Baseline autoantibodies preferentially impact abatacept efficacy in patients with rheumatoid arthritis who are biologic naïve: 6-month results from a real-world, international, prospective study

Alten, Rieke; Nüßlein, H.; Mariette, Xavier; Gargiulo, Mauro; Lorenz, Hanns‐Martin; Cantagrel, Alain; Chartier, M.; Poncet, Coralie; Rauch, C.; Bars, Manuela Le

doi:10.1136/rmdopen-2016-000345

Cited by 38 publications

(28 citation statements)

References 13 publications

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“…In this study, we analyzed the relationship between the disease activity and anti-CCP antibody levels after starting abatacept in a cohort of patients with RA. As reported previously [3,[6][7][8][9], abatacept reduced disease activity more efficiently in those with higher levels of anti-CCP antibody levels. However, in our case, this could be owing to the floor effect, as patients with low levels of anti-CCP antibody levels had lower disease activity at baseline.…”

Section: Discussionsupporting

confidence: 69%

“…It is also possible that abatacept reduces disease activity of RA by interfering T-B cell interaction required for ACPA production. Interestingly, there have been reports showing higher efficiency of abatacept in ACPA-positive patients with RA, especially in those with high antibody levels, in either clinical trials or clinical practice settings [3,[6][7][8][9]. It is unknown why the clinical efficiency of abatacept correlates with the ACPA levels and whether it is related to the modulation of antibody production.…”

Section: Introductionmentioning

confidence: 99%

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Abatacept reduces disease activity of rheumatoid arthritis independently of modulating anti-citrullinated peptide antibody production

Yamada

Tsuru

Otsuka³

et al. 2020

Immunological Medicine

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Abatacept may exert its clinical effect on rheumatoid arthritis (RA) by suppressing anti-cyclic citrullinated peptide (CCP) antibody production. This study was undertaken to test this hypothesis by examining the changes of disease activity of RA and anti-CCP antibody levels over time after starting abatacept. Sixty Japanese RA patients who started abatacept were included in this multicenter, prospective observational study. Simple Disease Activity Index (SDAI) and anti-CCP antibody levels were evaluated at 12, 24, and 52 weeks. The mean SDAI score significantly decreased within 12 weeks after starting abatacept and was maintained thereafter. On the contrary, the mean anti-CCP antibody levels did not change until 52 weeks. At the individual level, there were substantial changes of anti-CCP antibody levels, but these were not correlated with the changes of disease activity at any time points. Thus, abatacept reduces the disease activity of RA independently of modulating anti-CCP antibody production.

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Section: Discussionsupporting

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Abatacept reduces disease activity of rheumatoid arthritis independently of modulating anti-citrullinated peptide antibody production

Yamada

Tsuru

Otsuka³

et al. 2020

Immunological Medicine

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“…Several interim analyses of ACTION have investigated potential predictors of clinical response in specific patient populations [31,32,43,44]. Identification of predictors in heterogeneous patient populations in a clinical setting may assist the prediction of clinical response with increased accuracy and improve the ability to attain treatment targets for the optimal management of RA [2].…”

Section: Discussionmentioning

confidence: 99%

Predictors of abatacept retention over 2 years in patients with rheumatoid arthritis: results from the real-world ACTION study

et al. 2019

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Objectives Evaluate abatacept retention over 2 years in the AbataCepT In rOutiNe clinical practice (ACTION) study. Method ACTION was an international, observational study of patients with moderate-to-severe rheumatoid arthritis (RA) who initiated intravenous abatacept. Crude abatacept retention rates over 2 years were estimated using Kaplan-Meier analyses in biologic-naive and -failure patients. Clinically relevant risk factors and significant prognostic factors for retention were evaluated using a Cox proportional hazards multivariable model. Results Overall, 2350/2364 enrolled patients were evaluable; 673 (28.6%) were biologic naive and 1677 (71.4%) had prior biologic failure (1 biologic, 728/1677 [43.4%]; ≥ 2 biologics, 949/1677 [56.6%]). Abatacept retention rate (95% confidence interval [CI]) at 2 years was 47.9% (45.7, 50.0): 54.5% (50.4, 58.3) for biologic-naive vs 45.2% (42.7, 47.7) for biologic-failure patients (log-rank P < 0.001). For patients with 1 and ≥ 2 prior biologic failures, respectively, retention rates (95% CI) were 50.2% (46.3, 53.9) vs 41.3% (38.0, 44.6; log-rank P < 0.001). Main reasons for discontinuation (biologic-naive vs biologic-failure, respectively) were lack of efficacy (61.4 vs 67.7%) and safety (21.3 vs 21.2%). Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) double positivity versus negativity were predictive of higher retention in both biologic-naive (hazard ratio [HR] [95% CI] 0.71 [0.53, 0.96]; P = 0.019) and biologic-failure patients (HR [95% CI] 0.76 [0.62, 0.94]; P = 0.035). Conclusions Abatacept initiation as earlier vs later line of therapy in RA may achieve higher 2-year retention rates. RF and anti-CCP seropositivity could predict increased abatacept retention, irrespective of treatment line. Trial registration NCT02109666

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“…In the ACTION study, anti-CCP-positive and/or RF-positive status was associated with greater efficacy of ABA than seronegative status 13 . Of note, we were unable to evaluate the independent effect of RF because we had too few patients who were RF-positive and anti-CCP-negative.…”

Section: Rheumatologymentioning

confidence: 99%

Effect of Anticitrullinated Protein Antibody Status on Response to Abatacept or Antitumor Necrosis Factor-α Therapy in Patients with Rheumatoid Arthritis: A US National Observational Study

Harrold

Litman²,

Connolly³

et al. 2017

J Rheumatol

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Objective.Assess whether baseline anticyclic citrullinated peptide antibodies (anti-CCP) status is associated with treatment response in patients with rheumatoid arthritis (RA) initiating abatacept (ABA) or a tumor necrosis factor-α inhibitor (TNFi).Methods.Using the Corrona RA registry, patients were identified who initiated ABA or a TNFi (June 2004–January 2015), had a followup visit 6 months (± 3 mos) after initiation, and anti-CCP measured at or prior to initiation. Primary outcome was mean change in Clinical Disease Activity Index (CDAI) from initiation to 6 months. Treatment response was evaluated based on a typical patient profile (female, aged 57 yrs, body mass index of 30 kg/m2, baseline CDAI of 20, 1 prior biologic, and no comorbidities other than RA). Secondary outcomes included remission and low disease activity.Results.There were 566 ABA initiators [anti-CCP+ (≥ 20 units/ml): n = 362; anti-CCP− (< 20 units/ml): n = 204] and 1715 TNFi initiators (anti-CCP+: n = 1113; anti-CCP−: n = 602). Differences between treatment groups included baseline disease duration, CDAI, and prior biologic use. At 6 months, anti-CCP+ ABA initiators were associated with significantly greater CDAI response versus anti-CCP− ABA initiators; no significant difference was observed for TNFi initiators. When considering a typical RA patient profile, CDAI response was greater in anti-CCP+ versus anti-CCP− ABA initiators; anti-CCP+ versus anti-CCP− TNFi initiators were similar. Secondary outcome responses were also greater in anti-CCP+ versus anti-CCP− ABA initiators; TNFi initiators did not differ by anti-CCP status.Conclusion.In a US-based clinical practice setting, anti-CCP status was associated with a differential treatment response to ABA, but not TNFi.

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Baseline autoantibodies preferentially impact abatacept efficacy in patients with rheumatoid arthritis who are biologic naïve: 6-month results from a real-world, international, prospective study

Cited by 38 publications

References 13 publications

Abatacept reduces disease activity of rheumatoid arthritis independently of modulating anti-citrullinated peptide antibody production

Abatacept reduces disease activity of rheumatoid arthritis independently of modulating anti-citrullinated peptide antibody production

Predictors of abatacept retention over 2 years in patients with rheumatoid arthritis: results from the real-world ACTION study

Effect of Anticitrullinated Protein Antibody Status on Response to Abatacept or Antitumor Necrosis Factor-α Therapy in Patients with Rheumatoid Arthritis: A US National Observational Study

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