Neutralizing Anti-Drug Antibodies Linked to Worse Disease Activity in Inflammatory Arthritis

Patients with inflammatory arthritis (IA) who had neutralizing anti-drug antibodies (nADAb) reported worse disease activity, physical function, and inflammatory markers when compared with patients without nADAb. Further research examining a possible association between smoking, which was found more frequently in nADAb-positive patients, is warranted, according to a study published in Springer.¹

“Over the course of the last few decades, the tumor necrosis factor inhibitors (TNFi) together with the implementation of a treat-to-target strategy have led to far better treatment outcomes for patients with IA,” investigators stated. “However, some patients still experience treatment failure and in some of these patients this may be related to the development of anti-drug antibodies against TNFi (ADAb). ADAb formation may not only be associated with reduced clinical efficacy, but also higher risk of adverse events like eg, infusion reactions.”

Patients with IA (including rheumatoid arthritis [RA], psoriatic arthritis [PsA], and ankylosing spondyloarthritis [AS]) from Sørlandet Hospital Kristiansand, Norway, who were treated with TNFi were enrolled in the study. Information on demographics, such as age, gender, disease duration, smoking status, body mass index (BMI), employment status, and treatment history, and patient-reported outcome measures (PROs) was collected. nADAb was assessed via a reporter gene assay. nADAb-positive and -negative patients were compared using unadjusted analyses, adjusted logistic regression, and general linear models.

In total, 282 patients were included in the study (114 RA, 99 AS, and 69 PsA), with 11 patients identified as nADAb. Among nADAb-positive patients, the median (IQR) TNFi trough level was 1.6 mg/l for infliximab (n = 9), 2.0 mg/l for etanercept (n = 1), and 4.4 (1.8, 7.7) mg/l for adalimumab (n = 1). Demographics were similar among nADAb-positive and -negative groups.

Patients in the nADAb cohort experienced worse joint pain and scored worse in the Health Assessment Questionnaire (HAQ), patient’s global assessment, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BADFI), and the Short-Form-36 (SF-36) physical functioning scale when compared with nADAb-negative patients (p < 0.04, adjusted analyses).

Further, the Simplified Disease Activity Index (SDAI), Maastricht Ankylosing Spondylitis Enthesitis score, and the 28-joint Disease Activity Score (DAS28) were significantly worse in the nADAb-positive cohort (p < 0.04, adjusted analyses). Laboratory markers of inflammation, such as C-reactive protein, circulating peripheral leukocytes, and serum calprotectin were also higher in this patient population (p ≤ 0.001). A significantly higher number of nADAb-positive patients were smokers (46% vs 15%, respectively) in both unadjusted and adjusted analyses (p ≤ 0.008).

The cross sectional, observational design and a lack of information on pack years of smoking limited the study. However, investigators believe the results of the study may be used to generate future hypotheses. Conversely, the study was strengthened by the detailed panel of demographics and disease-activity measures evaluated, which is uncommon in other nADAb research. It was also one of the first studies to assess the impact smoking has on nADAb.

“The association between smoking and nADAb positivity warrants further examination, preferably in a randomized controlled trial, to explore if causality may be established,” investigators concluded.

Reference:

Michelsen B, Berget KT, Kavanaugh A, Haugeberg G. Association between TNFi anti-drug antibodies, smoking, and disease activity in patients with inflammatory arthritis: Results from a Norwegian cross-sectional observational study [published online ahead of print, 2022 May 20]. Rheumatol Ther. 2022;10.1007/s40744-022-00464-7. doi:10.1007/s40744-022-00464-7