On-drug and drug-free remission by baseline symptom duration: abatacept with methotrexate in patients with early rheumatoid arthritis

Abstract

Clinical outcomes in patients with early rheumatoid arthritis (RA) were assessed by baseline symptom duration in the Assessing Very Early Rheumatoid arthritis Treatment trial (ClinicalTrials.gov; NCT01142726). Patients with early, active RA were randomized to subcutaneous (SC) abatacept 125 mg/week plus methotrexate (MTX), SC abatacept alone, or MTX monotherapy for 12 months. All RA treatments were withdrawn after 12 months in patients with Disease Activity Score in 28 joints (C-reactive protein; DAS28-CRP) < 3.2. In this post hoc analysis, the proportion of patients achieving protocoldefined remission (DAS28-CRP < 2.6) or improvement in physical function at 12 and at both 12 and 18 months was assessed according to symptom duration (≤ 3 months, > 3 to ≤ 6 months, or > 6 months) and treatment group. No clinically significant differences were seen in baseline demographics or characteristics across symptom duration groups. Irrespective of baseline symptom duration, a numerically higher proportion of abatacept plus MTX-treated patients achieved DAS-defined remission at month 12 and sustained remission at month 18 compared with MTX monotherapy. A numerically higher proportion of abatacept plus MTX-treated patients with symptom duration ≤ 3 months maintained DAS-defined remission after complete treatment withdrawal from 12 to 18 months compared with longer symptom duration groups. This subgroup also had the fastest onset of clinical response (DAS28-CRP < 2.6) after initiation of treatment. Health Assessment Questionnaire-Disability Index response was similar regardless of baseline symptom duration. Overall, symptom duration of ≤ 3 months was associated with a faster onset of clinical response and higher rates of drug-free remission following treatment with abatacept plus MTX.

Identification of poor prognostic joint locations in an early rheumatoid arthritis cohort at risk of rapidly progressing disease: a post-hoc analysis of the Phase III AGREE study

“…Finally, the mean Boolean remission rates were higher in patients on ABA + MTX compared to MTX alone with the most significant impact of the combined treatment ( p < 0.001) observed in patients with a swollen wrist at baseline. This observed efficacy is in line with findings of other studies assessing treatment responses to ABA + MTX in RA patients [ 48 , 49 ]. Compared to MTX alone, treatment with ABA + MTX also resulted in overall better swelling resolution of the large and medium joints.…”

Mechanism‐driven strategies for prevention of rheumatoid arthritis

“…This phase of RA has been extensively explored through the initiation of treatment at earlier and earlier time points after the appearance of clinical IA/RA using conventional therapies, especially corticosteroids and methotrexate, alone 115 and in combination with other conventional and biologic disease modifying antirheumatic drugs (DMARDs). 116 Ongoing prevention trials in RA targeting individuals with abnormal autoantibodies in absence of clinical IA/RA have also used DMARDs, including hydroxychloroquine in the StopRA trial 17 as well as abatacept in the APIPPRA trial 94 ; in these studies, the hypothesis is that these agents may act to prevent the initiation of articular inflammation although they may also affect nonarticular sites and "checkpoints" in RA development. Aside from conventional small molecules and biologics, it is also possible that immune complex-mediated processes that utilize Fc receptors and activated complement fragments play important very early roles, as suggested in an intriguing synovial biopsy finding, 117 or that restricting the generation of citrullinated antigens in the joint as targets of ACPA may be beneficial.…”

“…This phase of RA has been extensively explored through the initiation of treatment at earlier and earlier time points after the appearance of clinical IA/RA using conventional therapies, especially corticosteroids and methotrexate, alone 115 and in combination with other conventional and biologic disease modifying anti‐rheumatic drugs (DMARDs) 116 . Ongoing prevention trials in RA targeting individuals with abnormal autoantibodies in absence of clinical IA/RA have also used DMARDs, including hydroxychloroquine in the StopRA trial 17 as well as abatacept in the APIPPRA trial 94 ; in these studies, the hypothesis is that these agents may act to prevent the initiation of articular inflammation although they may also affect nonarticular sites and “checkpoints” in RA development.…”