Efficacy and safety of immunosuppressive therapies in the treatment of high-risk IgA nephropathy

Abstract

Background: IgA nephropathy (IgAN) is one of the significant contributing factors of end-stage renal disease (ESRD). It is reported that over half of patients with IgAN accompany multiple high-risk factors, which increase the risk of ESRD progression. Studies have shown that immunosuppressive agents were beneficial in high-risk IgAN, but the efficacy and safety have not been fully demonstrated yet. The present study aims to elucidate the efficacy of commonly used immunosuppressants in high-risk IgAN and their relative safety profiles via a network meta-analysis strategy. Methods: Randomized controlled trials (RCTs) eligible for this network meta-analysis were included to evaluate the efficacy and safety of different immunosuppressants for high-risk IgAN. Main outcomes and measures include incidence of renal composite end point, the rate of total remission, adverse events, and proteinuria. Besides, subgroup analysis and cluster analysis were carried out. Results: This network meta-analysis of 37 RCTs involving 3012 participants found that Mycophenolate mofetil (MMF) combined with corticosteroids (CS) was superior to other interventions in end point events and proteinuria. Cyclosporine A (CsA) plus CS was the best option for clinical remission rate, and supportive care (SC) was the safest treatment. Cluster analysis showed that MMF+CS and Leflunomide (LEF)+CS were best protocols in efficacy and safety. Subgroup analysis indicated the best benefits of MMF were presented among the Asian population, and the benefits increased with the increase of follow-up duration. The effect of Cyclophosphamide (CTX) +CS on crescent IgAN was better than that of other risk factors. Moreover, the increasing follow-up duration was negatively associated with the effect. Conclusions: MMF+CS and LEF+CS appear to serve as the best choice for treating high-risk IgAN than other immunosuppressive therapies.

Efficacy and safety of leflunomide combined with corticosteroids for the treatment of IgA nephropathy: a Meta-analysis of randomized controlled trials

“…Moreover, the inclusion criteria for the meta-analysis are not restricted, and studies with various treatment regimens in control groups were included, such as those with CS alone, ACEI/ARB alone, placebo or blank treatment, or the other immunosuppressants, which made the interpretation of the result difficult. Recently, a well-designed network meta-analysis was performed to evaluate the efficacy and safety of different immunosuppressants for high-risk IgAN [ 41 ]. Although this study could provide more information and consistently showed that combined leflunomide with CS could serve as one of the best choices for patients with high-risk IgAN [ 41 ], results of network meta-analysis were generally based on studies of indirect comparison, which may limit the reliability of the findings.…”

“…Recently, a well-designed network meta-analysis was performed to evaluate the efficacy and safety of different immunosuppressants for high-risk IgAN [ 41 ]. Although this study could provide more information and consistently showed that combined leflunomide with CS could serve as one of the best choices for patients with high-risk IgAN [ 41 ], results of network meta-analysis were generally based on studies of indirect comparison, which may limit the reliability of the findings. For the comparison of LEF + CS vs CS, RCTs are adequate for a meta-analysis of head-to-head comparison, like ours.…”

Red-light-activatable "AND gated" antitumor immunosuppressant

“…Recently, immunosuppressants are emerging as a new class of drugs that exhibit anti-tumor effects [1][2][3] . Compared to traditional chemotherapy drugs, such as cis-platin and others which possess strong cytotoxicity [4][5] , immunosuppressants have significantly reduced toxicity [6][7] . FTY720 is a clinically approved immunosuppressant 8 and has recently been shown to exert efficient antitumor activity 9 .…”

Red-Light-Activatable AND-Gated Antitumor Immunosuppressant

“…Representative candidates include rapalogs such as rapamycin and everolimus [1,3], fingolimod (FTY720) [4], prodigiosins (PrGs) [5], capecitabine [6], and others. Compared to traditional chemotherapy drugs, such as cis-platin and others, which possess strong cytotoxicity [7,8], immunosuppressants have significantly reduced toxicity [9,10]. FTY720 is a clinically approved immunosuppressant [11] and has recently been shown to exert efficient antitumor activity [4].…”