Impact of anti-citrullinated protein antibody on tumor necrosis factor inhibitor or abatacept response in patients with rheumatoid arthritis

Tymms, Kathleen; Butcher, Belinda; Smith, Tegan; Littlejohn, Geoffrey

doi:10.5152/eurjrheum.2020.20024

Cited by 4 publications

(3 citation statements)

References 17 publications

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“…However, short-term follow-up period and low proportions of concomitant use of MTX (59.7–62.4%) and corticosteroid (37.0–38.5%) may affect the outcomes, resulting in a less pronounced improvement of CDAI (− 9.85 for abatacept and − 8.53 for TNFi) compared to our study. The longitudinal CDAI changes reported in another study for abatacept in ACPA-positive patients were similar to our study; −8.53 and −19.01 at 6 and 12 months, respectively [ 34 ].…”

Section: Discussionsupporting

confidence: 89%

Efficacy of Abatacept Versus Tumor Necrosis Factor Inhibitors in Anti-citrullinated Protein Antibody-Positive Patients with Rheumatoid Arthritis: Results from a Korean Nationwide Biologics Registry

Kim

Lee

et al. 2022

Rheumatol Ther

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Introduction To compare the efficacy of abatacept and tumor necrosis factor inhibitor (TNFi) in patients with anti-citrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA) and identify those who benefit most from abatacept over TNFi. Methods This observational study identified RA patients who were ACPA-positive and initiated abatacept or TNFi from the Korean College of Rheumatology Biologics and Targeted therapy registry. Propensity score (PS) matching was performed to balance baseline confounding in abatacept- or TNFi-treated patients. The major endpoints were changes in Clinical Disease Activity Index (CDAI) and achievement of CDAI remission/low disease activity after 1 year of treatment. Subgroup analysis was mainly performed stratified by prior biologics use. Results A total of 291 PS-matched, ACPA-positive RA patients who initiated abatacept ( n = 97) and TNFi ( n = 194) were included. From baseline CDAI scores of 26.52 in the abatacept group and 26.38 in the TNFi group, the mean changes after 1 year were − 16.78 and − 13.61, respectively (difference − 3.17, p = 0.020). The proportion of patients achieving CDAI remission/low disease activity was 68.0% with abatacept and 52.6% with TNFi ( p = 0.013). In the subgroup analysis, patients that were biologics-naïve had better improvement in CDAI after treatment with abatacept than TNFi (difference − 3.35, p = 0.021). Conclusions This real-world study suggests that abatacept may have better clinical response compared to TNFi in patients with established ACPA-positive RA, especially in those that were biologics-naïve. Supplementary Information The online version contains supplementary material available at 10.1007/s40744-022-00467-4.

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Section: Discussionsupporting

confidence: 89%

Efficacy of Abatacept Versus Tumor Necrosis Factor Inhibitors in Anti-citrullinated Protein Antibody-Positive Patients with Rheumatoid Arthritis: Results from a Korean Nationwide Biologics Registry

Kim

Lee

et al. 2022

Rheumatol Ther

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“…At the time of collection of the present data only one Janus kinase (JAK) inhibitor (tofacitinib) [ 29 ] and one IL-6 inhibitor (tocilizumab) [ 30 ] were FDA approved; consequently patients treated with other JAK or IL-6 inhibitors were not included. Additionally, selection bias should be considered as a limitation due to prescribing patterns potentially being influenced by serological status – the impact of serological status in the efficacy of some bDMARDs has gained increasing evidence [ 31 – 34 ]; as such, selection bias may have increased during the study period. As with all real-world studies, patients enrolled in the registry may not fully reflect patients with RA observed in other regions or areas of general practice.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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.

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“…A total of 2052 patients were included of which 1415 were in the TNFis cohort ( n = 1053 ACPA positive) and 637 in the Abatacept cohort ( n = 445 ACPA positive). The baseline ACPA score was associated with an improvement in clinical response using a measure of clinical disease-activity index at 12 months for Abatacept therapy, but not for TNFis therapy [ 172 ].…”

Section: Diagnostic and Therapeutic Potential Of Citrullinationmentioning

confidence: 99%

Citrullination in the pathology of inflammatory and autoimmune disorders: recent advances and future perspectives

Ciesielski

Biesiekierska

Panthu

et al. 2022

Cell. Mol. Life Sci.

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Numerous post-translational modifications (PTMs) govern the collective metabolism of a cell through altering the structure and functions of proteins. The action of the most prevalent PTMs, encompassing phosphorylation, methylation, acylations, ubiquitination and glycosylation is well documented. A less explored protein PTM, conversion of peptidylarginine to citrulline, is the subject of this review. The process of citrullination is catalysed by peptidylarginine deiminases (PADs), a family of conserved enzymes expressed in a variety of human tissues. Accumulating evidence suggest that citrullination plays a significant role in regulating cellular metabolism and gene expression by affecting a multitude of pathways and modulating the chromatin status. Here, we will discuss the biochemical nature of arginine citrullination, the enzymatic machinery behind it and also provide information on the pathological consequences of citrullination in the development of inflammatory diseases (rheumatoid arthritis, multiple sclerosis, psoriasis, systemic lupus erythematosus, periodontitis and COVID-19), cancer and thromboembolism. Finally, developments on inhibitors against protein citrullination and recent clinical trials providing a promising therapeutic approach to inflammatory disease by targeting citrullination are discussed.

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Impact of anti-citrullinated protein antibody on tumor necrosis factor inhibitor or abatacept response in patients with rheumatoid arthritis

Cited by 4 publications

References 17 publications

Efficacy of Abatacept Versus Tumor Necrosis Factor Inhibitors in Anti-citrullinated Protein Antibody-Positive Patients with Rheumatoid Arthritis: Results from a Korean Nationwide Biologics Registry

Efficacy of Abatacept Versus Tumor Necrosis Factor Inhibitors in Anti-citrullinated Protein Antibody-Positive Patients with Rheumatoid Arthritis: Results from a Korean Nationwide Biologics Registry

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

Citrullination in the pathology of inflammatory and autoimmune disorders: recent advances and future perspectives

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