방법 개선 신장 예후 in 환자 포함 ANCA 관련 혈관염?

Successful treatment of antineutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitis (AAV) focuses on suppressing disease activity while minimizing treatment-related toxicities. In recent years, a common treatment option is to use rituximab (RTX) plus glucocorticoids to relieve the disease.

클릭 to 육종 for 신장 질병

In the phase 3 ADVOCATE randomized trial, patients with AAV [granulomatosis with polyangiitis (GPA)] or micropolyangiitis (MPA) were treated with immunosuppressive therapies such as RTX, cyclophosphamide (CYC), and thiazolin while 복용 퓨린, receive Avacopan (잠정 translation: Avacopan) 치료. The study showed that the response rate of patients in the avacopan treatment group was non-inferior to that of the prednisone reduction group at week 26, and was better than that of the prednisone reduction group in maintaining remission at week 52. This study performed a subgroup analysis of the ADVOCATE trial to evaluate the efficacy and safety of avacopan in patients with GPA or MPA receiving background induction therapy with RTX.

1 연구 방법

The 실험적 그룹 의 이 연구 is RTX + avacopan (30 mg, twice a day), and the control group is RTX + 프레드니손 (60 mg a day, 점진적으로 테이퍼링 to 중단 at the 21st week) (Note: RTX 375 mg 정맥내 한 번 a 주 /m2 4 주). 무작위화 기반 온 혈관염 질병 상태 (새로운 진단 또는 재발), ANCA 유형 %5반티프로테아제 3 (PR3) 또는 항 골수과산화효소 (MPO) 양성], 및 면역억제제 사용 (RTX, CYC 아자티오프린 포함) 레이어링. The 환자 포함 in this 연구 모두 충족 the 조건 for 새로운 진단 또는 재발 GPA 또는 MPA, had 양성 PR3-ANCA 또는 MPO-ANCA 항체 검사 결과, 및 추정 사구체 여과 속도 (eGFR) Greater than or equal to 15mL/min/1.73m2 body surface area.

The 1차 효능 결과 의 the 연구 were 질병 반응 at week 26 (defined as BVAS of 0}} and no glucocorticoid therapy in the 이전 4 주 before 측정) and sustained response (defined as response at weeks 26 and 52 without glucocorticoid therapy). 호르몬 치료), and 4 weeks before the end of the study, and no recurrence between weeks 26 and 52. 우리 또한 분석된 the 비율 의 환자 누가 재발한 안에 the 다음 two 상황: (1) 처음 재발 이후 달성 관해 at week 26; (2) 처음 재발 후 달성 관해 at any time (BVAS 0). 기타 결과 분석 포함된 변화 from 기준선 in the 글루코코르티코이드 독성 지수 (GTI), 글루코코르티코이드 사용 (발현된 in mg 프레드니손 등가물), 및 건강 관련 품질 의 생명 (HRQoL). 안전 결과 포함 발생률 의 불리한 사건 (AE) 및 심각한 AEs (SAEs).

2 연구 결과

A 총 의 331 환자 있었다 등록 in the ADVOCATE trial, 1 의 whom 했다 하지 않았다 받다 연구 약물. 의 the 330 환자 누가 받은 the 연구 약물, 214 환자 (64.8%) 받은 RTX. The 평균 (SD) 연령 의 등록된 환자 있었다 59.8 (15.7) 년; 52.8% 의 환자 were male, and 84.6% were white. PR3-AAV 발생 in 46.7% of patients in the avacopam group 및 45.8% in the 프레드니손 감소 그룹.

(1) Efficacy results

At week 26, the response rate was 77.6% in the avacopam group and 75.7% in the prednisone-reduction group (estimated shared difference of 3.0 percentage points; 95% CI -8.3 to 14.2)). At week 52, the sustained remission rate was 71.0% in the avacopan group and 56.1% in the prednisone reduction group.

The 재발 비율 후 모든 시간 관해 was 8.7% in the avacopan group and 20.2% in the 프레드니손 테이퍼링 그룹. The 위험 비율 (HR) for 재발 after remission at any time (avacopan vs 프레드니손 테이퍼링) was 0.42 (95% CI 0.19 to 0.91), representing a 58% reduction in the 위험 of 재발. 중 환자 who achieved remission at week 26, 재발 비율 WAS 7.2% IN THE 아바코판 그룹 및 13.6% IN THE 프레드니손 테이퍼링 그룹.

Note: *Remission is defined as a BVAS of {{0}} and no corticosteroids for vasculitis within 4 weeks before the Week 26 visit. †Sustained remission was defined as BVAS of 0 at weeks 26 and 52 and no use of any glucocorticoids for vasculitis in the 4 weeks before and including weeks 26 and 52 visits, and there was no recurrence between weeks 26 and 52. The number of patients who achieved remission at any time was 104 in the prednisone tapering group and 104 in the avacopam group. BVAS, Birmingham Vasculitis Activity Score.

글루코코르티코이드 유도 독성, as 평가 by GTI, was greater in the the 프레드니손-환원 group than in the avacopam group (표 2). 총 글루코코르티코이드 사용 동안 52 weeks was lower in the avacopam group than in the 프레드니손 테이퍼링 그룹. In both groups, patients with abnormal renal function at baseline return to normal after 52 weeks of treatment (Figure 1); in patients with renal disease and proteinuria at baseline, prednisone tapering Compared with the group, the urinary albumin to creatinine ratio (UACR) improved faster in the avacopam group. HRQoL tended to reke in both treatment groups. 크게 개선 from baseline in the EQ-5D-5L visual analog scale (VAS) and EQ-5D-5L index were reported in the avacopam group at weeks 26 and 52.

참고: *데이터 대표 LS 평균 (95%CI). 더 누적 악화 점수 켜기 더 글루코코르티코이드 독성 지수 범위 시작 0} to 410, with higher scores indicating more 심각 독성 effects. The total 개선 score on the 글루코코르티코이드 독성 지수 범위 from –317 to 410, with higher scores indicating more severe toxic effects. All doses were converted to prednisone equivalents (mg) and calculated as the total dose 동안 the 표시 기간. 프레드니손 등가물 용량 포함 정맥 주사 및 경구 코르티코스테로이드. n (%) 데이터 are the number of patients 복용 any 글루코코르티코이드 동안 the period, and mean and 중앙값 (범위) data are for for all patients during the period. All patients received rituximab; 그러나, 7 환자 in the 프레드니손 테이퍼링 그룹 및 10 환자 in the 아바코판 그룹 did not receive 정맥 주사 코르티코스테로이드 동안 the 처음 4 주 의 the 연구. 사용량 기록. LS 평균, 최소 제곱 평균.

참고: LS 평균 및 SEM 아르 에서 반복 측정 혼합 효과 모델 포함 처리 그룹, 방문, 및 the 상호작용 의 처리 at 각 방문 as 요인 및 기준선 as a 공변량. eGFR, 추정 사구체 여과 비율; LS 평균, 최소 제곱 평균.

(2) 안전 평가

34.6% 의 환자 인 더 아바코판 그룹 경험 62 불리 사건; 39.3% 의 환자 인 더 프레드니손 감소 그룹 경험 91 불리 사건. 중 them, 10.3% 의 환자 in the 아바코판 그룹 had 12 심각 감염 사건, 및 14.0% 의 환자 in the 프레드니손 감소 그룹 had 19 사건. 저기 있었다 아니 사망자 안에 the 아바코판 그룹, 그러나 셋 환자 사망 안 the 프레드니손 감소 그룹, 포함 전신 진균 감염 with 설사 및 구토, 급성 근간섬유 경색, 및 설명할 수 없음 사망.

3 연구 토론

The results of this subgroup analysis showed that avacopan plus RTX induction therapy was equally effective as RTX plus prednisone tapering therapy in achieving remission at week 26, and had a higher rate of sustained remission at week 52. Although the use of RTX has provided an available treatment option for patients with AAV, challenges in maintaining remission remain, including increased risk of infection and hypogammaglobulinemia due to RTX and risk of disease recurrence after discontinuation of RTX therapy. Patients receiving RTX without maintenance therapy had lower rates of sustained remission at 12 months; multiple studies have shown the benefit of avacopan in patients receiving RTX for induction treatment of AAV.

In addition to efficacy results on remission and relapse rates, the results of this study demonstrate the benefits of avacopan combined with background induction RTX therapy, including renal recovery and improvement in HRQoL. Among patients receiving RTX, the number of SAEs was 47% higher in the prednisone tapering group than the avacopam group, and there were more infections, serious infections, and deaths in the prednisone 테이퍼링 그룹 than in the avacopam group.

The strengths of this study include the recruitment of a large number of patients with GPA or MPA from 143 centers internationally to participate in clinical trials, the trial cohort being representative of other trial populations in AAV, and the study design and analysis being relatively rigorous. further, the results of this report are generally consistent with the overall results of the ADVOCATE trial. 의 과정, 이 연구 또한 있다 일부 한계, such as the 효능 and 안전성 of avacopan when used together with RTX to maintain remission is unclear, patients with eGFR Less than or equal to 15mL/min/min/1.73m2, and alveolar hemorrhage requiring mechanical ventilation patients were not included in this study, and there are limited data on the use of avacopan after 52 weeks.

In conclusion, the results of this subgroup analysis indicate that among patients with GPA or MPA receiving RTX, response rates at week 26 were similar in the the prednisone 테이퍼링 그룹 and the 아바코판 그룹, 그러나 not in the 아바코판 그룹 at week 52. The sustained remission rate is 높은 및 the safety profile is 좋음. 게다가, 더 아바코판 그룹 유의하게 개선 신장 기능 감소 알부민뇨 빠름, 및 had 낮은 글루코 코르티코이드 독성.

어떻게 합니까 육종 치료 신장 질병?

육종 is a 전통 한자 약초 중고 세기 to 치료 다양한 건강 조건, 포함 신장 질병육종 데저티콜라, a 식물 네이티브 to the the 사막 의 중국 및 몽골. The main active components of cistanche are 페닐에타노이드 배당체, 에키나코사이드, 및 , which have been found to have 유익한 효과 on 신장 건강.

신장 질병, 또한 알려진 as 신장 질병, 참조 to a 상태 in which the 신장 are not 기능 제대로. this can result in a 축적 의 폐기물 제품 and 독소 in the body, leading to 다양한 증상 and 합병증. 육종 may help 치료 신장 질병 ase through several mechanisms.

첫째, 시스탄체 있다 발견 있다 있다 이뇨제 속성, 의미 그것 할 수 있다 증가 소변 생산 및 도움 제거 낭비 제품 에서 더 몸. 이 할 수 있다 도움 완화하다 그 부담 위에 더 신장 및 예방하다 그의 축적 의 독소. 바이 촉진 이뇨, 시스탄치 5월 또한 도움 감소 높은 혈액 압력, a 공통 합병증 의 신장 질병.

더욱이, 시스탄체 있다 있었다 보여진 to 가지고 항산화제 효과. 산화 스트레스, 원인 by an 불균형 사이 the 생산 의 자유 라디칼 및 the body's 항산화제 방어, plays a key 역할 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 자유 라디칼 및 억제 지질 과산화.

추가, cistanche has been found to have 항염증제 효과. 염증 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 alievating inflammation in the kidneys.

또한, cistanche has been show 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 as T cells and macrophages. This immune regulation helps reduce inflammation and prevent further damage to the kidneys.

더욱이, cistanche has been found to 개선 신장 기능 by 촉진 the 재생 의 신장 튜브 with 세포. 신장 관 상피 세포 재생 a 결정적 역할 in the 여과 및 재흡수 의 폐기물 제품 및 전해질. In 신장 질병, 이들 세포 can be damaged, leading to 손상된 신장 기능. Cistanche's 능력 to 촉진 the 재생 의 이들 세포 도움 복원 적절한 신장 기능 및 개선 전체 신장 건강.

In addition to these direct effects on the kidneys, cistanche has been found to have benefit 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 show to have protective effects on the liver, heart, and blood vessels, which are commonly affected by kidney disease. By 증진 건강 의 이들 장기, 시스탄체 도움 개선 전반 신장 기능 및 예방 추가 합병증.

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 reenerative effects, which help improve renal function and protect the kidneys from further damage. , cistanche has benefitial effects on other organs and systems, making it a holistic approach to treating kidney disease.