Occurrence and prediction of flare after tapering of tnf inhibitors in patients with axial spondyloarthritis

BackgroundPatients with axial spondyloarthritis (axSpA) in clinical remission tapered Tumor Necrosis Factor inhibitor (TNFi) therapy according to a clinical guideline and had 2 years´ follow-up [1].ObjectivesWe aimed to investigate flare frequency, dose at which flare occurred, type of flare (clinical/ Bath ankylosing spondylitis disease activity index (BASDAI)/magnetic resonance imaging (MRI)) and predictors of flare.MethodsPatients in clinical remission (BASDAI<40, physician global score<40 and without disease activity the previous year) tapered TNFi to 2/3 standard dose at baseline, 1/2 at week (w)16, 1/3 at w32 and 0 (discontinuation) at w48. Patients who flared were increased to previous dose. Predictors of flare at each dose step were investigated by regression analyses.ResultsOf 108 patients, 106 (99%) flared before year 2 (flare occurring mean (SD) 99(44.3) days after last tapering). Twenty-nine patients (27%) flared at 2/3 standard dose, 21 (20%) at 1/2 dose, 29 (27%) at 1/3 dose and 27 (25%) after discontinuation. One-hundred-and-five (99%) had clinical flare, 25 (24%) BASDAI flare and 23 (29% of patients with MRI at flare) MRI flare; and forty-one patients (41%) fulfilled the ASAS-definition of clinically important worsening (≥0.9 increase since baseline) (Figure 1). Most common flare symptoms were back/buttock pain (n=93 (89%)) and pain in peripheral joints/entheseal regions (n=48 (46%)). Higher baseline physician global score was an independent predictor of flare after tapering to 2/3 (Odds ratio=1.19 (95% Confidence Interval=1.05-1.41); p=0.011) (Table 1). Changes in clinical and/or imaging variables in the 16 weeks prior to tapering did not predict flare (data not shown).Table 1.Prediction of flare within 16 weeks after tapering to 2/3 dose (n=74)Values are from timepoint of tapering from full dose to 2/3 doseUnivariate analysesFinal multivariable analyses*OR(95% CI)p-valueOR(95% CI)p-valueMale gender0.96(0.25 - 4.14)0.955Age1.00(0.96 - 1.04)0.880Time since diagnosis1.00(0.95 - 1.06)0.863Current smoker0.70(0.20 - 2.20)0.543HLA-B27 positive0.66(0.18 - 2.41)0.515Previous bDMARDs1.28(0.66 - 2.49)0.458Patient pain VAS1.02(0.98 - 1.06)0.310Physician global VAS1.19(1.04 - 1.41)0.0121.19(1.04 - 1.41)0.011ASDAS1.66(0.70 - 4.10)0.251mNYc positive0.78(0.29 - 2.09)0.615SPARCC SIJ Inflammation Index1.01(0.90 - 1.12)0.861CANDEN Total inflammation0.95(0.65 - 1.25)0.702SPARCC SSS Erosion1.11(0.91 - 1.37)0.293CANDEN Fat0.99(0.96 - 1.02)0.705AUC (95% CI)0.66 (0.54 - 0.78)Predictors were selected by applying backward selection in stacked data. p-values by likelihood ratio tests. Bold indicates p-values<0.1 in univariate analyses. Predictors were selected by backward selection in stacked imputed datasets after applying a fixed weight to all observations, accounting for the average fraction of missing data across all variables under consideration. *Results were derived in non-imputed data (no missing values in selected predictors). CIs given as profile likelihood CIs. AUC estimated based on internal validation by bootstrapping with 1000 samples.ASDAS, Ankylosing Spondylitis Disease Activity Score; bDMARDs, biological disease modifying anti-rheumatic drugs; AUC, Area Under the receiver operating characteristic Curve; CANDEN, Canada-Denmark MRI scoring system of the spine in patients with axial spondyloarthritis; CI, confidence interval; mNYc, modified New York criteria; SIJ, sacroiliac joint; SPARCC SIJ inflammation, Spondyloarthritis Research Consortium of Canada Sacroiliac joint inflammation; SPARCC SSS, Spondyloarthritis Research Consortium of Canada Sacroiliac joint Structural Score; VAS, visual analogue scale.ConclusionAlmost all (99%) axSpA patients in clinical remission flared during tapering to discontinuation, but above half not before receiving 1/3 dose or less. Higher physician global score was the only independent predictor of flare.References[1]Wetterslev M, et al. Rheumatology (Oxford) 2021;10.1093/rheumatology/keab755.Disclosure of InterestsMarie Wetterslev: None declared, Stylianos Georgiadis: None declared, Sara Nysom Christiansen Speakers bureau: BMS and GE, Grant/research support from: Novartis, Susanne Juhl Pedersen Speakers bureau: MSD, Pfizer, AbbVie, Novartis and UCB, Consultant of: AbbVie and Novartis, Grant/research support from: AbbVie, MSD, and Novartis, Inge Juul Sørensen: None declared, Merete Lund Hetland Consultant of: MSD, Biogen, Pfizer, Eli Lilly, Orion Pharma, CellTrion, Samsung Bioepis, and Janssen Biologics BV, Grant/research support from: MSD, Biogen, Pfizer, Bristol-Myers Squibb, AbbVie, Roche and Novartis, Anne Duer: None declared, Mikael Boesen Speakers bureau: Image Analysis Group, Esaote, AbbVie, Celgene, Eli-Lilly, Janssen, Novartis, Pfizer, UCB, Novo, GSK, Takeda, Geurbet, Biogen, Radiobotics and Chondrometrics, Consultant of: Image Analysis Group, Esaote, AbbVie, Celgene, Eli-Lilly, Janssen, Novartis, Pfizer, UCB, Novo, GSK, Takeda, Geurbet, Biogen, Radiobotics and Chondrometrics, Grant/research support from: Image Analysis Group, Esaote, AbbVie, Celgene, Eli-Lilly, Janssen, Novartis, Pfizer, UCB, Novo, GSK, Takeda, Geurbet, Biogen, Radiobotics and Chondrometrics, Kasper K Gosvig: None declared, Jakob Møllenbach Møller: None declared, Mads Bakkegaard: None declared, Cecilie Heegaard Brahe: None declared, Niels Steen Krogh: None declared, Bente Jensen: None declared, Ole Madsen: None declared, Jan Christensen: None declared, Annette Hansen Speakers bureau: speaker fees from Elly Lilly, Jesper Noerregaard: None declared, Henrik Røgind: None declared, Mikkel Østergaard Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Consultant of: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Grant/research support from: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB