TY - JOUR

T1 - Flare during tapering of biological DMARDs in patients with rheumatoid arthritis in routine care

T2 - characteristics and predictors

AU - Terslev, L.

AU - Ostergaard, Mikkel

AU - Georgiadis, Stylianos

AU - Brahe, Cecilie Heegaard

AU - Ellegaard, Karen

AU - Dohn, U. M.

AU - Fana, Viktoria

AU - Møller, Torsten

AU - Juul, Lars

AU - Huynh, Tuan Khai

AU - Krabbe, Simon

AU - Ornbjerg, L. M.

AU - Glinatsi, Daniel

AU - Røgind, Henrik

AU - Hansen, Annette

AU - Nørregaard, Jesper

AU - Jacobsen, Søren

AU - Jensen, Dorte V.

AU - Manilo, Natalia

AU - Asmussen, Karsten

AU - Boesen, Mikael

AU - Rastiemadabadi, Zoreh

AU - Morsel-Carlsen, Lone

AU - Møller, Jakob Møllenbach

AU - Krogh, Niels Steen

AU - Hetland, Merete Lund

N1 - Publisher Copyright: © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

PY - 2022

Y1 - 2022

N2 - OBJECTIVE: To identify predictors of flare in a 2-year follow-up study of patients with rheumatoid arthritis (RA) in sustained clinical remission tapering towards withdrawal of biological disease-modifying anti-rheumatic drugs (bDMARDs). METHODS: Sustained clinical remission was defined as Disease Activity Score for 28 joints (DAS28)-C reactive protein (CRP) ≤2.6 without radiographic progression for >1 year. bDMARDs were tapered according to a mandatory clinical guideline to two-thirds of standard dose at baseline, half of dose at week 16 and discontinuation at week 32. Prospective assessments for 2 years included clinical evaluation, conventional radiography, ultrasound and MRI for signs of inflammation and bone changes. Flare was defined as DAS28-CRP ≥2.6 with ∆DAS28-CRP ≥1.2 from baseline. Baseline predictors of flare were assessed by logistic regression analyses. RESULTS: Of 142 included patients, 121 (85%) flared during follow-up of which 86% regained remission within 24 weeks after flare. Patients that flared were more often rheumatoid factor positive, had tried more bDMARDs and had higher baseline ultrasound synovitis sum scores than those not flaring. For patients on standard dose, predictors of flare within 16 weeks after reduction to two-thirds of standard dose were baseline MRI-osteitis (OR 1.16; 95% CI 1.03 to 1.33; p=0.014), gender (female) (OR 6.71; 95% CI 1.68 to 46.12; p=0.005) and disease duration (OR 1.06; 95% CI 1.01 to 1.11; p=0.020). Baseline predictors for flare within 2 years were ultrasound grey scale synovitis sum score (OR 1.19; 95% CI 1.02 to 1.44; p=0.020) and number of previous bDMARDs (OR 4.07; 95% CI 1.35 to 24.72; p=0.007). CONCLUSION: The majority of real-world patients with RA tapering bDMARDs flared during tapering, with the majority regaining remission after stepwise dose increase. Demographic and imaging parameters (MR-osteitis/ultrasound greyscale synovitis) were independent predictors of immediate flare and flare overall and may be of importance for clinical decision-making in patients eligible for tapering.

AB - OBJECTIVE: To identify predictors of flare in a 2-year follow-up study of patients with rheumatoid arthritis (RA) in sustained clinical remission tapering towards withdrawal of biological disease-modifying anti-rheumatic drugs (bDMARDs). METHODS: Sustained clinical remission was defined as Disease Activity Score for 28 joints (DAS28)-C reactive protein (CRP) ≤2.6 without radiographic progression for >1 year. bDMARDs were tapered according to a mandatory clinical guideline to two-thirds of standard dose at baseline, half of dose at week 16 and discontinuation at week 32. Prospective assessments for 2 years included clinical evaluation, conventional radiography, ultrasound and MRI for signs of inflammation and bone changes. Flare was defined as DAS28-CRP ≥2.6 with ∆DAS28-CRP ≥1.2 from baseline. Baseline predictors of flare were assessed by logistic regression analyses. RESULTS: Of 142 included patients, 121 (85%) flared during follow-up of which 86% regained remission within 24 weeks after flare. Patients that flared were more often rheumatoid factor positive, had tried more bDMARDs and had higher baseline ultrasound synovitis sum scores than those not flaring. For patients on standard dose, predictors of flare within 16 weeks after reduction to two-thirds of standard dose were baseline MRI-osteitis (OR 1.16; 95% CI 1.03 to 1.33; p=0.014), gender (female) (OR 6.71; 95% CI 1.68 to 46.12; p=0.005) and disease duration (OR 1.06; 95% CI 1.01 to 1.11; p=0.020). Baseline predictors for flare within 2 years were ultrasound grey scale synovitis sum score (OR 1.19; 95% CI 1.02 to 1.44; p=0.020) and number of previous bDMARDs (OR 4.07; 95% CI 1.35 to 24.72; p=0.007). CONCLUSION: The majority of real-world patients with RA tapering bDMARDs flared during tapering, with the majority regaining remission after stepwise dose increase. Demographic and imaging parameters (MR-osteitis/ultrasound greyscale synovitis) were independent predictors of immediate flare and flare overall and may be of importance for clinical decision-making in patients eligible for tapering.

KW - arthritis, rheumatoid

KW - inflammation

KW - Magnetic Resonance Imaging

KW - ultrasonography

U2 - 10.1136/rmdopen-2022-002796

DO - 10.1136/rmdopen-2022-002796

M3 - Journal article

C2 - 36549857

AN - SCOPUS:85144568565

VL - 8

JO - RMD Open

JF - RMD Open

SN - 2056-5933

IS - 2

ER -