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FRI0100 Determining minimum clinically important change in multi biomarker disease activity score associated with clinical improvement in methotrexate naÏve patients with early rheumatoid arthritis
  1. K Chatzidionysiou1,
  2. AH Hensvold1,
  3. S Saevarsdottir1,
  4. RJ Bolce2,
  5. D Chernoff2,
  6. CC Hwang2,
  7. X Wang2,
  8. AI Catrina1
  1. 1Karolinska University and Institutet, Stockholm, Sweden
  2. 2Crescendo Bioscience Inc., South San Francisco, United States

Abstract

Background The Multi-Biomarker Disease Activity (MBDA) score is a validated tool that quantifies 12 biomarkers to assess disease activity in rheumatoid arthritis (RA) patients. Many studies have demonstrated usefulness of the score for assessing RA disease activity.

Objectives To determine minimum clinically important change in MBDA score (ΔMBDA) from baseline (BL) to Month 3 (M3) associated with clinical improvement (decrease in DAS-ESR >1.2) in early RA patients after initiating methotrexate (MTX).

Methods We evaluated the MBDA test in patients from one of the sites participating in the Solna Epidemiological Investigation of RA (EIRA) cohort. EIRA patients were eligible if they were ≥18 years; RA diagnosis within 12 months of symptom duration; had serum and clinical assessments at BL and M3; and clinical follow-up data in the Swedish Rheumatology Quality Register. Patients naïve to disease modifying anti-rheumatic drugs who received MTX were included. Kruskal-Wallis was used to test the null hypothesis that medians of ΔMBDA scores of 3 EULAR response groups are equal. Receiver operating characteristic (ROC) analysis was performed. The optimal threshold of ΔMBDA associated with DAS28-ESR improvement (decrease in DAS-ESR >1.2 at M3) was determined by Youden criterion maximizing sum of sensitivity and specificity.

Results 176 patients were included: 72% women, mean age 51 (SD: 11.7) years, mean DAS28-ESR score 5.6 (SD: 0.99); 51% had ESR <28 mm/hr, 66% were anti-CCP2+, and 22% received prednisone. Mean BL MBDA score was 56.8 (SD: 14.7) with 8 (5%) patients in low (<30), 29 (16%) patients in moderate (30–44) and 139 (79%) patients in high MBDA disease activity categories. Median MBDA scores for patients with no EULAR response worsened by 2 points and for patients with moderate and good response improved by 12 and 16 points, respectively (p<0.0001 across groups, Fig 1A). Median MBDA scores improved by 10 points for all patients and 15 points in patients with a DAS28-ESR decrease >1.2. The best combination of sensitivity and specificity to achieve a DAS28-ESR decrease >1.2 was provided by a ≥8 point MBDA score improvement (Fig 1B). A similar result was obtained using the bootstrap method. AUROC was 0.77 (95% CI: 0.71, 0.84). 125 patients (71%) had concordance between DAS28-ESR improvement and ΔMBDA improvement at the optimal threshold (Table 1).

Table 1.

Performance Measures (95% CI) Based on Optimal Threshold of ΔMBDA Score from BL to M3 Associated with DAS28-ESR Improvement

Conclusions The optimal threshold of ΔMBDA score associated with a clinically relevant decrease of DAS28 was 8 points. Using this threshold, the MBDA test is informative to detect clinical improvement. Thus, based on these results improvement in MBDA score ≥8 points at M3 after initiating MTX is indicative of meaningful clinical improvement.

Disclosure of Interest K. Chatzidionysiou Consultant for: AbbVie, Pfizer, Eli Lilly, UCB, Roche, A. Hensvold: None declared, S. Saevarsdottir: None declared, R. Bolce Shareholder of: Myriad Genetics, Inc., Employee of: Crescendo Bioscience Inc., D. Chernoff Shareholder of: Myriad Genetics, Inc., Employee of: Crescendo Bioscience Inc., C. Hwang Shareholder of: Myriad Genetics, Inc., Employee of: Crescendo Bioscience Inc., X. Wang Shareholder of: Myriad Genetics, Inc., Employee of: Crescendo Bioscience Inc., A. Catrina Grant/research support from: Roche, Abbvie, Consultant for: BMS, GSK, Pfizer, Roche, Lilly, Abbvie

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