OP0139 A TIME-SHIFTED EFFECT OF TUMOR NECROSIS FACTOR INHIBITORS ON RADIOGRAPHIC SPINAL PROGRESSION IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS: LONG-TERM RESULTS FROM THE GERMAN SPONDYLOARTHRITIS INCEPTION COHORT
Authors: D. Poddubnyy, V. Rios Rodriguez, M. Torgutalp, A. Dilbaryan, M. Verba, F. Proft, M. Protopopov, J. Rademacher, H. Haibel, J. Sieper, M. Rudwaleit
Journal: Annals of the Rheumatic Diseases (2021)

Background: There are inconclusive data on the effect of tumor necrosis factor inhibitors (TNFi) on radiographic spinal progression in axial spondyloarthritis (axSpA). Although inflammation and new bone formation are linked in axSpA, TNFi failed to show inhibition of radiographic spinal progression over two years compared to historical cohorts in pivotal studies in radiographic axSpA. Subsequent observational studies suggested that a longer treatment duration, earlier treatment initiation and effective inflammation suppression might be required to achieve inhibition of radiographic progression. Objectives: The aim of the current study was to evaluate the effect of TNFi on radiographic spinal progression in patients with early axSpA in a long-term inception cohort. Methods: A total of 266 patients with early axSpA (with r-axSpA with symptom duration ≤10 years and nr-axSpA with symptom duration ≤5 years) from the German Spondyloarthritis Inception Cohort (GESPIC) with at least two sets of spinal radiographs obtained at least 2 years apart during a 10-year follow-up were included. These patients contributed with a total of 542 2-year radiographic intervals. Spinal radiographs were evaluated by three trained and calibrated readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The final mSASSS was calculated as a mean of three reader scores. The association between the current TNFi, previous TNFi and radiographic spinal progression defined as the absolute mSASSS change score over 2 years was analyzed using longitudinal generalized estimating equations (GEE) analysis. Results: Only 9 patients were treated with a tumor necrosis factor inhibitor (TNFi) at baseline, and a total of 77 patients received TNFi during the entire follow-up period that gave 103 2-year intervals covered by TNFi of any duration, and 78 intervals covered by TNFi with treatment duration of at least 12 months. Radiographic spinal progression in axSpA patients receiving TNFi in the current 2-year interval was not different from progression in patients not treated with TNFi, while TNFi in the previous 2-year interval was associated with lower progression compared to patients without TNFi in this interval (Figure 1). The latter was also evident for patients who received TNFi in both previous and current 2-year intervals, i.e. patients treated with TNFi over 4 years. The longitudinal GEE analysis confirmed no significant association between current TNFi treatment and radiographic spinal progression but a significant association between TNFi in the previous 2-year interval (especially if this was continued also in the current interval giving 4 years in total) and the progression in the current one (Table 1). Table 1. The association between the change of the mSASSS over two years and current and/or previous treatment with TNFi in the longitudinal generalized estimation equation analysis. TNFi treatment definition Reference β* (95% CI ) TNFi for ≥12 months in the previous 2-year interval TNFi for ≥12 months in the current 2-year interval Yes No TNFi for ≥12 months in the current 2-year interval -0.19 (-0.56 to 0.18) Yes No TNFi for ≥12 months in the previous 2-year interval -0.56 (-0.95 to -0.17 ) Yes Yes No TNFi for ≥12 months in the current and previous 2-year intervals -0.59 (-1.03 to -0.15 ) *Parameter estimates from the multivariable models adjusted for sex, symptom duration at the beginning of the current 2-year interval, time-averaged ASDAS in the current 2-year interval, smoking in the current 2-year interval, classification as non-radiographic or radiographic axSpA, and mSASSS at the beginning of the current 2-year interval. Conclusion: TNFi treatment exhibits a time-shifted inhibitory effect on radiographic spinal progression in axSpA that becomes evident only in the second 2-year interval after treatment initiation. Acknowledgements: GESPIC was initially supported by the BMBF. As consequence of the funding reduction by BMBF according to schedule in 2005 and stopped in 2007, complementary financial support has been obtained also from Abbott, Amgen, Centocor, Schering–Plough, and Wyeth. Starting from 2010, the core GESPIC cohort was supported by AbbVie. Disclosure of Interests: Denis Poddubnyy Speakers bureau: AbbVie, Bristol-Myers Squibb, Lilly, MSD, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Biocad, Gilead, GlaxoSmithKline, Eli Lilly, MSD, Novartis, Pfizer, Samsung Bioepis, and UCB, Grant/research support from: AbbVie, MSD, Novartis, and Pfizer, Valeria Rios Rodriguez: None declared, Murat Torgutalp: None declared, Ani Dilbaryan: None declared, Maryna Verba: None declared, Fabian Proft: None declared, Mikhail Protopopov: None declared, Judith Rademacher: None declared, Hildrun Haibel: None declared, Joachim Sieper: None declared, Martin Rudwaleit Consultant of: AbbVie, BMS, Celgene, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB Pharma