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Frontiers in Pharmacology 2022Pharmacological therapy is currently the main treatment method for patients with Wilson disease (WD). We aimed to evaluate the efficacy and safety of the common...
Pharmacological therapy is currently the main treatment method for patients with Wilson disease (WD). We aimed to evaluate the efficacy and safety of the common treatment regimens in these patients. We conducted a systemic review and meta-analysis by searching multiple databases for studies from inception to October 2021. Outcomes of interest were the improved rate and safety of d-penicillamine and zinc salts treatment in WD patients. Two independent reviewers performed the study selection and data extraction. Sixteen studies were included in this meta-analysis. The pooled improved rate for all included symptomatic WD patients was 78.0% (95% CI: 70.8%-85.2%). In symptomatic hepatic WD patients, there is no difference in the treatment efficiency of d-penicillamine and zinc salts (RR: 0.98, 95% CI: 0.86%-1.12%; = 0.765). In neurological WD patients, the pooled improved rate of those who received d-penicillamine and zinc salts was 56.3% (95% CI: 37.5%-75.1%) and 80.2% (95% CI: 67.2%-93.2%), respectively. The incidence of adverse effects (RR: 2.42, 95% CI: 1.20%-4.88%; = 0.014) and neurological deterioration (RR: 1.96, 95% CI: 1.31%-2.93%; = 0.001) in all symptomatic WD patients treated with d-penicillamine was both higher than that of patients treated with zinc salts. Our analysis suggests that symptomatic WD patients treated with d-penicillamine have higher incidence of adverse effects and neurological deterioration than that of zinc salts. The therapeutic effectiveness of these two regimens does not seem to be significantly different, and these results must be interpreted with caution. : PROSPERO registration, identifier CRD 42021287126.
PubMed: 35370752
DOI: 10.3389/fphar.2022.847436 -
International Immunopharmacology Mar 2021Pemphigus encompasses a rare heterogeneous group of autoimmune blistering diseases characterized by cutaneous and/or mucosal blistering. Multiple factors, such as some...
Pemphigus encompasses a rare heterogeneous group of autoimmune blistering diseases characterized by cutaneous and/or mucosal blistering. Multiple factors, such as some specific types of drugs, have been found to be involved in the induction of pemphigus. Here, we have designed a systematic review by searching PubMed/Medline and Embase databases to find the drugs, involved in pemphigus induction and exacerbation (updated on 19 August 2019). From 1856 initially found articles, 134 studies (198 patients; 170 patients in the drug-induced patients and 28 in exacerbation group) have been included. Regarding drug-induced cases, the mean age was 57.19 ± 16.9-year-old (ranged 8-105), and patients had developed pemphigus within a mean of 154.27 days. Pemphigus vulgaris (38.9%), pemphigus foliaceus (33.5%), and paraneoplastic pemphigus (3.6%) were the most common subtypes. Furthermore, penicillamine (33.1%), captopril (7.7%), and bucillamine (6.5%) were the most reported drugs related to pemphigus induction; penicillamine was associated with the most persistent disease. Regardless of disease subtype, cutaneous, mucocutaneous, and mucosal involvements were reported in 68.6%, 30.1%, and 1.3% of patients, respectively. In total, the IgG deposition in the pathological studies, being positive for autoreactive antibodies in the serum against desmoglein 3 (Dsg3), and desmoglein 1 (Dsg1), were reported in 93%, 34.9%, and 72.7% of reported patients, respectively. Regarding the management of such patients, in 75% of healed cases, treatment (mainly transient systemic and topical corticosteroids and/or azathioprine) was needed besides stopping the probable pemphigus-inducing culprit drug, while drug cessation was enough to control the disease in 25%. As the outcomes, the lesions in 129 of 147 (87.8%) patients had been healed, while in 18 (12.2%), no healing was reported; fifteen out of 18 had died. In conclusion, some specific groups of treatments can induce pemphigus, including penicillamine, captopril, and bucillamine; despite the similar clinical and pathological manifestations to classical pemphigus, most of the cases are less severe and have a better prognosis.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Antihypertensive Agents; Antirheumatic Agents; Captopril; Cysteine; Drug-Related Side Effects and Adverse Reactions; Humans; Pemphigus; Penicillamine
PubMed: 33418246
DOI: 10.1016/j.intimp.2020.107299 -
Kidney International Jan 2021Cystinuria (OMIM 220100) is an autosomal recessive hereditary disorder in which high urinary cystine excretion leads to the formation of cystine stones because of the...
Cystinuria (OMIM 220100) is an autosomal recessive hereditary disorder in which high urinary cystine excretion leads to the formation of cystine stones because of the low solubility of cystine at normal urinary pH. We developed clinical practice recommendation for diagnosis, surgical and medical treatment, and follow-up of patients with cystinuria. Elaboration of these clinical practice recommendations spanned from June 2018 to December 2019 with a consensus conference in January 2019. Selected topic areas were chosen by the co-chairs of the conference. Working groups focusing on specific topics were formed. Group members performed systematic literature review using MEDLINE, drafted the statements, and discussed them. They included geneticists, medical biochemists, pediatric and adult nephrologists, pediatric and adult urologists experts in cystinuria, and the Metabolic Nephropathy Joint Working Group of the European Reference Network for Rare Kidney Diseases (ERKNet) and eUROGEN members. Overall 20 statements were produced to provide guidance on diagnosis, genetic analysis, imaging techniques, surgical treatment (indication and modalities), conservative treatment (hydration, dietetic, alkalinization, and cystine-binding drugs), follow-up, self-monitoring, complications (renal failure and hypertension), and impact on quality of life. Because of the rarity of the disease and the poor level of evidence in the literature, these statements could not be graded. This clinical practice recommendation provides guidance on all aspects of the management of both adults and children with cystinuria, including diagnosis, surgery, and medical treatment.
Topics: Adult; Child; Consensus; Cystine; Cystinuria; Humans; Kidney; Quality of Life
PubMed: 32918941
DOI: 10.1016/j.kint.2020.06.035 -
Minerva Urologica E Nefrologica = the... Aug 2020To systematically review the effect of additional drug therapy as metaphylaxis in patients with cystinuria.
INTRODUCTION
To systematically review the effect of additional drug therapy as metaphylaxis in patients with cystinuria.
EVIDENCE ACQUISITION
A literature search of three databases (MEDLINE, Embase and the Cochrane Library) was performed according to the PRISMA-guidelines enclosing articles published up to May 2019. A total of 1117 articles were screened. Thirty-four publications met the inclusion criteria for this review.
EVIDENCE SYNTHESIS
Male-female ratio in the studied cohorts was 49.9% - 50.1%. The majority of studies showed a positive effect in reducing stone events and/or urinary cystine excretion. D-Penicillamine showed success in 13/14 (92%) studies, whereas Tiopronin-treatment showed a reduction in all (8/8; 100%) studies. All studies on Captopril (4/4) showed a decrease, however not all significant. The same is true for studies on Thiols in combination with Captopril (2/2). Furthermore, Tiopronin showed less side effects compared to D-penicillamine, respectively 30% and 37%. Captopril showed the least adverse events, with one event in nine patients.
CONCLUSIONS
The evidence on benefit of additional drug therapy in patients with cystinuria is scarce. All studied medications showed an effect on stone event and urinary cystine excretion, when used in addition to hyperhydration, alkalization and a diet low on methionine. Based on this systematic review, no drug can be preferred over another. An important aspect in the choice of drug is the risk of side effects. Therefore, the choice of additional drug should be personalized for every patient where the risk of side effects should be taken into consideration.
Topics: Captopril; Cystine; Cystinuria; Drug Therapy, Combination; Evidence-Based Medicine; Female; Humans; Male; Penicillamine; Tiopronin
PubMed: 32083421
DOI: 10.23736/S0393-2249.20.03704-2 -
Liver International : Official Journal... Nov 2019Wilson disease (WD) is a rare disorder of copper metabolism. The objective of this systematic review was to determine the comparative effectiveness and safety of common... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND & AIMS
Wilson disease (WD) is a rare disorder of copper metabolism. The objective of this systematic review was to determine the comparative effectiveness and safety of common treatments of WD.
METHODS
We included WD patients of any age or stage and the study drugs D-penicillamine, zinc salts, trientine and tetrathiomolybdate. The control could be placebo, no treatment or any other treatment. We included prospective, retrospective, randomized and non-randomized studies. We searched Medline and Embase via Ovid, the Cochrane Central Register of Controlled Trials, and screened reference lists of included articles. Where possible, we applied random-effects meta-analyses.
RESULTS
The 23 included studies reported on 2055 patients and mostly compared D-penicillamine to no treatment, zinc, trientine or succimer. One study compared tetrathiomolybdate and trientine. Post-decoppering maintenance therapy was addressed in one study only. Eleven of 23 studies were of low quality. When compared to no treatment, D-penicillamine was associated with a lower mortality (odds ratio 0.013; 95% CI 0.0010 to 0.17). When compared to zinc, there was no association with mortality (odds ratio 0.73; 95% CI 0.16 to 3.40) and prevention or amelioration of clinical symptoms (odds ratio 0.84; 95% CI 0.48 to 1.48). Conversely, D-penicillamine may have a greater impact on side effects and treatment discontinuations than zinc.
CONCLUSIONS
There are some indications that zinc is safer than D-penicillamine therapy while being similarly effective in preventing or reducing hepatic or neurological WD symptoms. Study quality was low warranting cautious interpretation of our findings.
Topics: Chelating Agents; Copper; Hepatolenticular Degeneration; Humans; Liver; Molybdenum; Penicillamine; Randomized Controlled Trials as Topic; Trientine; Zinc
PubMed: 31206982
DOI: 10.1111/liv.14179