Discussion
RA, tumor necrosis, ACPA-positive
TUMOR NECROSIS, INFLAMMATION, DISEASE, REMISSION, DISEASE, COMPLICATIONS
In this subanalysis of a phase IIIb study in ACPA-positive patients with early RA, a higher number of individual patients who received SC abatacept QW + MTX achieved clinically stringent (SDAI and Boolean remission) endpoints early at IP week 24 and sustained these responses through IP week 52 than patients who initially received abatacept placebo + MTX. Furthermore, of the patients who achieved early sustained SDAI remission through IP week 52, numerically more of those who continued abatacept QW + MTX during the DE period maintained SDAI remission at further follow-up visits than patients who tapered and then withdrew abatacept therapy or those who continued treatment with abatacept placebo + MTX.As previously reported for the overall population in the AVERT-2 study, patients who continued abatacept + MTX during the DE period demonstrated better maintenance of SDAI remission and inhibition of structural damage than patients who de-escalated/withdrew abatacept or who continued with abatacept monotherapy [The ability of individual patients to achieve a deeper level of remission, that is both early in the course of a particular treatment regimen and sustained over time, should be beneficial in terms of future joint function and control of inflammation, potentially resulting in less systemic complications of disease. Being able to determine relatively early for each individual patient whether a particular drug or regimen is likely to lead to sustained remission would allow clinicians to make more informed treatment choices, including whether additions or changes to treatment are required to achieve better long-term outcomes. Previous studies have suggested that early improvement in disease activity in response to treatment predicts longer-term outcomes. For example, pooled patient data from early RA clinical trials of MTX, tumor necrosis factor inhibitor (TNFi) monotherapy, or TNFi + MTX combination therapy demonstrated significant correlation between disease activity (SDAI) during the first 3 months of treatment and disease activity after 1 year of therapy [Following the advent of treat-to-target and tight control strategies for the management of RA, together with the wide availability of biologic/targeted synthetic DMARDs, RA is now a disease that can be controlled in many patients [Potential indicators of patients suitable for successful tapering of other DMARDs have been investigated previously. For example, in a post hoc analysis of data from three clinical trials, among patients with moderate-to-severe RA, those who achieved sustained Boolean or Clinical Disease Activity Index remission or DAS28 (CRP) < 2.6 and/or “deep remission” (DAS28 [CRP] ≤ 1.98) were more likely to maintain remission/LDA after etanercept dose reduction/withdrawal than patients who only achieved remission or LDA [There were several strengths and limitations to the AVERT-2 study and this subsequent post hoc analysis. This is the first study to use stringent sustained SDAI remission (≤ 3.3 at both weeks 40 and 52) as a criterion for de-escalation/withdrawal, and de-escalation/withdrawal strategies were assessed in a relatively large population of patients (