Can Belimumab Prevent/delay Organ Damage?

Organ damage is an important risk factor for poor long-term prognosis and early death in patients with systemic lupus erythematosus (SLE). The cardiovascular, neuropsychiatric, musculoskeletal, and renal systems are most commonly affected, and other commonly affected organs include the lungs, eyes, skin, and peripheral vascular system. The 2020 Chinese Guidelines for the Diagnosis and Treatment of Systemic Lupus Erythematosus point out that reducing organ damage is one of the treatment principles for SLE. Other treatment principles include early, individualized treatment to delay disease progression to the greatest extent and improve prognosis.

Click to Cistanche for kidney disease

Belimumab is a monoclonal antibody that inhibits B lymphocyte stimulator (BLyS) and is approved for the treatment of SLE and lupus nephritis. This article will mainly review the clinical trials and real-world data on the effects of belimumab on organ damage in adult SLE patients.

Main drivers of organ damage

Factors associated with organ damage include black African ancestry/Hispanic race, older age, male sex, preexisting organ damage, use of glucocorticoids and/or other SLE treatments, severe relapses, persistent disease activity, dyslipidemia, hypertension, and active/previous nephritis. Up to 80% of organ damage can be attributed to the use of glucocorticoids, and there is a clear dose-dependency relationship.

Organ damage assessment tool

The SLE International Collaboration Group Damage Index (SDI) is the only internationally recognized and validated SLE organ damage assessment standard. This standard independently scores 12 organ systems and is an effective tool for evaluating organ damage in clinical practice, providing a basis for better judging the prognosis of SLE patients. It is reported that the International Lupus Research Clinical Collaboration (SLICC), the American Lupus Foundation, and the ACR are developing a revised SDI to reflect the changes in the concept of organ damage. The revised SDI may be mainly used as a research tool for clinical trials.

Effect of Belimumab on Organ Damage in SLE Patients

LBSL02/LBSL99: SLE patients received belimumab treatment for ≤12 years (median exposure time: 3334 days). This study did not prospectively collect SDI data. However, the study observed improvements in patients' organ damage-related drivers, including reduced disease activity, reduced relapses, and reduced glucocorticoid use, suggesting that belimumab may have potential benefits for the progression of organ damage.

BLISS-52, BLISS-76, BLISS-NEA, BLISS-SC: All four trials evaluated the effect of intravenous or subcutaneous belimumab in the background treatment of adult SLE. Compared with background treatment alone, belimumab + background treatment significantly reduced the patient's SRI-4 score (Figure 1). Except for BLISS-76, belimumab treatment in other studies reduced the risk of severe relapse.

There was also a trend toward reducing the use of glucocorticoids in the study, but it was only statistically significant in BLISS-NEA. This feature of belimumab regarding glucocorticoids was confirmed in a post hoc pooled analysis combining the data from the BLISS-52 and BLISS-76 trials, which found that glucocorticoids had fewer increments and more reductions compared with background treatment alone.

BEL112233 and BEL112234: Based on the BLISS-52 and BLISS-76 trials, all patients can continue to receive open-label belimumab (intravenous) + background treatment during a follow-up period of more than 8 years, and organ damage is assessed every 48 weeks using SDI. At year 7, after long-term treatment with belimumab, 69.8% and 86.9% of patients had no change in SDI scores (i.e., index <1), respectively, compared with baseline SDI scores of 1.2 (1.51) and 0.6 (1.02), with changes of 0.4 (0.68) and 0.2 (0.45), respectively.

Real-world data

Study 206347: To overcome some limitations of the clinical and open-label extension study, propensity score matching (PSM) was used to evaluate the effect of belimumab versus background treatment on SLE organ damage. This is a 5-year post hoc longitudinal analysis using PSM to compare organ damage outcomes in the TLC cohort of patients in the BEL112233 study who received belimumab + background therapy with those who received background therapy alone. During the 5-year follow-up, the change in SDI score in patients treated with belimumab was significantly reduced compared with those who received background therapy alone (p<0.001); at the same time, the risk of increased SDI score in any year of follow-up was also reduced by 61% with belimumab compared with background therapy alone (HR=0.391, 95%CI: 0.253, 0.605; p<0.001).

BeRLiSS: A retrospective study (median follow-up time: 18 months) enrolled patients with active SLE to evaluate the efficacy of intravenous belimumab + background therapy, with annual SDI assessment of organ damage. Patients without organ damage at baseline (SDI score = 0) had no damage progression within 3 years of starting belimumab treatment.

Effect of belimumab on organ damage in lupus nephritis

BLISS-LN is a phase 3 randomized controlled trial evaluating renal outcomes of intravenous belimumab versus placebo (both added to background induction and maintenance therapy) for 104 weeks in patients with active lupus nephritis (N=448). Compared with placebo, belimumab reduced the risk of renal-related events or death by approximately 50%.

In a post hoc analysis of BLISS-LN, belimumab treatment reduced the risk of estimated glomerular filtration rate (eGFR) decline and reduced the risk of lupus nephritis relapse by 55% at week 24 compared with placebo (HR=0.45, 95%CI: 0.28, 0.72).

In short, data from the above series of studies show that belimumab treatment helps reduce key drivers of organ damage, including disease activity, severe relapses, and glucocorticoid exposure. Based on the SDI, it also helps reduce the progression of organ damage in SLE patients. These data suggest that belimumab has a beneficial effect on organ damage in SLE or has a disease-modifying effect in SLE, including lupus nephritis.

How Does Cistanche Treat Kidney Disease?

Cistanche is a traditional Chinese herbal medicine used for centuries to treat various health conditions, including kidney disease. It is derived from the dried stems of Cistanche deserticola, a plant native to the deserts of China and Mongolia. The main active components of cistanche are phenylethanoid glycosides, echinacoside, and acteoside, which have been found to have beneficial effects on kidney health.

Kidney disease, also known as renal disease, refers to a condition in which the kidneys are not functioning properly. This can result in a buildup of waste products and toxins in the body, leading to various symptoms and complications. Cistanche may help treat kidney disease ase through several mechanisms.

Firstly, cistanche has been found to have diuretic properties, meaning it can increase urine production and help eliminate waste products from the body. This can help relieve the burden on the kidneys and prevent the buildup of toxins. By promoting diuresis, cistanche may also help Reduce high blood pressure, a common complication of kidney disease.

Moreover, cistanche has been shown to have antioxidant effects. Oxidative stress, caused by an imbalance between the production of free radicals and the body's antioxidant defenses, plays a key role in the progression of kidney disease. ies help neutralize free radicals and reduce Oxidative stress, thereby protecting the kidneys from damage. The phenylethanoid glycosides found in cistanche have been particularly effective in scavenging free radicals and inhibiting lipid peroxidation.

Additionally, cistanche has been found to have anti-inflammatory effects. Inflammation is another key factor in the development and progression of kidney disease. Cistanche's anti-inflammatory properties help reduce the production of pro-inflammatory cytokines and inhibit the activation of inflammation mandatory pathways, thus alleviating inflammation in the kidneys.

Furthermore, cistanche has been shown to have immunomodulatory effects. In kidney disease, the immune system can be dysregulated, leading to excessive inflammation and tissue damage. Cistanche helps regulate the immune response by modulating the production and activity of immune cells, such as T cells and macrophages. This immune regulation helps reduce inflammation and prevent further damage to the kidneys.

Moreover, cistanche has been found to improve renal function by promoting the regeneration of renal tubes with cells. Renal tubular epithelial cells play a crucial role in the filtration and reabsorption of waste products and electrolytes. In kidney disease, these cells can be damaged, leading to damaged renal function. Cistanche's ability to promote the regeneration of these cells helps restore proper renal function and improve overall kidney health.

In addition to these direct effects on the kidneys, cistanche has been found to have beneficial effects on other organs and systems in the body. This holistic approach to health is particularly important in kidney disease, as the condition often affects multiple organs and systems. che has been shown to have protective effects on the liver, heart, and blood vessels, which are commonly affected by kidney disease. By promoting the health of these organs, cistanche helps improve overall kidney function and prevent further complications.

In conclusion, cistanche is a traditional Chinese herbal medicine used for centuries to treat kidney disease. Its active components have diuretic, antioxidant, anti-inflammatory, immunomodulatory, and regenerative effects, which help improve renal function and protect the kidneys from further damage. , cistanche has beneficial effects on other organs and systems, making it a holistic approach to treating kidney disease.