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BackgroundMethotrexate (MTX) remains the anchor drug in rheumatoid arthritis (RA) treatment, but is poorly tolerated or contraindicated in some patients. There is a wealth of data supporting the use of abatacept in combination with MTX, but data on alternative conventional synthetic disease-modifying antirheumatic drug (csDMARD) combinations with abatacept are scarce.MethodsIn this post-hoc exploratory analysis, efficacy and safety data were extracted from abatacept RA studies in which combination with csDMARDs other than MTX was permitted: three interventional trials (ATTAIN, ASSURE, and ARRIVE) and one real-world study (ACTION). Patients with moderate-to-severe RA received abatacept in combination with MTX, hydroxychloroquine, sulfasalazine, azathioprine, or leflunomide for 6 months to 2 years according to the study design. Change from baseline in physical function (Health Assessment Questionnaire—Disability Index (HAQ-DI); all studies) and 28-joint Disease Activity Score (C-reactive protein) (DAS28 (CRP); ATTAIN, ARRIVE, and ACTION), American College of Rheumatology response rates (ATTAIN), and safety were assessed for individual and pooled csDMARD combinations for each trial. A meta-analysis was also performed on pooled data for HAQ-DI and DAS28 (CRP) across interventional trials.ResultsAcross all four studies, 731 patients received abatacept plus one non-MTX csDMARD (hydroxychloroquine n = 152; sulfasalazine n = 123; azathioprine n = 59; and leflunomide n = 397) and 2382 patients received abatacept plus MTX. Mean changes from baseline in HAQ-DI scores for abatacept plus MTX (all csDMARDs pooled) vs abatacept plus a non-MTX csDMARD were –0.54 vs –0.44 (ATTAIN), –0.43 vs –0.43 (ASSURE), and –0.39 vs –0.36 (ARRIVE). Mean changes from baseline in DAS28 (CRP) and ACR response rates were also similar with abatacept plus MTX or non-MTX csDMARDs. Data for individual non-MTX csDMARDs (pooled across studies) and real-world data were consistent with these findings. Rates of treatment-related adverse events and serious adverse events, respectively, for abatacept plus one non-MTX csDMARD vs abatacept plus MTX were 35.7% vs 41.7% and 2.4% vs 2.3% (ATTAIN), 58.0% vs 55.9% and 4.2% vs 1.7% (ASSURE), and 38.1% vs 44.3% and 0.6% vs 2.9% (ARRIVE).ConclusionsAbatacept in combination with non-MTX csDMARDs is clinically effective and well tolerated in patients with moderate-to-severe RA, providing similar benefits to those seen with abatacept plus MTX.Trial registrationClinicalTrials.gov NCT00048581. Registered 2 November 2002.ClinicalTrials.gov NCT00048932. Registered 11 November 2002.ClinicalTrials.gov NCT00124982. Registered 30 June 2005.ClinicalTrials.gov NCT02109666. Registered 8 April 2014.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1488-5) contains supplementary material, which is available to authorized users.

BackgroundDiscontinuation of rheumatoid arthritis (RA) treatment for lack or loss of initial response, tolerability issues, or development of antibodies against the therapeutic agent remains a challenge in clinical practice. Here we present a 6-month interim analysis of a 2-year prospective observational trial in Europe and Canada aiming to assess the real-world effectiveness, safety, and tolerability of intravenous abatacept for the treatment of moderate-to-severe RA.MethodsACTION (AbataCepT In rOutiNe clinical practice) is a prospective, observational study assessing effectiveness, safety, and tolerability of abatacept in patients with RA enrolled in Europe and Canada between May 2008 and January 2011. The patient population was divided into two groups: biologic naïve (‘first-line’) patients and patients who had previously failed treatment with at least one biologic agent (‘second-line’). Retention rates were calculated using Kaplan–Meier curve estimates. Effectiveness was measured using European League Against Rheumatism (EULAR) response criteria, the 28-item Disease Activity Score, the Clinical Disease Activity Index (CDAI), and physical function, as assessed by the Health Assessment Questionnaire-Disability Index (HAQ-DI). Serious adverse events (SAEs) were reported for all enrolled patients.ResultsOf 1138 consecutively enrolled patients, 1114 and 1079 patients were evaluable for retention and effectiveness, respectively. Overall, retention rates were 88.6% (95% confidence interval [CI]: 86.4, 90.4); 67.4% of patients achieved good/moderate EULAR response; 32.8% had a CDAI Low Disease Activity State (LDAS); and 44.7% a HAQ-DI response. Retention rates among first- and second-line patients were 93.0% (95% CI: 85.9, 96.6) and 88.1% (95% CI: 85.7, 90.0), respectively. The percentage of patients achieving CDAI LDAS was 40.0% (95% CI: 26.4, 53.6) for first- and 32.2% (95% CI: 28.4, 36.0) for second-line patients and the proportion achieving a HAQ-DI response was 60.3% (95% CI: 47.8, 72.9) versus 43.1% (95% CI: 39.0, 47.2), respectively. The incidence of SAEs was 4.7%.ConclusionsEvidence from this 6-month interim analysis suggests that abatacept offers an effective and well-tolerated treatment option for patients with RA, including those who have previously failed anti-tumor necrosis factor treatment. In addition, higher retention rates and effectiveness outcomes were observed when abatacept treatment was initiated earlier in the course of the disease.

ObjectivesTo determine the impact of baseline rheumatoid factor (RF) and anticyclic citrullinated peptide (anti-CCP) status on the clinical efficacy of intravenous abatacept in biologic-naïve patients with rheumatoid arthritis (RA) enrolled in the real-world ACTION study.MethodsClinical outcomes (European League Against Rheumatism (EULAR) response, mean Clinical Disease Activity Index (CDAI) and Boolean remission) at 6 months were compared by baseline RF and anti-CCP status.ResultsOf 672 biologic-naïve patients, RF status was reported in 577 (86%) (412 (71%) positive) and anti-CCP status in 552 (82%) (364 (66%) positive); of 511 patients for whom data were available, 308/511 (60%) were double positive and 127/511 (25%) were double negative. Clinical outcomes were improved with RF-positive or anti-CCP-positive versus RF-negative/anti-CCP-negative status—good or moderate EULAR response: RF: 84.6 vs 72.9%, p=0.012; anti-CCP: 85.2 vs 74.2%, p=0.015; mean CDAI (calculated): RF: 10.8 vs 15.3, p<0.001; anti-CCP: 10.9 vs 14.3, p=0.002; and Boolean remission: RF: 13.3 vs 4.0%, p=0.008; anti-CCP: 12.5 vs 6.3%, p=0.096. Clinical outcomes were also improved with single or double RF-positive/anti-CCP-positive versus double-negative status.ConclusionsIn biologic-naïve patients with RA, RF-positive and/or anti-CCP-positive status is associated with greater efficacy of intravenous abatacept than seronegative status.Trial registration numberNCT02109666.

IntroductionAn understanding of real-world predictors of abatacept retention is limited. We analysed retention rates and predictors of abatacept retention in biologic-naïve and biologic-failure patients in a 12-month interim analysis of the 2-yearAbataCepTIn rOutiNe clinical practice (ACTION) study.MethodsACTION was an international, observational study of patients with moderate-to-severe rheumatoid arthritis (RA) who initiated intravenous abatacept. In this 12-month interim analysis, crude abatacept retention rates, predictors of retention and European League Against Rheumatism (EULAR) response were evaluated in both biologic-naïve and biologic-failure patients. Retention by rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) status was also assessed, in patients with or without baseline radiographic erosions, and by body mass index (BMI).ResultsOverall, 2350/2364 enrolled patients were evaluable (674 biologic naїve; 1676 biologic failure). Baseline characteristics were largely similar in biologic-naïve and biologic-failure groups. Crude retention rates (95% CI) at 12 months were significantly higher in biologic-naїve (78.1%(74.7% to 81.2%)) versus biologic-failure patients (69.9%(67.6% to 72.1%); P<0.001). RF/anti-CCP double positivity predicted higher retention in both patient groups, and remained associated with higher retention in patients with erosive disease. BMI did not impact abatacept retention in either patient group, irrespective of RF/anti-CCP serostatus. Good/moderate EULAR response rate at 12 months was numerically higher in biologic-naїve (83.8%) versus biologic-failure (73.3%) patients. There were no new safety signals.ConclusionHigh levels of intravenous abatacept retention in clinical practice were confirmed, particularly in biologic-naïve patients, including in those with poor RA prognostic factors. Retention was unaffected by BMI, regardless of RF/anti-CCP serostatus.Trial registration numberNCT02109666; retrospectively registered 8 April 2014.

BackgroundThe emergence of new therapies for the treatment of rheumatoid arthritis (RA), the paucity of head-to-head studies, and the heterogeneous nature of responses to current biologics highlight the need for the identification of prognostic factors for treatment response and retention in clinical practice. Prognostic factors for patient retention have not been explored thoroughly despite data for abatacept and other biologics being available from national registries. Real-world data from the ACTION study may supplement the findings of randomized controlled trials and show how abatacept is used in clinical practice. The aim of this interim analysis was to identify prognostic factors for abatacept retention in patients with RA who received at least one prior biologic agent.MethodsA large, international, non-interventional cohort of patients with moderate-to-severe RA who initiated intravenous abatacept in Canada and Europe (May 2008–January 2011) enrolled in the ACTION study. Potential prognostic factors for retention in this interim analysis (data cut-off February 2012; including patients from Canada, Germany, Greece, and Italy) were baseline demographics and disease characteristics, medical history, and previous and concomitant medication. Clinically relevant variables with p ≤ 0.20 in univariate analysis and no collinearity were entered into a Cox proportional hazards regression model, adjusted for clustered data. Variables with p ≤ 0.10 were retained in the final model (backward selection).ResultsThe multivariate model included 834 patients. Anti-cyclic citrullinated peptide (CCP) antibody positivity (hazard ratio [95 % confidence interval]: 0.55 [0.40, 0.75], p < 0.001), failure of <2 prior anti-tumor necrosis factors (TNFs) (0.71 [0.56, 0.90], p = 0.005 versus ≥2 prior anti-TNFs), and cardiovascular comorbidity at abatacept initiation (0.48 [0.28, 0.83], p = 0.009) were associated with lower risk of abatacept discontinuation. Patients in Greece and Italy were less likely to discontinue abatacept than patients in Germany and Canada (Greece: 0.30 [0.16, 0.58]; Italy: 0.50 [0.33, 0.76]; Canada: 1.04 [0.78, 1.40], p < 0.001 versus Germany).ConclusionsReal-world prognostic factors for abatacept retention include anti-CCP positivity and fewer prior anti-TNF failures. Differences in retention rates between countries may reflect differences in healthcare systems. The finding that abatacept has potential advantages in patients with cardiovascular comorbidities needs to be confirmed in further research.Electronic supplementary materialThe online version of this article (doi:10.1186/s12891-015-0636-9) contains supplementary material, which is available to authorized users.

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

Objectives To evaluate retention, efficacy, and safety of subcutaneous (SC) abatacept over 2 years in patients with moderate-to-severe RA in the Abatacept SubCutaneOus in Routine clinical practicE (ASCORE) study. Methods Patients with RA who initiated SC abatacept 125 mg once weekly were enrolled in the international, observational, prospective multicentre ASCORE study into biologic-naïve or ≥ 1 prior biologic failure cohorts. Primary endpoint: abatacept retention rate at 2 years. Secondary endpoints: proportion of patients with good/moderate EULAR response rates based on DAS28 (ESR), low disease activity and/or remission according to DAS28 (ESR; ≤ 3.2/ < 2.6), SDAI (≤ 11/ ≤ 3.3), CDAI (≤ 10/ ≤ 2.8), and Boolean criteria. Retention rate by baseline serostatus was evaluated post hoc. Results Overall, 47% of patients remained on abatacept for 2 years, irrespective of treatment line. Higher abatacept retention rates were associated with lower prior biologic exposure. Generally, clinical outcomes showed that the proportion of patients with low disease activity/remission was higher in biologic-naïve patients (vs biologic-failure) and similar in those with 1 and ≥ 2 prior biologic failures. In patients on treatment at 2 years, good/moderate EULAR response rates of ~ 80% were consistently noted irrespective of prior biologic exposure. Across treatment lines, retention was greater in patients with seropositive (vs seronegative) RA. Patients with rheumatoid factor/anti-citrullinated protein antibody single-positive RA who were bio-naïve had higher retention than patients who were bio-experienced. Conclusions In the ASCORE study, SC abatacept retention was 47% at 2 years with good clinical outcomes and was well-tolerated in the real-world setting. Abatacept retention and clinical response rates were higher in patients who received abatacept as an earlier- versus later-line biologic drug treatment and in those with seropositive RA. Trial registration ClinicalTrials.gov, NCT02090556.