Try our mobile app
PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol-Myers Squibb Company (NYSE: BMY)today announced new data from the randomized Phase IIIb Assessing Very Early Rheumatoid arthritis Treatment (AVERT)-2 trial exploring de-escalation of therapy in early, seropositive rheumatoid arthritis (RA) patients who achieved sustained Simplified Disease Activity Index (SDAI) remission following induction with ORENCIA® (abatacept) and methotrexate (MTX). The study showed that, across all ORENCIA treatment arms, patients achieved maintenance of remission and inhibition of structural damage progression at week 48 after de-escalation. These results will be featured in a late-breaking oral presentation at the 2019 American College of Rheumatology and Association of Rheumatology Professionals (ACR/ARP) Annual Meeting, November 8-13, 2019, in Atlanta. Results to be presented from a second study, CERTAIN (Comparative Effectiveness Registry to study Therapies for Arthritis and Inflammatory CoNditions), a prospective cohort study of adult patients with RA recruited from the Corrona® registry, demonstrate that in a sample of 138 ORENCIA-treated patients, higher anti-citrullinated protein antibody (ACPA) concentrations at baseline were associated with improvement in patient-reported outcomes (PROs) in adjusted and unadjusted models, Clinical Disease Activity Index (CDAI) score in the adjusted model and CDAI score in the unadjusted model after six months.2 This association was not observed in a similar sample size of patients treated with other common therapies, TNF inhibitors (TNFi).2
“The AVERT-2 and Corrona CERTAIN abstracts presented at the 2019 ACR/ARP Meeting reinforce the potential benefit of ORENCIA in patients with biomarkers indicating a more severe disease course, and the consistent maintenance of disease response following de-escalation treatment,1,2” said Brian Gavin, Ph.D., development lead, ORENCIA, Bristol-Myers Squibb. “More and more, our research suggests that the presence of certain biomarkers such as ACPA may prove useful when selecting a treatment regimen in early rheumatoid arthritis. Bristol-Myers Squibb remains committed to advancing biomarker science in support of expanding the treatment options for patients with immune-mediated diseases.”
AVERT-2 data demonstrate maintenance of remission at 48 weeks following de-escalation in early RA ACPA-positive patients treated with ORENCIA
In AVERT-2, ACPA-positive patients with early (ACR/EULAR 2010 criteria; disease duration 11) were randomized 3:2 to blinded subcutaneous (SC) ORENCIA (125 mg QW) + methotrexate (MTX) or placebo (PBO) + MTX induction treatment for 56 weeks. The SDAI assesses disease activity in RA. Generally, remission is considered achieved if the score is between 0 and 3.3 included. Patients who completed induction with ORENCIA + MTX and had sustained SDAI remission (≤3.3 at Weeks 40 and 52) were re-randomized 1:1:1 to ORENCIA QW + MTX for 48 weeks, ORENCIA every other week (EOW) + MTX for 24 weeks followed by ORENCIA PBO + MTX for 24 weeks, or ORENCIA QW + MTX PBO for 48 weeks in the de-escalation (DE) period. Methotrexate and oral corticosteroid doses in the DE period were stable. Patients with sustained SDAI remission who received ORENCIA PBO + MTX during induction were not re-randomized and continued this treatment in the DE period in a blinded fashion; no comparisons between this arm and the ORENCIA arms were made. Endpoints were proportion of patients in SDAI remission, adjusted mean change from DE Day 1 in SDAI score, safety to DE Week 48 and radiographic progression at DE Week 48.
Results demonstrated that combination therapy (ORENCIA QW + MTX) resulted in the best maintenance of remission, yet remission maintenance was observed across the study arms:
Adjusted mean change in SDAI score in the ORENCIA arms in the DE period was numerically low, but varied between arms and increased (patients’ disease activity worsened) following ORENCIA withdrawal from the ORENCIA EOW + MTX arm at DE Week 24.1 Sustained inhibition of structural damage was seen in all ORENCIA arms.1 Safety was similar across treatments with no new signals.1
“Although the American College of Rheumatology and European League Against Rheumatism guidelines suggest tapering of biologic therapy following a period of sustained remission in rheumatoid arthritis patients,3,4 additional research has been needed to identify appropriate de-escalation regimens for individual therapies,” said Paul Emery, M.D., Director of the Leeds NIHR Biomedical Research Centre, Leeds Teaching Hospitals Trust. “The findings from the AVERT-2 study are important because they reveal the potential for maintenance of clinical remission and inhibition of structural damage with ORENCIA in early, moderate-to-severe rheumatoid arthritis positive for anti-citrullinated protein antibody, a population that historically has faced a poor prognosis and a more severe disease course,1,5,6 and provide important scientific information related to de-escalation of ORENCIA therapy.”
Corrona CERTAIN analysis finds greater improvement in PROs and CDAI at six months in ORENCIA-treated early RA, ACPA-positive patients
Previous ORENCIA clinical trial research demonstrated that RA patients who test positive for higher ACPA concentrations show a better response to treatment with ORENCIA than those with lower concentrations.7 With the Corrona CERTAIN analysis, researchers assessed the association between baseline ACPA concentration and six-month treatment responses to ORENCIA or TNFis in a real-world setting.2 The Corrona RA Registry is the largest RA real-world prospective cohort study in the world.8
The study found significant differences between ACPA quartiles at baseline in mean CDAI, SJC28, CRP, DAS28 (CRP), RF, mHAQ and physician global assessment, and in mean RF, mHAQ and PtGA among TNFi initiators.2 Among ORENCIA initiators, but not TNFi initiators, a greater improvement at six months in CDAI and all PROs was observed with increasing ACPA quartile. 2 In the adjusted analysis, among ORENCIA initiators, there was a numerically greater improvement in CDAI (p=0.208) and statistically significantly greater improvements in all PROs (p10) and either started therapy with or switched to a TNFi or non-TNF biologic.2 Patients were followed for 12 months or until they switched/discontinued biologic therapy.2
This analysis included patients from CERTAIN who initiated ORENCIA or any TNFi, were ACPA-positive (>20 U/mL), had CDAI >10 at baseline and had serum samples at baseline and at six months.2 Eligible patients also had known baseline ACPA concentration and serostatus (–, ≤10 U/mL; +, >10 U/mL) and prior biologic exposure.2 TNFi initiators were matched to ORENCIA initiators based on CDAI by line of therapy.2 Baseline demographics, patient and disease characteristics were compared within treatment groups using descriptive statistics.2 Treatment response by baseline ACPA quartile in ACPA-positive patients, assessed by change from baseline at six months in CDAI and patient-reported outcomes (PROs: modified [m]HAQ, pain, fatigue and patient global assessment [PtGA]), was evaluated separately in the ORENCIA and TNFi groups using a linear regression model adjusted for age, sex, CDAI or PROs at initiation, co-morbidity index and current MTX use.2
In total, 151 matched biologic-experienced ORENCIA and TNFi initiators were included (13 and 14 were ACPA negative and 138 and 137 were ACPA-positive, respectively).2 At baseline, median age was 57–60 years, 74–75% were female, median duration of RA was 10–12 years and mean BMI was 29.2–29.8.2
About Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a destructive immune-mediated disease characterized by inflammation in the lining of joints (or synovium), causing joint damage with chronic pain, stiffness, and swelling.9,10 RA causes limited range of motion and decreased joint function.9,10 The condition is more common in women than in men, who account for 75 percent of patients diagnosed with RA.9
About ORENCIA
ORENCIA® is an immunomodulator that disrupts the continuous cycle of T-cell activation that characterizes RA.
U.S. Indications/Usage and Important Safety Information for ORENCIA® (abatacept)
Indication and Usage
Adult Rheumatoid Arthritis (RA): ORENCIA® (abatacept) is indicated for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active RA. ORENCIA may be used as monotherapy or concomitantly with disease-modifying, anti-rheumatic drugs (DMARDs) other than tumor necrosis factor (TNF) antagonists.
Juvenile Idiopathic Arthritis (JIA): ORENCIA® (abatacept) is indicated for reducing signs and symptoms in patients 2 years of age and older with moderately to severely active polyarticular JIA. ORENCIA may be used as monotherapy or concomitantly with methotrexate (MTX).
Adult Psoriatic Arthritis (PsA): ORENCIA® (abatacept) is indicated for the treatment of adult patients with active PsA.
Important Limitations of Use: ORENCIA should not be administered concomitantly with TNF antagonists, and is not recommended for use concomitantly with other biologic RA therapy, such as anakinra.
Important Safety Information for ORENCIA® (abatacept)
Concomitant Use with TNF Antagonists: Concurrent therapy with ORENCIA and a TNF antagonist is not recommended. In controlled clinical trials, adult RA patients receiving concomitant intravenous ORENCIA and TNF antagonist therapy experienced more infections (63%) and serious infections (4.4%) compared to patients treated with only TNF antagonists (43% and 0.8%, respectively), without an important enhancement of efficacy.
Hypersensitivity: Anaphylaxis or anaphylactoid reactions can occur during or after an infusion and can be life-threatening. There were 2 cases (
