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The Cochrane Database of Systematic... Aug 2015Psoriasis is a chronic inflammatory skin condition that can markedly reduce life quality. Several systemic therapies exist for moderate to severe psoriasis, including... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Psoriasis is a chronic inflammatory skin condition that can markedly reduce life quality. Several systemic therapies exist for moderate to severe psoriasis, including oral fumaric acid esters (FAE). These contain dimethyl fumarate (DMF), the main active ingredient, and monoethyl fumarate. FAE are licensed for psoriasis in Germany but used off-licence in many countries.
OBJECTIVES
To assess the effects and safety of oral fumaric acid esters for psoriasis.
SEARCH METHODS
We searched the following databases up to 7 May 2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library (Issue 4, 2015), MEDLINE (from 1946), EMBASE (from 1974), and LILACS (from 1982). We searched five trials registers and checked the reference lists of included and excluded studies for further references to relevant randomised controlled trials. We handsearched six conference proceedings that were not already included in the Cochrane Skin Group Specialised Register.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of FAE, including DMF monotherapy, in individuals of any age and sex with a clinical diagnosis of psoriasis.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial quality and extracted data. Primary outcomes were improvement in Psoriasis Area and Severity Index (PASI) score and the proportion of participants discontinuing treatment due to adverse effects.
MAIN RESULTS
We included 6 studies (2 full reports, 2 abstracts, 1 brief communication, and 1 letter), with a total of 544 participants. Risk of bias was unclear in several studies because of insufficient reporting. Five studies compared FAE with placebo, and one study compared FAE with methotrexate. All studies reported data at 12 to 16 weeks, and we identified no longer-term studies. When FAE were compared with placebo, we could not perform meta-analysis for the primary outcome of PASI score because the three studies that assessed this outcome reported the data differently, although all studies reported a significant reduction in PASI scores with FAE. Only 1 small study designed for psoriatic arthritis reported on the other primary outcome of participants discontinuing treatment due to adverse effects (2 of 13 participants on FAE compared with none of the 14 participants on placebo; risk ratio (RR) 5.36, 95% confidence interval (CI) 0.28 to 102.1; 27 participants; very low-quality evidence). However, these findings are uncertain due to indirectness and a very wide confidence interval. Two studies, containing 247 participants and both only reported as abstracts, allowed meta-analysis for PASI 50, which showed superiority of FAE over placebo (RR 4.55, 95% CI 2.80 to 7.40; low-quality evidence), with a combined PASI 50 of 64% in those given FAE compared with a PASI 50 of 14% for those on placebo, representing a number needed to treat to benefit of 2. The same studies reported more participants achieving PASI 75 with FAE, but we did not pool the data because of significant heterogeneity; none of the studies measured PASI 90. One study reported significant improvement in participants' quality of life (QoL) with FAE, measured with Skindex-29. However, we could not compute the mean difference because of insufficient reporting in the abstract. More participants experienced adverse effects, mainly gastrointestinal disturbance and flushing, on FAE (RR 4.72, 95% CI 2.45 to 9.08; 1 study, 99 participants; moderate-quality evidence), affecting 76% of participants given FAE and 16% of the placebo group (representing a number needed to treat to harm of 2). The other studies reported similar findings or did not report adverse effects fully.One study of 54 participants compared methotrexate (MTX) with FAE. PASI score at follow-up showed superiority of MTX (mean Difference (MD) 3.80, 95% CI 0.68 to 6.92; 51 participants; very low-quality evidence), but the difference was not significant after adjustment for baseline disease severity. The difference between groups for the proportion of participants who discontinued treatment due to adverse effects was uncertain because of imprecision (RR 0.19, 95% CI 0.02 to 1.53; 1 study, 51 participants; very low-quality evidence). Overall, the number of participants experiencing common nuisance adverse effects was not significantly different between the 2 groups, with 89% of the FAE group affected compared with 100% of the MTX group (RR 0.89, 95% CI 0.77 to 1.03; 54 participants; very low-quality evidence). Flushing was more frequent in those on FAE, with 13 out of 27 participants affected compared with 2 out of 27 given MTX. There was no significant difference in the number of participants who attained PASI 50, 75, and 90 in the 2 groups (very low-quality evidence) whereas this study did not measure the effect of treatments on QoL. The included studies reported no serious adverse effects of FAE and were too small and of limited duration to provide evidence about rare or delayed effects.
AUTHORS' CONCLUSIONS
Evidence suggests that FAE are superior to placebo and possibly similar in efficacy to MTX for psoriasis; however, the evidence provided in this review was limited, and it must be noted that four out of six included studies were abstracts or brief reports, restricting study reporting. FAE are associated with nuisance adverse effects, including flushing and gastrointestinal disturbance, but short-term studies reported no serious adverse effects.
Topics: Administration, Oral; Arthritis, Psoriatic; Dermatologic Agents; Fumarates; Humans; Methotrexate; Psoriasis; Randomized Controlled Trials as Topic; Severity of Illness Index
PubMed: 26258748
DOI: 10.1002/14651858.CD010497.pub2 -
Human Genetics Jul 2022Inherited disorders of cobalamin (cbl) metabolism (cblA-J) result in accumulation of methylmalonic acid (MMA) and/or homocystinuria (HCU). Clinical presentation includes... (Review)
Review
Inherited disorders of cobalamin (cbl) metabolism (cblA-J) result in accumulation of methylmalonic acid (MMA) and/or homocystinuria (HCU). Clinical presentation includes ophthalmological manifestations related to retina, optic nerve and posterior visual alterations, mainly reported in cblC and sporadically in other cbl inborn errors.We searched MEDLINE EMBASE and Cochrane Library, and analyzed articles reporting ocular manifestations in cbl inborn errors. Out of 166 studies a total of 52 studies reporting 163 cbl and 24 mut cases were included. Ocular manifestations were found in all cbl defects except for cblB and cblD-MMA; cblC was the most frequent disorder affecting 137 (84.0%) patients. The c.271dupA was the most common pathogenic variant, accounting for 70/105 (66.7%) cases. One hundred and thirty-seven out of 154 (88.9%) patients presented with early-onset disease (0-12 months). Nystagmus and strabismus were observed in all groups with the exception of MMA patients while maculopathy and peripheral retinal degeneration were almost exclusively found in MMA-HCU patients. Optic nerve damage ranging from mild temporal disc pallor to complete atrophy was prevalent in MMA-HCU.and MMA groups. Nystagmus was frequent in early-onset patients. Retinal and macular degeneration worsened despite early treatment and stabilized systemic function in these patients. The functional prognosis remains poor with final visual acuity < 20/200 in 55.6% (25/45) of cases. In conclusion, the spectrum of eye disease in Cbl patients depends on metabolic severity and age of onset. The development of visual manifestations over time despite early metabolic treatment point out the need for specific innovative therapies.
Topics: Amino Acid Metabolism, Inborn Errors; Homocystinuria; Humans; Macular Degeneration; Methylmalonic Acid; Mutation; Retina; Retinal Degeneration; Vitamin B 12
PubMed: 34652574
DOI: 10.1007/s00439-021-02350-8 -
Canadian Journal of Gastroenterology &... Nov 2014Constipation is an uncomfortable and common condition that affects many, irrespective of age. Since 1500 BC and before, health care practitioners have provided... (Review)
Review
BACKGROUND
Constipation is an uncomfortable and common condition that affects many, irrespective of age. Since 1500 BC and before, health care practitioners have provided treatments and prevention strategies to patients for chronic constipation despite the significant variation in both medical and personal perceptions of the condition.
OBJECTIVE
To review relevant research evidence from clinical studies investigating the efficacy and safety of commercially available pharmacological laxatives in Canada, with emphasis on studies adopting the Rome criteria for defining functional constipation.
SEARCH METHODS
PubMed, Medline, Embase and Evidence-Based Medicine Reviews databases were searched for blinded or randomized clinical trials and meta-analyses assessing the efficacy of nonstimulant and stimulant laxatives for the treatment of functional constipation.
RESULTS
A total of 19 clinical studies and four meta-analyses were retrieved and abstracted regarding study design, participants, interventions and outcomes. The majority of studies focused on polyethylene glycol compared with placebo. Both nonstimulant and stimulant laxatives provided better relief of constipation symptoms than placebo according to both objective and subjective measures. Only one study compared the efficacy of a nonstimulant versus a stimulant laxative, while only two reported changes in quality of life. All studies reported minor side effects due to laxative use, regardless of treatment duration, which ranged from one week to one year. Laxatives were well tolerated by both adults and children.
Topics: Bisacodyl; Canada; Citrates; Constipation; Dioctyl Sulfosuccinic Acid; Humans; Lactulose; Laxatives; Magnesium Oxide; Organometallic Compounds; Paraffin; Picolines; Polyethylene Glycols; Psyllium; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 25390617
DOI: 10.1155/2014/631740 -
Current Medical Research and Opinion Mar 2017The introduction of disease-modifying therapies (DMTs) - with varying degrees of efficacy for reducing annual relapse rate and disability progression - has considerably... (Review)
Review
OBJECTIVE
The introduction of disease-modifying therapies (DMTs) - with varying degrees of efficacy for reducing annual relapse rate and disability progression - has considerably transformed the therapeutic landscape of relapsing-remitting multiple sclerosis (RRMS). We aim to develop rational evidence-based treatment recommendations and algorithms for the management of clinically isolated syndrome (CIS) and RRMS that conform to the healthcare system in a fast-developing economic country such as Qatar.
RESEARCH DESIGN AND METHODS
We conducted a systematic review using a comprehensive search of MEDLINE, PubMed, and Cochrane Database of Systematic Reviews (1 January 1990 through 30 September 2016). Additional searches of the American Academy of Neurology and European Committee for Treatment and Research in Multiple Sclerosis abstracts from 2012 through 2016 were performed, in addition to searches of the Food and Drug Administration and European Medicines Agency websites to obtain relevant safety information on these DMTs.
RESULTS
For each of the DMTs, the mode of action, efficacy, safety and tolerability are briefly discussed. To facilitate the interpretation, the efficacy data of the pivotal phase III trials are expressed by their most clinically useful measure of therapeutic efficacy, the number needed to treat (NNT). In addition, an overview of head-to-head trials in RRMS is provided as well as a summary of the several different RRMS management strategies (lateral switching, escalation, induction, maintenance and combination therapy) and the potential role of each DMT. Finally, algorithms were developed for CIS, active and highly active or rapidly evolving RRMS and subsequent breakthrough disease or suboptimal treatment response while on DMTs. The benefit-to-risk profiles of the DMTs, taking into account patient preference, allowed the provision of rational and safe patient-tailored treatment algorithms.
CONCLUSIONS
Recommendations and algorithms for the management of CIS and RRMS have been developed relevant to the healthcare system of this fast-developing economic country.
Topics: Alemtuzumab; Antibodies, Monoclonal, Humanized; Daclizumab; Dimethyl Fumarate; Fingolimod Hydrochloride; Humans; Immunoglobulin G; Interferons; Multiple Sclerosis, Relapsing-Remitting; Qatar
PubMed: 27892723
DOI: 10.1080/03007995.2016.1261818 -
Drug Safety Aug 2020Bempedoic acid (ETC-1002) is a first-in-class lipid-lowering agent recently approved by the United States (US) Food and Drug Administration (FDA) and the European... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Bempedoic acid (ETC-1002) is a first-in-class lipid-lowering agent recently approved by the United States (US) Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for commercialization.
OBJECTIVE
The aim was to assess, through a systematic review of the literature and a meta-analysis of the available phase 2 and phase 3 clinical studies, the effect of treatment with bempedoic acid on serum uric acid (SUA) concentration. Secondary outcomes were treatment-related variations in creatinine serum level and incidence of gout.
METHODS
A systematic literature search in SCOPUS, PubMed Medline, ISI Web of Science and Google Scholar databases was conducted up to November 13th, 2019, in order to identify clinical trials potentially eligible for the meta-analysis. Effect sizes were expressed as absolute mean differences (MDs) and 95% confidence intervals (CIs).
RESULTS
Data were pooled from four clinical studies comprising ten arms, which included overall 3369 subjects, with 2213 in the active-treatment arm and 1156 in the control one. Meta-analysis of data suggested that treatment with bempedoic acid is related to a significant increase in SUA (MD 0.73, 95% CI 0.54-0.91, P < 0.001), serum creatinine (MD 0.04, 95% CI 0.03-0.05, P < 0.001) and the incidence of gout (odds ratio 3.56, 95% CI 1.24-10.19, P = 0.018). The relatively small number of subjects involved in the studies and the exclusion of patients with renal impairment from the clinical trials are important limitations of the meta-analysis. However, our data indicate potential safety issues with bempedoic acid and suggest that further studies are performed both to elucidate the pathogenetic mechanisms underlying these associations and to verify the long-term safety of this treatment.
CONCLUSION
Bempedoic acid seems to have unfavourable effects on SUA, creatinine level and the incidence of gout. The ongoing Cardiovascular Outcomes Trial (CVOT) will explore the longer-term safety of treatment with bempedoic acid and clarify its effect on cardiovascular events and mortality.
PROSPERO DATABASE REGISTRATION
CRD42019146126.
Topics: Humans; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Dicarboxylic Acids; Fatty Acids; Hypolipidemic Agents; Treatment Outcome; Uric Acid
PubMed: 32358698
DOI: 10.1007/s40264-020-00931-6 -
Surgery For Obesity and Related... 2016Earlier publications have shown renal stone complications after bariatric surgery. Multiple reports have also linked metabolic changes that alter the urinary chemistry... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Earlier publications have shown renal stone complications after bariatric surgery. Multiple reports have also linked metabolic changes that alter the urinary chemistry profiles, especially hyperoxaluria, after bariatric surgery. However, evidence on change of other urine chemistry studies and type of bariatric surgery and risk of stone has been inconclusive so far.
OBJECTIVES
To explore the association between bariatric surgery and postoperative urinary chemistry change and risk of stone formation SETTING: A systematic review and meta-analysis.
METHODS
We comprehensively searched the databases of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from their dates of inception to January 2016. The inclusion criteria were published studies of association between bariatric surgery and postoperative renal stone formation or urine chemistry profiles. We used random-effects model meta-analysis and calculated the pooled risk of renal stone and difference in 24-hour urine chemistry profiles.
RESULTS
Twelve observational studies were included in the meta-analysis. There was significantly higher risk of stone formation after Roux-en-Y gastric bypass surgery with pooled relative risk = 1.79 (95% CI: 1.54-2.10). In the analysis of urine chemistry profiles, there was significantly higher calcium oxalate supersaturation, lower citrate, and lower volume postoperatively compared with preoperatively. There was also higher urine oxalate in patients who had bariatric surgery compared with nonsurgery controls.
CONCLUSIONS
Roux-en-Y gastric bypass surgery is associated with higher risk of renal stone and increased urine oxalate and calcium oxalate supersaturation.
Topics: Calcium Oxalate; Controlled Clinical Trials as Topic; Female; Gastric Bypass; Humans; Hyperoxaluria; Kidney Calculi; Male; Obesity; Observational Studies as Topic; Postoperative Complications; Risk Factors
PubMed: 27396545
DOI: 10.1016/j.soard.2016.04.004 -
The Cochrane Database of Systematic... Oct 2015Kidney stones affect people worldwide and have a high rate of recurrence even with treatment. Recurrences are particularly prevalent in people with low urinary citrate... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Kidney stones affect people worldwide and have a high rate of recurrence even with treatment. Recurrences are particularly prevalent in people with low urinary citrate levels. These people have a higher incidence of calcium phosphate and calcium oxalate stones. Oral citrate therapy increases the urinary citrate levels, which in turn binds with calcium and inhibits the crystallisation thus reduces stone formation. Despite the widespread use of oral citrate therapy for prevention and treatment of calcium oxalate stones, the evidence to support its clinical efficacy remains uncertain.
OBJECTIVES
The objective of this review was to determine the efficacy and adverse events associated with citrate salts for the treatment and prevention of calcium containing kidney stones.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Specialised Register to 29 July 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that assessed the efficacy and adverse events associated with citrate salts for the treatment and prevention of calcium containing kidney stones in adults treated for a minimum of six months.
DATA COLLECTION AND ANALYSIS
Two authors assessed studies for inclusion in this review. Data were extracted according to predetermined criteria. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes.
MAIN RESULTS
We included seven studies that included a total of 477 participants, most of whom had oxalate stones. Of these, three studies (247 participants) compared potassium citrate with placebo or no intervention; three (166 participants) compared potassium-sodium citrate with no intervention; and one (64 participants) compared potassium-magnesium citrate with placebo. Overall, quality of the reporting of the included studies was considered moderate to poor, and there was a high risk of attrition bias in two studies.Compared with placebo or no intervention, citrate therapy significantly reduced the stone size (4 studies, 160 participants: RR 2.35, 95% CI 1.36 to 4.05). New stone formation was significantly lower with citrate therapy compared to control (7 studies, 324 participants: RR 0.26, 95% CI 0.10 to 0.68). The beneficial effect on stone size stability was also evident (4 studies, 160 participants: RR 1.97, 95% CI 1.19 to 3.26). Adverse events were reported in four studies, with the main side effects being upper gastrointestinal disturbance and one patient reported a rash. There were more gastrointestinal adverse events in the citrate group; however this was not significant (4 studies, 271 participants: RR 2.55, 95% CI 0.71 to 9.16). There were significantly more dropouts due to adverse events with citrate therapy compared to control (4 studies, 271 participants: RR 4.45, 95% CI 1.28 to 15.50). The need for retreatment was significantly less with citrate therapy compared to control (2 studies, 157 participants: RR 0.22, 95% CI 0.06 to 0.89).
AUTHORS' CONCLUSIONS
Citrate salts prevent new stone formation and reduce further stone growth in patients with residual stones that predominantly contain oxalate. The quality of reported literature remains moderate to poor; hence a well-designed statistically powered multi-centre RCT is needed in order to answer relevant questions concerning the efficacy of citrate salts.
Topics: Adult; Calcium Oxalate; Calcium Phosphates; Citrates; Drug Combinations; Humans; Kidney Calculi; Magnesium Compounds; Potassium Compounds; Randomized Controlled Trials as Topic; Recurrence; Secondary Prevention
PubMed: 26439475
DOI: 10.1002/14651858.CD010057.pub2 -
Diabetes & Vascular Disease Research Sep 2017Aliskiren was shown to increase adverse events in patients with diabetes and concomitant renin-angiotensin blockade. We aim to investigate the efficacy and safety of... (Meta-Analysis)
Meta-Analysis Review
Effects of aliskiren on mortality, cardiovascular outcomes and adverse events in patients with diabetes and cardiovascular disease or risk: A systematic review and meta-analysis of 13,395 patients.
BACKGROUND
Aliskiren was shown to increase adverse events in patients with diabetes and concomitant renin-angiotensin blockade. We aim to investigate the efficacy and safety of aliskiren in patients with diabetes and increased cardiovascular risk or established cardiovascular disease.
METHODS
MEDLINE and Embase were searched for prospective studies comparing addition of aliskiren to standard medical therapy in patients with diabetes and cardiovascular disease, or ⩾1 additional cardiovascular risk factor (hypertension, abnormal lipid profile, microalbuminuria/proteinuria, chronic kidney disease). Relative risk for efficacy (all-cause mortality, combined cardiovascular mortality and hospitalisation) and safety (hyperkalaemia, hypotension, renal impairment) outcomes was calculated.
RESULTS
Of 2151 studies identified in the search, seven studies enrolling 13,395 patients were included. Aliskiren had no effect on all-cause mortality (relative risk: 1.05, 95% confidence interval: 0.90 to 1.24, p = 0.53), or combined cardiovascular mortality or heart failure hospitalisation (relative risk: 1.07, 95% confidence interval: 0.81 to 1.40, p = 0.64). Patients receiving aliskiren had a greater risk of developing hyperkalaemia (relative risk: 1.32, 95% confidence interval: 1.14 to 1.53, p = 0.0003) and renal impairment (relative risk: 1.15, 95% confidence interval: 1.02 to 1.30, p = 0.03), but not hypotension.
CONCLUSION
Patients with diabetes and cardiovascular disease or cardiovascular risk do not benefit from the addition of aliskiren to standard medical therapy. Detrimental safety profile in pooled analysis supports current warnings.
Topics: Amides; Cardiovascular Agents; Cardiovascular Diseases; Chi-Square Distribution; Diabetes Mellitus; Fumarates; Humans; Odds Ratio; Renin-Angiotensin System; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 28844155
DOI: 10.1177/1479164117715854 -
BMC Pharmacology & Toxicology Dec 2020Bempedoic acid is a new drug that reduces cholesterol synthesis via inhibiting ATP citrate lyase. It remains unclear whether the combination of bempedoic acid and other... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of bempedoic acid alone or combining with other lipid-lowering therapies in hypercholesterolemic patients: a meta-analysis of randomized controlled trials.
BACKGROUND
Bempedoic acid is a new drug that reduces cholesterol synthesis via inhibiting ATP citrate lyase. It remains unclear whether the combination of bempedoic acid and other lipid-lowering drugs is better than these drugs alone. This study systematically reviewed the efficacy and safety of bempedoic acid monotherapy or combination togethers in hypercholesterolemic patients.
METHODS
Randomized controlled trials were searched across Medline, Embase, Cochrane library, web of science, etc. The net change scores [least squares mean (LSM) percentage change] in LDL-C level were meta-analyzed using weighted mean difference. The reductions in other lipids including total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein (ApoB) and high sensitivity C reactive protein (hsCRP) were also assessed. Odds ratio (OR) of the incidence of adverse events (AEs) were calculated to evaluate the safety of bempedoic acid.
RESULTS
A total of 13 trials (4858 participates) were included. Pooled data showed that the combination togethers resulted in greater reductions in LDL-C level than monotherapies (bempedoic acid + statin vs. statin: LSM difference (%), - 18.37, 95% CI, - 20.16 to - 16.57, I = 0; bempedoic acid + ezetimibe vs. ezetimibe: LSM difference (%), - 18.89, 95% CI, - 29.66 to - 8.13, I = 87%). But the difference in efficacy between bempedoic acid and ezetimibe was not obvious. Meta-regression analysis showed the treatment duration was a source of heterogeneity (adj R = 16.92, 95% CI, 0.04 to 0.72). Furthermore, the background therapy of statin before screening decreased the efficacy of bempedoic acid. In addition, bempedoic acid also resulted in a significant reduction in TC, non-HDL-C, ApoB and hsCRP level. The OR of muscle-related AEs by the combination of bempedoic acid and statin was 1.29 (95% CI, 1.00 to 1.67, I = 0) when compared with statin alone.
CONCLUSION
This study showed the efficacy of combination togethers were similar but stronger than these drugs alone. Of note, a trend of high risk of muscle-related AEs by the combination of bempedoic acid and statin was observed, though it is not statistically significant, such risk is needed to be confirmed by more trials, because it is important for us to determine which is the better combinative administration for statin-intolerant patients.
Topics: Anticholesteremic Agents; Dicarboxylic Acids; Drug Therapy, Combination; Fatty Acids; Humans; Hypercholesterolemia; Hypolipidemic Agents; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 33276805
DOI: 10.1186/s40360-020-00463-w -
The British Journal of Dermatology Nov 2016Fumaric acid esters (FAEs) are licensed for the treatment of moderate-to-severe psoriasis in Germany but are also used off-label in many other countries. We conducted... (Meta-Analysis)
Meta-Analysis Review
Fumaric acid esters (FAEs) are licensed for the treatment of moderate-to-severe psoriasis in Germany but are also used off-label in many other countries. We conducted this systematic review to synthesize the highest-quality evidence for the benefits and risks of FAEs for psoriasis. Our primary outcomes were change in Psoriasis Area and Severity Index score and dropout rates due to adverse effects. Randomized controlled trials (RCTs) of FAEs or dimethylfumarate were included, with no restriction on age or psoriasis subtype. We searched the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library, Medline, Embase, LILACS and five trials registers, and hand searched six conference proceedings. Six RCTs with a total of 544 participants were included, four of which were published only as abstracts or brief reports, limiting study reporting. Five RCTs compared FAEs with placebo, and all demonstrated benefit in favour of FAEs. However, meta-analysis was possible only for PASI 50 response after 12-16 weeks, which was achieved by 64% of participants on FAEs compared with 14% on placebo: risk ratio (RR) 4·55, 95% confidence interval (CI) 2·80-7·40; two studies; 247 participants; low-quality evidence). There was no difference in dropout rates due to adverse effects (RR 5·36, 95% CI 0·28-102·12; one study; 27 participants; very low-quality evidence and wide CI). More participants experienced nuisance adverse effects with FAEs (76%) than with placebo (16%) (RR 4·72, 95% CI 2·45-9·08; one study; 99 participants; moderate-quality evidence), mainly abdominal pain, diarrhoea and flushing. One head-to-head study of very low-quality evidence comparing FAEs with methotrexate reported comparable efficacy and dropout rates, although FAEs caused more flushing. The evidence in this review was limited and must be interpreted with caution; studies with better design and outcome reporting are needed.
Topics: Administration, Oral; Dermatologic Agents; Fumarates; Humans; Methotrexate; Placebos; Psoriasis; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 27087044
DOI: 10.1111/bjd.14676