Reducing abatacept feasible for poor-prognosis early RA patients

Patients with poor-prognosis early rheumatoid arthritis who have been on a regimen of abatacept for at least 1 year and have low disease activity scores can safely scale back their medication doses, according to the findings of a substudy of a phase III trial.

“Drug-free remission remains a therapeutic goal in RA [rheumatoid arthritis], [but] in established RA, withdrawal of biological therapy generally leads to loss of remission for the majority of patients,” wrote the study’s authors, led by Dr. René Westhovens of the Katholieke Universiteit in Leuven, Belgium. “However, dose reduction is a feasible strategy for some patients ... [and] in early RA, dose reduction is possible for the large majority of patients.”

Dr. Westhovens and his coinvestigators crafted a substudy from the existing AGREE (Abatacept study to gauge remission and joint damage progression in methotrexate-naive patients with early erosive rheumatoid arthritis) trial, using 35 of the 87 sites enrolling patients in the larger study. Substudy participants were required to have a 28-joint disease activity score with erythrocyte sedimentation rate (DAS28-ESR) of less than 2.6 after 2 years (701 days) in the AGREE trial (Ann. Rheum. Dis. 2014 Dec. 30 [doi:10.1136/annrheumdis-2014-206149]).

In total, 108 patients were randomized into two groups: Fifty-eight subjects stayed on the AGREE trial dose of about 10 mg/kg abatacept, and 50 subjects began a lower dose of about 5 mg/kg abatacept. Mean age of patients in these groups was 50-51 years, and 76%-82% were female. From the 10-mg/kg and 5-mg/kg groups, three and five patients, respectively, discontinued, while four per group returned to open-label abatacept. The primary outcome over 12 months was time to disease relapse, which was defined as additional disease-modifying antirheumatic drugs, at least two courses high-dose steroids, return to open-label abatacept at about 10 mg/kg, or a DAS28 (with C-reactive protein [CRP]) of at least 3.2 at two consecutive visits. At baseline, the mean DAS28-CRP score in each group was 2.1.

The proportion of subjects experiencing disease relapse did not differ significantly between the two groups: 18 out of 58 (31%) in the 10-mg/kg group, and 17 out of 50 (34%) in the 5-mg/kg group (hazard ratio, 0.87; 95% confidence interval, 0.45-1.69). That occurred despite an average steady-state trough serum concentration of 20.3-24.1 mcg/mL in the 10-mg/kg group and 8.8-12.0 mcg/mL in the 5-mg/kg group.

“Considering the potential to alter the course of disease in some patients with early RA, along with the safety and health economic benefits in avoiding unnecessary drug exposure, timely induction of biological agents (preferably in combination with methotrexate), followed by dose reduction, might be a therapeutic option in [appropriate] patients,” Dr. Westhovens and his associates wrote.

The AGREE study and related statistical analyses were funded and performed by Bristol-Myers Squibb. Several coauthors are affiliated with or employed by Bristol-Myers Squibb, and disclosed other potential conflicts of interest.

[email protected]

Patients with poor-prognosis early rheumatoid arthritis who have been on a regimen of abatacept for at least 1 year and have low disease activity scores can safely scale back their medication doses, according to the findings of a substudy of a phase III trial.

“Drug-free remission remains a therapeutic goal in RA [rheumatoid arthritis], [but] in established RA, withdrawal of biological therapy generally leads to loss of remission for the majority of patients,” wrote the study’s authors, led by Dr. René Westhovens of the Katholieke Universiteit in Leuven, Belgium. “However, dose reduction is a feasible strategy for some patients ... [and] in early RA, dose reduction is possible for the large majority of patients.”

Dr. Westhovens and his coinvestigators crafted a substudy from the existing AGREE (Abatacept study to gauge remission and joint damage progression in methotrexate-naive patients with early erosive rheumatoid arthritis) trial, using 35 of the 87 sites enrolling patients in the larger study. Substudy participants were required to have a 28-joint disease activity score with erythrocyte sedimentation rate (DAS28-ESR) of less than 2.6 after 2 years (701 days) in the AGREE trial (Ann. Rheum. Dis. 2014 Dec. 30 [doi:10.1136/annrheumdis-2014-206149]).

In total, 108 patients were randomized into two groups: Fifty-eight subjects stayed on the AGREE trial dose of about 10 mg/kg abatacept, and 50 subjects began a lower dose of about 5 mg/kg abatacept. Mean age of patients in these groups was 50-51 years, and 76%-82% were female. From the 10-mg/kg and 5-mg/kg groups, three and five patients, respectively, discontinued, while four per group returned to open-label abatacept. The primary outcome over 12 months was time to disease relapse, which was defined as additional disease-modifying antirheumatic drugs, at least two courses high-dose steroids, return to open-label abatacept at about 10 mg/kg, or a DAS28 (with C-reactive protein [CRP]) of at least 3.2 at two consecutive visits. At baseline, the mean DAS28-CRP score in each group was 2.1.

The proportion of subjects experiencing disease relapse did not differ significantly between the two groups: 18 out of 58 (31%) in the 10-mg/kg group, and 17 out of 50 (34%) in the 5-mg/kg group (hazard ratio, 0.87; 95% confidence interval, 0.45-1.69). That occurred despite an average steady-state trough serum concentration of 20.3-24.1 mcg/mL in the 10-mg/kg group and 8.8-12.0 mcg/mL in the 5-mg/kg group.

“Considering the potential to alter the course of disease in some patients with early RA, along with the safety and health economic benefits in avoiding unnecessary drug exposure, timely induction of biological agents (preferably in combination with methotrexate), followed by dose reduction, might be a therapeutic option in [appropriate] patients,” Dr. Westhovens and his associates wrote.

The AGREE study and related statistical analyses were funded and performed by Bristol-Myers Squibb. Several coauthors are affiliated with or employed by Bristol-Myers Squibb, and disclosed other potential conflicts of interest.

[email protected]

Patients with poor-prognosis early rheumatoid arthritis who have been on a regimen of abatacept for at least 1 year and have low disease activity scores can safely scale back their medication doses, according to the findings of a substudy of a phase III trial.

“Drug-free remission remains a therapeutic goal in RA [rheumatoid arthritis], [but] in established RA, withdrawal of biological therapy generally leads to loss of remission for the majority of patients,” wrote the study’s authors, led by Dr. René Westhovens of the Katholieke Universiteit in Leuven, Belgium. “However, dose reduction is a feasible strategy for some patients ... [and] in early RA, dose reduction is possible for the large majority of patients.”

Dr. Westhovens and his coinvestigators crafted a substudy from the existing AGREE (Abatacept study to gauge remission and joint damage progression in methotrexate-naive patients with early erosive rheumatoid arthritis) trial, using 35 of the 87 sites enrolling patients in the larger study. Substudy participants were required to have a 28-joint disease activity score with erythrocyte sedimentation rate (DAS28-ESR) of less than 2.6 after 2 years (701 days) in the AGREE trial (Ann. Rheum. Dis. 2014 Dec. 30 [doi:10.1136/annrheumdis-2014-206149]).

In total, 108 patients were randomized into two groups: Fifty-eight subjects stayed on the AGREE trial dose of about 10 mg/kg abatacept, and 50 subjects began a lower dose of about 5 mg/kg abatacept. Mean age of patients in these groups was 50-51 years, and 76%-82% were female. From the 10-mg/kg and 5-mg/kg groups, three and five patients, respectively, discontinued, while four per group returned to open-label abatacept. The primary outcome over 12 months was time to disease relapse, which was defined as additional disease-modifying antirheumatic drugs, at least two courses high-dose steroids, return to open-label abatacept at about 10 mg/kg, or a DAS28 (with C-reactive protein [CRP]) of at least 3.2 at two consecutive visits. At baseline, the mean DAS28-CRP score in each group was 2.1.

The proportion of subjects experiencing disease relapse did not differ significantly between the two groups: 18 out of 58 (31%) in the 10-mg/kg group, and 17 out of 50 (34%) in the 5-mg/kg group (hazard ratio, 0.87; 95% confidence interval, 0.45-1.69). That occurred despite an average steady-state trough serum concentration of 20.3-24.1 mcg/mL in the 10-mg/kg group and 8.8-12.0 mcg/mL in the 5-mg/kg group.

“Considering the potential to alter the course of disease in some patients with early RA, along with the safety and health economic benefits in avoiding unnecessary drug exposure, timely induction of biological agents (preferably in combination with methotrexate), followed by dose reduction, might be a therapeutic option in [appropriate] patients,” Dr. Westhovens and his associates wrote.

The AGREE study and related statistical analyses were funded and performed by Bristol-Myers Squibb. Several coauthors are affiliated with or employed by Bristol-Myers Squibb, and disclosed other potential conflicts of interest.

[email protected]