ACR Annual Meeting: Patients with early rheumatoid arthritis and serological biomarkers of a poor prognosis who initiated treatment with abatacept plus methotrexate, sustained remission across all arms of a 48-week dose de-escalation trial, though the full combination produced the best maintenance, researchers reported November 12 at the American College of Rheumatology annual meeting in Atlanta.
Patients with early rheumatoid arthritis and serological biomarkers of a poor prognosis who initiated treatment with abatacept plus methotrexate, sustained remission across all arms of a 48-week dose de-escalation trial, though the full combination produced the best maintenance, researchers reported November 12 at the American College of Rheumatology annual meeting in Atlanta.
“The main message is that the continued combination works best at full doses,” said Paul Emery, M.D., professor of rheumatology and director of the Leeds NIHR Biomedical Research Centre, Leeds Teaching Hospitals Trust, in the UK, who presented the findings.
Guidelines from the American College of Rheumatology and the European League Against Rheumatism suggest tapering biologics for rheumatoid arthritis patients in sustained remission, but don’t offer specific strategies for how this should be done for individual therapies.
In this phase 3b trial, investigators randomized patients with early rheumatoid arthritis(≤6 months) 3:2 to 56 weeks of blinded treatment with once-weekly 125-mg abatacept injection plus methotrexate or abatacept placebo plus methotrexate. Patients were positive for anti-citrullinated protein antibody (ACPA), an established biomarker for rapidly progressing rheumatoid arthritis.
Patients receiving abatacept plus methotrexate who achieved sustained Simplified Disease Activity Index (SDAI) remission (≤3.3 at weeks 40 and 52) were re-randomized 1:1:1 in a 48-week de-escalation (DE) period to:
• weekly abatacept plus methotrexate (n=50)
• abatacept every other week plus methotrexate for 24 weeks then abatacept placebo plus methotrexate for 24 weeks (n=50); or
• weekly abatacept plus methotrexate placebo (n=47)
The abatacept placebo group continued that treatment during de-escalation and wasn’t re-randomized or compared in this analysis with the above arms. Methotrexate and corticosteroid doses were stable during de-escalation. Endpoints were the proportion of patients in SDAI remission, adjusted mean change from de-escalation day one in SDAI score, safety to de-escalationweek 48, and radiographic progression at de-escalationweek 48.
Weekly abatacept plus methotrexate produced the best remission maintenance and structural damage inhibition, with 74% of those patients sustaining remission at de-escalation week 48. Withdrawing methotrexate caused an initial drop in remission to 64%, but rates stabilized by week 12.
Tapering abatacept every other week to methotrexate alone produced the greatest remission loss, decreasing it from 88% at de-escalation week 0 to 74% at week 24 to 48% by week 48. In the group who received abatacept placebo at induction, 59% maintained remission at de-escalationweek 48.
Investigators reported inhibition of radiographic progression in all active abatacept groups and identified no new safety signals. They concluded that abatacept-containing de-escalation regimens should be investigated further as a viable option in clinical practice.
Dr. Emery reported disclosures related to AbbVie, Bristol-Myers Squibb, Gilead, Lilly, MSD, Novartis, Pfizer, Roche, Samsung, Samsung Bioepis Co., Ltd., Sandoz, and UCB.
REFERENCE“L11 - Maintenance of Remission Following Dose De-Escalation of Abatacept in Early, MTX-NaÃ¯ve, ACPA-Positive Patients with RA: Results from a Randomized Phase IIIb Study,” Paul Emery, MD, 9 a.m., Nov 12. American College of Rheumatology 2019 annual meeting, Atlanta.