Background Anti-TNF therapy has been grown to a standard therapeutic strategy for rheumatoid arthritis (RA). To date, we have developed a multi-biomarker disease activity algorithm (MBDA) as a potential index to provide objective biological information about RA activity. However, the relationship between MBDA and SDAI/CDAI focusing on anti-TNF therapy has not been investigated.
Objectives To determine whether the MBDA score can assess disease activity and therapeutic response in RA patients treated with anti-TNF therapy.
Methods 149 patients who started anti-TNF therapy (50 adalimumab (ADA), 49 etanercept (ETN), 50 infliximab (IFX)) were enrolled. Since two patients were treated with two different anti-TNF therapies, 147 records for unique patients were analyzed. Twelve biomarkers were measured using custom immunoassays on the Meso Scale Discovery MULTI-ARRAY platform and combined in a pre-specified algorithm to generate a MBDA score between 1 and 100 at 0 (baseline), 24, and 52 weeks after induction of anti-TNF therapy. Associations between MBDA score and DAS28/SDAI/CDAI were evaluated by Spearman correlation and by area under the receiver operating characteristic curve (AUROC). MBDA score changes in patients with EULAR responses were compared by Wilcoxon test. Differences in the MBDA/DAS28 relationship between TNF inhibitors were evaluated by fitting linear models models for DAS28 as a function of MBDA score, therapy and an MBDA/therapy interaction term. A model was fit for each combination of two therapies with the therapy term as an indicator variable.
Results At baseline, patients had median age of 60 (interquartile range (IQR) 50-68), DAS28 of 5.7 (5.0-6.5) and disease duration of 60 months (18-168). Methotrexate was used in 86% of cases, at a median dose of 8.0 (8.0-10) mg/week. MBDA scores were correlated with DAS28, SDAI and CDAI (ρ=0.64, 0.57, 0.50 respectively, all p<0.001) and distinguished low and moderate/high disease activity for all three clinical indices (AUROC=0.80, 0.76, 0.76 respectively, all p<0.001). No differences were found in the relationship between the MBDA score and DAS28 between ADA, ETN and IFX (p>0.05 for all comparisons). At 52 weeks, the median change in the MBDA score was greater for patients with moderate EULAR response than those with no response (-21.5 vs -5.5, p<0.001) and greater for those with good response than those with moderate response (-29 vs -21.5, p=0.007).
Conclusions This is the first report regarding the correlation of MBDA with SDAI/CDAI in a cohort receiving anti-TNF therapy. The MBDA score reflects clinical disease activity and therapeutic response. A fully objective biomarker-based disease activity score may have advantages over clinical disease activity indices with subjective components.
Disclosure of Interest S. Hirata: None Declared, D. Haney Employee of: Crescendo Bioscience Inc., G. Cavet Employee of: Crescendo Bioscience Inc., W. Li Employee of: Crescendo Bioscience Inc., N. Sawamukai: None Declared, K. Yamaoka: None Declared, K. Saito: None Declared, Y. Tanaka Grant/Research support from: Bristol-Myers Squibb, Mitsubishi-Tanabe, MSD, Takeda Industrial, Astellas, Eisai, Chugai, Pfizer and Daiichi-Sankyo, Consultant for: Chugai, Mitsubishi-Tanabe, Eisai, Pfizer, Abbott Immunology, Janssen, Takeda Industrial, Astra-Zeneca, Astellas, Asahi-kasei and GlaxoSmithKline