DAS28 and Mental Health Could Predict Disease Flare in Patients Tapering Anti-TNF Drugs


Currently, beyond the evaluation of a patient’s 28-joint disease activity score (DAS28), there are no standard methods to determine whether patients will respond well to dose reduction of anti–tumor necrosis factor therapy.

Dose tapering or discontinuation of anti—tumor necrosis factor (anti-TNF) therapy has been shown to be safe and effective in certain patients with rheumatoid arthritis (RA). However, beyond the evaluation of a patient’s 28-joint disease activity score (DAS28), there are no standard methods to determine whether patients will respond well to dose reduction.

Researchers have identified mental health as a possible marker for disease flare due to the connection between poor mental health and its possible influence on symptom reporting and interference with self-management behavior. In addition, poor mental health has been associated with increased pain and fatigue, as well as higher disease activity in patients with RA.

A study newly published in Rheumatic and Musculoskeletal Diseases sought to evaluate whether fatigue, baseline mental health (assessed via depression, anxiety, or low mood), and functional states (as measured by self-reported questionnaires) can indicate the risk of flares in patients who are tapering therapy.

Researchers analyzed results from the Optimizing TNF Tapering in RA (OPTTIRA) trial, a multicenter, prospective, randomized, open-label study that investigated anti-TNF tapering in patients with RA who were in sustained low disease activity (LDA).

The study comprised 2 phases: the randomized, controlled, open-label, proof-of-principle phase (from month 0 to month 6), followed by the open, exploratory phase (month 6 to month 12) for patients who completed the initial trial period.

Between 2011 and 2013, 244 patients were screened, 103 were randomized, and 97 accepted their allocated treatment. The majority of patients participating in the study were receiving methotrexate in combination with their anti-TNF therapy (n = 67, 69%) and the median disease duration was 11 years (interquartile range, 7-17), with 73 patients (75%) fulfilling DAS28 remission criteria (a DAS28 score of less than 2.6).

In the first phase of the study, 3 patients who tapered anti-TNF therapy by 33% (experimental group 1) and 6 patients who tapered anti-TNF therapy by 66% (experimental group 2) flared, versus 8 patients in the control arm.

In the second phase, flares were observed in 9 patients in experimental group 1 and 4 patients in experimental group 2 who continued to taper therapy until complete termination of treatment. Of the control group, 3 patients who tapered anti-TNF treatment by 33% and 8 patients who tapered anti-TNF agents by 66% flared.

Overall, a higher DAS28 score at the start of the study was associated with an increased risk of flare. The association remained significant even after adjusting for co-variates (HR, 1.96; 95% CI, 1.18-3.24; P =.04).

A fatigue and a short-form mental health survey (SF-36) also predicted flare in univariate models, but when analyses were adjusted, only mental health continued to be a statistically significant predictor of flare (adjusted HR per 10 units, 0.74; 95% CI, 0.60-0.93; P =.01).

The researchers concluded that baseline depression as measured by SF-36 mental health scale, as well as DAS28, can independently predict flare events in patients with sustained LDA who taper anti-TNF therapy. Based on the findings of the analysis, researchers have recommended that an assessment of mental health and functional status should be considered prior to beginning dose reduction in patients with RA.


Bechman K, Sin EF, Ibrahim F, et al. Mental health, fatigue and function are associated with increased risk of disease flare following TNF inhibitor tapering in patients with rheumatoid arthritis: an exploratory analysis of data from the Optimizing TNF Tapering in RA (OPTTIRA) trial. RMD Open. 2018; 4(1):e000676. doi: 10.1136/rmdopen-2018-000676.

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