Tag: fenofibrate

Categories : Metabolic DisordersTags :

Fenofibrate Confers Modest Risk Reduction for Diabetic Retinal Disease

On By ModernMedia
Retina showing reticular pseudodrusen. Credit: National Eye Institute

Taking the cholesterol-lowering drug fenofibrate had a modest but statistically significant association with reduced risk of vision-threatening diabetic retinopathy (VTDR), according to results of a large study published in JAMA Ophthalmology. In the study, fenofibrate use was associated with an 8% lower risk of progression compared to non-use.

Fenofibrate use had a greater effect on the risk of proliferative diabetic retinopathy, with a 24% decrease in progression (PDR) but did not significantly affect the risk of developing diabetic macular oedema (DME).

The researchers noted that these findings are in line with evidence showing fenofibrate may protect against diabetes-associated breakdown of the blood-retinal barrier, although ophthalmologists rarely use the drug to treat diabetic eye disease.

“Our positive association for progression to PDR coincides with results of previous clinical trials and adds new information with regards to the impact on DME,” the researchers stated.

Protection against progression to PDR “was found without regards to underlying NPDR [nonproliferative diabetic retinopathy] severity level, which is not well coded within the claims database,” the researchers continued. “Understanding this limitation and how the inclusion of NPDR severity levels that may not benefit from fenofibrates would bias our findings to the null means that the positive association seen in our study is actually an underestimate of the true association.”

While fenofibrate’s mechanism of action in diabetic retinopathy is not well understood, “interest in the use of this oral agent has become substantial,” noted Robert N. Frank, MD. author of an accompanying editorial.

“From the point of view of a clinician with a long-time interest in diabetic retinopathy, its causal mechanisms, and its evolving treatments, the possibility that an oral medication originally used for a different disease may be beneficial for the management of diabetic eye disease is exciting,” Dr Frank wrote.

“The evidence that fenofibrate can slow the progression of diabetic retinopathy is growing, but it has not yet become a widely accepted treatment,” he added. “It will be interesting to see how this large population analysis and the results from the ongoing DRCR Retina Network  randomised clinical trial will affect clinical practice in the years to come.”

Two clinical trials that evaluated fenofibrate’s effect on diabetic eye disease, the FIELD study and the ACCORD-Eye trial yielded conflicted findings regarding DME, PDR and progression of diabetic retinopathy. Both trials suggested that only patients with mild nonproliferative eye disease were likely to benefit.

To help inform decision-making on fenofibrate in eye disease, researchers drew on a large health insurer database for 150 252 adults who had NPDR-associated lab values from January 2002 through June 2019. The primary outcomes were a new diagnosis of VTDR (composite of PDR or DME) or DME and PDR individually.

The analysis showed 5835 (3.9%) used fenofibrate. During follow-up, 27 325 patients progressed to VTDR, including 4 086 to PDR and 22 750 to DME. While men accounted for a larger proportion of fenofibrate users (61.1% vs 51.0% of nonusers), patients had similar baseline characteristics.

Study limitations included lack of clinical applicability, not accounting for duration of fenofibrate use, and data being drawn from a single database.

Source: MedPage Today

Categories : COVIDTags :

Small Trial Sees ‘Astounding’ Effect of Fenofibrate in Severe COVID

On By ModernMedia
Source: Fusion Medical Animation on Unsplash

A small interventional trial with 15 severely ill COVID patients showed an ‘astounding’ effect of fenofibrate as a treatment.

Recently, Professor Yaakov Nahmias’ team at the Hebrew University of Jerusalem (HU) reported that COVID causes abnormal accumulation of lipids, known to initiate severe inflammation through a process called lipotoxicity. In 2020, the researchers conducted lab testing of fenofibrate, a lipid-lowering drug, showing it both reduced lung cell damage while blocked virus replication. These results have since been confirmed by other studies, and in October 2020 an observational study was reported to support the original findings. This led to an interventional, single-arm open-label study to validate the findings.

The study recruited 15 severe-hospitalised COVID patients with pneumonia requiring oxygen support, who were given 145 mg/day of fenofibrate for 10 days in addition to standard care and continuously monitored for disease progression and outcomes. 

‘Astounding’ results
“The results were astounding,” Prof Nahmias declared. “Progressive inflammation markers, that are the hallmark of deteriorative COVID, dropped within 48 hours of treatment. Moreover, 14 of the 15 severe patients didn’t require oxygen support within a week of treatment, while historical records show that the vast majority severe patients treated with the standard of care require lengthy respiratory support,” he added. 

No ‘silver bullet’
Fenofibrate is a well-known, FDA-approved drug for the treatment of hypertriglyceridemia, primary hypercholesterolemia, or mixed dyslipidemia and has a good safety profile. “There are no silver bullets,” cautioned Nahmias, “but fenofibrate is far safer than other drugs proposed to date, and its mechanism of action makes is less likely to be variant-specific.”

“All patients were discharged within less than a week after the treatment began and were discharged to complete the 10-day treatment at home, with no drug-related adverse events reported,” noted Professor Shlomo Maayan, head of Infectious Disease Unit at Barzilai, where the study was conducted. “Further, fewer patients reported COVID side effects during their 4-week follow-up appointment,” he added. These preliminary findings are promising for patients who severe the acute phase of severe COVID.

However, the researchers stressed that while the results were extremely promising, only randomised placebo-controlled studies can serve as basis for clinical decisions. “We entered the second phase of the study and are actively recruiting patients,” explained Prof Nahmias, noting that two Phase 3 studies are already being conducted.

The findings, which are currently under peer review, were released on Research Square.

Source: Medical Xpress