Tapering of TNF Inhibitors in Patients with Axial Spondyloartritis – Can Flare Be Predicted?

Marie Wetterslev¹, Stylianos Georgiadis², Sara Nysom Christiansen³, Susanne Juhl Pedersen², Inge Juul Sørensen⁴, Merete Lund Hetland¹, Anne Duer⁵, Mikael Boesen⁶, Kasper Kjærulf Gosvig⁷, Jakob Møllenbach Møller⁷, Mads Bakkegaard⁸, Cecilie Heegaard Brahe², Niels Steen Krogh⁹, Bente Jensen⁸, Ole Rintek Madsen⁸, Jan Christensen⁸, Annette Hansen⁸, Jesper Nørregaard⁸, Henrik Røgind⁸ and Mikkel Ostergaard¹⁰, ¹Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark, ²Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen, Denmark, ³Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark, ⁴Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark, ⁵Department of Radiology, Rigshospitalet, Glostrup, Copenhagen, Denmark, ⁶Department of Radiology, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark, ⁷Department of Radiology, Herlev and Gentofte Hospital, Copenhagen, Denmark, ⁸Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen, Denmark, ⁹ZiteLab ApS, Copenhagen, Denmark, Frederiksberg, Denmark, ¹⁰Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, and Department of Clinical Medicine, University of Copenhagen, Glostrup, Denmark

Meeting: ACR Convergence 2021

Keywords: Anti-TNF Drugs, flare, PREDICTION, spondyloarthritis, tapering

Session Information

Date: Sunday, November 7, 2021

Title: Spondyloarthritis Including PsA – Treatment Poster I: Axial Spondyloarthritis (0908–0939)

Session Type: Poster Session B

Session Time: 8:30AM-10:30AM

Background/Purpose: Patients with axial spondyloarthritis (axSpA) in clinical remission tapered Tumor Necrosis Factor inhibitor (TNFi) treatment according to a clinical guideline and were followed for 2-years. We aimed to investigate 1) potential ‘baseline’ predictors of flare within 16 weeks after tapering to 2/3, 1/2, 1/3 and 0 of standard dose and 2) if change in clinical and/or imaging variables in the previous 16-weeks (i.e. during the previous dose reduction step) could predict flare within 16 weeks after tapering to 1/2, 1/3 and 0 dose.

Methods: In all, 109 patients (78(72%) on standard dose, 31(28%) on reduced dose) in clinical remission with Bath ankylosing spondylitis disease activity index (BASDAI)< 40, physician global score< 40 and no signs of disease activity the previous year tapered TNFi to 2/3 of standard dose at baseline, 1/2 at week 16, 1/3 at week 32 and withdrew at week 48. Patients who experienced clinical, BASDAI or magnetic resonance imaging (MRI) flare stopped tapering and escalated to the previous dose. Prediction analyses were done by multivariable regression.

Results: Of 107 patients who followed the tapering algorithm for 2 years, 106 patients flared: 30 (28%) flared at 2/3 of standard dose, 20 (19%) at 1/2, 29 (27%) at 1/3 and 27 (25%) after discontinuation of TNFi (Table 1). Of the 106 patients who flared, 105 had clinical flare, 25 BASDAI flare and 23 MRI flare (Figure 1). Higher baseline physician global score was an independent predictor of flare after tapering to 2/3 (Odds ratio (OR)=1.21 (95% Confidence Interval=1.05 to1.44); p=0.007). When changes from baseline to week 16 in addition to demographics were investigated as predictors of flare, higher age predicted flare within 16 weeks after tapering to 1/2 dose (OR=1.07(1.01 to 1.15); p=0.015) (Table 2). Prediction analyses on lower dose steps were not possible due to small sample sizes.

Conclusion: In axSpA patients in clinical remission who tapered TNFi according to a clinical guideline, higher baseline physician global score was the only independent predictor of flare within 16 weeks after tapering to 2/3 of standard dose.

Values are median (IQR) unless otherwise stated. Kruskal-Wallis, chi-squared or Fisher’s test was used for analysing between-group differences, as appropriate; bold indicates statistically significant p-values; p-value<0.05 was considered statistically significant.

Predictors were selected by applying backward selection in stacked imputed data. p-values by likelihood ratio tests. Bold indicates p-values<0.1 in univariate analyses. Results of final multivariable analyses were derived in non-imputed data (no missing values in selected predictors) and CIs were given as profile likelihood CIs. AUC was estimated based on internal validation by bootstrapping with 1000 samples.

Disclosures: M. Wetterslev, None; S. Georgiadis, None; S. Christiansen, Novartis, 5, BMS, 6, GE, 6; S. Juhl Pedersen, MSD, 5, 6, Pfizer, 6, AbbVie, 1, 5, 6, Novartis, 1, 5, 6, UCB, 6; I. Sørensen, None; M. Lund Hetland, Bristol-Myers Squibb, 5, AbbVie, 5, Roche, 5, 12, Novartis, 5, MSD, 5, 12, Biogen, 5, 12, Elly Lilly, 12, Orion Pharma, 12, CellTrion, 12, Samsung Bioepis, 12, Janssen Biologics BV, 12, Pfizer, 5, 12; A. Duer, None; M. Boesen, Image Analysis Group, 2, 5, 6, Esaote, 2, 5, 6, AbbVie, 2, 5, 6, Celgene, 2, 5, 6, Eli-Lilly, 2, 5, 6, Janssen, 2, 5, 6, Novartis, 2, 5, 6, Pfizer, 2, 5, 6, UCB, 2, 5, 6, Novo, 2, 5, 6, GSK, 2, 5, 6, Takeda, 2, 5, 6, Geurbet, 2, 5, 6, Biogen, 2, 5, 6, Radiobotics, 2, 5, 6, Chondrometrics, 2, 5, 6; K. Kjærulf Gosvig, None; J. Møllenbach Møller, None; M. Bakkegaard, None; C. Heegaard Brahe, None; N. Krogh, None; B. Jensen, None; O. Rintek Madsen, None; J. Christensen, None; A. Hansen, None; J. Nørregaard, None; H. Røgind, None; M. Ostergaard, AbbVie, 2, 5, 6, Bristol-Myers Squibb, 2, 6, Celgene, 2, 6, Novartis, 2, 5, 6, Boehringer Ingelheim, 2, 6, Eli Lilly, 2, 6, Hospira, 2, 6, Janssen, 2, 6, Merck, 2, 5, 6, Novo, 2, 6, Orion, 2, 6, Pfizer Inc, 2, 6, Regeneron, 2, 6, Roche, 2, 6, UCB, 2, 6, GSK, 2, 6, Mundipharma, 2, 6, Schering-Plough, 2, 6, Takeda, 2, 6, Wyeth, 2, 6, Centocor, 2, 5, 6.

To cite this abstract in AMA style:

Wetterslev M, Georgiadis S, Christiansen S, Juhl Pedersen S, Sørensen I, Lund Hetland M, Duer A, Boesen M, Kjærulf Gosvig K, Møllenbach Møller J, Bakkegaard M, Heegaard Brahe C, Krogh N, Jensen B, Rintek Madsen O, Christensen J, Hansen A, Nørregaard J, Røgind H, Ostergaard M. Tapering of TNF Inhibitors in Patients with Axial Spondyloartritis – Can Flare Be Predicted? [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/tapering-of-tnf-inhibitors-in-patients-with-axial-spondyloartritis-can-flare-be-predicted/. Accessed .

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