Baseline Anti-Citrullinated Protein Antibody Status and Response to Abatacept or Non-TNFi Biologic/Targeted-Synthetic DMARDs: US Observational Study of Patients with RA

Leslie R Harrold; Sean E Connolly; Keith Wittstock; Joe Zhuo; Sheila Kelly; Thomas Lehman; Ying Shan; Sabrina Rebello; Lin Guo; Vadim Khaychuk

doi:10.1007/s40744-021-00401-0

Baseline Anti-Citrullinated Protein Antibody Status and Response to Abatacept or Non-TNFi Biologic/Targeted-Synthetic DMARDs: US Observational Study of Patients with RA

Rheumatol Ther. 2022 Apr;9(2):465-480. doi: 10.1007/s40744-021-00401-0. Epub 2021 Dec 23.

Authors

Leslie R Harrold^{1

2}, Sean E Connolly³, Keith Wittstock⁴, Joe Zhuo⁵, Sheila Kelly³, Thomas Lehman³, Ying Shan⁶, Sabrina Rebello⁷, Lin Guo⁶, Vadim Khaychuk⁸

Affiliations

¹ CorEvitas, LLC, Waltham, MA, USA. lharrold@corevitas.com.
² University of Massachusetts Medical School, Worcester, MA, USA. lharrold@corevitas.com.
³ Bristol Myers Squibb, Princeton, NJ, USA.
⁴ US Immunology, Bristol Myers Squibb, Princeton, NJ, USA.
⁵ Worldwide Health Economics and Outcomes Research, Bristol Myers Squibb, Princeton, NJ, USA.
⁶ Department of Biostatistics, CorEvitas, LLC, Waltham, MA, USA.
⁷ CorEvitas, LLC, Waltham, MA, USA.
⁸ US Medical Immunology and Fibrosis, Bristol Myers Squibb, Princeton, NJ, USA.

Abstract

Introduction: Patients with rheumatoid arthritis (RA) may respond to treatments differently based on their underlying serology and biomarker status, but real-world data comparing treatment responses to abatacept versus other non-TNFi biologic or targeted-synthetic DMARDs by anti-citrullinated protein antibody (ACPA) status remain limited. We assessed the association between ACPA status and response to treatment in patients with RA.

Methods: Adults from CorEvitas' RA Registry were identified who initiated abatacept, rituximab, tocilizumab, or tofacitinib, and had ACPA measured at/prior to treatment initiation and at the 6-month follow-up visit. Three cohorts were included: abatacept/rituximab (2006-2019), abatacept/tocilizumab (2010-2019), and abatacept/tofacitinib (2012-2019). Patient characteristics at initiation were compared by ACPA status (positive [+], anti-cyclic citrullinated peptide-2 [anti-CCP2] ≥ 20 U/ml; negative [-], anti-CCP2 < 20 U/ml). Outcomes over 6 months: changes in Clinical Disease Activity Index (CDAI), modified Health Assessment Questionnaire (mHAQ), patient global assessment (PGA) scores, and proportion of patients achieving a clinical response. Adjusted mean differences and odds ratios were estimated using mixed-effects linear regression models.

Results: Overall, 982 abatacept, 246 rituximab, 404 tocilizumab, and 429 tofacitinib initiators were identified. ACPA+ (vs. ACPA-) patients had longer disease duration and more erosive disease. During most time periods adjusted mean changes in CDAI, mHAQ, and PGA scores and the proportion of patients achieving a clinical response were significantly higher for ACPA+ versus ACPA- patients initiating abatacept. Adjusted mean change in PGA score and patient fatigue were significantly higher for ACPA+ versus ACPA- patients initiating rituximab. No significant differences were seen by ACPA status for patients initiating tocilizumab or tofacitinib.

Conclusions: Patients who initiated abatacept or rituximab and were ACPA+ had a greater clinical response at 6-month follow-up post index compared to patients who were ACPA- treated with the same biologic.

Keywords: Anti-cyclic citrullinated antibodies; Biological therapy; Disease-modifying antirheumatic drugs; Outcome assessment; Rheumatoid arthritis.