Tocilizumab and tofacitinib increase lipids in RA patients

Rheumatoid arthritis patients treated with the biologic tocilizumab and the Janus kinase inhibitor tofacitinib had significant changes to their lipid levels in a meta-analysis of randomized, controlled trials.

No changes in lipid profiles were observed for patients taking anti–tumor necrosis factor–alpha inhibitors in the analysis of 25 randomized, controlled trials of chronic inflammatory arthritis. The study, according to lead author Alejandro Souto of the rheumatology unit at Complejo Hospitalario Universitario de Santiago (Spain) de Compostela and his colleagues, is the first study to summarize all the data about lipid changes in patients treated with biologics and tofacitinib.

The authors found that RA patients who took tocilizumab were significantly more likely to have hypercholesterolemia (>240 mg/dL), high HDL cholesterol levels (>60 mg/dL), and high LDL cholesterol levels (>130 mg/dL) at the end of the trial than did placebo patients. In RA trials, tofacitinib treatment led to significantly greater increases in levels of HDL cholesterol (13.00 mg/dL for 5 mg twice daily and 15.21 mg/dL for 10 mg twice daily) and LDL cholesterol (11.20 mg/dL for 5 mg twice daily and 15.42 mg/dL for 10 mg twice daily) than in those who took placebo, all of which were calculated with a weight mean difference (or mean percentage increase) for the continuous variable.

The exact mechanism by which the drugs affect lipid levels is unclear. “Whether the encountered changes relate to the control of inflammation or an independent mechanism of action remains to be determined,” the study authors wrote (Arthritis Rheumatol. 2014 Oct. 9 [doi:10.1002/art.38894]).

Changes in lipid levels could not be entirely explained by reduced inflammation because several drugs for RA were effective at reducing inflammation, but only tocilizumab and tofacitinib produced significant changes in lipid profiles, they noted. Results from animal models of arthritis showed decreased levels of interleukin (IL)-6 after the administration of tofacitinib, suggesting the drug may change lipid patterns by inhibiting the inflammatory cytokine.

“Interestingly, the modulation of inflammation seems to lead to lower cardiovascular events and a reduction in mortality despite increasing lipid levels,” they wrote. “It is possible that hypercholesterolemia produced by JAK [Janus kinase] inhibitors may be caused by the inhibition of IL-6 signaling.”

The long-term consequence for cardiovascular outcomes in this population should be assessed, the authors said.

The review had several limitations, which affected the generalization of their findings, the authors said. These included a lack of data on the effects of rituximab and abatacept on lipids, or in spondyloarthritis treated with biologics. It was also limited by the fact that only 25 of 307 studies contained data on lipid pattern changes and the heterogeneous way of presenting the data.

The study was supported by an unrestricted grant from Pfizer. Two authors reported having ties to Pfizer as well as other companies that market drugs for inflammatory arthritis.

Rheumatoid arthritis patients treated with the biologic tocilizumab and the Janus kinase inhibitor tofacitinib had significant changes to their lipid levels in a meta-analysis of randomized, controlled trials.

No changes in lipid profiles were observed for patients taking anti–tumor necrosis factor–alpha inhibitors in the analysis of 25 randomized, controlled trials of chronic inflammatory arthritis. The study, according to lead author Alejandro Souto of the rheumatology unit at Complejo Hospitalario Universitario de Santiago (Spain) de Compostela and his colleagues, is the first study to summarize all the data about lipid changes in patients treated with biologics and tofacitinib.

The authors found that RA patients who took tocilizumab were significantly more likely to have hypercholesterolemia (>240 mg/dL), high HDL cholesterol levels (>60 mg/dL), and high LDL cholesterol levels (>130 mg/dL) at the end of the trial than did placebo patients. In RA trials, tofacitinib treatment led to significantly greater increases in levels of HDL cholesterol (13.00 mg/dL for 5 mg twice daily and 15.21 mg/dL for 10 mg twice daily) and LDL cholesterol (11.20 mg/dL for 5 mg twice daily and 15.42 mg/dL for 10 mg twice daily) than in those who took placebo, all of which were calculated with a weight mean difference (or mean percentage increase) for the continuous variable.

The exact mechanism by which the drugs affect lipid levels is unclear. “Whether the encountered changes relate to the control of inflammation or an independent mechanism of action remains to be determined,” the study authors wrote (Arthritis Rheumatol. 2014 Oct. 9 [doi:10.1002/art.38894]).

Changes in lipid levels could not be entirely explained by reduced inflammation because several drugs for RA were effective at reducing inflammation, but only tocilizumab and tofacitinib produced significant changes in lipid profiles, they noted. Results from animal models of arthritis showed decreased levels of interleukin (IL)-6 after the administration of tofacitinib, suggesting the drug may change lipid patterns by inhibiting the inflammatory cytokine.

“Interestingly, the modulation of inflammation seems to lead to lower cardiovascular events and a reduction in mortality despite increasing lipid levels,” they wrote. “It is possible that hypercholesterolemia produced by JAK [Janus kinase] inhibitors may be caused by the inhibition of IL-6 signaling.”

The long-term consequence for cardiovascular outcomes in this population should be assessed, the authors said.

The review had several limitations, which affected the generalization of their findings, the authors said. These included a lack of data on the effects of rituximab and abatacept on lipids, or in spondyloarthritis treated with biologics. It was also limited by the fact that only 25 of 307 studies contained data on lipid pattern changes and the heterogeneous way of presenting the data.

The study was supported by an unrestricted grant from Pfizer. Two authors reported having ties to Pfizer as well as other companies that market drugs for inflammatory arthritis.

Rheumatoid arthritis patients treated with the biologic tocilizumab and the Janus kinase inhibitor tofacitinib had significant changes to their lipid levels in a meta-analysis of randomized, controlled trials.

No changes in lipid profiles were observed for patients taking anti–tumor necrosis factor–alpha inhibitors in the analysis of 25 randomized, controlled trials of chronic inflammatory arthritis. The study, according to lead author Alejandro Souto of the rheumatology unit at Complejo Hospitalario Universitario de Santiago (Spain) de Compostela and his colleagues, is the first study to summarize all the data about lipid changes in patients treated with biologics and tofacitinib.

The authors found that RA patients who took tocilizumab were significantly more likely to have hypercholesterolemia (>240 mg/dL), high HDL cholesterol levels (>60 mg/dL), and high LDL cholesterol levels (>130 mg/dL) at the end of the trial than did placebo patients. In RA trials, tofacitinib treatment led to significantly greater increases in levels of HDL cholesterol (13.00 mg/dL for 5 mg twice daily and 15.21 mg/dL for 10 mg twice daily) and LDL cholesterol (11.20 mg/dL for 5 mg twice daily and 15.42 mg/dL for 10 mg twice daily) than in those who took placebo, all of which were calculated with a weight mean difference (or mean percentage increase) for the continuous variable.

The exact mechanism by which the drugs affect lipid levels is unclear. “Whether the encountered changes relate to the control of inflammation or an independent mechanism of action remains to be determined,” the study authors wrote (Arthritis Rheumatol. 2014 Oct. 9 [doi:10.1002/art.38894]).

Changes in lipid levels could not be entirely explained by reduced inflammation because several drugs for RA were effective at reducing inflammation, but only tocilizumab and tofacitinib produced significant changes in lipid profiles, they noted. Results from animal models of arthritis showed decreased levels of interleukin (IL)-6 after the administration of tofacitinib, suggesting the drug may change lipid patterns by inhibiting the inflammatory cytokine.

“Interestingly, the modulation of inflammation seems to lead to lower cardiovascular events and a reduction in mortality despite increasing lipid levels,” they wrote. “It is possible that hypercholesterolemia produced by JAK [Janus kinase] inhibitors may be caused by the inhibition of IL-6 signaling.”

The long-term consequence for cardiovascular outcomes in this population should be assessed, the authors said.

The review had several limitations, which affected the generalization of their findings, the authors said. These included a lack of data on the effects of rituximab and abatacept on lipids, or in spondyloarthritis treated with biologics. It was also limited by the fact that only 25 of 307 studies contained data on lipid pattern changes and the heterogeneous way of presenting the data.

The study was supported by an unrestricted grant from Pfizer. Two authors reported having ties to Pfizer as well as other companies that market drugs for inflammatory arthritis.