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EULAR 2017 | Daily Highlights
TUMOR NECROSIS FACTOR INHIBITOR TREATMENT REDUCES SPINAL RADIOGRAPHIC PROGRESSION IN ANKYLOSING SPONDYLITIS BY DECREASING DISEASE ACTIVITY: A LONGITUDINAL ANALYSIS IN A LARGE PROSPECTIVE COHORTAbstract: OP0189
Authors: C. Molnar1, A. Scherer1, X. Baraliakos2, M. de Hooge3, R. Micheroli4, P. Exer5, R. Kissling6, G. Tamborrini5, L. Wildi4, M. Nissen7, P. Zufferey8, J. Bernhard9, U. Weber10, R. Landewé11, D. van der Heijde3, A. Ciurea4,*
1SCQM, Zurich, Switzerland, 2Rheumazentrum, Herne, Germany, 3LUMC, Leiden, Netherlands, 4USZ, Zurich, 5Private Practice, Basel, 6Balgrist, Zurich, 7HCUGE, Geneva, 8CHUV, Lausanne, 9Bürgerspital, Solothurn, Switzerland, 10Univ Southern Denmark, Odense, Denmark, 11AMC, Amsterdam, Netherlands
Whether tumor necrosis factor inhibitors (TNFi) have an influence on radiographic progression in ankylosing spondylitis (AS) remains controversial.
To investigate the impact of TNFi use on spinal radiographic progression in AS.
Patients fulfilling the modified NY Criteria for AS (as assessed by central reading) in the Swiss Clinical Quality Management Cohort with at least 2 years of clinical and radiographic follow-up were included. Spinal X-rays were taken every 2 years and scored independently by 2 blinded readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) in chronological time order. Average score of the readers was used. Radiographic progression was defined as an increase by ≥2 mSASSS units over 2 years. The relationship between TNFi use before a 2 year X-ray interval and progression within the interval was investigated using binomial generalized estimating equation models with adjustment for potential confounding and multiple imputation of missing covariate data. Ankylosing Spondylitis Disease Activity Score (ASDAS) was regarded as a potential intermediate variable mediating the effect of TNFi on radiographic progression. It was added to the model as a time-varying variable in a sensitivity analysis.
A total of 420 patients with AS contributed to data for 597 x-ray intervals in adjusted analyses (1-5 intervals per patient); BL characteristics: male sex 66%, HLA-B27 81%, mean (SD) age 40.4 (10.9) years, disease duration 13.9 (9.8) years, mSASSS 6.4 (12.4), ASDAS 2.8 (1.1)). 39% of the patients were already on TNFi at first X-ray. Mean mSASSS progression in 2 years was 0.9 (2.7) units. The multivariable model (Table) shows that prior use of TNFi reduced the odds of progression in the next 2 year interval by 49% (odds ratio (OR) 0.51, 95% confidence interval (CI) 0.28-0.92, p=0.03). BL mSASSS and male sex also significantly affected progression. Adding ASDAS as a covariate to the model decreased the estimated effect of TNFi on progression: OR 0.65, 95% CI 0.36-1.17, p=0.15. In this model, a decrease in ASDAS by 1 unit would lower the odds for progression by 0.62 (p=0.001).
Table. Longitudinal multivariable analysis of radiographic progression
TNFi seem to reduce radiographic progression in patients with AS and this effect is mediated, at least in part, by a decrease in disease activity.
Supported by the Stiftung für Rheumaforschung and a research grant from the investigator initiated studies program of MSD.
Disclosure of Interest:
C. Molnar: None declared, A. Scherer: None declared, X. Baraliakos: None declared, M. de Hooge: None declared, R. Micheroli: None declared, P. Exer: None declared, R. Kissling: None declared, G. Tamborrini: None declared, L. Wildi: None declared, M. Nissen: None declared, P. Zufferey: None declared, J. Bernhard Consultant for: Merck Sharp & Dohme, Pfizer, Roche, U. Weber Consultant for: Abbvie, R. Landewé: None declared, D. van der Heijde: None declared, A. Ciurea Consultant for: Abbvie, Celgene, Eli Lilly, Janssen-Cilag, Merck Sharp & Dohme, Novartis, Pfizer, UCB
Although TNF inhibitors have been introduced for the treatment of ankylosing spondylitis almost 15 years ago, there is an ongoing debate whether this treatment might also delay the appearance of osteoproliferative changes of the spine. Previous analyses have been criticized for methodological issues. This longitudinal analysis of the SCQM cohort, with spinal radiographs taken every 2 years for up to 10 years, avoided several pitfalls by choosing a validated spinal damage score as well as validated definitions of radiographic progression, by using average scores of two trained readers blinded to all clinical data, by taking into account that most of the patients do not show progression at all and that some patients could contribute to multiple progression intervals and by adjusting the analyses for known confounders, as well as explanatory variables (sex, baseline radiographic damage, disease duration, HLA-B27, peripheral arthritis, smoking, physical exercise and the use of NSAIDS). As previous analyses had suggested that the effect of TNF inhibitors on spinal progression might be delayed, the authors have analyzed the effect of prior use of anti-TNF agents before a radiographic 2-year interval on the respective radiographic interval and find that the odds of progression is reduced by 50%. By contrast, TNFi treatment within the radiographic interval had no influence on radiographic progression, indicating that treatment has to be continued for at least 2 years for an effect on progression to be detectable. Treatment with TNF inhibitors for >4 years before a radiographic 2-year interval (a total of at least 6 years of treatment) reduced the odds of progression in the respective interval by 68%. In patients treated with TNF inhibitors and reaching an ASDAS <1.3 (definition of inactive disease), radiographic progression in the following 2-year interval was nearly completed abrogated, thus providing a potential target for a treat-to-target treatment strategy. As with all observational study designs, residual confounding by unmeasured factors cannot be excluded and therefore causality remains difficult to prove. However, randomized-controlled trials to definitively answer this issue will never be performed for ethical reasons.
PD Dr. Adrian Ciurea