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Oncotarget Sep 2015Most comprehensive treatments for PBC include UDCA, combination of methotrexate (MTX), corticosteroids (COT), colchicine (COC) or bezafibrate (BEF), cyclosporin A (CYP),... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Most comprehensive treatments for PBC include UDCA, combination of methotrexate (MTX), corticosteroids (COT), colchicine (COC) or bezafibrate (BEF), cyclosporin A (CYP), D-penicillamine (DPM), methotrexate (MTX), or azathioprine (AZP). Since the optimum treatment regimen remains inconclusive, we aimed to compare these therapies in terms of patient mortality or liver transplantation (MOLT) and adverse event (AE).
METHODS
We searched PubMed, Embase, Scopus and the Cochrane Library for randomized controlled trials until August 2014. We estimated HRs for MOLT and ORs for AE. The sensitivity analysis based on dose of UDCA was also performed.
RESULTS
The search identified 49 studies involving 12 different treatment regimens and 4182 patients. Although no statistical significance can be found in MOLT, COT plus UDCA was ranked highest for efficacy outcome amongst all the treatment regimes. While for AEs, compared with OBS or UDCA, monotherapy with COC (OR 5.6, P < 0.001; OR 5.89, P < 0.001), CYP (OR 3.24, P < 0.001; OR 3.42, P < 0.001), DPM (OR 8.00, P < 0.001; OR 8.45, P < 0.001) and MTX (OR 5.31, P < 0.001; OR 5.61, P < 0.001) were associated with statistically significant increased risk of AEs. No significant differences were found for other combination regimes. Effect estimates from indirect comparisons matched closely to estimates derived from pairwise comparisons. Consistently, in the sensitivity analysis, results closely resembled our primary analysis.
CONCLUSIONS
COT plus UDCA was the most efficacious among treatment regimens both for MOLT and AEs.
Topics: Adrenal Cortex Hormones; Adult; Aged; Azathioprine; Bezafibrate; Bile Ducts; Colchicine; Cyclosporine; Drug Therapy, Combination; Female; Humans; Liver Cirrhosis, Biliary; Male; Methotrexate; Middle Aged; Penicillamine; Treatment Outcome; Ursodeoxycholic Acid
PubMed: 26109432
DOI: 10.18632/oncotarget.4528 -
The Cochrane Database of Systematic... Jun 2014Methotrexate is a folic acid antagonist widely used for the treatment of neoplastic disorders. Methotrexate inhibits the synthesis of deoxyribonucleic acid (DNA),... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Methotrexate is a folic acid antagonist widely used for the treatment of neoplastic disorders. Methotrexate inhibits the synthesis of deoxyribonucleic acid (DNA), ribonucleic acid (RNA) and proteins by binding to dihydrofolate reductase. Currently, methotrexate is among the most commonly used drugs for the treatment of rheumatoid arthritis (RA). This is an update of the previous Cochrane systematic review published in 1997.
OBJECTIVES
To evaluate short term benefits and harms of methotrexate for treating RA compared to placebo.
SEARCH METHODS
The Cochrane Musculoskeletal Group Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE were searched from 1966 to 1997 and then updated to November 2013. The search was complemented with a bibliography search of the reference lists of trials retrieved from the electronic search.
SELECTION CRITERIA
Randomized controlled trials and controlled clinical trials comparing methotrexate (MTX) monotherapy against placebo alone in people with RA. Any trial duration and MTX doses were included.
DATA COLLECTION AND ANALYSIS
Two review authors independently determined which studies were eligible for inclusion, extracted data and assessed risk of bias. Outcomes were pooled using mean differences (MDs) for continuous variables or standardized mean differences (SMDs) when different scales were used to measure the same outcome. Pooled risk ratio (RR) was used for dichotomous variables. Fixed-effect models were used throughout, although random-effects models were used for outcomes showing heterogeneity.
MAIN RESULTS
Five trials with 300 patients were included in the original version of the review. An additional two trials with 432 patients were added to the 2013 update of the review for a total of 732 participants. The trials were generally of unclear to low risk of bias with a follow-up duration ranging from 12 to 52 weeks. All trials included patients who have failed prior treatment (for example, gold therapy, D-penicillamine, azathioprine or anti-malarials); mean disease duration that ranged between 1 and 14 years with six trials reporting more than 4 years; and weekly doses that ranged between 5 mg and 25 mg.
BENEFITS
Statistically significant and clinically important differences were observed for most efficacy outcomes. MTX monotherapy showed a clinically important and statistically significant improvement in the American College of Rheumatology (ACR) 50 response rate when compared with placebo at 52 weeks (RR 3.0, 95% confidence interval (CI) 1.5 to 6.0; number needed to treat (NNT) 7, 95% CI 4 to 22). Fifteen more patients out of 100 had a major improvement in the ACR 50 outcome compared to placebo (absolute treatment benefit (ATB) 15%, 95% CI 8% to 23%).Statistically significant improvement in physical function (scale of 0 to 3) was also observed in patients receiving MTX alone compared with placebo at 12 to 52 weeks (MD -0.27, 95% CI -0.39 to -0.16; odds ratio (OR) 2.8, 95% CI 0.23 to 32.2; NNT 4, 95% CI 3 to 7). Nine more patients out of 100 improved in physical function compared to placebo (ATB -9%, 95% CI -13% to -5.3%). Similarly, the proportion of patients who improved at least 20% on the Short Form-36 (SF-36) physical component was higher in the MTX-treated group compared with placebo at 52 weeks (RR 1.5, 95% CI 1.0 to 2.1; NNT 9, 95% CI 4 to 539). Twelve more patients out of 100 showed an improvement of at least 20% in the physical component of the quality of life measure compared to placebo (ATB 12%, 95% CI 1% to 24%). No clinically important or statistically significant differences were observed in the SF-36 mental component.Although no statistically significant differences were observed in radiographic scores (that is, Total Sharp score, erosion score, joint space narrowing), radiographic progression rates (measured by an increase in erosion scores of more than 3 units on a scale ranging from 0 to 448) were statistically significantly lower for patients in the MTX group compared with placebo-treated patients (RR 0.31, 95% CI 0.11 to 0.86; NNT 13, 95% CI 10 to 60). Eight more patients out of 100 showed less damage to joints measured by an increase in erosion scores compared to placebo (ATB -8%, 95% CI -16% to -1%). In the one study measuring remission, no participants in either group met the remission criteria. These are defined by at least five of (≥ 2 months): morning stiffness of < 15 minutes, no fatigue, no joint pain by history, no joint tenderness, no joint swelling, and Westergren erythrocyte sedimentation rate (ESR) of < 20 mm/hr in men and < 30 mm/hr in women.
HARMS
Patients in the MTX monotherapy group were twice as likely to discontinue from the study due to adverse events compared to patients in the placebo group, at 12 to 52 weeks (16% versus 8%; RR 2.1, 95% CI 1.3 to 3.3; NNT 13, 95% CI 6 to 44). Compared to placebo, nine more people out of 100 who took MTX withdrew from the studies because of side effects (ATB 9%, 95% CI 3% to 14%). Total adverse event rates at 12 weeks were higher in the MTX monotherapy group compared to the placebo group (45% versus 15%; RR 3.0, 95% CI 1.4 to 6.4; NNT 4, 95% CI 2 to 17). Thirty more people out of 100 who took MTX compared to those who took placebo experienced any type of side effect (common or rare) (ATB 30, 95% CI 13% to 47%). No statistically significant differences were observed in the total number of serious adverse events between the MTX group and the placebo group at 27 to 52 weeks. Three people out of 100 who took MTX alone experienced rare but serious side effects compared to 2 people out of 100 who took a placebo (3% versus 2%, respectively).
AUTHORS' CONCLUSIONS
Based on mainly moderate to high quality evidence, methotrexate (weekly doses ranging between 5 mg and 25 mg) showed a substantial clinical and statistically significant benefit compared to placebo in the short term treatment (12 to 52 weeks) of people with RA, although its use was associated with a 16% discontinuation rate due to adverse events.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Female; Folic Acid Antagonists; Humans; Male; Medication Adherence; Methotrexate; Randomized Controlled Trials as Topic
PubMed: 24916606
DOI: 10.1002/14651858.CD000957.pub2 -
The Cochrane Database of Systematic... Sep 2013The rate of retinopathy of prematurity (ROP) in moderately premature infants has decreased dramatically with improved care in the neonatal intensive care unit. A low... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The rate of retinopathy of prematurity (ROP) in moderately premature infants has decreased dramatically with improved care in the neonatal intensive care unit. A low rate of this disorder was unexpectedly observed among infants treated with intravenous D-penicillamine to prevent hyperbilirubinaemia. This observation led to the investigation of its use, both enterally as well as intravenously, to prevent ROP.
OBJECTIVES
To determine the effect of prophylactic administration of D-penicillamine on the incidence of acute ROP or severe ROP and other morbidities in preterm infants.
SEARCH METHODS
We used the Cochrane Neonatal Review Group search strategy. Two review authors independently searched multiple electronic databases, previous reviews including cross references, abstracts, conference/symposia proceedings, and expert informants. We updated the search on November 27, 2012.
SELECTION CRITERIA
We included randomised or quasi-randomised controlled trials if they administered D-penicillamine and compared it with no treatment or placebo to premature infants and reported on the outcome of ROP.
DATA COLLECTION AND ANALYSIS
We used the criteria and standard methods of the Cochrane Neonatal Review Group to assess the methodological quality of the included trials. One review author examined trials for validity. A second review author checked validity and they reached consensus on the final data before entry into this review. We used the standards of the Neonatal Cochrane Review Group to analyse data.
MAIN RESULTS
Three randomised trials met the inclusion criteria. The meta-analysis showed no significant differences in the risk of any stage ROP (typical risk ratio (RR) 0.32, 95% confidence interval (CI) 0.03 to 3.70), severe ROP (typical RR 0.38, 95% CI 0.03 to 4.26) or death (typical RR 0.95, 95% CI 0.68 to 1.32) in all treated infants. When the subgroup of infants under 1500 g birth weight was examined, the results were similar. No side effects were reported, and follow-up at one year revealed no significant differences in spasticity or developmental delay.
AUTHORS' CONCLUSIONS
Administration of prophylactic D-penicillamine in preterm infants does not prevent acute or severe ROP, death or neurodevelopmental delay. D-penicillamine cannot be recommended for the prevention of ROP based on the available evidence.
Topics: Chelating Agents; Humans; Infant, Newborn; Infant, Premature; Penicillamine; Randomized Controlled Trials as Topic; Retinopathy of Prematurity
PubMed: 24002688
DOI: 10.1002/14651858.CD001073.pub2 -
The Cochrane Database of Systematic... Sep 2012Arthritis remains a relatively infrequent complication of cystic fibrosis, but is a cause of significant morbidity when it does occur. Two distinct types of arthritis... (Review)
Review
BACKGROUND
Arthritis remains a relatively infrequent complication of cystic fibrosis, but is a cause of significant morbidity when it does occur. Two distinct types of arthritis are described in cystic fibrosis: cystic fibrosis-related arthropathy and hypertrophic osteoarthropathy. Management of arthritis in people with cystic fibrosis is uncertain and complex because of the underlying disease and its treatment.
OBJECTIVES
To review the effectiveness and safety of disease-modifying anti-rheumatic drugs for the management of arthritis related to cystic fibrosis in adults and children.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Cystic Fibrosis Trials Register which comprises references identified from comprehensive electronic database handsearches of relevant journal and abstract books of conference proceedings.Date of most recent search: 10 July 2012.
SELECTION CRITERIA
Randomised controlled trials which compared the efficacy and safety of disease-modifying anti-rheumatic drugs (e.g. methotrexate, gold, sulfasalazine, penicillamine, leflunomide, hydroxychloroquine and newer agents such as biologic disease modifying agents and monoclonal antibodies) with each other, with no treatment or with placebo for cystic fibrosis-related arthropathy or hypertrophic osteoarthropathy.
DATA COLLECTION AND ANALYSIS
No relevant studies were identified.
MAIN RESULTS
No studies were included in this review.
AUTHORS' CONCLUSIONS
Although it is generally recognised that cystic fibrosis-related arthritis can be episodic and resolve spontaneously, treatment with analgesics and anti-inflammatory agents may be needed. But when episodic symptoms progress to persistent disease, disease-modifying anti-rheumatic drugs may be needed to limit the course of the disease. It is disappointing that no randomised controlled trials to rigorously evaluate these drugs could be found. This systematic review has identified the need for a well-designed adequately powered randomised controlled trial to assess the efficacy and safety of disease-modifying anti-rheumatic drugs for the management of cystic fibrosis-related arthropathy and hypertrophic osteoarthropathy in adults and children with cystic fibrosis. However, given the infrequency of cystic fibrosis-related arthritis and the range of symptoms and severity, randomised controlled trials may not be feasible and well-designed non-randomised observational studies may be more appropriate. Studies should also better define the two conditions.
Topics: Antirheumatic Agents; Arthritis; Cystic Fibrosis; Humans
PubMed: 22972107
DOI: 10.1002/14651858.CD007336.pub3 -
Alimentary Pharmacology & Therapeutics May 2009No consensus is available on the optimal initial treatment in Wilson disease. (Review)
Review
BACKGROUND
No consensus is available on the optimal initial treatment in Wilson disease.
AIM
To assess systematically the available literature of treatment in newly presenting patients with a presymptomatic, hepatic or neurological presentation of Wilson disease.
METHODS
A systematic literature search of the MEDLINE, EMBASE and COCHRANE databases was performed. Original studies on clinical efficacy of D-penicillamine, trientine, tetrathiomolybdate or zinc monotherapy as initial treatment in Wilson disease were included. A descriptive analysis of the relevant published data was performed.
RESULTS
One randomized trial and 12 observational studies met the inclusion criteria. These studies were quite heterogeneous and generally of low validity. Nevertheless, according to currently available data, patients with hepatic presentation of Wilson disease are probably most effectively treated by D-penicillamine. Zinc seems to be preferred above d-penicillamine for treatment of presymptomatic and neurological patients, as in these subgroups, the tolerance profile is in favour of zinc, while no obvious differences in clinical efficacy could be observed.
CONCLUSIONS
There is lack of high-quality evidence to estimate the relative treatment effects of the available drugs in Wilson disease. Therefore, multicentre prospective randomized controlled comparative trials are necessary.
Topics: Adolescent; Adult; Chelating Agents; Child; Child, Preschool; Female; Hepatolenticular Degeneration; Humans; Infant; Male; Middle Aged; Randomized Controlled Trials as Topic; Trace Elements; Treatment Outcome; Young Adult; Zinc
PubMed: 19210288
DOI: 10.1111/j.1365-2036.2009.03959.x -
Annals of the Rheumatic Diseases Jul 2009To perform a systematic literature review of the long-term safety of methotrexate (MTX) monotherapy in rheumatoid arthritis (RA). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To perform a systematic literature review of the long-term safety of methotrexate (MTX) monotherapy in rheumatoid arthritis (RA).
METHODS
A search was performed in Medline, Cochrane and EMBASE. Adults with RA who had received MTX monotherapy for more than 2 years were studied.
RESULTS
88 published studies were included. Over 12 years of treatment, the termination rate of MTX due to toxicity was less than for sulfasalazine, gold, d-penicillamine and higher than for hydroxychloroquine (level of evidence 2a-2b). Long-term use of MTX does not appear to be a risk factor for serious infections, including herpes zoster (2b-4), and could provide a survival benefit by reducing cardiovascular mortality (2b). The prevalence of raised liver enzymes (more than twice the upper limit of normal) is close to 13% of patients; 3.7% of patients stopped MTX permanently owing to liver toxicity (2b). Data on the risk for liver fibrosis/cirrhosis are conflicting: a meta-analysis showed an incidence of fibrosis of 2.7% after 4 years of MTX (2a). However, two other studies on sequential liver biopsies did not show evidence for developing severe damage (2b). Insufficient data are available to fully assess the risk of lymphoma and malignancies, although there is no strong evidence of increased risk (2b-4).
CONCLUSION
This systematic literature search on MTX monotherapy with relatively low-dose use during at least 2 years shows favourable long-term safety.
Topics: Adult; Antirheumatic Agents; Arthritis, Rheumatoid; Cardiovascular Diseases; Chemical and Drug Induced Liver Injury; Humans; Infections; Long-Term Care; Methotrexate; Neoplasms; Pneumonia; Risk Factors
PubMed: 19060002
DOI: 10.1136/ard.2008.093690 -
Alimentary Pharmacology & Therapeutics Dec 2006D-Penicillamine is used for patients with primary biliary cirrhosis due to its ability to decrease hepatic copper and modulate the immune response. The results on... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
D-Penicillamine is used for patients with primary biliary cirrhosis due to its ability to decrease hepatic copper and modulate the immune response. The results on effects of D--penicillamine in randomized-clinical trials of primary biliary cirrhosis patients are inconsistent.
AIM
To systematically evaluate the benefits and harms of D-penicillamine for patients with primary biliary cirrhosis.
METHODS
We have performed a systematic review with meta-analyses of randomized-clinical trials to evaluate the effects of D-penicillamine for primary biliary cirrhosis. The primary outcomes are mortality and mortality or liver transplantation. We analysed the data by fixed-effect and random-effect models.
RESULTS
Seven randomized trials including 706 patients were analysed. d-Penicillamine was without significant effects on mortality (RR 1.08, 95% CI: 0.82-1.43, P = 0.56), mortality or liver transplantation (RR 1.11, 95% CI: 0.74-1.68, P = 0.62), pruritus, liver complications, progression of liver histological stage and liver biochemical variables. D--Penicillamine significantly decreased serum alanine aminotransferase activity (weighted mean difference -45 IU/L, 95% CI: -75 to -15, P < 0.05) and led to significantly more adverse events (RR 4.18, 95% CI: 1.38-12.69, P = 0.01).
CONCLUSION
D-Penicillamine did not appear to reduce the risk of mortality or morbidity, and led to more adverse events in patients with primary biliary cirrhosis.
Topics: Chelating Agents; Female; Humans; Liver Cirrhosis, Biliary; Male; Middle Aged; Penicillamine; Randomized Controlled Trials as Topic
PubMed: 17206942
DOI: 10.1111/j.1365-2036.2006.03164.x -
BMJ Clinical Evidence Aug 2007Rheumatoid arthritis usually starts as a symmetrical polyarthritis, and its course is marked by flares and remissions. The aims of treatment are to relieve pain and... (Review)
Review
INTRODUCTION
Rheumatoid arthritis usually starts as a symmetrical polyarthritis, and its course is marked by flares and remissions. The aims of treatment are to relieve pain and swelling, and to improve function. In addition, disease-modifying antirheumatic drugs (DMARDs) may reduce disease progression.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments in people with rheumatoid arthritis who have not previously received any disease-modifying antirheumatic drug treatment? How do different drug treatments compare in people with rheumatoid arthritis who have either not responded to or are intolerant of first-line disease-modifying antirheumatic drugs? We searched: Medline, Embase, The Cochrane Library and other important databases up to June 2005 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 62 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: adalimumab, anakinra, antimalarial drugs, azathioprine, ciclosporin, corticosteroids, cyclophosphamide, etanercept, infliximab plus methotrexate, leflunomide, methotrexate (alone; or plus sulfasalazine plus hydroxychloroquine), oral gold, parenteral gold, penicillamine, sulfasalazine.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Interleukin 1 Receptor Antagonist Protein; Methotrexate; Treatment Outcome
PubMed: 19454108
DOI: No ID Found -
The Cochrane Database of Systematic... Jan 2006Primary sclerosing cholangitis is a cholestatic disease. D-penicillamine is suggested as a treatment option due to its copper reducing and immunomodulatory potential. (Review)
Review
BACKGROUND
Primary sclerosing cholangitis is a cholestatic disease. D-penicillamine is suggested as a treatment option due to its copper reducing and immunomodulatory potential.
OBJECTIVES
To evaluate the beneficial and harmful effects of D-penicillamine for patients with primary sclerosing cholangitis.
SEARCH STRATEGY
Eligible trials were identified through searches of The Cochrane Hepato-Biliary Group Controlled Trials Register (August 2005), The Cochrane Central Register of Controlled Trials in The Cochrane Library (Issue 3, 2005), MEDLINE (1950 to August 2005), EMBASE (1980 to August 2005), Science Citation Index EXPANDED (1945 to August 2005), and reference lists of relevant articles. Authors of trials and pharmaceutical companies known to produce D-penicillamine were also contacted.
SELECTION CRITERIA
Randomised clinical trials comparing D-penicillamine in any dose, duration, and route of administration versus placebo, no intervention, or other intervention(s). Trials were included irrespective of publication status, year of publication, language, or blinding.
DATA COLLECTION AND ANALYSIS
Both authors selected the trials, extracted data, and evaluated the methodological quality of the trials with respect to the generation of allocation sequence, allocation concealment, blinding, and follow-up. The results were reported by intention-to-treat analysis. The outcomes were presented as relative risk (RR) or weighted mean difference (WMD), both with 95% confidence intervals (CI).
MAIN RESULTS
One randomised trial was identified and included in the review. It was of low methodological quality. The trial compared D-penicillamine versus placebo in 70 patients with primary sclerosing cholangitis. Compared with placebo, D-penicillamine therapy had no significant effect on mortality (RR 1.14, 95% CI 0.49 to 2.64), liver transplantation (RR 1.11, 95% CI 0.39 to 3.17), hepatic histologic progression (RR 1.17, 95% CI 0.79 to 1.74), or cholangiographic deterioration (RR 0.87, 95% CI 0.43 to 1.79). D-penicillamine led to a significant improvement in the serum aspartate aminotransferase (WMD -23.00 U/L; 95% CI -30.66 to -15.34), but not in serum bilirubin level (WMD 0.40 mg/L; 95% CI -0.19 to 0.99) and serum alkaline phosphatases activity (WMD 44.00 U/L; 95% CI -37.89 to 125.89). There were significantly more adverse events in patients receiving D-penicillamine (P = 0.013).
AUTHORS' CONCLUSIONS
There is not sufficient evidence to support or refute the use of D-penicillamine for patients with primary sclerosing cholangitis. We do not recommend the use of D-penicillamine for patients with primary sclerosing cholangitis outside randomised trials.
Topics: Cholangitis, Sclerosing; Humans; Penicillamine; Randomized Controlled Trials as Topic
PubMed: 16437475
DOI: 10.1002/14651858.CD004182.pub3 -
The Cochrane Database of Systematic... Oct 2004D-penicillamine is used for patients with primary biliary cirrhosis due to its hepatic copper decreasing and immunomodulatory potentials. The results from randomised... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
D-penicillamine is used for patients with primary biliary cirrhosis due to its hepatic copper decreasing and immunomodulatory potentials. The results from randomised clinical trials have been inconsistent.
OBJECTIVES
To systematically review the beneficial and harmful effects of D-penicillamine for patients with primary biliary cirrhosis.
SEARCH STRATEGY
We identified trials through electronic searches of The Cochrane Hepato-Biliary Group Controlled Trials Register (September 2003), The Cochrane Central Register of Controlled Trials on The Cochrane Library (Issue 3, 2003), MEDLINE (January 1966 to September 2003), EMBASE (January 1980 to September 2003), The Chinese Biomedical CD Database (January 1979 to August 2003), and LILACS (1982 to 2003); through manual searches of bibliographies; and by contacting authors of the trials and pharmaceutical companies.
SELECTION CRITERIA
We included randomised clinical trials comparing D-penicillamine with placebo/no intervention or other control intervention irrespective of language, year of publication, and publication status.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed the methodological quality of the trials and extracted data, validated by a third reviewer. The primary outcomes were 1) mortality and 2) a combination of those who died or underwent liver transplantation. We analysed dichotomous outcomes as relative risk (RR) with 95% confidence interval (CI) by a fixed effect model and a random effects model. We investigated sources of heterogeneity by subgroup analyses and tested the robustness of our findings by sensitivity analyses.
MAIN RESULTS
We included seven trials randomising 706 patients with primary biliary cirrhosis. D-penicillamine compared with placebo/no intervention tended to increase mortality (RR 1.34, 95% CI 1.09 to 1.64, fixed; RR 1.46, 95% CI 0.85 to 2.50, random). However, there was substantial heterogeneity. No significant differences were detected regarding the risks of mortality or liver transplantation, pruritus, liver complications, progression of liver histological stage, or the levels of liver biochemical variables (except alanine aminotransferase). D-penicillamine versus placebo/no intervention significantly increased the risk of adverse events (RR 3.11, 95% CI 2.33 to 4.16, fixed; RR 4.18, 95% CI 1.38 to 12.69, random).
REVIEWERS' CONCLUSIONS
D-penicillamine did not appear to reduce the risk of mortality, but significantly increased the occurrences of adverse events in patients with primary biliary cirrhosis. We do not support the use of D-penicillamine for patients with primary biliary cirrhosis.
Topics: Chelating Agents; Humans; Liver Cirrhosis, Biliary; Penicillamine; Randomized Controlled Trials as Topic
PubMed: 15495127
DOI: 10.1002/14651858.CD004789.pub2