RA: Psychological State Predicts Disease Flare Following TNF Tapering

hand arthritis
hand arthritis
Based on these results, clinicians should consider assessing functional and mental health states before biologic tapering.
The following article is part of conference coverage from the European League Against Rheumatism (EULAR) Congress 2018 in Amsterdam, The Netherlands. Rheumatology Advisor’s staff will be reporting breaking news associated with research conducted by leading experts in rheumatology. Check back for the latest news from EULAR 2018.

Baseline Disease Activity Score of 28 joints (DAS28) and mental health states both predicted flare events in patients with rheumatoid arthritis (RA) with low disease activity, according to data presented at the European League Against Rheumatism (EULAR) Congress held in Amsterdam, June 13 to 16, 2018.1

“[Depression] is an independent predictor for flare in patients with active disease and is negatively associated with remission,”2 the researchers wrote.1 “To date, there are no studies directly addressing the role of depression, anxiety, or low mood in predicting flares in patients tapering their biological therapy.”

The researchers conducted a post-hoc analysis of the OPTTIRA trial,3 a multicenter prospective randomized open label study investigating anti-TNF tapering in established patients with RA with sustained low disease activity.

Researchers collected baseline patient-reported outcomes, including the Health Assessment Questionnaire Disability Index (HAQ-DI), EuroQol 5-dimension scale (EQ-5D), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and 36-Item Short Form Health Survey (SF-36), including the Mental Health Index (MHI) component.

Flare was the primary outcome, defined as an increase in DAS28 ≥0.6 and at least 1 additional swollen joint. The researchers used logistic regression to identify patient-reported outcomes that predict flare, adjusting for baseline covariates (age, gender, treatment group, DAS28, and BMI).

In the study, 97 participants were randomly assigned to a group of either a 33% or 66% tapering of their anti-TNF dose. The majority of the participants were on methotrexate in combination with anti-TNF therapy (n=67; 69%). The median disease duration was 11 years (interquartile range, 7 to 17 years).

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Of the 97 participants, 73 (75%) fulfilled DAS28 remission criteria (DAS28 <2.6). The median SF-36 MHI score was 84. Depression was found in 11% of patients using a cutoff score of ≤56. A total of 41 participants (42%) experienced flare.

Baseline DAS28 score was associated with flare, and remained significant after adjusting for covariates (hazard ratio [HR], 1.96; 95% CI, 1.18-3.24; P =.01). Disability (SF-36 physical component), fatigue (FACIT-F), and mental health (SF-36 MHI) predicted flare in univariate models. In multivariate analyses, only MHI score remained a statistically significant independent predictor of flare (HR per 10 units, 0.74; 95% CI, 0.60-0.93; P =.01).

“Baseline DAS28 and mental health predict flare events in patients [with low disease activity] who taper their anti-TNF agents,” the researchers wrote. “Other psychological and functional states, measured by patient-reported outcome, do predict flare events, although the effect size is small and does not persist when adjusting for known predictors.”

The researchers concluded that based on these results, clinicians should consider assessing functional and mental health states before biologic tapering.

For more coverage of EULAR 2018, click here. 


  1. Bechman K, Sin FE, Ibrahim F, et al. Psychological and functional states predict disease flare following TNF inhibitor tapering in patients with rheumatoid arthritis: a post-hoc analysis of data from the optimizing TNF tapering in RA (OPTTIRA) cohort. Presented at: European League Against Rheumatism (EULAR) Congress 2018; June 13-16, 2018; Amsterdam, The Netherlands. Abstract THU0115.
  2. Michelsen B, Kristianslund EK, Sexton J, et al. Do depression and anxiety reduce the likelihood of remission in rheumatoid arthritis and psoriatic arthritis? Data from the prospective multicentre NOR-DMARD study. Ann Rheum Dis. 2017;76(11):1906-1910.
  3. Ibrahim F, Lorente-Cánovas B, Doré CJ, et al. Optimizing treatment with tumour necrosis factor inhibitors in rheumatoid arthritis—a proof of principle and exploratory trial: is dose tapering practical in good responders?Rheumatology. 2017;56(11):2004-2014.