Abatacept Improves Life When Methotrexate Fails

Concomitant use of abatacept can significantly improve physical and mental health and physical functioning in patients with rheumatoid arthritis who have had an inadequate response to methotrexate treatment, reported Dr. Anthony Russell of the University of Alberta, Edmonton.

Dr. Russell and his colleagues analyzed health-related quality of life data from the Abatacept in Inadequate responders to Methotrexate (AIM) trial, a 1-year, randomized, double-blind, placebo-controlled, phase III trial conducted at 116 sites worldwide.

The AIM trial was designed to evaluate once-monthly abatacept as an adjunct to methotrexate (MTX) for treatment of rheumatoid arthritis (RA) in patients who continued to have active disease despite MTX therapy. An earlier report describes the primary efficacy and safety results of the AIM study (Ann Intern Med 2006;144:865–76). The AIM study population consisted of RA patients who had persistent, active disease despite treatment with MTX for at least 3 months.

Participants also were required to be at least 18 years old; to have had RA for at least 1 year since diagnosis; to have functional status I, II, or III disease; and to have active disease, defined as 10 or more swollen joints, 12 or more tender joints, and C-reactive protein levels of 10 mg/L or higher. Patients were required to maintain a steady dose of MTX for at least 28 days before enrollment.

Patients were not allowed to take any other disease-modifying antirheumatic drugs (DMARDs) during the study, and patients were required to undergo washout of other DMARDs at least 28 days before randomization.

Patients were randomized 2:1 to receive a fixed dose of abatacept (approximately 10 mg/kg) or placebo by intravenous infusion on days 1, 15, and 29 for the first month and every 28 days thereafter for up to 12 months. All patients remained on MTX at a weekly dose of 15 mg or greater throughout the study.

A total of 652 patients participated in the trial, with 433 in the abatacept-MTX group and 219 patients in the placebo-MTX group. The mean age of the patients was 51.5 years, and the mean disease duration was 8.6 years.

Health outcomes were assessed using the Medical Outcomes Study Short Form (SF)-36 Health Survey, consisting of eight scales covering physical and mental health, and the Health Assessment Questionnaire (HAQ), designed to assess physical functioning. Both questionnaires were self-administered. Patients completed the SF-36 at baseline and at months 1, 3, 6, and 12. Patients completed the HAQ at baseline, at days 15 and 29 within the first month of treatment, and every 28 days thereafter.

“[T]he physical functioning of these patients is comparable to that of patients with congestive heart failure in the general U.S. population,” wrote Dr. Russell. In both treatment groups mean baseline scores were approximately one standard deviation below the U.S. population norm for most of the eight subscales of the SF-36.

The mean physical component summary (PCS) scores of the SF-36 were 30.6 for the abatacept-MTX group and 30.7 for the placebo-MTX group at baseline, approximately two SD below the U.S. population norm of 50. Baseline mean scores in the mental component summary (MCS) of the SF-36 were 41.8 in the abatacept-MTX group and 40.8 in the placebo-MTX group, approximately one SD below the U.S. population norm of 50.

Differences between the two treatment groups in quality-of-life measures emerged within the first month of treatment. Relative to the placebo-MTX group, the abatacept-MTX group showed significant improvement by day 29 for five of the eight SF-36 subdomains: self-reported bodily pain, role physical, general health, vitality, and social functioning.

“After 3 months of treatment, the difference between abatacept and placebo widened for all of the SF-36 domains,” reported Dr. Russell (Ann. Rheum. Dis. 2007 [Epub doi: 10.1136/ard.2006.057018]).

For each of the various health outcome categories, investigators calculated the proportion of patients in each treatment group whose score improved by at least 0.5 SD over the 12-month study period. Significant differences were observed in the abatacept-MTX group relative to the placebo-MTX group after 12 months in the proportion of patients who showed improvement in PCS (67.2% vs. 51.1%, respectively) and in HAQ (72.4% vs. 55.2%, respectively).

“Combined abatacept and MTX treatment produces significant improvements across a wide range of health-related quality of life domains in patients with RA,” concluded Dr. Russell.

The project was supported financially by Bristol-Myers Squibb, makers of Orencia (abatacept).

Concomitant use of abatacept can significantly improve physical and mental health and physical functioning in patients with rheumatoid arthritis who have had an inadequate response to methotrexate treatment, reported Dr. Anthony Russell of the University of Alberta, Edmonton.

Dr. Russell and his colleagues analyzed health-related quality of life data from the Abatacept in Inadequate responders to Methotrexate (AIM) trial, a 1-year, randomized, double-blind, placebo-controlled, phase III trial conducted at 116 sites worldwide.

The AIM trial was designed to evaluate once-monthly abatacept as an adjunct to methotrexate (MTX) for treatment of rheumatoid arthritis (RA) in patients who continued to have active disease despite MTX therapy. An earlier report describes the primary efficacy and safety results of the AIM study (Ann Intern Med 2006;144:865–76). The AIM study population consisted of RA patients who had persistent, active disease despite treatment with MTX for at least 3 months.

Participants also were required to be at least 18 years old; to have had RA for at least 1 year since diagnosis; to have functional status I, II, or III disease; and to have active disease, defined as 10 or more swollen joints, 12 or more tender joints, and C-reactive protein levels of 10 mg/L or higher. Patients were required to maintain a steady dose of MTX for at least 28 days before enrollment.

Patients were not allowed to take any other disease-modifying antirheumatic drugs (DMARDs) during the study, and patients were required to undergo washout of other DMARDs at least 28 days before randomization.

Patients were randomized 2:1 to receive a fixed dose of abatacept (approximately 10 mg/kg) or placebo by intravenous infusion on days 1, 15, and 29 for the first month and every 28 days thereafter for up to 12 months. All patients remained on MTX at a weekly dose of 15 mg or greater throughout the study.

A total of 652 patients participated in the trial, with 433 in the abatacept-MTX group and 219 patients in the placebo-MTX group. The mean age of the patients was 51.5 years, and the mean disease duration was 8.6 years.

Health outcomes were assessed using the Medical Outcomes Study Short Form (SF)-36 Health Survey, consisting of eight scales covering physical and mental health, and the Health Assessment Questionnaire (HAQ), designed to assess physical functioning. Both questionnaires were self-administered. Patients completed the SF-36 at baseline and at months 1, 3, 6, and 12. Patients completed the HAQ at baseline, at days 15 and 29 within the first month of treatment, and every 28 days thereafter.

“[T]he physical functioning of these patients is comparable to that of patients with congestive heart failure in the general U.S. population,” wrote Dr. Russell. In both treatment groups mean baseline scores were approximately one standard deviation below the U.S. population norm for most of the eight subscales of the SF-36.

The mean physical component summary (PCS) scores of the SF-36 were 30.6 for the abatacept-MTX group and 30.7 for the placebo-MTX group at baseline, approximately two SD below the U.S. population norm of 50. Baseline mean scores in the mental component summary (MCS) of the SF-36 were 41.8 in the abatacept-MTX group and 40.8 in the placebo-MTX group, approximately one SD below the U.S. population norm of 50.

Differences between the two treatment groups in quality-of-life measures emerged within the first month of treatment. Relative to the placebo-MTX group, the abatacept-MTX group showed significant improvement by day 29 for five of the eight SF-36 subdomains: self-reported bodily pain, role physical, general health, vitality, and social functioning.

“After 3 months of treatment, the difference between abatacept and placebo widened for all of the SF-36 domains,” reported Dr. Russell (Ann. Rheum. Dis. 2007 [Epub doi: 10.1136/ard.2006.057018]).

For each of the various health outcome categories, investigators calculated the proportion of patients in each treatment group whose score improved by at least 0.5 SD over the 12-month study period. Significant differences were observed in the abatacept-MTX group relative to the placebo-MTX group after 12 months in the proportion of patients who showed improvement in PCS (67.2% vs. 51.1%, respectively) and in HAQ (72.4% vs. 55.2%, respectively).

“Combined abatacept and MTX treatment produces significant improvements across a wide range of health-related quality of life domains in patients with RA,” concluded Dr. Russell.

The project was supported financially by Bristol-Myers Squibb, makers of Orencia (abatacept).

Concomitant use of abatacept can significantly improve physical and mental health and physical functioning in patients with rheumatoid arthritis who have had an inadequate response to methotrexate treatment, reported Dr. Anthony Russell of the University of Alberta, Edmonton.

Dr. Russell and his colleagues analyzed health-related quality of life data from the Abatacept in Inadequate responders to Methotrexate (AIM) trial, a 1-year, randomized, double-blind, placebo-controlled, phase III trial conducted at 116 sites worldwide.

The AIM trial was designed to evaluate once-monthly abatacept as an adjunct to methotrexate (MTX) for treatment of rheumatoid arthritis (RA) in patients who continued to have active disease despite MTX therapy. An earlier report describes the primary efficacy and safety results of the AIM study (Ann Intern Med 2006;144:865–76). The AIM study population consisted of RA patients who had persistent, active disease despite treatment with MTX for at least 3 months.

Participants also were required to be at least 18 years old; to have had RA for at least 1 year since diagnosis; to have functional status I, II, or III disease; and to have active disease, defined as 10 or more swollen joints, 12 or more tender joints, and C-reactive protein levels of 10 mg/L or higher. Patients were required to maintain a steady dose of MTX for at least 28 days before enrollment.

Patients were not allowed to take any other disease-modifying antirheumatic drugs (DMARDs) during the study, and patients were required to undergo washout of other DMARDs at least 28 days before randomization.

Patients were randomized 2:1 to receive a fixed dose of abatacept (approximately 10 mg/kg) or placebo by intravenous infusion on days 1, 15, and 29 for the first month and every 28 days thereafter for up to 12 months. All patients remained on MTX at a weekly dose of 15 mg or greater throughout the study.

A total of 652 patients participated in the trial, with 433 in the abatacept-MTX group and 219 patients in the placebo-MTX group. The mean age of the patients was 51.5 years, and the mean disease duration was 8.6 years.

Health outcomes were assessed using the Medical Outcomes Study Short Form (SF)-36 Health Survey, consisting of eight scales covering physical and mental health, and the Health Assessment Questionnaire (HAQ), designed to assess physical functioning. Both questionnaires were self-administered. Patients completed the SF-36 at baseline and at months 1, 3, 6, and 12. Patients completed the HAQ at baseline, at days 15 and 29 within the first month of treatment, and every 28 days thereafter.

“[T]he physical functioning of these patients is comparable to that of patients with congestive heart failure in the general U.S. population,” wrote Dr. Russell. In both treatment groups mean baseline scores were approximately one standard deviation below the U.S. population norm for most of the eight subscales of the SF-36.

The mean physical component summary (PCS) scores of the SF-36 were 30.6 for the abatacept-MTX group and 30.7 for the placebo-MTX group at baseline, approximately two SD below the U.S. population norm of 50. Baseline mean scores in the mental component summary (MCS) of the SF-36 were 41.8 in the abatacept-MTX group and 40.8 in the placebo-MTX group, approximately one SD below the U.S. population norm of 50.

Differences between the two treatment groups in quality-of-life measures emerged within the first month of treatment. Relative to the placebo-MTX group, the abatacept-MTX group showed significant improvement by day 29 for five of the eight SF-36 subdomains: self-reported bodily pain, role physical, general health, vitality, and social functioning.

“After 3 months of treatment, the difference between abatacept and placebo widened for all of the SF-36 domains,” reported Dr. Russell (Ann. Rheum. Dis. 2007 [Epub doi: 10.1136/ard.2006.057018]).

For each of the various health outcome categories, investigators calculated the proportion of patients in each treatment group whose score improved by at least 0.5 SD over the 12-month study period. Significant differences were observed in the abatacept-MTX group relative to the placebo-MTX group after 12 months in the proportion of patients who showed improvement in PCS (67.2% vs. 51.1%, respectively) and in HAQ (72.4% vs. 55.2%, respectively).

“Combined abatacept and MTX treatment produces significant improvements across a wide range of health-related quality of life domains in patients with RA,” concluded Dr. Russell.

The project was supported financially by Bristol-Myers Squibb, makers of Orencia (abatacept).