• Astrid Wanders, Désirée van der Heijde, Robert Landewé, Jéhan-Michel Béhier, Andrei Calin, Ignazio Olivieri, Henning Zeidler, and Maxime Dougados.
• University Hospital, Maastricht, The Netherlands.
• Arthritis Rheum. 2005 Jun 1;52(6):1756-65.

ObjectiveA 2-year randomized controlled trial was performed to test the hypothesis that long-term, continuous treatment with nonsteroidal antiinflammatory drugs (NSAIDs), in comparison with NSAID treatment on demand only, influences radiographic progression in patients with ankylosing spondylitis (AS).MethodsPatients with AS (n = 215), who had previously participated in a 6-week, randomized, double-blind clinical trial that compared celecoxib, ketoprofen, and placebo, were randomly allocated to receive either continuous treatment with NSAIDs or on-demand treatment with NSAIDs for a period of 2 years. All patients began treatment with celecoxib, at a starting dosage of 100 mg twice daily; patients could increase this dosage to 200 mg twice daily or could switch to another NSAID while maintaining the same treatment strategy. Structural changes were assessed by radiographs of the lumbar and cervical spine and scored according to the modified Stoke Ankylosing Spondylitis Spine Score by one observer who was blinded to the treatment strategy and temporal order of the radiographs. Statistical analyses included a between-group comparison of 1) radiographic progression scores (by Mann-Whitney U test), 2) time-averaged values of variables reflecting signs and symptoms of AS (by linear regression analysis), and 3) the frequency of reported site-specific adverse events (by chi-square test or Fisher's exact test, as appropriate).ResultsComplete sets of radiographs were available for 76 of the 111 patients in the continuous-treatment group and for 74 of the 104 patients in the on-demand group. The mean +/- SD scores for radiographic progression were 0.4 +/- 1.7 in the continuous-treatment group and 1.5 +/- 2.5 in the on-demand treatment group (P = 0.002). Parameters reflecting signs and symptoms were not statistically significantly different between groups. The between-group difference in radiographic progression did not disappear after adjusting for baseline values of radiographic damage or disease activity variables and for time-averaged values of disease activity variables, nor after input of missing data. Relevant adverse events tended to occur more frequently in the continuous-treatment group than in the on-demand group (for hypertension, 9% versus 3%; for abdominal pain, 11% versus 6%; for dyspepsia, 41% versus 38%), but the differences were not statistically significant.ConclusionA strategy of continuous use of NSAIDs reduces radiographic progression in symptomatic patients with AS, without increasing toxicity substantially.

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