Exploring the Safety of the New Subcutaneous Abatacept

NEW YORK – Recent data indicate that the subcutaneous formulation of abatacept is comparable in safety to the intravenous formulation in the management of rheumatoid arthritis, according to Dr. Yusuf Yazici, who spoke at "The ‘Tightrope’ of RA Therapy" course sponsored by New York University.

"For the first time, we have a biologic that is available in both infusible and injectable versions, giving patients an option of using one or the other," said Dr. Yazici, director of the Seligman Center for Advanced Therapeutics at New York University.

The subcutaneous formulation of abatacept became commercially available in September 2011.

Safety data were presented as part of the phase IIIb, double-blind, 6-month ACQUIRE (Abatacept Comparison of Sub(Qu)cutaneous vs. Intravenous in Inadequate Responders to Methotrexate) registration trial of subcutaneous abatacept. That study, however, included fewer than 700 patients with rheumatoid arthritis (RA) in both the subcutaneous and intravenous arms (Arthritis Rheum. 2011;63:2854-64). Injection site reactions, including hematoma, pruritus, and erythema, were found in 2.6% of the subcutaneous group and 2.5% of the intravenous group. Serious infections were reported in 0.7% of the subcutaneous group and 1.4% of the intravenous group, said Dr. Yazici, who also is with the Behcet’s Syndrome Evaluation, Treatment, and Research Center at New York University.

A study presented at the 2011 EULAR (European League Against Rheumatism) annual congress by Dr. Rieke Alten, of the University of Medicine in Berlin, provided data on the long-term safety of subcutaneous abatacept. The study included pooled safety data from five clinical trials on 1,879 RA patients who had up to 4.5 years of exposure, representing 3,086 patient-years of use. The subcutaneous formulation was found to produce effects generally consistent with those of the intravenous formulation. Mean duration of exposure was 20 months in the subcutaneous group, compared with 36 months for the intravenous group. Data on the safety of the intravenous formulation came from an integrated safety analysis from the abatacept RA clinical trial program, which included 4,149 patients with 12,132 patient-years of exposure. These data were presented at the 2010 annual meeting of the American College of Rheumatology.

Dr. Alten found the incidence rate for death to be 0.55 events/100 patient-years in the subcutaneous group, compared with 0.60 in the intravenous group. The incidence rate for serious adverse events was 9.53 in the subcutaneous group vs. 14.61 in the intravenous group, and did not increase with increasing abatacept exposure over time. The incidence of injection site reactions in the subcutaneous group was 2.22, and more than 95% of reactions were mild.

As far as serious infections, the incidence rates of the most common ones after subcutaneous injections were 0.36 for pneumonia (vs. 0.46 in the intravenous group), 0.10 for lobar pneumonia (vs. 0.11), 0.10 for herpes zoster (vs. 0.03), and 0.03 (vs. 0.03) for tuberculosis. The incidence rates for malignancies, excluding nonmelanoma skin cancer, were 0.68 in patients receiving subcutaneous abatacept and 0.73 in the intravenous group. The incidence rates for autoimmune events, including psoriasis and Sjögren’s syndrome, were 1.28 with subcutaneous administration and 1.99 with intravenous use.

Unlike the intravenous formulation, subcutaneous abatacept can be self-administered, allowing patients to forego trips to the physician’s office for infusions – a benefit for those who have busy schedules or transportation limitations. Diabetics may prefer the subcutaneous formulation because it does not contain maltose, which can interfere with the accuracy of blood sugar readings. On the other hand, some patients may be anxious about self-injection or unwilling to take the time to secure their own supplies (such as bandages, alcohol swabs, cotton balls, and puncture-resistant containers for syringes) or prepare the syringes, which must be kept cool before use and then warmed before injection; they may prefer the monthly infusions given at the doctor’s office.

The label’s product information for abatacept recommends a single intravenous infusion as a loading dose (based on body weight) preceding the first 125-mg subcutaneous injection. Dr. Yazici reviewed recent data that challenged that recommendation. These findings come from a study by Dr. Peter T. Nash of the University of Queensland, Brisbane, that were presented at the 2011 EULAR congress. The study involved a comparison of open-label data from two phase III trials that showed comparable improvements with subcutaneous abatacept, with or without an intravenous loading dose, on physical function, as assessed by the Health Assessment Questionnaire–Disease Index, and disease activity, as assessed by the Disease Activity Score 28/C-reactive protein.

Dr. Yazici serves as a consultant to Bristol-Myers Squibb and Genentech. Dr. Alten receives grant or research support from, is a consultant for, or is on the speakers bureau of Abbott Laboratories, Bristol-Myers Squibb, Horizon Pharma, Merck Pharma GmbH, Nitec Pharma GmbH, Norvartis Pharmaceuticals, Roche, and Wyeth Pharmaceuticals.

NEW YORK – Recent data indicate that the subcutaneous formulation of abatacept is comparable in safety to the intravenous formulation in the management of rheumatoid arthritis, according to Dr. Yusuf Yazici, who spoke at "The ‘Tightrope’ of RA Therapy" course sponsored by New York University.

"For the first time, we have a biologic that is available in both infusible and injectable versions, giving patients an option of using one or the other," said Dr. Yazici, director of the Seligman Center for Advanced Therapeutics at New York University.

The subcutaneous formulation of abatacept became commercially available in September 2011.

Safety data were presented as part of the phase IIIb, double-blind, 6-month ACQUIRE (Abatacept Comparison of Sub(Qu)cutaneous vs. Intravenous in Inadequate Responders to Methotrexate) registration trial of subcutaneous abatacept. That study, however, included fewer than 700 patients with rheumatoid arthritis (RA) in both the subcutaneous and intravenous arms (Arthritis Rheum. 2011;63:2854-64). Injection site reactions, including hematoma, pruritus, and erythema, were found in 2.6% of the subcutaneous group and 2.5% of the intravenous group. Serious infections were reported in 0.7% of the subcutaneous group and 1.4% of the intravenous group, said Dr. Yazici, who also is with the Behcet’s Syndrome Evaluation, Treatment, and Research Center at New York University.

A study presented at the 2011 EULAR (European League Against Rheumatism) annual congress by Dr. Rieke Alten, of the University of Medicine in Berlin, provided data on the long-term safety of subcutaneous abatacept. The study included pooled safety data from five clinical trials on 1,879 RA patients who had up to 4.5 years of exposure, representing 3,086 patient-years of use. The subcutaneous formulation was found to produce effects generally consistent with those of the intravenous formulation. Mean duration of exposure was 20 months in the subcutaneous group, compared with 36 months for the intravenous group. Data on the safety of the intravenous formulation came from an integrated safety analysis from the abatacept RA clinical trial program, which included 4,149 patients with 12,132 patient-years of exposure. These data were presented at the 2010 annual meeting of the American College of Rheumatology.

Dr. Alten found the incidence rate for death to be 0.55 events/100 patient-years in the subcutaneous group, compared with 0.60 in the intravenous group. The incidence rate for serious adverse events was 9.53 in the subcutaneous group vs. 14.61 in the intravenous group, and did not increase with increasing abatacept exposure over time. The incidence of injection site reactions in the subcutaneous group was 2.22, and more than 95% of reactions were mild.

As far as serious infections, the incidence rates of the most common ones after subcutaneous injections were 0.36 for pneumonia (vs. 0.46 in the intravenous group), 0.10 for lobar pneumonia (vs. 0.11), 0.10 for herpes zoster (vs. 0.03), and 0.03 (vs. 0.03) for tuberculosis. The incidence rates for malignancies, excluding nonmelanoma skin cancer, were 0.68 in patients receiving subcutaneous abatacept and 0.73 in the intravenous group. The incidence rates for autoimmune events, including psoriasis and Sjögren’s syndrome, were 1.28 with subcutaneous administration and 1.99 with intravenous use.

Unlike the intravenous formulation, subcutaneous abatacept can be self-administered, allowing patients to forego trips to the physician’s office for infusions – a benefit for those who have busy schedules or transportation limitations. Diabetics may prefer the subcutaneous formulation because it does not contain maltose, which can interfere with the accuracy of blood sugar readings. On the other hand, some patients may be anxious about self-injection or unwilling to take the time to secure their own supplies (such as bandages, alcohol swabs, cotton balls, and puncture-resistant containers for syringes) or prepare the syringes, which must be kept cool before use and then warmed before injection; they may prefer the monthly infusions given at the doctor’s office.

The label’s product information for abatacept recommends a single intravenous infusion as a loading dose (based on body weight) preceding the first 125-mg subcutaneous injection. Dr. Yazici reviewed recent data that challenged that recommendation. These findings come from a study by Dr. Peter T. Nash of the University of Queensland, Brisbane, that were presented at the 2011 EULAR congress. The study involved a comparison of open-label data from two phase III trials that showed comparable improvements with subcutaneous abatacept, with or without an intravenous loading dose, on physical function, as assessed by the Health Assessment Questionnaire–Disease Index, and disease activity, as assessed by the Disease Activity Score 28/C-reactive protein.

Dr. Yazici serves as a consultant to Bristol-Myers Squibb and Genentech. Dr. Alten receives grant or research support from, is a consultant for, or is on the speakers bureau of Abbott Laboratories, Bristol-Myers Squibb, Horizon Pharma, Merck Pharma GmbH, Nitec Pharma GmbH, Norvartis Pharmaceuticals, Roche, and Wyeth Pharmaceuticals.

NEW YORK – Recent data indicate that the subcutaneous formulation of abatacept is comparable in safety to the intravenous formulation in the management of rheumatoid arthritis, according to Dr. Yusuf Yazici, who spoke at "The ‘Tightrope’ of RA Therapy" course sponsored by New York University.

"For the first time, we have a biologic that is available in both infusible and injectable versions, giving patients an option of using one or the other," said Dr. Yazici, director of the Seligman Center for Advanced Therapeutics at New York University.

The subcutaneous formulation of abatacept became commercially available in September 2011.

Safety data were presented as part of the phase IIIb, double-blind, 6-month ACQUIRE (Abatacept Comparison of Sub(Qu)cutaneous vs. Intravenous in Inadequate Responders to Methotrexate) registration trial of subcutaneous abatacept. That study, however, included fewer than 700 patients with rheumatoid arthritis (RA) in both the subcutaneous and intravenous arms (Arthritis Rheum. 2011;63:2854-64). Injection site reactions, including hematoma, pruritus, and erythema, were found in 2.6% of the subcutaneous group and 2.5% of the intravenous group. Serious infections were reported in 0.7% of the subcutaneous group and 1.4% of the intravenous group, said Dr. Yazici, who also is with the Behcet’s Syndrome Evaluation, Treatment, and Research Center at New York University.

A study presented at the 2011 EULAR (European League Against Rheumatism) annual congress by Dr. Rieke Alten, of the University of Medicine in Berlin, provided data on the long-term safety of subcutaneous abatacept. The study included pooled safety data from five clinical trials on 1,879 RA patients who had up to 4.5 years of exposure, representing 3,086 patient-years of use. The subcutaneous formulation was found to produce effects generally consistent with those of the intravenous formulation. Mean duration of exposure was 20 months in the subcutaneous group, compared with 36 months for the intravenous group. Data on the safety of the intravenous formulation came from an integrated safety analysis from the abatacept RA clinical trial program, which included 4,149 patients with 12,132 patient-years of exposure. These data were presented at the 2010 annual meeting of the American College of Rheumatology.

Dr. Alten found the incidence rate for death to be 0.55 events/100 patient-years in the subcutaneous group, compared with 0.60 in the intravenous group. The incidence rate for serious adverse events was 9.53 in the subcutaneous group vs. 14.61 in the intravenous group, and did not increase with increasing abatacept exposure over time. The incidence of injection site reactions in the subcutaneous group was 2.22, and more than 95% of reactions were mild.

As far as serious infections, the incidence rates of the most common ones after subcutaneous injections were 0.36 for pneumonia (vs. 0.46 in the intravenous group), 0.10 for lobar pneumonia (vs. 0.11), 0.10 for herpes zoster (vs. 0.03), and 0.03 (vs. 0.03) for tuberculosis. The incidence rates for malignancies, excluding nonmelanoma skin cancer, were 0.68 in patients receiving subcutaneous abatacept and 0.73 in the intravenous group. The incidence rates for autoimmune events, including psoriasis and Sjögren’s syndrome, were 1.28 with subcutaneous administration and 1.99 with intravenous use.

Unlike the intravenous formulation, subcutaneous abatacept can be self-administered, allowing patients to forego trips to the physician’s office for infusions – a benefit for those who have busy schedules or transportation limitations. Diabetics may prefer the subcutaneous formulation because it does not contain maltose, which can interfere with the accuracy of blood sugar readings. On the other hand, some patients may be anxious about self-injection or unwilling to take the time to secure their own supplies (such as bandages, alcohol swabs, cotton balls, and puncture-resistant containers for syringes) or prepare the syringes, which must be kept cool before use and then warmed before injection; they may prefer the monthly infusions given at the doctor’s office.

The label’s product information for abatacept recommends a single intravenous infusion as a loading dose (based on body weight) preceding the first 125-mg subcutaneous injection. Dr. Yazici reviewed recent data that challenged that recommendation. These findings come from a study by Dr. Peter T. Nash of the University of Queensland, Brisbane, that were presented at the 2011 EULAR congress. The study involved a comparison of open-label data from two phase III trials that showed comparable improvements with subcutaneous abatacept, with or without an intravenous loading dose, on physical function, as assessed by the Health Assessment Questionnaire–Disease Index, and disease activity, as assessed by the Disease Activity Score 28/C-reactive protein.

Dr. Yazici serves as a consultant to Bristol-Myers Squibb and Genentech. Dr. Alten receives grant or research support from, is a consultant for, or is on the speakers bureau of Abbott Laboratories, Bristol-Myers Squibb, Horizon Pharma, Merck Pharma GmbH, Nitec Pharma GmbH, Norvartis Pharmaceuticals, Roche, and Wyeth Pharmaceuticals.