OP0145 Continuous Versus on Demand Treatment of Ankylosing Spondylitis with Diclofenac Over 2 Years Does not Prevent Radiographic Progression of the Spine – Results from a Randomized Prospective Multi-Center Trial (Enradas)
Authors: J. Sieper, J. Listing, D. Poddubnyy, I.-H. Song, K.-G. Hermann, J. Callhoff, J. Braun, M. Rudwaleit
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Previously it was shown that non-steroidal antiinflammatory drugs (NSAIDs) given continuously reduce radiographic progression compared to an on demand therapy over 2 years in patient with ankylosing spondylitis (AS) [1]. A similar effect was found in an analysis from a prospective AS cohort [2]. <h3>Objectives</h3> In the current study we tested whether such an effect of NSAIDs could be confirmed in another prospective randomized trial. <h3>Methods</h3> AS patients were randomized to be treated with either continuous (at least 50% per day of the maximum dose of 150 mg) or on demand diclofenac for 2 years. Switching to another NSAID was possible in case of side effects or inefficacy. TNF-blockers were not allowed during the whole study period. Primary outcome was the difference in radiographic spinal progression measured by the mSASSS, scored by two readers blinded to treatment arm and time point. <h3>Results</h3> 62 of 85 patients enrolled in the continuous arm (mean age 42 years, BASDAI 4.2, CRP 8.4 mg/l, disease duration 12.2 y, 74% male, mSASSS 11.3, HLA-B27 positivity 83.5%) and 60 of 82 enrolled in the on demand arm (mean age 44 years, BASDAI 4.5, CRP 12.9 mg/l, disease duration 15.2 y, 68% male, mSASSS 14.0, HLA-B27 84%) completed the study. Surprisingly, the mSASSS progression was numerically higher in the continuous group compared to the on demand group (1.28; 95%CI 0.68-1.92 vs 0.79; 95%CI 0.17-1.38 in the completer population), although this difference was not statistically significant (figure). When only patients were analysed who were CRP positive at baseline (54% cont., 58% demand) or had syndesmophytes at baseline (55% cont., 57% on demand), both known risk factors for radiographic progression, again there was numerically a higher radiographic progression in the continuous vs the on demand group: 1.68 vs 0.83 and 2.1 vs 0.89, respectively. We used the ASAS NSAIDs index (0-100) to quantify NSAIDs intake over the 2 years, which was 75 (mean) for the continuous and 44 (mean) for the on demand group. At the end of year 2, 73% of the patients were still on diclofenac and had not switched to another NSAID. There were no differences between the 2 treatment groups regarding side effects: 19 serious adverse event (SAEs) occurred in the continuous group vs 19 in the on demand group. <h3>Conclusions</h3> In our study continuous vs on demand treatment with diclofenac over 2 years did not prevent radiographic progression in AS. It is highly unlikely that the results would have been different with a higher number of patients because we found even a trend for less progression in the on demand group. Since 73% of patients were still on diclofenac at the end of the study we do not know whether other NSAIDs such as Celecoxib [1] would have had a different effect on radiographic progression in our patients. <h3>References</h3> Wanders et al, Arthritis Rheum 2005;52:1756-65. Poddubnyy et al, Ann Rheum Dis 2012;71:1616-22. <h3>Acknowledgements</h3> This study was supported by a grant (FKZ 01KG0801) from the German Ministry for Education and Research. The drug diclofenac was provided by Novartis which did not have any influence on design, conduct or analysis of the study. <h3>Disclosure of Interest</h3> None declared