ACTION was the first international, non-interventional, multicenter, prospective cohort study to evaluate patient retention and effectiveness of abatacept treatment in patients with moderate-to-severe RA. The current interim analysis evaluated a 6-month dataset from this ongoing 2-year study. This 6-month interim analysis may be particularly pertinent to clinicians because, according to the treat-to-target approach, the decision to switch a biologic therapy is usually made 3–6 months after initiating treatment. Here, we demonstrate high patient retention on abatacept, efficacy benefits with regards to disease activity and physical function, and a safety profile consistent with observations from both RCTs and local national registries. Benefits were observed in biologic-naïve and anti-TNF-refractory patients, regardless of the number of previously failed anti-TNF agents, or whether failure was due to primary or secondary inefficacy, or safety and tolerability reasons. In the current study, approximately 70% of enrolled patients were RF positive, which is consistent with the proportion of RF-positive patients enrolled in abatacept RCTs (ATTAIN study, 73.3%; ARRIVE, 61.3%) [13, 32] and in real-life abatacept studies (ORA, 72.5%) .
It has been reported that treatment response rates are often lower in routine clinical practice compared with RCT evidence , as a result of the patient populations in observational studies not being subject to the strict inclusion and exclusion criteria of RCTs. However, the heterogeneity of patient populations and disease characteristics in observational studies provide a real-world perspective of routine clinical practice. The efficacy, safety, and tolerability of abatacept for the treatment of moderate-to-severe RA have been demonstrated in RCTs [10–14], in local national registries [15, 16], and in a small, single-site observational study . Therefore, the objective of the ACTION study was to translate the validity of RCT results into a real-life setting. Given the objective of the study, a single-arm design was considered appropriate to describe a cohort of patients treated with abatacept and assess their drug utilization in accordance with the European Medicines Agency and Health Technology Assessment Programmes’ recommendations.
Retention rates reported in the current trial were high – >80.0% for second-line and 93.0% for first-line patients – compared with evidence from other real-world observational studies. Evidence from the Swedish national registry ARTIS showed that, 1 year after initiating abatacept treatment, retention rates were 80% for biologic-naïve patients and 64% for patients previously treated with 1–2 biologics . Similarly, 6-month retention rates with abatacept treatment were 72.0% in the Danish DANBIO registry  and 80.0% in a US observational study . Although retention rates for RCTs are expected to be higher than for real-world studies , the retention rates in the current study were consistent with an 82–90% retention rate reported from two abatacept RCTs, the ATTAIN and ARRIVE studies [13, 32]. Of note was the high retention rate for biologic-naïve patients in the current study (93.0%), which is consistent with evidence from abatacept RCTs showing that patient retention is higher when abatacept is initiated earlier in the treatment regimen [11, 14].
The efficacy of abatacept in the current report was assessed using multiple disease activity measures (DAS28, CDAI, and EULAR response); each of the clinical indices showed the same trend for improved effectiveness with abatacept, including the CDAI. Changes in disease activity in the current study were consistent with those reported in the DANBIO national registry  and the French ORA registry . A good-to-moderate treatment response, as defined by EULAR, was achieved by more than 67% of both first- and second-line patients in the current analysis; this was consistent with 6-month evidence from the French ORA national registry  and the Danish DANBIO registry . In addition, response and remission rates with abatacept in the ACTION study were similar to those reported in the two previously mentioned abatacept RCTs in patients with a prior inadequate response to anti-TNF agents, the ATTAIN  and ARRIVE studies . Subgroup analysis from ACTION – according to the number of prior anti-TNFs failed or according to the reason for discontinuation of the last biologic prior to abatacept – highlight that abatacept has favorable safety and tolerability in a real-world setting, regardless of the number of prior anti-TNFs failed or the reason for failure. These data support previously reported favorable outcomes from the ARRIVE  trial in patients with similar characteristics. Furthermore, the subgroup analyses in ACTION showed consistent numerically superior outcomes for patients treated with abatacept earlier in their disease course. As the study was not powered for subgroups analysis, definitive conclusions cannot be drawn.
Overall, no new safety signals were identified in the ACTION patient population compared with the safety profile previously reported for abatacept from real-world studies [16, 18]. Of note is the absence of any cases of active tuberculosis and one report of opportunistic infection. It is important to note that a large number of patients enrolled in the ACTION study had cardiovascular and pulmonary comorbidities, as well as chronic infections, at baseline, reflecting the type of patient profile often found in routine clinical practice compared with RCTs.
Although the results of some observational studies indicate that, after the failure of 1 or ≥2 anti-TNF agents, the choice of a biological agent with a different mechanism of action may lead to better clinical outcomes, there are a number of limitations associated with such analyses . To our knowledge, there is little evidence from real-life settings that directly compares abatacept with another biologic agent or biologic agents with each other. When interpreting the results of the current study, there are a number of potential limitations to be considered including lack of an active comparator and/or selection bias based on factors such as disease severity or AEs. In addition, failure of multiple biologics prior to abatacept treatment may have influenced physicians to wait longer before deciding that a treatment was ineffective, potentially affecting the retention rate by Month 6. This interim analysis was also vulnerable to missing data as none of the study assessments were mandatory; thus, most missing clinical outcome data may have been attributed to assessments not performed routinely at all locations. Consequently, of the 24.7% of patients with missing numerical DAS28 scores, 15.9% were reported by the investigators as score ‘not calculated’. Here, we report data ‘as observed’ with no imputation for missing values, which is consistent with other non-interventional studies.