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20-05-2022 | TNF inhibitors | Adis Journal Club | Article

Rheumatology and Therapy

Association between TNFi anti-drug antibodies, smoking, and disease activity in patients with inflammatory arthritis: Results from a Norwegian cross-sectional observational study


Authors: Brigitte Michelsen, Kristine Thomassen Berget, Arthur Kavanaugh & Glenn Haugeberg



We aimed to compare demographics and clinical characteristics between patients with inflammatory arthritis (IA) with vs. without neutralizing anti-drug antibodies (nADAb) against tumor necrosis factor inhibitors (TNFi). A secondary aim of the study was to explore if current smokers were more frequently nADAb-positive.


TNFi-treated outpatients with IA were recruited and a broad range of disease activity measures were assessed. nADAb were assessed using a reporter gene assay. Comparisons between nADAb-positive and -negative patients were done in unadjusted analyses as well as in adjusted logistic regression and general linear models.


A total of 282 patients with IA currently under treatment with TNFi were included. nADAb were identified in 11 patients (nine treated with infliximab, one with etanercept and one with certolizumab pegol). Patients with nADAb reported significantly worse joint pain, patient’s global assessment, Health Assessment Questionnaire, Bath Ankylosing Spondylitis Disease Activity/Functional Index and Short-Form-36 physical functioning scale score than patients without nADAb (p < 0.04, adjusted analyses). 28-joint Disease Activity Score, Simplified Disease Activity Index and Maastricht Ankylosing Spondylitis Enthesitis score were also significantly worse in the nADAb-positive patients (p < 0.04, adjusted analyses), as were serum calprotectin, C-reactive protein and numbers of circulating peripheral leukocytes (p ≤ 0.001). A significantly higher proportion of nADAb-positive patients were current smokers (46 vs. 15%), in unadjusted as well as adjusted analyses (p ≤ 0.008).


nADAb-positive patients were more frequently smokers and had significantly worse disease activity, physical function, and inflammatory markers, than patients without nADAb. The association between smoking and nADAb positivity warrants further examination.

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Key Summary Points

Real-life studies on the clinical impact of neutralizing TNFi anti-drug antibodies (nADAb) including a broad range of disease activity metrics are needed, as well as studies exploring the impact of smoking on formation of nADAb.

The study included patients with inflammatory arthritis treated with TNF inhibitors as part of standard care.

nADAb-positive patients had higher disease activity, including serum calprotectin, and worse physical function than nADAb-negative patients. Furthermore, an association between nADAb positivity and current smoking was found.

nADAb positivity may preclude treatment efficacy in TNFi-treated patients.