Dataset Information

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.

SUBMITTER: Harrold LR

PROVIDER: S-EPMC8964884 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

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

Harrold Leslie R LR Connolly Sean E SE Wittstock Keith K Zhuo Joe J Kelly Sheila S Lehman Thomas T Shan Ying Y Rebello Sabrina S Guo Lin L Khaychuk Vadim V

Rheumatology and therapy 20211223 2

<h4>Introduction</h4>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.<h4>Methods</h4>Adults from CorEvitas' RA Registry were id ...[more]

PMID: 34940957

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Project description:IntroductionAnti-cyclic citrullinated peptide (anti-CCP) antibodies are associated with poor prognosis in patients with rheumatoid arthritis (RA). Previous data from randomized controlled trials and clinical practice have shown anti-CCP-positive (+) patients had a better response to treatment with abatacept or tumor necrosis factor inhibitor (TNFi) treatment than those who were anti-CCP negative. This study assessed the association between baseline anti-CCP2 [a surrogate for anti-citrullinated protein antibody (ACPA)] concentration and 6-month treatment responses to abatacept or TNFi in patients with RA.MethodsThis real-world analysis included biologic-experienced patients from CERTAIN (Comparative Effectiveness Registry to study Therapies for Arthritis and Inflammatory CoNditions) who initiated abatacept or TNFi, had prior biologic disease-modifying drug exposure and baseline anti-CCP2 concentration/serostatus and serum samples (baseline and 6 months). Baseline demographics and disease characteristics were compared. Change from baseline at 6 months in Clinical Disease Activity Index (CDAI) score and patient-reported outcomes [PROs: pain, fatigue, patient global assessment (PtGA), modified Health Assessment Questionnaire (mHAQ) score], by baseline anti-CCP2 quartile and binary cut-off (> 10-250 and > 250 U/ml), were evaluated separately in the abatacept and TNFi groups using a linear regression model adjusted for age, sex, CDAI/PROs, comorbidity index, and methotrexate use.ResultsIncluded were 138 abatacept and 137 TNFi initiators who were anti-CCP2+. At baseline, there were significant differences between anti-CCP2 quartiles and mean CDAI, swollen joint count 28, C-reactive protein (CRP), Disease Activity Score 28 (CRP), rheumatoid factor (RF), mHAQ and physician global assessment among abatacept initiators, and in mean RF, mHAQ, and PtGA among TNFi initiators. Among abatacept (but not TNFi) initiators, CDAI numerically improved (p = 0.208) and PROs significantly improved (p < 0.05) with increasing baseline anti-CCP2.ConclusionsIn patients treated with abatacept, not TNFi, higher anti-CCP2 concentrations at baseline were associated with numerically greater improvements in CDAI and significant improvements in PROs after 6 months.Clinical trial numberNCT01625650.

Project description:BackgroundTo assess the risks of malignancies, infections and autoimmune diseases in patients with rheumatoid arthritis (RA) treated with abatacept compared with other biologic (b) disease-modifying antirheumatic drugs (DMARDs) or conventional synthetic (cs)DMARDs, in a US-wide observational RA cohort METHODS: Data were reviewed from patients (≥ 18 years) with RA who were registered with FORWARD, the National Databank for Rheumatic Diseases, and who initiated abatacept, other bDMARDs or csDMARDs between 2005 and 2015. Patients who switched treatment during the study could be allocated to more than one group. The incidence rates (IRs) by treatment were calculated for malignancies, hospitalized infections and autoimmune diseases identified by six monthly questionnaires and medical records. The hazard ratios (HRs) (95% confidence intervals [CIs]) for all outcomes with abatacept compared with other bDMARDs or csDMARDs were determined using marginal structural models adjusted for clinical confounders.ResultsIn the study sample, 1496 initiated abatacept, 3490 initiated another bDMARD and 1520 initiated a csDMARD. The risk of malignancies with abatacept was not statistically significant versus other bDMARDs (HR [95% CI)] 1.89 [0.93, 3.84]) or versus csDMARDs (HR [95% CI] 0.93 [0.20, 4.27]). Patients receiving abatacept versus other bDMARDs were at a lower risk of hospitalized infections (HR [95% CI] 0.37 [0.18, 0.75]); the risk versus csDMARDs was lower with wide CIs (HR [95% CI] 0.31 [0.09, 1.05]). The relative risks for psoriasis were similar between treatment groups (HR [95% CI] 1.46 [0.76, 2.81] and HR [95% CI] 2.05 [0.59, 7.16] for abatacept versus other bDMARDs and versus csDMARDS, respectively). The IR (95% CI) of severe infusion/injection reactions was lower with abatacept compared with other bDMARDs (1.57 [1.11, 2.17] vs 2.31 [1.87, 2.82] per 100 patient-years, respectively).ConclusionsIn this analysis, abatacept was well tolerated and did not result in an overall increased risk of malignancies, infections or autoimmune diseases compared with other bDMARDs or csDMARDs.

Project description:Cycling of biologic or targeted synthetic disease modifying antirheumatic drugs (b/tsDMARDs) in rheumatoid arthritis (RA) patients due to non-response is a problem preventing and delaying disease control. We aimed to assess and validate treatment response of b/tsDMARDs among clusters of RA patients identified by deep learning. We clustered RA patients clusters at first-time b/tsDMARD (cohort entry) in the Swiss Clinical Quality Management in Rheumatic Diseases registry (SCQM) [1999-2018]. We performed comparative effectiveness analyses of b/tsDMARDs (ref. adalimumab) using Cox proportional hazard regression. Within 15 months, we assessed b/tsDMARD stop due to non-response, and separately a ≥20% reduction in DAS28-esr as a response proxy. We validated results through stratified analyses according to most distinctive patient characteristics of clusters. Clusters comprised between 362 and 1481 patients (3516 unique patients). Stratified (validation) analyses confirmed comparative effectiveness results among clusters: Patients with ≥2 conventional synthetic DMARDs and prednisone at b/tsDMARD initiation, male patients, as well as patients with a lower disease burden responded better to tocilizumab than to adalimumab (hazard ratio [HR] 5.46, 95% confidence interval [CI] [1.76-16.94], and HR 8.44 [3.43-20.74], and HR 3.64 [2.04-6.49], respectively). Furthermore, seronegative women without use of prednisone at b/tsDMARD initiation as well as seropositive women with a higher disease burden and longer disease duration had a higher risk of non-response with golimumab (HR 2.36 [1.03-5.40] and HR 5.27 [2.10-13.21], respectively) than with adalimumab. Our results suggest that RA patient clusters identified by deep learning may have different responses to first-line b/tsDMARD. Thus, it may suggest optimal first-line b/tsDMARD for certain RA patients, which is a step forward towards personalizing treatment. However, further research in other cohorts is needed to verify our results.

Dataset Information

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

Introduction

Methods

Results

Conclusions

Publications

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

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