司帕生坦的作用功效及副作用？

(sparsentan) Phase III clinical studies have shown that sparsentan is not only a dual-target antihypertensive drug, but also can reduce proteinuria in patients with primary immunoglobulin A nephropathy due to rapid disease progression, and effectively reduce proteinuria in patients with immunoglobulin A nephropathy (IgAN) and focal segmental glomerulosclerosis. Common side effects of this drug include: swelling of the hands, legs, ankles, and feet (peripheral edema), dizziness, and low red blood cells (anemia).

About Sparsentan

Sparsentan is a dual endothelin-angiotensin receptor antagonist (DEARA), developed by the American company Travere Therapeutics, with the trade name Filspari. On February 17, 2023, the U.S. FDA accelerated the marketing approval of Sparsentan, which is used to reduce proteinuria in adult patients with primary IgA (immunoglobulin A) nephropathy (usually the urine protein to creatinine ratio (UP/C) is greater than or equal to 1.5) to reduce the risk of rapid disease progression.

For more information about sparsentan, please refer to: This article details the usage and dosage.

The role of sparsentan

Sparsentan is a dual endothelin-angiotensin receptor antagonist (DEARA) that acts on dual targets and has antihypertensive effects. The drug can reduce proteinuria in patients with primary immunoglobulin A nephropathy (IgAN) that occurs due to rapid disease progression, effectively reducing the risk of disease progression in such patients.

At the same time, sparsentan has also been proven to have a certain effect on proteinuria in patients with focal segmental glomerulosclerosis, helping to improve the patients' renal function. By acting on dual targets, sparsentan not only lowers blood pressure, but also plays a positive role in the treatment of kidney disease, providing patients with a new treatment option.

Efficacy of Sparsentan

Research Methods: PROTECT was an international, randomized, double-blind, active-controlled study conducted at 134 clinical practice sites in 18 countries. This study examined the efficacy of sparsentan versus irbesartan in adults (≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1.0 g/day or greater despite maximal treatment with a renin-angiotensin system inhibitor for at least 12 weeks [1].

Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, based on estimated glomerular filtration rate at screening (30 to <60 mL/min/1.73 m/min in strata 2 and ≥60 mL/min/1.73 m2) and urinary protein excretion at screening (≤1.75 g/day and >1.75 g/day). The primary efficacy endpoint was the change from baseline to week 36 in urine protein-to-creatinine ratio based on 24-hour urine samples, assessed using a mixed model for repeated measures. Treatment-emergent adverse events (TEAEs) were the safety endpoint. All endpoints were examined in subjects who received at least one randomized dose of treatment. The study is ongoing and registered with ClinicalTrials.gov NCT03762850.

Study findings: Between December 20, 2018, and May 26, 2021, 404 subjects were randomly assigned and treated with either the spaxentan group (n=202) or the irbesartan group (n=202). The geometric least squares mean percentage change from baseline in the urinary protein-to-creatinine ratio at week 36 was statistically significantly greater in the sparsentan group (-49·8%) than in the irbesartan group (-15·1%), resulting in a 41% relative reduction between groups (least squares mean ratio=0·59; 95% CI 0·51-0·69; p<0·0001). TEAEs containing sparsentan are similar to those of irbesartan. There were no cases of severe edema, heart failure, hepatotoxicity, or edema-related discontinuation. Changes in body weight from baseline did not differ between the sparsentan and irbesartan groups.

Study conclusion: Compared with irbesartan, once-daily sparsentan treatment can significantly reduce proteinuria in adult patients with IgA nephropathy. The safety profile of sparsentan is similar to that of irbesartan.

Sparsentan's side effects

Common side effects of Sparsentan include: swelling of hands, legs, ankles and feet (peripheral edema), dizziness, low red blood cells (anemia), etc. The following are general treatment measures:

1. For swelling of hands, legs, ankles and feet (peripheral edema): It is recommended that patients avoid standing or sitting for long periods of time and try to elevate the affected parts. You can use cold compresses or gentle massage to relieve swelling. If it is serious, you should seek medical treatment in time.

2. For dizziness: Patients should avoid standing up or changing their position suddenly while taking sparsentan, maintain adequate water intake, and avoid dizziness caused by hypotension. If dizziness symptoms persist, they should seek medical treatment in time.

3. For low red blood cells (anemia): It is recommended that patients increase their intake of foods rich in iron, vitamin B12 and folic acid, such as meat, vegetables, fruits, etc., and at the same time follow the doctor's advice to supplement relevant nutrients or drug treatment, regularly monitor hemoglobin levels, and adjust the treatment plan if necessary. If symptoms are severe or persistent, seek medical attention promptly.

References

[1]Heerspink HJL, Radhakrishnan J, Alpers CE, Barratt J, Bieler S, Diva U, Inrig J, Komers R, Mercer A, Noronha IL, Rheault MN, Rote W, Rovin B, Trachtman H, Trimarchi H, Wong MG, Perkovic V; PROTECT Investigators. Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomized, double-blind, active-controlled clinical trial. Lancet. 2023 May 13;401(10388):1584-1594. doi: 10.1016/S0140-6736(23)00569-X. Epub 2023 Apr 1. PMID: 37015244.

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