Statins with TNFa Treatment Lowers LDL levels in PsA

Among rheumatic disease patients, cardiovascular disease is the main cause of death. Consequently, controlling the inflammation that promotes atherosclerosis in this group is critical. Recent research indicates adding a statin to an existing therapy could reduce cardiovascular disease risk in patients with autoimmune disease.

The new study, published in Arthritis Research & Therapy, looked at how tumor necrosis factor-⍺ (TNF-⍺) influences the lipid profile and atherogenic index (AI) in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) patients.

To date, research into the effect of TNF-⍺ has been inconsistent. This is the first study to examine the impact on patients with autoimmune diseases. The study’s central aim was to assess TNF-⍺’s influence on total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and AI. It also evaluated the role statins played.

“The influence of TNF-⍺ inhibitors on lipid profile is controversial,” said Devy Zisman, M.D. , a rheumatologist in the Carmel Medical Center in Haifa, Israel. “Our study documents the real-life, long-term follow-up influence on TNF-⍺ inhibitors treatment on lipid profile of patients with rheumatic diseases. We found that this treatment promotes an atherogenic lipid profile most pronounced in patients not treated by statins, expressed by a significant increase in LDL, TC, and TG levels.”

The Study

The study is a retrospective cohort analysis conducted with patient records from the Clalit Health Services in Haifa and the Western Galilee districts in northern Israel. Investigators reviewed medical records for RA, PsA, and AS patients treated between 2001 and 2011, beginning TNF-⍺ treatment during that time. Treatment continued for at least 270 consecutive days with a lipid profile taken at baseline, 0-6 months, 6-12 months, 12-18 months and 18-24 months.

Patients were divided into three categories:Patients not treated with statins.

• Patients who started statin therapy during the study period, after the initiation of treatment with TNF-⍺ inhibitors.
• Patients who were treated with statins prior to and during the entire study period.

Patients from Group 2 and 3 were included if their type and dose of statin remained constant during the study period.

During the study, investigators also collected data on various co-morbidities, including diabetes, hypertension, hyperlipidemia, and ischemic heart disease, as well as various medications, such as TNF-⍺ inhibitors, steroids, disease-modifying anti-rheumatic drugs, statins, and fibrates.

Results

Overall, researchers analyzed the records of 311 patients – 152 RA patient, 90 PsA, and 69 AS. Based on the data, TC and TG increased following TNF-⍺ inhibitors, rising from 180.85 +/- 2.12 mg/dl and 116.00 +/- 3.55 mg/dl at baseline to 188.12 +/- 2.35 mg/dl (p=0.02) and 132.02 +/- 4.63 mg/dl at 6 months (p<0.01), respectively. It also increased to 184.44 +/- 2.09 mg/dl (p=0.02) and 129.36 +/- 4.32 mg/dl at 18-24 months (p<0.01), respectively.

In addition, AI increased following TNF-⍺ inhibitor treatment from 0.032 +/- 0.017 at baseline to 0.004 +/- 0.019 at 18-24 months (p<0.01). However, LDL decreased in patients who were treated with statins before and during the overall study period, dropping from 119.97 +/- 2.86 mg/dl at baseline to 104.02 +/- 3.57 mg/dl at 18-24 months (p<0.01). LDL increased in patients not treated with statins.

Real-Life Impact

According to Zisman, the main finding, is that starting therapy before and during treatment with TNF-⍺ inhibitors protects against anticipated leaps in LDL values. Consequently, starting treatment with statins before TNF-⍺ inhibitor therapy begins can help patients side-step that increase, promoting a drop in cardiovascular risk in rheumatic patients while simultaneously treating inflammation.

These results were seen long-term for RA, PsA, and AS patients that were treated with TNF-⍺ inhibitors. The research revealed this treatment supports an atherogenic lipid profile most often seen in patients who don’t take statins. These patients experience a substantive increase in the AI, LDL, TC, and TG levels. Consequently, statin therapy could also lower LDL levels if a patient starts it during TNF-⍺ inhibitors.

According to researchers, no other study has revealed and highlighted the benefit to LDL levels of adding in statin treatment to TNF-⍺ inhibitors.

Any lipid profile changes with TNF-⍺ inhibitor treatment were relatively small and statistically non-significant with unclear clinical ramifications. Initially, HDL initially increased during the first 24 weeks of treatment, but overtime, they slowly returned to baseline levels.

Some of this study’s findings supported existing research, and others didn’t. For example, this study agreed with published research that a significant increase in TC levels occurs following TNF-⍺ inhibitor treatment, as well as an increase in TG levels following TNF-⍺ inhibitors. Other studies disagreed with these findings of an increase in AI.

Overall, the study findings support the need for further research into how adding statin therapy impacts LDL levels in patients with increased TNF-⍺ activity levels versus patients with low TNF-⍺ activity levels, such as those receiving TNF-⍺ inhibitors.

Limitations

Not only was the study retrospective and observational without a control group, but the study cohort included a small sample group. Included patients took various medications, such as steroids and fibrates and had other conditions, including diabetes, that could affect lipid metabolism.

Because the study was retrospective, follow-up wasn’t completed on all included patients. Researchers also estimated drug intake based on pharma-dispensed prescriptions.

In the future, investigators said, evaluating long-term TNF-⍺ therapy effects on carotid artery findings and its connection to lipid profile changes would be intriguing. They would shed light on cardiovascular risks.

References:

Zisman, Devy, et al. “Effects of anti-TNF-⍺ treatment on lipid profile in rheumatic disease: an analytical cohort study,” Arthritis Research & Therapy. Nov. 10, 2016. DOI: 10/1186/s13075-016-1148-1

Jacobsson, LT, et al. “Treatment with TNF blockers and mortality risk in patients with rheumatoid arthritis,” Annals of the Rheumatic Diseases. Dec. 11, 2006. DOI:  DOI:10.1136/ard.2006.062497