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.

OBJECTIVES: To 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. METHODS: Clinical 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. RESULTS: Of 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. CONCLUSIONS: In 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 NUMBER: NCT02109666.

The effect of body mass index on clinical response to abatacept as a first-line biologic for rheumatoid arthritis: 6-month results from the 2-year, observational, prospective ACTION study.

OBJECTIVE: To assess the impact of baseline body mass index (BMI) on the efficacy and retention of intravenous abatacept at 6 months in biologic-naïve patients with rheumatoid arthritis (RA). METHODS: This was a 6-month analysis of a 2-year, non-interventional, international, prospective study. Baseline characteristics, clinical response and retention rates were compared by BMI subgroup: underweight/normal, overweight and obese (<25, 25 to <30 and ≥30kg/m2, respectively). RESULTS: BMI was reported in 643/672 (96%) patients: 264 (41%) were underweight/normal, 224 (35%) overweight and 155 (24%) obese. At baseline, the obese group had more active disease (mean [95% confidence intervals] 28-joint Disease Activity Score [C-reactive protein; derived] 4.6 [4.5, 4.7], 4.8 [4.7, 5.0] and 5.1 [4.9, 5.2] for underweight/normal, overweight and obese groups, respectively), a higher prevalence of metabolic disorders, a greater proportion of women and a lower proportion of patients with rheumatoid factor positivity. There were no significant differences in the percentages of patients achieving a good/moderate European League Against Rheumatism response by BMI group (80.7, 86.1 and 77.0% for underweight/normal, overweight and obese groups, respectively; P=0.178). Overall retention rates at 6 months did not differ across groups (89, 92 and 89% for underweight/normal, overweight and obese groups, respectively; log-rank P=0.382). After adjustment for baseline characteristics, BMI was not significantly associated with risk of discontinuation (reference BMI<25kg/m2; hazard ratio [95% confidence intervals] 0.46 [0.22, 0.99] and 0.69 [0.34, 1.41] for overweight and obese patients, respectively). CONCLUSION: BMI does not impact abatacept clinical response or retention in biologic-naïve patients with RA.

Real-world predictors of 12-month intravenous abatacept retention in patients with rheumatoid arthritis in the ACTION observational study.

INTRODUCTION: An 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. METHODS: ACTION 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). RESULTS: Overall, 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. CONCLUSION: High 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 NUMBER: NCT02109666; retrospectively registered 8 April 2014.

Efficacy and prognostic factors of treatment retention with intravenous abatacept for rheumatoid arthritis: 24-month results from an international, prospective, real-world study.

OBJECTIVES: To evaluate retention of abatacept over 24 months in patients with rheumatoid arthritis (RA) in routine clinical practice across Europe and Canada. METHODS: ACTION (AbataCepT In rOutiNe clinical practice) was a prospective, observational, multicentre study of adult patients with moderate-to-severe RA who, at their physician's discretion, initiated treatment with intravenous abatacept. Enrolment occurred from May 2008 to December 2010, with up to 30 months of follow-up. The primary endpoint was the abatacept retention rate over 24 months. Crude abatacept retention rate was estimated using the Kaplan-Meier method. Prognostic factors of abatacept retention in patients with ≥1 prior biologic failure were derived from a Cox proportional hazards regression model, accounting for clustered data. RESULTS: A total of 1137 patients were enrolled (1573 patient-years on abatacept); most (89.2%) had experienced prior biologic failure. The overall crude abatacept retention rate at 24 months was 54.4% (95% confidence interval: 51.3, 57.4). Positivity for both rheumatoid factor and anti-cyclic citrullinated antibody, previous exposure to one or no anti-tumour necrosis factor agents, and cardiovascular comorbidity were prognostic of higher abatacept retention. Erythrocyte sedimentation rate ≥51 mm/hour and introduction of corticosteroid use at abatacept initiation were predictors of lower abatacept retention. Abatacept retention varied according to country. Abatacept was well tolerated without any unexpected safety signals. CONCLUSIONS: In a real-world setting, intravenous abatacept treatment retention was more than 50% at 24 months. The identification of prognostic factors of abatacept retention could support individualised biologic treatment strategies in patients with moderate-to-severe RA.

Prognostic factors for abatacept retention in patients who received at least one prior biologic agent: an interim analysis from the observational, prospective ACTION study.

BACKGROUND: The 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. METHODS: A 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). RESULTS: The 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). CONCLUSIONS: Real-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.

Real-world effectiveness of abatacept for rheumatoid arthritis treatment in European and Canadian populations: a 6-month interim analysis of the 2-year, observational, prospective ACTION study.

BACKGROUND: Discontinuation 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. METHODS: ACTION (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. RESULTS: Of 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%. CONCLUSIONS: Evidence 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.