Background/Purpose: Traditional efficacy endpoints of disease activity (DA) in studies of anti-rheumatic drugs can be confounded by subjective (patient-/physician-reported) assessments, comorbidities, and pre-existing joint damage. Limitations of these efficacy endpoints have prompted regulatory authorities to encourage use of biomarkers as endpoints in clinical trials evaluating biosimilars. The multi-biomarker disease activity (MBDA; Vectra^® DA, Myriad Genetics, Inc.) score provides a validated, objective, and composite measure of DA in patients with RA based upon concentrations of 12 serum protein biomarkers. An exploratory analysis was performed to compare MBDA scores between treatment groups in a randomized, double-blind trial to determine the utility of this approach as an assessment for biosimilarity. Biosimilar adalimumab-afzb (ADL-afzb; PF‑06410293) was compared with reference adalimumab sourced from the European Union (ADL-EU; AbbVie Deutschland GmbH & Co KG, Ludwigshafen, Germany) in adult patients with active moderate to severe RA inadequately responsive to MTX (Fleischmann et al. Arthritis Res Ther. 2018;20:178).

Methods: All 597 patients in the study met the 2010 ACR/EULAR classification criteria for RA and had disease duration of ≥4 months. Patients were randomized 1:1 to ADL‑afzb (n=297) or ADL-EU (n=300) (40-mg subcutaneously every other week) and continued to receive MTX. The concentrations of 12 biomarkers were measured and combined using the Vectra^® DA algorithm. Mean MBDA scores (low, ≤29; moderate, 30–44; high, >44–100) were calculated at baseline and at weeks 6, 12, and 26. Mean MBDA scores were compared between treatment groups. Data were summarized using descriptive statistics in the intent to treat population.

Results: At baseline, mean (± standard deviation [SD]) MBDA scores for ADL-afzb and ADL-EU groups were 57.2 (± 14.44) and 58.3 (± 15.34), respectively. Mean values of MBDA scores were comparable between treatment groups at all measured time points through 26 weeks (Figure). Similar proportions of patients in the ADL-afzb (78.5%) and ADL-EU (81.7%) treatment groups had high MBDA scores ( >44) at baseline; the proportions of patients with high MBDA scores decreased to 45.5% and 41.7%, respectively, at week 26. Mean MBDA scores decreased from baseline in the ADL-afzb and ADL-EU groups by 11.9 and 12.4 at week 6, by 11.7 and 12.4 at week 12, and by 14.3 and 15.5 at week 26, respectively. Mean log-transformed values for each of the individual 12 biomarkers over time up to week 26 were consistently similar between ADL-afzb and ADL-EU groups. MBDA scores correlated with the high-sensitivity CRP (hs-CRP) assay results (Table).

Conclusion: Over 26 weeks, mean values for MBDA scores were similar between the ADL-afzb and ADL-EU groups throughout this randomized, double-blind trial in which the adalimumab biosimilar was compared with its reference product. MBDA score based on 12 serum biomarkers provides a sensitive and objective clinical assessment of biosimilarity that does not require physical examination of the patient or subjective patient global assessment of DA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/use-of-multi-biomarker-disease-activity-scores-to-compare-biosimilar-adalimumab-afzb-pf-06410293-with-eu-sourced-reference-adalimumab-in-a-phase-3-randomized-double-blind-trial-in-patients-with-ac/