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Patients with refractory rheumatoid arthritis who switched to tocilizumab showed no increased cardiovascular risk when compared with those who switched to a tumor necrosis factor inhibitor in a large cohort study.
Rheumatoid arthritis is known to approximately double the risk of cardiovascular morbidity and mortality partly because of its associated chronic systemic inflammation. Several small trials and observational studies have reported that tocilizumab, an interleukin-6 receptor antagonist typically used as a second-line treatment for RA, elevates serum lipids, including LDL cholesterol. These serum lipid elevations caused by tocilizumab have brought concerns that the drug may further heighten CV risk in people with RA, said Seoyoung C. Kim, MD, ScD, of the division of pharmacoepidemiology and pharmacoeconomics and the division of rheumatology, immunology, and allergy at Brigham and Women’s Hospital, Boston, and her associates.
To minimize the effect of confounding by the severity of RA and the baseline CV risk, the researchers adjusted the data to account for more than 90 variables related to CV events and to RA severity.
The primary outcome — a composite of MI and stroke — occurred in 125 patients, 36 taking tocilizumab and 89 taking TNF inhibitors. The rate of this composite outcome was 0.52 per 100 person-years with tocilizumab and 0.59 per 100 person-years for TNF inhibitors, a nonsignificant difference, Dr. Kim and her associates reported (Arthritis Rheumatol. 2017 Feb 28. doi: 10.1002/art.40084).
There also were no significant differences between the two study groups in secondary endpoints, including rates of coronary revascularization, acute coronary syndrome, heart failure, and all-cause mortality. In addition, all subgroup analyses confirmed that tocilizumab did not raise CV risk, regardless of patient age (younger than or older than 60 years), the presence of cardiovascular disease at baseline, the presence of diabetes, the use of methotrexate, the use of oral steroids, or the use of statins.
These “reassuring” findings show that even though tocilizumab appears to raise LDL levels, “such increases do not appear to be associated with an increased risk of clinical CV events,” the investigators said.
The results confirm those reported at the 2016 American College of Rheumatology annual meeting for the 5-year, randomized, postmarketing ENTRACTE trial in which the lipid changes induced by tocilizumab did not translate into an increased risk of heart attack or stroke in RA patients.
This cohort study was sponsored by Genentech, which markets tocilizumab (Actemra). Dr. Kim reported ties to Genentech, Lilly, Pfizer, Bristol-Myers Squibb, and AstraZeneca. Her associates reported ties to Genentech, Lilly, Pfizer, AstraZeneca, Amgen, Corrona, Whiscon, Aetion, and Boehringer Ingelheim. Three of the seven authors were employees of Genentech.
Patients with refractory rheumatoid arthritis who switched to tocilizumab showed no increased cardiovascular risk when compared with those who switched to a tumor necrosis factor inhibitor in a large cohort study.
Rheumatoid arthritis is known to approximately double the risk of cardiovascular morbidity and mortality partly because of its associated chronic systemic inflammation. Several small trials and observational studies have reported that tocilizumab, an interleukin-6 receptor antagonist typically used as a second-line treatment for RA, elevates serum lipids, including LDL cholesterol. These serum lipid elevations caused by tocilizumab have brought concerns that the drug may further heighten CV risk in people with RA, said Seoyoung C. Kim, MD, ScD, of the division of pharmacoepidemiology and pharmacoeconomics and the division of rheumatology, immunology, and allergy at Brigham and Women’s Hospital, Boston, and her associates.
To minimize the effect of confounding by the severity of RA and the baseline CV risk, the researchers adjusted the data to account for more than 90 variables related to CV events and to RA severity.
The primary outcome — a composite of MI and stroke — occurred in 125 patients, 36 taking tocilizumab and 89 taking TNF inhibitors. The rate of this composite outcome was 0.52 per 100 person-years with tocilizumab and 0.59 per 100 person-years for TNF inhibitors, a nonsignificant difference, Dr. Kim and her associates reported (Arthritis Rheumatol. 2017 Feb 28. doi: 10.1002/art.40084).
There also were no significant differences between the two study groups in secondary endpoints, including rates of coronary revascularization, acute coronary syndrome, heart failure, and all-cause mortality. In addition, all subgroup analyses confirmed that tocilizumab did not raise CV risk, regardless of patient age (younger than or older than 60 years), the presence of cardiovascular disease at baseline, the presence of diabetes, the use of methotrexate, the use of oral steroids, or the use of statins.
These “reassuring” findings show that even though tocilizumab appears to raise LDL levels, “such increases do not appear to be associated with an increased risk of clinical CV events,” the investigators said.
The results confirm those reported at the 2016 American College of Rheumatology annual meeting for the 5-year, randomized, postmarketing ENTRACTE trial in which the lipid changes induced by tocilizumab did not translate into an increased risk of heart attack or stroke in RA patients.
This cohort study was sponsored by Genentech, which markets tocilizumab (Actemra). Dr. Kim reported ties to Genentech, Lilly, Pfizer, Bristol-Myers Squibb, and AstraZeneca. Her associates reported ties to Genentech, Lilly, Pfizer, AstraZeneca, Amgen, Corrona, Whiscon, Aetion, and Boehringer Ingelheim. Three of the seven authors were employees of Genentech.
Patients with refractory rheumatoid arthritis who switched to tocilizumab showed no increased cardiovascular risk when compared with those who switched to a tumor necrosis factor inhibitor in a large cohort study.
Rheumatoid arthritis is known to approximately double the risk of cardiovascular morbidity and mortality partly because of its associated chronic systemic inflammation. Several small trials and observational studies have reported that tocilizumab, an interleukin-6 receptor antagonist typically used as a second-line treatment for RA, elevates serum lipids, including LDL cholesterol. These serum lipid elevations caused by tocilizumab have brought concerns that the drug may further heighten CV risk in people with RA, said Seoyoung C. Kim, MD, ScD, of the division of pharmacoepidemiology and pharmacoeconomics and the division of rheumatology, immunology, and allergy at Brigham and Women’s Hospital, Boston, and her associates.
To minimize the effect of confounding by the severity of RA and the baseline CV risk, the researchers adjusted the data to account for more than 90 variables related to CV events and to RA severity.
The primary outcome — a composite of MI and stroke — occurred in 125 patients, 36 taking tocilizumab and 89 taking TNF inhibitors. The rate of this composite outcome was 0.52 per 100 person-years with tocilizumab and 0.59 per 100 person-years for TNF inhibitors, a nonsignificant difference, Dr. Kim and her associates reported (Arthritis Rheumatol. 2017 Feb 28. doi: 10.1002/art.40084).
There also were no significant differences between the two study groups in secondary endpoints, including rates of coronary revascularization, acute coronary syndrome, heart failure, and all-cause mortality. In addition, all subgroup analyses confirmed that tocilizumab did not raise CV risk, regardless of patient age (younger than or older than 60 years), the presence of cardiovascular disease at baseline, the presence of diabetes, the use of methotrexate, the use of oral steroids, or the use of statins.
These “reassuring” findings show that even though tocilizumab appears to raise LDL levels, “such increases do not appear to be associated with an increased risk of clinical CV events,” the investigators said.
The results confirm those reported at the 2016 American College of Rheumatology annual meeting for the 5-year, randomized, postmarketing ENTRACTE trial in which the lipid changes induced by tocilizumab did not translate into an increased risk of heart attack or stroke in RA patients.
This cohort study was sponsored by Genentech, which markets tocilizumab (Actemra). Dr. Kim reported ties to Genentech, Lilly, Pfizer, Bristol-Myers Squibb, and AstraZeneca. Her associates reported ties to Genentech, Lilly, Pfizer, AstraZeneca, Amgen, Corrona, Whiscon, Aetion, and Boehringer Ingelheim. Three of the seven authors were employees of Genentech.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point: Patients with refractory RA who switch to tocilizumab show no increased cardiovascular risk, compared with those who switch to a TNF inhibitor.
Major finding: The primary outcome – the rate of a composite of MI and stroke – was 0.52 per 100 person-years with tocilizumab and 0.59 per 100 person-years for TNF inhibitors, a nonsignificant difference.
Data source: A cohort study involving 28,028 adults with RA enrolled in three large health care claims databases from all 50 states who were followed for a median of 1 year.
Disclosures: This study was sponsored by Genentech, which markets tocilizumab (Actemra). Dr. Kim reported ties to Genentech, Lilly, Pfizer, Bristol-Myers Squibb, and AstraZeneca. Her associates reported ties to Genentech, Lilly, Pfizer, AstraZeneca, Amgen, Corrona, Whiscon, Aetion, and Boehringer Ingelheim. Three of the seven authors were employees of Genentech.
