Abatacept Arms Research Articles

LB1531. Administration of Abatacept or Infliximab Reduces Mortality in Hospitalized Patients with COVID-19 Pneumonia: Results from the ACTIV-1 IM Master Protocol

Abstract Background Severe COVID-19 infection is characterized by a dysregulated hyperinflammatory state that contributes to morbidity and mortality. Immunomodulatory therapy has been shown to improve outcomes. We investigated if abatacept, CTLA-4-Ig, a selective costimulation modulator, provides additional benefit when added to standard of care. Methods We conducted a double-blind, randomized, placebo-controlled trial evaluating abatacept (given as a single infusion of 10mg/kg, to a maximum of 1000 mg) compared to standard of care (including remdesivir and dexamethasone) in patients hospitalized with COVID-19 pneumonia. The primary outcome was median time to recovery by day 29. Key secondary endpoints included 28-day mortality. Results A total of 1019 patients received an infusion (509 assigned to abatacept and 510 to placebo), constituting the analyzed modified intention-to-treat cohort. The mean age 54.9 years (SD 14.65), 60.5% were male, 44.2% Hispanic or Latino and 13.7% black. Patients were evenly matched in terms of severity of illness, and comorbidities. Participants randomized to abatacept did not show a statistically significant difference in the primary endpoint with a recovery rate ratio of 1.135 (95% CI 0.996-1.294, p=0.057) compared to placebo. The median (IQR) time to recovery was 9 days (8, 10) for both groups. The 28-day mortality in the abatacept arm was 11.0% and in control arm 15.0% (OR 0.62 (95% CI 0.41, 0.94)), with a 37.8% lower odds of dying in patients receiving abatacept. The improvement in mortality was demonstrated for patients requiring low or high flow O2 at baseline but was not seen in patients who required mechanical ventilation or ECMO at time of randomization. Subgroup analysis identified the strongest effect in those with baseline CRP >75mg/L, age >65 and diabetics. Safety data demonstrated slightly lower risk of adverse events. Rates of secondary infections were similar (abatacept 16.1% and placebo 14.3%). Conclusion Although single-dose IV abatacept did not demonstrate statistically significant improvement in time to recovery, it did show a substantial reduction in 28-day mortality compared to standard of care. Disclosures All Authors: No reported disclosures.

LB1531A. Administration of abatacept, reduces mortality in hospitalized patients with COVID pneumonia. Results of a randomized controlled trial.

Abstract Background Severe COVID-19 infection is characterized by a dysregulated hyperinflammatory state that contributes to morbidity and mortality. Immunomodulatory therapy has been shown to improve outcomes. We investigated if abatacept, CTLA-4-Ig, a selective costimulation modulator, provides additional benefit when added to standard of care. Methods We conducted a double-blind, randomized, placebo-controlled trial evaluating abatacept (given as a single infusion of 10mg/kg, to a maximum of 1000 mg) compared to standard of care (including remdesivir and dexamethasone) in patients hospitalized with COVID-19 pneumonia. The primary outcome was median time to recovery by day 29. Key secondary endpoints included 28-day mortality. Results A total of 1019 patients received an infusion (509 assigned to abatacept and 510 to placebo), constituting the analyzed modified intention-to-treat cohort. The mean age 54.9 years (SD 14.65), 60.5% were male, 44.2% Hispanic or Latino and 13.7% black. Patients were evenly matched in terms of severity of illness, and comorbidities. Participants randomized to abatacept did not show a statistically significant difference in the primary endpoint with a recovery rate ratio of 1.135 (95% CI 0.996-1.294, p=0.057) compared to placebo. The median (IQR) time to recovery was 9 days (8, 10) for both groups. The 28-day mortality in the abatacept arm was 11.0% and in control arm 15.0% (OR 0.62 (95% CI 0.41, 0.94)), with a 37.8% lower odds of dying in patients receiving abatacept. The improvement in mortality was demonstrated for patients requiring low or high flow O2 at baseline but was not seen in patients who required mechanical ventilation or ECMO at time of randomization. Subgroup analysis identified the strongest effect in those with baseline CRP >75mg/L, age >65 and diabetics. Safety data demonstrated slightly lower risk of adverse events. Rates of secondary infections were similar (abatacept 16.1% and placebo 14.3%). Conclusion Although single-dose IV abatacept did not demonstrate statistically significant improvement in time to recovery, it did show a substantial reduction in 28-day mortality compared to standard of care. Disclosures Reynold Panettieri, Jr., MD, AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|AstraZeneca: Honoraria|Equillium: Grant/Research Support|Genentech: Advisor/Consultant|Genentech: Grant/Research Support|Janssen: Grant/Research Support|MedImmune: Grant/Research Support|Merck: Honoraria|Novartis: Grant/Research Support|Origo: Grant/Research Support|RIFM: Advisor/Consultant|RIFM: Grant/Research Support|Sanofi: Honoraria|Vault Health: Grant/Research Support Jane A. O'Halloran, MD PhD, Janssen Scientific Affairs, LLC: Grant/Research Support Michael A. Maldonado, MD, Bristol Myers Squibb: Employee|Bristol Myers Squibb: Stocks/Bonds William G. Powderly, MD, Merck: Advisor/Consultant.

FRI0039 Modulation of the ACPA Fine Specificity in Patients with RA Treated with Either Abatacept or Adalimumab in the AMPLE Study

BackgroundAnti-citrullinated protein antibodies (ACPAs) are markers of RA and emerging evidence suggests they may play a role in disease progression. Analysis of biomarkers from AMPLE provides a unique opportunity to...

OP0022 Abatacept sc versus adalimumab on background methotrexate in RA: One year results from the ample study

BackgroundThe availability of multiple biologic agents to treat RA has created a need for comparative assessment. To date, there have been no randomized, controlled studies designed to directly compare the...

OP0044 Head-To-Head Comparison of Subcutaneous Abatacept Versus Adalimumab on Background Methotrexate in RA: Two Year Results from the Ample Study

BackgroundAMPLE (Abatacept Versus Adalimumab Comparison in Biologic-Naive RA Subjects with Background Methotrexate) is the first 2 year, active comparator study in RA patients utilizing biologic agents. At Year 1, SC...

Abatacept in the treatment of patients with psoriatic arthritis: Results of a six‐month, multicenter, randomized, double‐blind, placebo‐controlled, phase II trial

To assess the safety and efficacy of abatacept, a selective T cell costimulation modulator, in patients with psoriatic arthritis (PsA). In this 6-month, multicenter, randomized, double-blind, placebo-controlled, phase II study, 170 PsA patients with a psoriasis target lesion (TL) ≥2 cm who had previously taken disease-modifying antirheumatic drugs (DMARDs), including anti-tumor necrosis factor (anti-TNF) agents, were randomized (1:1:1:1) to receive placebo or abatacept at doses of 3 mg/kg, 10 mg/kg, or 30/10 mg/kg (2 initial doses of 30 mg/kg, followed by 10 mg/kg) on days 1, 15, and 29 and then once every 28 days thereafter. The primary end point was the American College of Rheumatology 20% criteria for improvement (ACR20 response) on day 169. Other key end points were magnetic resonance imaging (MRI) scores for joint erosion, osteitis, and synovitis, scores on the Health Assessment Questionnaire (HAQ) and the Short Form-36 (SF-36) health survey, the investigator's global assessment of psoriasis, the TL score, and the Psoriasis Area and Severity Index (PASI) score. Proportions of patients achieving an ACR20 response were 19%, 33%, 48%, and 42% in the placebo, the abatacept 3 mg/kg, the abatacept 10 mg/kg, and the abatacept 30/10 mg/kg groups, respectively. Compared with placebo, improvements were significantly higher for the abatacept 10 mg/kg (P = 0.006) and 30/10 mg/kg (P = 0.022) groups, but not for 3 mg/kg group (P = 0.121). All abatacept regimens resulted in improved MRI, HAQ, and SF-36 scores, with 10 mg/kg showing the greatest improvements. Improvements in the TL and PASI scores were observed in all abatacept arms; a response according to the investigator's global assessment was seen only with 3 mg/kg of abatacept. The safety profiles were similar among the treatment arms. The results of this study suggest that 10 mg/kg of abatacept, the approved dosage for rheumatoid arthritis and juvenile idiopathic arthritis, may be an effective treatment option for PsA.