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

Abstract

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.

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

“…Abatacept treatment achieved continued clinical improvement over 2 years and was well tolerated; the safety profile was consistent with that previously reported in clinical trials and the real-world setting [27][28][29] with no new safety signals identified. In general, the current findings confirm earlier observations from interim analyses of the ACTION study [30][31][32]18] and provide clinically applicable data on various parameters of disease activity in both biologic-naive patients and in those with previous biologic failure.…”

“…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].…”

Multicenter, observational clinical study of abatacept in Japanese patients with rheumatoid arthritis

“…The lower retention rate in our study may have been due to our inclusion of a higher percentage of biologic-failure patients (56% vs. 38%). A higher drug retention rate has been reported in RA patients with fewer anti-TNF failures [17]. Another possible explanation for the lower retention rate was the high percentage of patients who withdrew consent (22%), resulting from the withdrawal of one institution from this multicenter clinical study.…”

The Effect of Abatacept on Blood Biomarkers in Patients With Rheumatoid Arthritis

“…Наличие АЦЦП являлось независимым преди-О р и г и н а л ь н ы е и с с л е д о в а н и я При анализе РФ-пози-тивных и РФ-негативных пациентов достоверных разли-чий не наблюдалось [21]. Также в исследовании ACTION (834 больных, включенных в мультивариативный ана-лиз) АЦЦП-позитивность достоверно ассоциировалась с «удержанием эффекта» терапии АБЦ [22]. Механизмы, объясняющие связь ответа на терапию АБЦ с продукци-ей аутоантител при РА, изучены недостаточно.…”

“…По-хожие результаты были получены при анализе француз-ского регистра ORA и международного регистра ACTION, в которых хороший ответ на терапию АБЦ достоверно ас-социировался с выявлением АЦЦП в крови независимо от активности заболевания. Однако уровень цитокинов при этом не исследовали [21,22]. Исследователи из Японии показали, что высокие титры ревматоидного фактора (РФ) ассоциировались с более выраженным снижением активности заболевания к 52-й неделе наблюдения на фо-не терапии АБЦ [23].…”