5/6 response (70.3%, 72.0% and 27.5%, respectively; p<0.001) and those with ASAS 40 response (58.1%, 53.3% and 21.6%, respectively; p<0.001) followed a similar pattern. Significant improvement (p<0.05) was seen in measures of disease activity, back pain, morning stiffness and C reactive protein levels as early as 2 weeks. Serum etanercept exposure was similar between the etanercept groups. Incidence of treatment-emergent adverse events, including infections, was similar among all three groups, and no unexpected safety issues were identified.
Conclusions: Patients with ankylosing spondylitis can expect a comparable significant improvement in clinical outcomes with similar safety when treated with etanercept 50 mg once weekly or with 25 mg twice weekly.
- ASAS, Assessment in Ankylosing Spondylitis
- AUC, area under the curve
- BASDAI, Bath Ankylosing Spondylitis Disease Activities Index
- CRP, C reactive protein
- NCI, National Cancer Institute
- TNF, tumour necrosis factor
- VAS, visual analogue scale
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Published Online First 28 September 2006
Etanercept Study 314 investigators: Claude-Laurent Benhamou, Orléans, France; Jürgen Braun, Herne, Germany; Marek Brzosko, Szczecin, Poland; Alain Cantagrel, Toulouse, France; Hanna Chwalinska-Sadowska, Warszawa, Poland; Laszlo Czirjak, Pécs, Hungary; Kurt De Vlam, Leuven, Belgium; Liana Euller-Ziegler, Nice, France; Flavio Fantini, Milano, Italy; Anna Filipowicz-Sosnowska, Warszawa, Poland; JS Hill Gaston, Cambridge, UK; Pal Geher, Budapest, Hungary; Piet Geusens, Diepenbeek, Belgium; Eugeniusz Kucharz, Katowice, Poland; Jolanta Lewandowicz, Lodz, Poland; Michel Malaise, Liège, Belgium; Emilio Martin Mola, Madrid, Spain; Neil McHugh, Bath, UK; Carlo Salvarani, Reggio Emilia, Italy; Jacques Sany, Montpellier, France; Lucas Settas, Thessaloniki, Greece; Jean Sibilia, Strasbourg, France; Fotini Skopouli, Athens, Greece; Zoltan Szekanecz, Debrecen, Hungary; Laszlo Tamasi, Miskolc, Hungary; Christiaan van Denderen, Amsterdam, The Netherlands; Jürgen Wollenhaupt, Hamburg, Germany; Henning Zeidler, Hannover, Germany; Irena Zimmermann-Gorska, Poznañ, Poland
Funding: This study was supported by Wyeth Pharmaceuticals, Collegeville, Pennsylvania, USA (study drug and grants to investigational sites).
Competing interests: DvdH was reimbursed by Wyeth, the manufacturer of etanercept, for attending several conferences and for running educational programmes, and has received research grants. JCdS was paid by Schering-Plough Pharma for running educational programmes and served as an advisory board member for Abbott. MD received grants from Wyeth to conduct clinical trials, and also fees for consulting and for speaking at symposia organised by Wyeth. PG was reimbursed by Wyeth, the manufacturer of etanercept, for attending a conference, and received fees for speaking at another conference. FR received fees for speaking to general practitioners who have been working with our hospital over the past 5 years. JS received fees for consulting and speaking, and funds for research. LP, JSW, SF and M-PB are employees of Wyeth Research. IvdH-B, XJ, IO, LS, JS and DW have no competing interests.