Background/Purpose:  To determine predictive factors of disease flares, including drug trough serum levels and anti-drug antibodies (Ab) in patients with rheumatoid arthritis (RA) or polyarticular psoriatic arthritis (PsA) in clinical remission (CR) or low disease activity (LDA) receiving TNF inhibitors during a 1-year follow-up.

Methods: Prospective, multicentre study of RA and PsA patients attended in 3 hospital outpatient clinics (Catalonia, Spain) treated with ADA, ETN or IFX for ≥3 months in CR or LDA measured by DAS28-ESR at ≥2 consecutive visits. Ab and trough serum levels (ELISA Kit Promonitor®, Progenika SA, Spain) were determined at 0, 4, 8 and 12 months. Disease flare was defined as DAS28>3.2 and a delta DAS28 > 0.6 during the 1 year follow-up compared with visit 0.Variables collected: demographic data; disease activity, diagnosis; disease duration; biologic drug; reduced dose, and concomitant csDMARD therapy. Differences between patients with and without disease flare were studied by univariate analysis. Associations between baseline variables and disease flares according to TNFi used were established using multivariate logistic regression analysis.

Results:  187 patients (RA 103 [57%], PsA 81 [43%]), 66% female, mean age 57±12 years, were included. 138 (74%) patients were in CR, 49 (26%) were on LDA, 69 ADA, 83 ETN and 35 IFX. Mean treatment duration was 60±41 months. Thirty-three out of 166 patients (19.9%) who completed follow-up had a disease flare (10 ADA, 13 ETN, 10 INF), 15 at month 4, 13 at month 8 and 5 at month 12. Six patients developed Ab (3 ADA, 3 INF): 3 at visit 0 and 3 during follow-up, of whom five had a disease flare. Patients with disease flares had lower mean baseline trough serum TNFi levels although the difference was significant only for ADA: 1.7 (1.1-2.7) μ/ml vs. 7.1 (3.5-11.4) p<0.01, higher baseline DAS28 (2.5±0.7 vs. 2.0±0.6 p<0.01), and a lower frequency of remission (54.5% vs. 78.9% p<0.01). In ADA-treated patients, but not in those treated with ETN and INF, drug serum levels at baseline were associated with disease flare in the logistic regression analysis (AUC 0.919). No other factors associated with disease flare were identified. During flares, trough serum levels of the three TNFi decreased in comparison with baseline values (median ADA 1.7 vs. 0.1, INF 1.3 vs. 0 and ETN 1.9 vs. 0.3. although the difference was significant only for ETN (p<0.01).

Conclusion:  Over a one-year follow up, disease flares were observed in 20%of RA and PsA patients treated with TNFi for a prolonged period who achieved clinical remission/low disease activity. Ab explained only 15% of disease flares. A higher DAS28 and lower drug trough serum levels of ADA at baseline (but not ETN or INF) were associated with disease flare. During disease flares, there was a pronounced decrease in TNFi drug serum levels.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/drug-trough-serum-levels-rather-than-antidrug-antibodies-explain-disease-flares-in-patients-with-rheumatoid-arthritis-and-psoriatic-arthritis-treated-with-tnf-inhibitors-in-clinical-remissionlow-dise/