AVERT-2 Study Shows Efficacy of Abatacept With Methotrexate in RA Treatment

Abatacept plus methotrexate (MTX) may be beneficial in the long-term treatment of rheumatoid arthritis (RA), according to study results published in Arthritis Research & Therapy.

Study eligibility criteria were age 18 years and older, a diagnosis of RA (based on the American College of Rheumatology/European Alliance of Associations for Rheumatology [ACR/EULAR] 2010 criteria) for 6 months or longer, anticitrullinated protein antibody (ACPA)-positivity, and disease-modifying antirheumatic drug (DMARD)-naive. Participants also had a tender joint count (TJC) of at least 3, a swollen joint count (SJC) of at least 3, C-reactive protein (CRP) of greater than 3.0 mg/L,  erythrocyte sedimentation rate (ESR) of at least 28 mm/h, and baseline Simplified Disease Activity Index (SDAI) score of greater than 11.

The AVERT-2 study was a phase 3b, double-blind, placebo-controlled trial (ClinicalTrial.gov Identifier: NCT02504268), in which participants were randomly assigned to receive abatacept plus MTX or abatacept placebo plus MTX for a 56-week induction phase.

Participants who completed the induction phase and also achieved sustained SDAI remission (≤3.3 at both weeks 40 and 52) were enrolled in a 48-week de-escalation period.

Participants who originally received treatment with abatacept plus MTX were again randomly assigned 1:1:1. The first arm received continuation (abatacept weekly plus MTX for 48 weeks). The second arm received stepwise de-escalation and withdrawal (abatacept every other week plus MTX for 24 weeks followed by abatacept placebo plus MTX for 24 weeks). The third arm received abatacept monotherapy (abatacept weekly plus MTX placebo for 48 weeks).

Participants who received abatacept placebo plus MTX during the induction phase and achieved sustained SDAI remission continued the same treatment during the de-escalation period.

During the induction phase, at week 24, 22% of participants who received abatacept plus MTX achieved SDAI remission, 17% achieved Boolean remission, and 42% achieved Disease Activity Score 28 (DAS28)-CRP of less than 2.6.

Of the participants who achieved endpoints at 24 weeks, 56%, 58%, and 74%, respectively, also sustained responses through the induction phase at weeks 40/52.

Of the participants who had a sustained response at the induction phase at  weeks 24/40/52, 82% who received abatacept weekly plus MTX , 81% who received abatacept monotherapy, 63% who de-escalated/withdrew abatacept, and 65% who received abatacept placebo plus MTX remained in SDAI remission at the end of the de-escalation period.

Study limitations included the inability to note when individual patients had fluctuating responses; the stringent criteria that limited the size of the study population; the lack of generalizability among a larger population of patients with RA; and the relatively short de-escalation phase.

The study authors concluded, “The achievement of early remission or other clinically relevant outcomes by individual patients treated with weekly [subcutaneous] abatacept [plus] MTX may be indicative of sustained efficacy over time.”

Disclosure: This research was supported by Bristol Myers Squibb. Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.