Chloroquine Is Effective for Maintenance of Remission in Autoimmune Hepatitis: Controlled, Double‐Blind, Randomized Trial

Diniz, Márcio A.; Falcão, Lydia Teófilo de Moraes; Guedes, Ana Luiza Vilar; Nakano, Larissa Akeme; Evangelista, Ana Catarina Jorge; Lima, Fábio; Abrantes-Lemos, Clarice Pires; Carrilho, Flair José; Cançado, Eduardo Luiz Rachid

doi:10.1002/hep4.1275

Cited by 14 publications

(7 citation statements)

References 36 publications

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“…Full-text articles were obtained for 33 publications. From these, 22 papers were excluded, leaving 11 placebo randomized controlled trials (RCTs) for final inclusion for quantitative synthesis and meta-analysis(14-24). The numbers identified at each stage through from initial searching to quantitative analyses, and the reasons for excluding studies, are given in a PRISMA 2009 flow diagram (Fig.…”

Section: Resultsmentioning

confidence: 99%

Benefits and Risks of Chloroquine and Hydroxychloroquine in The Treatment of Viral Diseases: A Meta-Analysis of Placebo Randomized Controlled Trials

Wang

2020

Preprint

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Background and Objective:Recently, in the scramble to find drugs to treat COVID-19, chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have rapidly gained the public's attention. In this study, we conducted a meta-analysis of randomized clinical trials (RCTs) to evaluate the efficacy and safety of CQ and HCQ in the treatment of viral diseases. Methods:We searched PubMed, EMBASE, Cochrane Central, Web of Science, Clinical Trials Registries, CNKI, Wanfang Data, CQVIP, and Preprint Servers through April 4, 2020, for randomized controlled trials (RCTs) that examined the efficacy and safety of CQ and HCQ against viral infection. We analyzed pooled data on the overall efficacy, the relative risks over the placebo, and the prevalence of adverse events. Trial sequential analysis (TSA) was also performed to evaluate the random errors in the meta-analysis. Potential moderators of drugplacebo efficacy differences were analyzed by meta-regression. Results:The analysis included 11 RCTs with 2613 adult patients. Both the plasma viral load (standard mean difference: 0.29, 95% CI: -1.19 -1.76, P = 0.70) and the improvement of clinical symptoms (odds ratio: 2.36, 95% CI: 0.81 -6.92, P = 0.11) were not different between the intervention and placebo arm. There was significant heterogeneity for the efficacy assessment, which was primarily explained by the mean patients' age and the sample size. Compared to the placebo, CQ and HCQ had increased risk of mild adverse events (risk ratio: 1.51, 95% CI: 1.35 -1.70, P < 0.05, TSA adjusted 95% CI: 1.31 -2.19), which were statistically significant in nervous, integumentary, and gastrointestinal systems. The most common adverse events were observed in the nervous system, with the pooled prevalence of 31.4 % (95% CI: 10.5% -56.7%). Conclusions:Insufficient data were available to support the antiviral efficacy of CQ and HCQ due to the high heterogeneity caused by patients' age. Mild side effects are expected for the current antiviral dose regimens of CQ and HCQ. Treatment outcomes may be enhanced by better-selected patients based on age and well-controlled adverse events.This meta-analysis was registered on OSF (ID: https://osf.io/386aw) P a g e 3 o f 2 1

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Section: Resultsmentioning

confidence: 99%

Benefits and Risks of Chloroquine and Hydroxychloroquine in The Treatment of Viral Diseases: A Meta-Analysis of Placebo Randomized Controlled Trials

Wang

2020

Preprint

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“…We have previously found that TLR-8 is inhibited by the N-glycans isolated from bLF (20). Inhibition of endosomal TLR-8 signaling is a possible approach to modulate the immune response in autoimmune diseases (30)(31)(32) as shown for CQN. If isolated N-glycans from bLF exert similar effects as TLR-8 antagonists, they may provide a food-based strategy for the management of inflammatory disorders and their intestinal symptoms.…”

Section: Differential Tlr-8 Inhibition By N-glycans Isolated From Blfmentioning

confidence: 99%

“…The dysregulation or overexpression of TLR-8 has been found to contribute to the pathogenesis and progression of autoimmune disorders, such as rheumatoid arthritis (27), systemic sclerosis (28), and inflammatory bowel disease (29). Inhibition of endosomal TLRs, such as TLR-8 has great therapeutic potential for the treatment of autoimmune diseases (30)(31)(32) as shown for the TLR7/8/9 antagonist chloroquine (CQN). Therefore, the inhibition of TLR-8 activation might be instrumental for the management of many inflammatory conditions (32,33).…”

Section: Introductionmentioning

confidence: 99%

Inhibitory Effects of Dietary N-Glycans From Bovine Lactoferrin on Toll-Like Receptor 8; Comparing Efficacy With Chloroquine

et al. 2020

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Toll-like receptor 8 (TLR-8) plays a role in the pathogenesis of autoimmune disorders and associated gastrointestinal symptoms that reduce quality of life of patients. Dietary interventions are becoming more accepted as mean to manage onset, progression, and treatment of a broad spectrum of inflammatory conditions. In this study, we assessed the impact of N-glycans derived from bovine lactoferrin (bLF) on the inhibition of TLR-8 activation. We investigated the effects of N-glycans in their native form, as well as in its partially demannosylated and partially desialylated form, on HEK293 cells expressing TLR-8, and in human monocyte-derived dendritic cells (MoDCs). We found that in HEK293 cells, N-glycans strongly inhibited the ssRNA40 induced TLR-8 activation but to a lesser extent the R848 induced TLR-8 activation. The impact was compared with a pharmaceutical agent, i.e., chloroquine (CQN), that is clinically applied to antagonize endosomal TLR-activation. Inhibitory effects of the N-glycans were not influenced by the partially demannosylated or partially desialylated N-glycans. As the difference in charge of the N-glycans did not influence the inhibition capacity of TLR-8, it is possible that the inhibition mediated by the N-glycans is a result of a direct interaction with the receptor rather than a result of pH changes in the endosome. The inhibition of TLR-8 in MoDCs resulted in a significant decrease of IL-6 when cells were treated with the unmodified (0.5-fold, p < 0.0001), partially demannosylated (0.3-fold, p < 0.0001) and partially desialylated (0.4-fold, p < 0.0001) N-glycans. Furthermore, the partially demannosylated and partially desialylated N-glycans showed stronger inhibition of IL-6 production compared with the native N-glycans. This provides evidence that glycan composition plays a role in the immunomodulatory activity of the isolated N-glycans from bLF on MoDCs. Compared to CQN, the N-glycans are specific inhibitors of TLR-8 activation and of IL-6 production in MoDCs. Our findings demonstrate that isolated N-glycans from bLF have attenuating effects on TLR-8 induced immune activation in HEK293 cells and human MoDCs. The inhibitory capacity of N-glycans isolated from bLF onTLR-8 activation may become a food-based strategy to manage autoimmune, infections or other inflammatory disorders.

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“…In vitro studies reported that CQ was able to inhibit influenza A replication in a pH-dependent manner ( Di Trani et al, 2007 ; Ooi, Chew, Loh, & Chua, 2006 ). Clinical studies suggested that CQ treatment may safely reduce the risk of relapse in patients with autoimmune hepatitis ( Mucenic, Mello, & Cançado, 2005 ; Raquel Benedita Terrabuio et al, 2019 ). In the recent trial, patients were randomized to receive CQ (250 mg/d), or placebo for 36 months.…”

Section: Anti-viral Activities Of Cq and Hcqmentioning

confidence: 99%

Chloroquine and hydroxychloroquine in the treatment of malaria and repurposing in treating COVID-19

Lei

Dong

et al. 2020

Pharmacology & Therapeutics

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Chloroquine (CQ) and Hydroxychloroquine (HCQ) have been commonly used for the treatment and prevention of malaria, and the treatment of autoimmune diseases for several decades. As their new mechanisms of actions are identified in recent years, CQ and HCQ have wider therapeutic applications, one of which is to treat viral infectious diseases. Since the pandemic of the coronavirus disease 2019 (COVID-19), CQ and HCQ have been subjected to a number of in vitro and in vivo tests, and their therapeutic prospects for COVID-19 have been proposed. In this article, the applications and mechanisms of action of CQ and HCQ in their conventional fields of anti-malaria and anti-rheumatism, as well as their repurposing prospects in anti-virus are reviewed. The current trials and future potential of CQ and HCQ in combating COVID-19 are discussed.

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Chloroquine Is Effective for Maintenance of Remission in Autoimmune Hepatitis: Controlled, Double‐Blind, Randomized Trial

Cited by 14 publications

References 36 publications

Benefits and Risks of Chloroquine and Hydroxychloroquine in The Treatment of Viral Diseases: A Meta-Analysis of Placebo Randomized Controlled Trials

Benefits and Risks of Chloroquine and Hydroxychloroquine in The Treatment of Viral Diseases: A Meta-Analysis of Placebo Randomized Controlled Trials

Inhibitory Effects of Dietary N-Glycans From Bovine Lactoferrin on Toll-Like Receptor 8; Comparing Efficacy With Chloroquine

Chloroquine and hydroxychloroquine in the treatment of malaria and repurposing in treating COVID-19

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