Date: Monday, November 6, 2017
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: The JAK1 selective inhibitor filgotinib (GLPG0634, GS-6034) was efficacious as both add-on to methotrexate (MTX) and monotherapy in two 24-week phase 2B studies in active rheumatoid arthritis (RA) patients with inadequate response to MTX (DARWIN 1 and 2)1. We evaluated the utility of a Multi Biomarker Disease Activity (MBDA) score in relation to clinical disease activity assessments in patients treated with filgotinib.
Methods: Serum samples from RA patients receiving either a stable dose of MTX and PBO, filgotinib 100mg or 200mg QD (DARWIN 1), or placebo (PBO) or filgotinib monotherapy at 100mg or 200mg once daily (QD, DARWIN 2), were collected and analyzed at baseline and week 12 with the MBDA test (Crescendo Biosciences, CA, US). Spearman’s rank correlations between MBDA score and clinical measures (e.g. DAS28-CRP, SJC28, TJC28) were estimated at baseline and week 12 and for their changes from baseline to week 12.
Results: At baseline, median MBDA scores were the same for both DARWIN 1 and 2 studies (58) with statistically significant correlation observed between MBDA score and DAS28-CRP (r=0.43, r=0.48, respectively, both p<0.001). There was weak correlation of MBDA score with SJC28 and TJC28 for DARWIN 1 (r=0.2, 0.11; p<0.01, ns) and DARWIN 2 (r=0.19, 0.17; both p<0.05). At week 12, statistically significant correlations were observed in 200mg filgotinib monotherapy cohort between MBDA score and DAS28, SJC28, and TJC28 (r=0.6, 0.36, 0.46; p<0.001, <0.01, <0.001) that were less so in 100mg (r=0.33, 0.16, 0.15; p<0.05, ns, ns) and PBO (r=0.49, 0.40, 0.22; p<0.001, <0.01, ns) treatment groups. When comparing change from baseline at week 12, the MBDA only correlated to DAS28-CRP for 200mg filgotinib monotherapy and PBO groups (r=0.36, 0.39; p<0.01). There was no statistically significant correlation between MBDA and clinical measures (or between their changes from baseline) for filgotinib on a background of MTX at week 12.
Conclusion: The MBDA score significantly correlated with disease activity measures in subjects treated with filgotinib as monotherapy for 12 weeks. Despite similar baseline associations and treatment efficacy no correlation was observed between MBDA score and DAS28-CRP for filgotinib with MTX add-on.
References: 1Westhovens R, et al. Ann Rheum Dis 2017; 76: 998-1008; Kavanaugh A, et al. Ann Rheum Dis 2017; 76: 1009–1019.
Figure: Scatter plot of MBDA score vs. DAS28-CRP at week 12 for DARWIN 1 and DARWIN 2
To cite this abstract in AMA style:Genovese MC, Galien R, Pan Y, Van der Aa A, Jamoul C, Harrison P, Tasset C, Goyal L, Li W, Tarrant J. Correlation of Multi-Biomarker Disease Activity Score with Clinical Disease Activity Measures for the JAK1-Selective Inhibitor Filgotinib As Monotherapy and in Combination with Methotrexate in Rheumatoid Arthritis Patients [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/correlation-of-multi-biomarker-disease-activity-score-with-clinical-disease-activity-measures-for-the-jak1-selective-inhibitor-filgotinib-as-monotherapy-and-in-combination-with-methotrexate-in-rheumat/. Accessed November 16, 2019.
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