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

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. Supplementary Information The online version contains supplementary material available at 10.1007/s40744-021-00401-0.

Rheumatoid arthritis as a clinical and immunological syndrome: focus on the seronegative subtype of the disease

“…Анти-В-клеточная терапия с использованием моноклональных антител к CD20 (ритуксимаб) более эффективна у серопозитивных, чем у серонегативных пациентов с РА [114][115][116][117]. Сходные данные получены в отношении абатацепта (блокатор ко-стимуляции Т-клеток) [118][119][120]. Связи между эффективностью терапии ингибиторами ИЛ-6 (тоцилизумаб) и серопозитивностью по РФ/АЦЦП не выявлено [120].…”

“…Сходные данные получены в отношении абатацепта (блокатор ко-стимуляции Т-клеток) [118][119][120]. Связи между эффективностью терапии ингибиторами ИЛ-6 (тоцилизумаб) и серопозитивностью по РФ/АЦЦП не выявлено [120]. Роль серопозитивности РФ/АЦЦП в отношении эффективности ингибиторов янус-киназы (JAK, Janus kinase) нуждается в дальнейших исследованиях [121][122][123].…”

ACPA-negative rheumatoid arthritis: From immune mechanisms to clinical translation

“…ACPA + RA patients displayed significant improvement in outcomes with abatacept or rituximab treatments, whereas no difference or a better clinical response was observed in ACPA – RA patients treated with tocilizumab or tofacitinib or TNF-α inhibitors. 76 , 77 However, the involvement of adaptive immunity should not be ignored in ACPA – RA, especially the specific pathogenic adaptive immune cell subsets as well as newly identified autoantibodies.…”

ACCP-negative rheumatoid arthritis – clinical and immunological features

“…Он в большей степени воздействует на JAK-1 и JAK-3 [192]. Не выявлено различий по эффективности терапии ТОФА между АЦЦП-негативными и АЦЦП-позитивными больными РА [193]. При этом у серонегативных пациентов «выживаемость» ТОФА в течение 3 лет выше, чем у серопозитивных [170].…”