Exploratory analyses of a phase 3 trial comparing adalimumab-afzb with reference adalimumab in patients with rheumatoid arthritis (RA) indicate a multibiomarker disease activity score may be a sensitive and objective assessment of biosimilarity that does not require subjective assessments needed for conventional disease activity measures.
Conventional disease activity efficacy end points typically utilized in studies of antirheumatic drugs may be confounded by subjective (patient-/physician-reported) assessments, comorbidities, and preexisting joint damage, underscoring the need for assessment of alternate end points, such as the use of biomarkers in clinical trials evaluating biosimilars. To evaluate the utility of the multibiomarker disease activity (MBDA) score as an assessment of biosimilarity, an exploratory analysis of the phase 3 randomized, double-blind trial that demonstrated equivalence of the adalimumab biosimilar adalimumab‑afzb (PF‑06410293) to the reference adalimumab sourced from the European Union (adalimumab-EU) in adult patients with active, moderate-to-severe rheumatoid arthritis (RA) inadequately responsive to methotrexate was conducted1,2; the results of this analysis were reported at the American College of Rheumatology (ACR) Convergence 2020 meeting.
Study inclusion criteria consisted of patients who met the 2010 ACR/European League Against Rheumatism classification criteria for RA and had disease duration of ≥4 months.2 Eligible patients were randomized 1:1 to receive adalimumab‑afzb or adalimumab-EU along with methotrexate. The MBDA score was calculated by measuring the concentrations of 12 biomarkers and using the Vectra DA algorithm. Mean values of MBDA scores were calculated at baseline and at weeks 6, 12, and 26, and categorized as low (1-≤29), moderate (30-44), and high (>44-100). Mean MBDA scores were compared between treatment groups.2
A total of 597 patients were included in the analysis; 297 patients received adalimumab-afzb and 300 patients received adalimumab-EU.2 The mean MBDA scores were similar between the groups at all time points assessed. At baseline, mean MBDA scores were 57.2 (standard deviation [SD], ±14.44) in the adalimumab-afzb group and 58.3 (SD, ±15.34) in the adalimumab-EU group; the majority of patients had high (>44) MBDA scores that were comparable between the groups (78.5% and 81.7%, respectively). At week 26, the frequency of high MBDA scores (>44) decreased to 45.5% in the adalimumab-afzb group and 41.7% in the adalimumab-EU group. In the adalimumab-afzb and adalimumab-EU groups, mean MBDA scores decreased from baseline 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. No between-group changes were seen in the concentrations of the individual 12 biomarkers over time. Changes in MBDA scores from baseline correlated positively with changes in high-sensitivity C-reactive protein.2
These results indicate that changes in MBDA scores over time were similar between adalimumab-afzb and adalimumab-EU, which was consistent with results obtained using conventional disease activity measures, leading to the conclusion that the MBDA score may represent a sensitive and objective assessment of biosimilarity that does not require subjective patient global assessment of disease activity.
References
- Fleischmann, et al. Arthritis Res Ther. 2018;20:178.
- Kay J, et al. Arthritis Rheumatol. 2020;72(suppl 10):Abstract 1233.