Ab0498 predictive Biomarkers of Tofacitinib Therapy in Rheumatoid Arthritis: Real World Data From Malaysian Rheumatology Biologic Registry (Marble)

Abstract

BackgroundTargeted synthetic therapies brought revolutionary progress in rheumatoid arthritis (RA) management and culminated a paradigm shift over a decade. However, only a subset of patients responded clinically and achieved sustained remission. The interindividual factors may vary resulting in failure of therapeutic target and clinical response.ObjectivesWe investigated the clinical and sociodemographic predictors of Tofacitinib response in RA patients at three, six and twelve months.MethodsThis retrospective study included 164 RA patients from the nationwide MARBLE registry who received Tofacitinib. Patients’ clinical data were extracted from medical records. The response to Tofacitinib in terms of clinical remission, low disease activity (LDA) and DAS28 improvement (EULAR response) were measured at baseline, 3 months, 6 months and 12 months of therapy based on disease activity score (DAS)28 for RA. Factors predicting treatment response were analysed using binary logistic regression analysis.ResultsOur data revealed that at 3-month, 6-month and 12-month of Tofacitinib treatment, 17.7%(n=29), 67.7%(n=111) and 60.4%(n=99) RA patients achieved low disease activity/clinical remission. Further analysis demonstrated that anti-cyclic citrullinated peptide antibody (anti-CCP)-positivity and joint erosion were independently associated with unsatisfactory EULAR response (ie., anti-CCP at 3-month, OR=2.270, p<0.05; 6-month, OR=7.773, p<0.0001; and 12-month, OR=4.645, p<0.0001). Lower frequencies of clinical remission were associated with the presence of erosive joint throughout the three follow-up periods of treatment (OR=2.040 to 3.868; p<0.05), while only anti-CCP positive was found to be significantly associated with lower frequencies of LDA at 6-month and 12-month of treatment (anti-CCP positive, 6-month OR=3.659, p<0.0001 and 12-month OR=2.130; p<0.0001)ConclusionOur data suggest that joint erosion and anti-CCP positivity are strong predictive biomarkers for lower achievement of clinical remission, LDA and satisfactory EULAR response in patients with RA receiving tofacitinib treatment.References[1]M. Sugawara YF, A. Noguchi, S. Tanimura, Y. Shimizu, I. Nakagawa MY, N. Abe, M. Kono, M. Kato, K. Oku, O. Amengual IY, H. Takahashi, T. Atsumi. Prediction of the intolerance or non-responder to Janus kinase inhibitors in patients with rheumatoid arthritis: a preliminary retrospective study with integrative cluster analysis. Clinical and experimental rheumatology. 2022;40:1674-80.[2]Bird P, Hall S, Nash P, Connell CA, Kwok K, Witcombe D, et al. Treatment outcomes in patients with seropositive versus seronegative rheumatoid arthritis in Phase III randomised clinical trials of tofacitinib. RMD open. 2019;5(1):e000742.[3]van Vollenhoven RF, Lee EB, Fallon L, Zwillich SH, Wilkinson B, Chapman D, et al. Tofacitinib in Rheumatoid Arthritis: Lack of Early Change in Disease Activity and the Probability of Achieving Low Disease Activity at Month 6. Arthritis care & research. 2019;71(1):71-9AcknowledgementsSpecial thanks to Director General of Health Malaysia for his permission to present this article and International Medical University Research Grant [PHMS I-2021 (04)] for financial support.Disclosure of InterestsNone Declared.