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Rheumatology (Oxford, England) Jul 2017To determine if urate-lowering treatment (ULT) in gout can reduce cardiovascular (CV) outcomes. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To determine if urate-lowering treatment (ULT) in gout can reduce cardiovascular (CV) outcomes.
METHODS
Randomized trials were searched for treatment with ULT in gout. Eligible trials had to report CV safety of a ULT. Potential medications included allopurinol, febuxostat, pegloticase, rasburicase, probenecid, benzbromarone, sulphinpyrazone, losartan, fenofibrate and sodium-glucose linked transporter 2 inhibitors.
RESULTS
A total of 3084 citations were found, with 642 duplicates. After the primary screen, 35 studies were selected for review. Several trials did not report CV events. Six were not randomized controlled trials (RCTs). Four studies reported no events in either intervention arm while the other four had 40 events in the febuxostat group ( n = 3631) and 5 in allopurinol group ( n = 1154). Overall, the pooled analysis did not show a significant difference between the two [febuxostat vs allopurinol: relative risk (RR) 1.69 (95% CI 0.54, 5.34), P = 0.37]. CV events did not decrease over time. Comparing shorter studies (<52 weeks) to longer ones did not reveal any statistical differences. However, in long-term studies with febuxostat vs allopurinol, results were nearly significant, with more CVE occurring with febuxostat treatment. Comparing any ULT to placebo (eight studies, n = 2221 patients) did not demonstrate a significant difference in non-Anti-Platelet Trialists' Collaboration events [any ULT vs placebo: RR 1.47 (95% CI 0.49, 4.40), P = 0.49] or all-cause mortality [any ULT vs placebo: RR 1.45 (95% CI 0.35, 5.77), P = 0.60].
CONCLUSION
RCT data do not suggest differences in CV events among ULTs in gout. Trials had few events despite high-risk patients being enrolled and may have been too short to show CV reduction by controlling inflammatory attacks and lowering uric acid.
Topics: Adult; Allopurinol; Arthritis, Gouty; Cardiovascular Diseases; Chronic Disease; Febuxostat; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Polyethylene Glycols; Prognosis; Randomized Controlled Trials as Topic; Treatment Outcome; Urate Oxidase
PubMed: 28379501
DOI: 10.1093/rheumatology/kex065 -
Clinical Rheumatology May 2020Hyperuricemia is a strong precursor of gout, which deteriorates patients' health and quality of life. Sustained adherence to urate-lowering therapies (ULTs) is crucial... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Hyperuricemia is a strong precursor of gout, which deteriorates patients' health and quality of life. Sustained adherence to urate-lowering therapies (ULTs) is crucial for efficacy and therapeutic cost-effectiveness. Recently, several new ULTs have been proposed. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to reassess the efficacy and safety of the current ULTs, focusing on adherence attrition-related adverse event reporting.
METHOD
The Bayesian network meta-analysis was applied to compare ULTs. Drug efficacy and safety were measured by whether the target level of serum urate acid was achieved and whether any adverse events occurred. The results were summarized using the pooled estimates of effect sizes (odds ratios), their precisions (95% credible interval), and the ranking probabilities.
RESULTS AND CONCLUSIONS
Thirty-nine RCTs were identified, accumulating 19,401 patients. Consistent with previous studies, febuxostat (≥ 40 mg/day) was superior to other monoagent ULTs. The new findings were as follows: (i) dual-agent ULTs were superior to febuxostat alone, and further surveillance on the adverse effects when lesinurad is uptitrated is needed, and (ii) terminalia bellerica 500 mg/day, a novel xanthine oxidase inhibitor (XOI) made of natural fruit extracts, and topiroxostat ≥ 80 mg/day, an XOI used mostly in Japan, could be new effective options for lowering the occurrence of adherence attrition events. Evidence from RCTs regarding second-line agents, such as probenecid and pegloticase, remains insufficient for clinical decision-making.Key Points• Dual-agent ULTs were superior to febuxostat alone, and further surveillance on the adverse-effects when lesinurad is uptitrated is needed.• Terminalia bellerica 500 mg/day, a novel xanthine oxidase inhibitor (XOI) made of natural fruit extracts, and topiroxostat 80 mg/day, an XOI used mostly in Japan, could be new effective options for lowering the occurrence of adherence attrition events.
Topics: Bayes Theorem; Gout; Gout Suppressants; Humans; Hyperuricemia; Network Meta-Analysis; Quality of Life; Randomized Controlled Trials as Topic; Uric Acid
PubMed: 31965378
DOI: 10.1007/s10067-019-04893-8 -
The Cochrane Database of Systematic... Feb 2018Gonorrhoea is a sexually transmitted infection that is caused by Neisseria gonorrhoeae, and is a major public health challenge today. N gonorrhoeae can be transmitted... (Review)
Review
BACKGROUND
Gonorrhoea is a sexually transmitted infection that is caused by Neisseria gonorrhoeae, and is a major public health challenge today. N gonorrhoeae can be transmitted from the mother's genital tract to the newborn during birth, and can cause gonococcal ophthalmia neonatorum as well as systemic neonatal infections. It can also cause endometritis and pelvic sepsis in the mother. This review updates and replaces an earlier Cochrane Review on antibiotics for treating this infectious condition.
OBJECTIVES
To assess the clinical effectiveness and harms of antibiotics for treating gonorrhoea in pregnant women.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2017), LILACS database (1982 to April 5, 2017), the WHO International Clinical Trials Registry Platform (ICTRP; April 5, 2017), ClinicalTrials.gov (April 5, 2017), the ISRCTN Registry (April 5, 2017), and Epistemonikos (April 5, 2017). We also searched reference lists of all retrieved articles.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing the use of antibiotics for treating gonorrhoea in pregnancy. The antibiotics could have been used alone or in combination, were administered parenterally, orally, or both, and were compared with another antibiotic.We included RCTs regardless of their publication status (published, unpublished, published as an article, an abstract, or a letter), language, or country. We applied no limits on the length of follow-up.We excluded RCTs using a cluster- or cross-over design, or quasi-RCTs.
DATA COLLECTION AND ANALYSIS
Three review authors independently assessed trials for inclusion and risk of bias, extracted data, and checked them for accuracy.
MAIN RESULTS
We included two RCTs, that randomised 514 pregnant women (347 women analysed) at a mean gestational age of 22 weeks. Both trials were conducted in the outpatient department of the same two hospitals in the USA between 1993 and 2001, and had a follow-up of 14 days. One of the trials was sponsored by a drug company. We considered both trials to be at a high risk of bias.One trial compared ceftriaxone (125 mg, intramuscular) with cefixime (400 mg, oral); the other trial had three arms, and assessed ceftriaxone (250 mg, intramuscular) versus either amoxicillin (3 g, oral) plus probenecid (1 g, oral) or spectinomycin (2 g, intramuscular). We did not include the spectinomycin data because this medication is no longer produced. We were unable to conduct meta-analysis because the trials compared different medications.We found inconclusive evidence that there were clear differences in the cure of gonococcal infections (genital, extragenital, or both) between intramuscular ceftriaxone versus oral amoxicillin plus oral probenecid (risk ratio (RR) 1.07, 95% confidence interval (CI) 0.98 to 1.16; one RCT; 168 women; very low-quality evidence) or intramuscular ceftriaxone versus oral cefixime (RR 0.99, 95% CI 0.91 to 1.08; one RCT; 95 women; very low-quality evidence).Neither of the trials reported on two of this review's primary maternal outcomes: incidence of obstetric complications (miscarriage, premature rupture of membranes, preterm delivery, or fetal death), or disseminated gonococcal infection, or on the incidence of neonatorum ophthalmia in the neonates.One trial reported one case of vomiting in the oral amoxacillin plus probenecid group. Trials reported pain at the injection sites, but did not quantify it. Hyperberbilurrubinemia was more frequent in neonates whose mothers were exposed to ceftriaxone. There were no clear differences between groups for neonatal malformation.
AUTHORS' CONCLUSIONS
This Cochrane Review found high levels of cure of gonococcal infections in pregnancy with the given antibiotic regimens. However, the evidence in this review is inconclusive as it does not support one particular regimen over another. This conclusion was based on very low-quality evidence (downgraded for poor trial design, imprecision) from two trials (involving 514 women), which we assessed to be at a high risk of bias for a number of domains. The harm profiles of the antibiotic regimes featured in this review remain unknown.High-quality RCTs are needed, with sufficient power to assess the clinical effectiveness and potential harms of antibiotics in pregnant women with gonorrhoea. These should be planned according to Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT),conducted following CONSORT recommendations, and based on Patient-Centered Outcomes Research Institute (PCORI) outcomes.
Topics: Amoxicillin; Anti-Bacterial Agents; Cefixime; Ceftriaxone; Female; Gonorrhea; Humans; Pregnancy; Pregnancy Complications, Infectious; Probenecid; Randomized Controlled Trials as Topic; Spectinomycin
PubMed: 29465747
DOI: 10.1002/14651858.CD011167.pub2 -
The Cochrane Database of Systematic... 2002Neisseria gonorrhoeae can be transmitted from the mother's genital tract to the newborn during birth and can cause gonococcal ophthalmia neonatorum as well as systemic... (Review)
Review
BACKGROUND
Neisseria gonorrhoeae can be transmitted from the mother's genital tract to the newborn during birth and can cause gonococcal ophthalmia neonatorum as well as systemic neonatal infection. It can also cause endometritis and pelvic sepsis in the mother.
OBJECTIVES
The objective of this review was to assess the effects of antibiotic regimens in the treatment of genital infection with gonorrhoea during pregnancy with respect to neonatal and maternal morbidity.
SEARCH STRATEGY
The Cochrane Pregnancy and Childbirth Group trials register (November 2001) and the Cochrane Controlled Trials Register (The Cochrane Library, Issue 3, 2001) were searched.
SELECTION CRITERIA
Randomised trials of one regimen of antibiotic versus another in pregnant women with culture confirmed genital gonococcal infection.
DATA COLLECTION AND ANALYSIS
Eligibility and trial quality were assessed by one reviewer.
MAIN RESULTS
Two trials involving 346 women were included. The only outcome included in these trials was the incidence of 'cure' assessed by bacterial culture. Failure to achieve 'microbiological cure' was similar for each antibiotic regimen: Amoxicillin plus probenecid compared with spectinomycin (odds ratio (OR) 2.40, 95% confidence interval (CI) 0.71-8.12), amoxicillin plus probenecid compared with ceftriaxone (OR 2.40, 95% CI 0.71-8.12) and ceftriaxone compared with cefixime (OR 1.22, 95% CI 0.16-9.04). Side effects were uncommon for all the tested regimens.
REVIEWER'S CONCLUSIONS
The number of women included in each of the comparisons is small and therefore, although no differences were detected between the different antibiotic regimens, the trials were limited in their ability to detect important but modest differences. For women who are allergic to penicillin, this review provides some reassurance that treatment with ceftriaxone or spectinomycin appears to have similar effectiveness in producing microbiological cure.
Topics: Anti-Bacterial Agents; Female; Gonorrhea; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Randomized Controlled Trials as Topic
PubMed: 12076381
DOI: 10.1002/14651858.CD000098 -
The Cochrane Database of Systematic... Oct 2014Allopurinol, a xanthine oxidase inhibitor, is considered one of the most effective urate-lowering drugs and is frequently used in the treatment of chronic gout. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Allopurinol, a xanthine oxidase inhibitor, is considered one of the most effective urate-lowering drugs and is frequently used in the treatment of chronic gout.
OBJECTIVES
To assess the efficacy and safety of allopurinol compared with placebo and other urate-lowering therapies for treating chronic gout.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE on 14 January 2014. We also handsearched the 2011 to 2012 American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) abstracts, trial registers and regulatory agency drug safety databases.
SELECTION CRITERIA
All randomised controlled trials (RCTs) or quasi-randomised controlled clinical trials (CCTs) that compared allopurinol with a placebo or an active therapy in adults with chronic gout.
DATA COLLECTION AND ANALYSIS
We extracted and analysed data using standard methods for Cochrane reviews. The major outcomes of interest were frequency of acute gout attacks, serum urate normalisation, pain, function, tophus regression, study participant withdrawal due to adverse events (AE) and serious adverse events (SAE). We assessed the quality of the body of evidence for these outcomes using the GRADE approach.
MAIN RESULTS
We included 11 trials (4531 participants) that compared allopurinol (various doses) with placebo (two trials); febuxostat (four trials); benzbromarone (two trials); colchicine (one trial); probenecid (one trial); continuous versus intermittent allopurinol (one trial) and different doses of allopurinol (one trial). Only one trial was at low risk of bias in all domains. We deemed allopurinol versus placebo the main comparison, and allopurinol versus febuxostat and versus benzbromarone as the most clinically relevant active comparisons and restricted reporting to these comparisons here.Moderate-quality evidence from one trial (57 participants) indicated allopurinol 300 mg daily probably does not reduce the rate of gout attacks (2/26 with allopurinol versus 3/25 with placebo; risk ratio (RR) 0.64, 95% confidence interval (CI) 0.12 to 3.52) but increases the proportion of participants achieving a target serum urate over 30 days (25/26 with allopurinol versus 0/25 with placebo, RR 49.11, 95% CI 3.15 to 765.58; number needed to treat for an additional beneficial outcome (NNTB) 1). In two studies (453 participants), there was no significant increase in withdrawals due to AE (6% with allopurinol versus 4% with placebo, RR 1.36, 95% CI 0.61 to 3.08) or SAE (2% with allopurinol versus 1% with placebo, RR 1.93, 95% CI 0.48 to 7.80). One trial reported no difference in pain reduction or tophus regression, but did not report outcome data or measures of variance sufficiently and we could not calculate the differences between groups. Neither trial reported function.Low-quality evidence from three trials (1136 participants) indicated there may be no difference in the incidence of acute gout attacks with allopurinol up to 300 mg daily versus febuxostat 80 mg daily over eight to 24 weeks (21% with allopurinol versus 23% with febuxostat, RR 0.89, 95% CI 0.71 to 1.1); however more participants may achieve target serum urate level (four trials; 2618 participants) with febuxostat 80 mg daily versus allopurinol 300 mg daily (38% with allopurinol versus 70% with febuxostat, RR 0.56, 95% CI 0.48 to 0.65, NNTB with febuxostat 4). Two trials reported no difference in tophus regression between allopurinol and febuxostat over a 28- to 52-week period; but as the trialists did not provide variance, we could not calculate the mean difference between groups. The trials did not report pain reduction or function. Moderate-quality evidence from pooled data from three trials (2555 participants) comparing allopurinol up to 300 mg daily versus febuxostat 80 mg daily indicated no difference in the number of withdrawals due to AE (7% with allopurinol versus 8% with febuxostat, RR 0.89, 95% CI 0.62 to 1.26) or SAE (4% with allopurinol versus 4% with febuxostat, RR 1.13, 95% CI 0.71 to 1.82) over a 24- to 52-week period.Low-quality evidence from one trial (65 participants) indicated there may be no difference in the incidence of acute gout attacks with allopurinol up to 600 mg daily compared with benzbromarone up to 200 mg daily over a four-month period (0/30 with allopurinol versus 1/25 with benzbromarone, RR 0.28, 95% CI 0.01 to 6.58). Based on the pooled results of two trials (102 participants), there was moderate-quality evidence of no probable difference in the proportion of participants achieving a target serum urate level with allopurinol versus benzbromarone (58% with allopurinol versus 74% with benzbromarone, RR 0.79, 95% CI 0.56 to 1.11). Low-quality evidence from two studies indicated there may be no difference in the number of participants who withdrew due to AE with allopurinol versus benzbromarone over a four- to nine-month period (6% with allopurinol versus 7% with benzbromarone, pooled RR 0.80, 95% CI 0.18 to 3.58). There were no SAEs. They did not report tophi regression, pain and function.All other comparisons were supported by small, single studies only, limiting conclusions.
AUTHORS' CONCLUSIONS
Our review found low- to moderate-quality evidence indicating similar effects on withdrawals due to AEs and SAEs and incidence of acute gout attacks when allopurinol (100 to 600 mg daily) was compared with placebo, benzbromarone (100 to 200 mg daily) or febuxostat (80 mg daily). There was moderate-quality evidence of little or no difference in the proportion of participants achieving target serum urate when allopurinol was compared with benzbromarone. However, allopurinol seemed more successful than placebo and may be less successful than febuxostat (80 mg daily) in achieving a target serum urate level (6 mg/dL or less; 0.36 mmol/L or less) based on moderate- to low-quality evidence. Single studies reported no difference in pain reduction when allopurinol (300 mg daily) was compared with placebo over 10 days, and no difference in tophus regression when allopurinol (200 to 300 mg daily) was compared with febuxostat (80 mg daily). None of the trials reported on function, health-related quality of life or participant global assessment of treatment success, where further research would be useful.
Topics: Allopurinol; Benzbromarone; Chronic Disease; Colchicine; Febuxostat; Gout; Gout Suppressants; Humans; Probenecid; Randomized Controlled Trials as Topic; Thiazoles; Uric Acid
PubMed: 25314636
DOI: 10.1002/14651858.CD006077.pub3 -
The Cochrane Database of Systematic... Oct 2014Tophi develop in untreated or uncontrolled gout. Their presence can lead to severe and potentially fatal complications. To date there have been no systematic reviews... (Review)
Review
BACKGROUND
Tophi develop in untreated or uncontrolled gout. Their presence can lead to severe and potentially fatal complications. To date there have been no systematic reviews focused on the management of tophi in gout.
OBJECTIVES
To assess the benefits and harms of non-surgical and surgical treatments for the management of tophi in gout.
SEARCH METHODS
We searched three databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE. We handsearched American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) abstracts from 2010 to 2011, references from included studies and trial registries. We completed the most recent search on 20 May 2013.
SELECTION CRITERIA
All published randomised controlled trials (RCTs) or controlled clinical trials with quasi-randomised methods of allocating participants to treatment examining interventions for tophi in gout in adults. Possible interventions included urate-lowering pharmacological treatment (e.g. benzbromarone, probenecid, allopurinol, febuxostat, pegloticase), surgical removal or other interventions such as haemodialysis.
DATA COLLECTION AND ANALYSIS
Two review authors extracted data from titles, abstracts and selected studies for detailed review, and extracted data and risk of bias independently. Major outcomes were number of participants with complete resolution of tophi, number of study participant withdrawals due to adverse events, joint pain reduction, function, quality of life, serum urate normalisation and total adverse events.
MAIN RESULTS
Only one study, at low risk of all biases, met the inclusion criteria. This was the pooled results from two RCTs (225 participants, 145 with tophi at baseline) randomised to one of three arms; pegloticase infusion every two weeks (biweekly), monthly pegloticase infusion (pegloticase infusion alternating with placebo infusion every two weeks) and placebo. Moderate-quality evidence from one study indicated that biweekly pegloticase 8 mg infusion reduced tophi in the subset of participants with tophi, but increased withdrawals due to adverse events in all participants, and monthly infusion appeared to result in less benefit.Biweekly pegloticase treatment resulted in resolution of tophi in 21/52 participants compared with 2/27 who received placebo (risk ratio (RR) 5.45, 95% confidence intervals (CI) 1.38 to 21.54; number needed to treat for an additional beneficial outcome (NNTB) 3 (95% CI 2 to 6).Eleven of 52 participants with monthly pegloticase treatment had complete resolution of one or more tophi compared with 2/27 who received placebo (RR 2.86, 95% CI 0.68 to 11.97).Participant-reported pain relief of 30% or greater, function, quality of life, serum urate normalisation, were reported for all participants but not separately for those with tophi; therefore, we did not include the results.Pegloticase administered biweekly resulted in more withdrawals due to adverse events compared with placebo (15/85 participants with pegloticase versus 1/43 participants with placebo; RR 7.59, 95% CI 1.04 to 55.55; number needed to treat for an additional harmful outcome (NNTH) 7, 95% CI 4 to 17). Pegloticase administered monthly also resulted in more withdrawals due to adverse events than placebo (16/84 participants with pegloticase versus 1/43 participants with placebo; RR 8.19, 95% CI 1.12 to 59.71; NNTH 6, 95% CI 4 to 14). Most withdrawals were due to infusion reactions.Total adverse events were high in all treatment groups: 80/85 participants administered pegloticase biweekly reported an adverse event compared with 41/43 from the placebo group (RR 0.99, 95% CI 0.91 to 1.07); 84/84 participants administered pegloticase monthly reported an adverse event versus 41/43 in the placebo group (RR 1.05, 95% CI 0.98 to 1.14). As 80% of adverse events were due to flares of gout, probably unrelated to the drug treatment per se, this may explain the high rate of adverse events in the placebo group - who were essentially untreated.
AUTHORS' CONCLUSIONS
This study showed pegloticase is probably beneficial in the management of tophi in gout, in terms of resolution of tophi, but with a high risk of adverse infusion reactions. However, there is a need for more RCT data considering other interventions, including surgical removal of tophi.
Topics: Gout; Humans; Polyethylene Glycols; Randomized Controlled Trials as Topic; Urate Oxidase; Uric Acid
PubMed: 25330136
DOI: 10.1002/14651858.CD010069.pub2 -
Drugs Feb 1999Lyme disease is a rapidly emerging infectious disease and there are still many unanswered questions with respect to appropriate laboratory tests required for diagnosis... (Review)
Review
Lyme disease is a rapidly emerging infectious disease and there are still many unanswered questions with respect to appropriate laboratory tests required for diagnosis of early Lyme disease, types of antimicrobials required for treatment and duration of therapy. A qualitative systematic review was used to summarise the existing data for the treatment of early Lyme disease. Eleven antibacterial therapy trials and 3 cost-effectiveness analyses met the inclusion criteria for this review. Antibacterial regimens that have been studied include phenoxymethylpenicillin (penicillin V), amoxicillin, amoxicillin/probenecid, tetracycline, doxycycline, cefuroxime axetil, erythromycin, roxithromycin, azithromycin and ceftriaxone. The data support the use of oral beta-lactam antibacterials [phenoxymethylpenicillin (penicillin V), amoxicillin, cefuroxime axetil] and oral tetracyclines as effective first-line treatment modalities for early Lyme disease. Oral macrolides are considered second-line agents as their clinical efficacy has been less than that of the beta-lactams and tetracyclines. Courses of therapy ranging from 10 to 21 days are supported by the available evidence, although the optimal duration of therapy is unknown.
Topics: Anti-Bacterial Agents; Clinical Trials as Topic; Humans; Lyme Disease; Time Factors
PubMed: 10188758
DOI: 10.2165/00003495-199957020-00003 -
Seminars in Arthritis and Rheumatism Oct 2012As many as half of all patients with gouty arthritis have some degree of renal impairment. The goal of this systematic review is to provide physicians with a... (Review)
Review
OBJECTIVE
As many as half of all patients with gouty arthritis have some degree of renal impairment. The goal of this systematic review is to provide physicians with a comprehensive examination of available data on the risks and benefits of gouty arthritis treatment options when used in patients with chronic kidney disease (CKD).
METHODS
We conducted a systematic literature review to determine what information is available to guide treatment decisions in this patient population. PubMed was searched for English-language articles indexed through July 2011 containing the terms "gout" or "hyperuricemia" and synonyms for renal impairment in combination with drug names. Publications were deemed relevant if they reported results from clinical studies, case reports, or prescribing practices of the drug of interest in patients with gouty arthritis and CKD.
RESULTS
Nonsteroidal anti-inflammatory drugs and colchicine are oftentimes not considered appropriate in patients with CKD. Corticosteroids may be an effective alternative in this population; however, their efficacy has not been confirmed in randomized controlled trials and these agents can cause serious side effects. Allopurinol can be used for the prophylactic management of chronic hyperuricemia in patients with CKD, but the recommended decreased dosage may limit efficacy and serious hypersensitivity reactions may preclude its use. Febuxostat and pegloticase are new treatment options for chronic urate-lowering prophylaxis; however, the safety of these drugs in patients with advanced CKD has not yet been reported.
CONCLUSIONS
There is currently an unmet need for additional treatment options for the management of gouty arthritis in patients with CKD.
Topics: Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Gouty; Colchicine; Comorbidity; Contraindications; Febuxostat; Glucocorticoids; Gout Suppressants; Humans; Hyperuricemia; Polyethylene Glycols; Probenecid; PubMed; Renal Insufficiency, Chronic; Secondary Prevention; Thiazoles; Urate Oxidase
PubMed: 22560299
DOI: 10.1016/j.semarthrit.2012.03.013 -
Journal of General Internal Medicine Mar 2018Urate-lowering therapy (ULT) is associated with low rates of adherence, leading to a potential risk of relapse of gouty arthritis, tophi, or urolithiasis. Our main aim...
BACKGROUND
Urate-lowering therapy (ULT) is associated with low rates of adherence, leading to a potential risk of relapse of gouty arthritis, tophi, or urolithiasis. Our main aim was to identify the recurrence of gouty arthritis, tophi, or urolithiasis after discontinuation of ULT. Secondary aims included an assessment of ULT reintroduction rates and factors associated with relapse.
METHODS
We conducted a systematic literature review of clinical studies investigating the effect of discontinuing any ULT (allopurinol, febuxostat, probenecid, sulfinpyrazone, benzbromarone) in adults on long-term therapy. We searched The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Science Citation Index, and ClinicalTrials.gov from inception to March 2016. Conference abstracts of the ACR/ARHP and EULAR annual conferences were hand-searched. Study quality was assessed using the first eight items of the methodological index for non-randomized studies (MINORS) tool. The review protocol is registered with PROSPERO (CRD42016042048).
RESULTS
A total of 4640 articles were identified, eight of which were ultimately included. Most of these studies predated 2000. MINORS scores ranged from 5 to 10 out of a possible 16. Mean follow-up duration after discontinuation ranged from 12 to 96 months. Five studies focused on discontinuation of ULT in gouty arthritis and tophi, two in urolithiasis, and one in asymptomatic hyperuricemia. Relapse rates were high in gout (36-81%) and lower in urolithiasis (15%). Relapses occurred 1-4.5 years after ULT discontinuation. In one study, a low serum urate level before and after ULT discontinuation was associated with lower gout recurrence.
DISCUSSION
Relapse of gout is common although delayed after discontinuation of ULT. Short-term prognosis after ULT discontinuation appears favorable if the serum urate level was low before ULT discontinuation. The results of this review are limited by the paucity of existing studies and their low quality. Further comparative studies should consider larger primary care populations and discontinuation of febuxostat.
Topics: Clinical Trials as Topic; Gout; Gout Suppressants; Humans; Observational Studies as Topic; Recurrence; Uric Acid; Withholding Treatment
PubMed: 29204974
DOI: 10.1007/s11606-017-4233-5