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Journal of the American Heart... Aug 2020Background Bempedoic acid (BA) is a novel lipid-lowering drug. We performed a systematic review and meta-analysis on efficacy and safety of BA compared with standard... (Meta-Analysis)
Meta-Analysis
Background Bempedoic acid (BA) is a novel lipid-lowering drug. We performed a systematic review and meta-analysis on efficacy and safety of BA compared with standard treatment in patients with hypercholesterolemia. Methods and Results Studies were systematically searched in the PubMed, Web of Science, Scopus, and EMBASE databases. Efficacy outcome was represented by percentage changes (mean difference [MD] with pertinent 95% CIs) in total cholesterol, low-density lipoprotein cholesterol, triglycerides, high-density lipoprotein cholesterol, apolipoprotein B, non-high-density lipoprotein cholesterol, and hs-CRP (high-sensitivity C-reactive protein) in BA patients and controls. Seven studies were included (2767 BA-treated patients and 1469 controls), showing a more significant reduction in low-density lipoprotein cholesterol (MD, -17.5%; 95% CI, -22.9% to -12.0%), total cholesterol (MD, -10.9%; 95% CI, -13.3% to -8.5%), non-high-density lipoprotein cholesterol (MD, -12.3%; 95% CI, -15.3% to -9.20%), apolipoprotein B (MD, -10.6%; 95% CI, -13.2% to -8.02%), and hs-CRP (MD, -13.2%; 95% CI, -16.7% to -9.79%) in BA-treated patients compared with controls. Results were confirmed when separately analyzing studies on patients with high cardiovascular risk, studies on statin-intolerant patients, and studies on patients with hypercholesterolemia on maximally tolerated lipid-lowering therapy. BA-treated subjects reported a higher rate of treatment discontinuation caused by adverse effects, of gout flare, and of increase in uric acid compared with controls. On the other hand, BA-treated patients showed a lower incidence of new-onset diabetes mellitus than controls. Conclusions BA is associated with a significant reduction in low-density lipoprotein cholesterol, total cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein B, and hs-CRP compared with standard treatment. Documented efficacy is accompanied by an acceptable safety profile.
Topics: Dicarboxylic Acids; Fatty Acids; Humans; Hypercholesterolemia; Hypolipidemic Agents; Randomized Controlled Trials as Topic
PubMed: 32689862
DOI: 10.1161/JAHA.119.016262 -
The Cochrane Database of Systematic... Jan 2021Inflammatory bowel disease affects approximately seven million people globally. Iron deficiency anaemia can occur as a common systemic manifestation, with a prevalence... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Inflammatory bowel disease affects approximately seven million people globally. Iron deficiency anaemia can occur as a common systemic manifestation, with a prevalence of up to 90%, which can significantly affect quality of life, both during periods of active disease or in remission. It is important that iron deficiency anaemia is treated effectively and not be assumed to be a normal finding of inflammatory bowel disease. The various routes of iron administration, doses and preparations present varying advantages and disadvantages, and a significant proportion of people experience adverse effects with current therapies. Currently, no consensus has been reached amongst physicians as to which treatment path is most beneficial.
OBJECTIVES
The primary objective was to evaluate the efficacy and safety of the interventions for the treatment of iron deficiency anaemia in people with inflammatory bowel disease.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, and two other databases on 21st November 2019. We also contacted experts in the field and searched references of trials for any additional trials.
SELECTION CRITERIA
Randomised controlled trials investigating the effectiveness and safety of iron administration interventions compared to other iron administration interventions or placebo in the treatment of iron deficiency anaemia in inflammatory bowel disease. We considered both adults and children, with studies reporting outcomes of clinical, endoscopic, histologic or surgical remission as defined by study authors.
DATA COLLECTION AND ANALYSIS
Two review authors independently conducted data extraction and 'Risk of bias' assessment of included studies. We expressed dichotomous and continuous outcomes as risk ratios and mean differences with 95% confidence intervals. We assessed the certainty of the evidence using the GRADE methodology.
MAIN RESULTS
We included 11 studies (1670 randomised participants) that met the inclusion criteria. The studies compared intravenous iron sucrose vs oral iron sulphate (2 studies); oral iron sulphate vs oral iron hydroxide polymaltose complex (1 study); oral iron fumarate vs intravenous iron sucrose (1 study); intravenous ferric carboxymaltose vs intravenous iron sucrose (1 study); erythropoietin injection + intravenous iron sucrose vs intravenous iron sucrose + injection placebo (1 study); oral ferric maltol vs oral placebo (1 study); oral ferric maltol vs intravenous ferric carboxymaltose (1 study); intravenous ferric carboxymaltose vs oral iron sulphate (1 study); intravenous iron isomaltoside vs oral iron sulphate (1 study); erythropoietin injection vs oral placebo (1 study). All studies compared participants with CD and UC together, as well as considering a range of disease activity states. The primary outcome of number of responders, when defined, was stated to be an increase in haemoglobin of 20 g/L in all but two studies in which an increase in 10g/L was used. In one study comparing intravenous ferric carboxymaltose and intravenous iron sucrose, moderate-certainty evidence was found that intravenous ferric carboxymaltose was probably superior to intravenous iron sucrose, although there were responders in both groups (150/244 versus 118/239, RR 1.25, 95% CI 1.06 to 1.46, number needed to treat for an additional beneficial outcome (NNTB) = 9). In one study comparing oral ferric maltol to placebo, there was low-certainty evidence of superiority of the iron (36/64 versus 0/64, RR 73.00, 95% CI 4.58 to 1164.36). There were no other direct comparisons that found any difference in the primary outcomes, although certainty was low and very low for all outcomes, due to imprecision from sparse data and risk of bias varying between moderate and high risk. The reporting of secondary outcomes was inconsistent. The most common was the occurrence of serious adverse events or those requiring withdrawal of therapy. In no comparisons was there a difference seen between any of the intervention agents being studied, although the certainty was very low for all comparisons made, due to risk of bias and significant imprecision due to the low numbers of events. Time to remission, histological and biochemical outcomes were sparsely reported in the studies. None of the other secondary outcomes were reported in any of the studies. An analysis of all intravenous iron preparations to all oral iron preparations showed that intravenous administration may lead to more responders (368/554 versus 205/373, RR 1.17, 95% CI 1.05 to 1.31, NNTB = 11, low-certainty due to risk of bias and inconsistency). Withdrawals due to adverse events may be greater in oral iron preparations vs intravenous (15/554 versus 31/373, RR 0.39, 95% CI 0.20 to 0.74, low-certainty due to risk of bias, inconsistency and imprecision).
AUTHORS' CONCLUSIONS
Intravenous ferric carboxymaltose probably leads to more people having resolution of IDA (iron deficiency anaemia) than intravenous iron sucrose. Oral ferric maltol may lead to more people having resolution of IDA than placebo. We are unable to draw conclusions on which of the other treatments is most effective in IDA with IBD (inflammatory bowel disease) due to low numbers of studies in each comparison area and clinical heterogeneity within the studies. Therefore, there are no other conclusions regarding the treatments that can be made and certainty of all findings are low or very low. Overall, intravenous iron delivery probably leads to greater response in patients compared with oral iron, with a NNTB (number needed to treat) of 11. Whilst no serious adverse events were specifically elicited with any of the treatments studied, the numbers of reported events were low and the certainty of these findings very low for all comparisons, so no conclusions can be drawn. There may be more withdrawals due to such events when oral is compared with intravenous iron delivery. Other outcomes were poorly reported and once again no conclusions can be made as to the impact of IDA on any of these outcomes. Given the widespread use of many of these treatments in practice and the only guideline that exists recommending the use of intravenous iron in favour of oral iron, research to investigate this key issue is clearly needed. Considering the current ongoing trials identified in this review, these are more focussed on the impact in specific patient groups (young people) or on other symptoms (such as fatigue). Therefore, there is a need for studies to be performed to fill this evidence gap.
Topics: Adolescent; Adult; Aged; Anemia, Iron-Deficiency; Bias; Colitis, Ulcerative; Crohn Disease; Disaccharides; Erythropoietin; Ferric Compounds; Ferric Oxide, Saccharated; Fumarates; Hematinics; Humans; Iron Compounds; Maltose; Middle Aged; Placebos; Pyrones; Randomized Controlled Trials as Topic; Young Adult
PubMed: 33471939
DOI: 10.1002/14651858.CD013529.pub2 -
BMJ Open Feb 2022Bempedoic acid (BA) is a novel oral low-density lipoprotein cholesterol lowering drug. This systematic review and meta-analysis aims to assess efficacy and safety for... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Bempedoic acid (BA) is a novel oral low-density lipoprotein cholesterol lowering drug. This systematic review and meta-analysis aims to assess efficacy and safety for clinical outcomes in high cardiovascular (CV) risk patients.
DATA SOURCES
MEDLINE, Cochrane Central Register of Controlled Trials, Google Scholar, Embase, ClinicalTrials.gov, Clinical Trial Results and the American College of Cardiology web site were searched.
STUDY SELECTION
Randomised controlled trials (RCTs) of BA versus placebo in high CV risk patients reporting clinical outcomes were included.
MAIN OUTCOMES AND MEASURES
Primary efficacy outcomes were major adverse cardiovascular events (MACE), all-cause mortality, CV mortality and non-fatal myocardial infarction (MI). Safety outcomes included new onset or worsening of diabetes mellitus (DM), muscular disorders, gout and worsening of renal function.
RESULTS
Six RCTs with a total of 3956 patients and follow-ups of four to 52 weeks were identified. Heterogeneity mainly derived from differing follow-up duration and baseline CV risk. No difference in MACE (OR 0.84; 95% CI 0.61 to 1.15), all-cause mortality (OR 2.37; CI 0.80 to 6.99) and CV mortality (OR 1.66; CI 0.45 to 6.04) for BA versus placebo was observed. BA showed beneficial trends for non-fatal MI (OR 0.57; CI 0.32 to 1.00) and was associated with a lower risk of new-onset or worsening of DM (OR 0.68; CI 0.49 to 0.94), but higher risk of gout (OR 3.29; CI 1.28 to 8.46) and a trend for muscular disorders (OR 2.60; CI 1.15 to 5.91) and worsening of renal function (OR 4.24; CI 0.98 to 18.39).
CONCLUSION
BA in high CV risk patients showed no significant effects on major CV outcomes in short-term follow-up. Unfavourable effects on muscular disorders, renal function and gout sound a note of caution. Hence, further studies with longer term follow-up in carefully selected populations are needed to clarify the risk/benefit ratio of this novel therapy.
Topics: Cholesterol, LDL; Dicarboxylic Acids; Fatty Acids; Humans; Treatment Outcome
PubMed: 35210334
DOI: 10.1136/bmjopen-2021-048893 -
Cardiovascular Diabetology Aug 2020Bempedoic acid is an oral, once-daily, first-in-class drug being developed for the treatment of hyperlipidemia. However, evidence of bempedoic acid use for the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bempedoic acid is an oral, once-daily, first-in-class drug being developed for the treatment of hyperlipidemia. However, evidence of bempedoic acid use for the prevention of cardiovascular events and diabetes is lacking. Thus, we aim to evaluate the benefit and safety of bempedoic acid use for the prevention of cardiovascular events and diabetes.
METHODS
We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials with no language restriction from inception until March 3, 2020. Pairs of reviewers independently identified randomized controlled trials comparing the use of bempedoic acid with placebo or no treatment for primary prevention of cardiovascular events in statin-intolerant patients with hypercholesterolemia. The primary outcomes were major adverse cardiac events, and percent change in LDL-C.
RESULTS
We identified 11 trials including a total of 4391 participants. Bempedoic acid use was associated with a reduction in composite cardiovascular outcome (RR 0.75, 95% CI 0.56-0.99; I = 0%). Bempedoic acid reduced LDL-C levels (MD - 22.91, 95% CI - 27.35 to - 18.47; I = 99%), and similarly reduced CRP levels (MD -24.70, 95% CI - 32.10 to - 17.30; I = 53%). Bempedoic acid was associated with a reduction in rates of new-onset or worsening diabetes (RR 0.65, 95% CI 0.44-0.96; I = 23%).
CONCLUSIONS
Bempedoic acid in patients with hypercholesterolemia was associated with a lower risk of cardiovascular events and diabetes.
Topics: Aged; Biomarkers; Cardiovascular Diseases; Cholesterol, LDL; Diabetes Mellitus; Dicarboxylic Acids; Down-Regulation; Fatty Acids; Female; Humans; Hypercholesterolemia; Hypolipidemic Agents; Male; Middle Aged; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 32787939
DOI: 10.1186/s12933-020-01101-9 -
Journal of Sport and Health Science Dec 2020Citrulline is one of the non-essential amino acids that is thought to improve exercise performance and reduce post-exercise muscle soreness. We conducted a systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Citrulline is one of the non-essential amino acids that is thought to improve exercise performance and reduce post-exercise muscle soreness. We conducted a systematic review and meta-analysis to determine the effect of citrulline supplements on the post-exercise rating of perceived exertion (RPE), muscle soreness, and blood lactate levels.
METHODS
A random effects model was used to calculate the effect sizes due to the high variability in the study design and study populations of the articles included. A systematic search of PubMed, Web of Science, and ClinicalTrials.gov was performed. Eligibility for study inclusion was limited to studies that were randomized controlled trials involving healthy individuals and that investigated the acute effect of citrulline supplements on RPE, muscle soreness, and blood lactate levels. The supplementation time frame was limited to 2 h before exercise. The types and number of participants, types of exercise tests performed, supplementation protocols for L-citrulline or citrulline malate, and primary (RPE and muscle soreness) and secondary (blood lactate level) study outcomes were extracted from the identified studies.
RESULTS
The analysis included 13 eligible articles including a total of 206 participants. The most frequent dosage used in the studies was 8 g of citrulline malate. Citrulline supplementation significantly reduced RPE (n = 7, p = 0.03) and muscle soreness 24-h and 48-h after post-exercise (n = 7, p = 0.04; n = 6, p = 0.25, respectively). However, citrulline supplementation did not significantly reduce muscle soreness 72-h post-exercise (n = 4, p = 0.62) or lower blood lactate levels (n = 8, p = 0.17).
CONCLUSION
Citrulline supplements significantly reduced post-exercise RPE and muscle soreness without affecting blood lactate levels.
Topics: Citrulline; Dietary Supplements; Fruit and Vegetable Juices; Humans; Lactic Acid; Malates; Myalgia; Perception; Physical Exertion; Resistance Training
PubMed: 33308806
DOI: 10.1016/j.jshs.2020.02.003 -
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 -
International Journal of Molecular... Oct 2022Mitochondria dysfunction is implicated in the pathogenesis of cardiovascular diseases (CVD). Exercise training is potentially an effective non-pharmacological strategy... (Meta-Analysis)
Meta-Analysis Review
Mitochondria dysfunction is implicated in the pathogenesis of cardiovascular diseases (CVD). Exercise training is potentially an effective non-pharmacological strategy to restore mitochondrial health in CVD. However, how exercise modifies mitochondrial functionality is inconclusive. We conducted a systematic review using the PubMed; Scopus and Web of Science databases to investigate the effect of exercise training on mitochondrial function in CVD patients. Search terms included “mitochondria”, “exercise”, “aerobic capacity”, and “cardiovascular disease” in varied combination. The search yielded 821 records for abstract screening, of which 20 articles met the inclusion criteria. We summarized the effect of exercise training on mitochondrial morphology, biogenesis, dynamics, oxidative capacity, antioxidant capacity, and quality. Amongst these parameters, only oxidative capacity was suitable for a meta-analysis, which demonstrated a significant effect size of exercise in improving mitochondrial oxidative capacity in CVD patients (SMD = 4.78; CI = 2.99 to 6.57; p < 0.01), but with high heterogeneity among the studies (I2 = 75%, p = 0.003). Notably, aerobic exercise enhanced succinate-involved oxidative phosphorylation. The majority of the results suggested that exercise improves morphology and biogenesis, whereas findings on dynamic, antioxidant capacity, and quality, were inadequate or inconclusive. A further randomized controlled trial is clearly required to explain how exercise modifies the pathway of mitochondrial quantity and quality in CVD patients.
Topics: Humans; Antioxidants; Exercise; Cardiovascular Diseases; Mitochondria; Succinates
PubMed: 36293409
DOI: 10.3390/ijms232012559 -
Frontiers in Immunology 2021The global prevalence and recurrence rate of kidney stones is very high. Recent studies of Randall plaques and urinary components , and including gene manipulation,...
BACKGROUND
The global prevalence and recurrence rate of kidney stones is very high. Recent studies of Randall plaques and urinary components , and including gene manipulation, have attempted to reveal the pathogenesis of kidney stones. However, the evidence remains insufficient to facilitate the development of novel curative therapies. The involvement of renal and peripheral macrophages in inflammatory processes offers promise that might lead to the development of therapeutic targets. The present systematic literature review aimed to determine current consensus about the functions of macrophages in renal crystal development and suppression, and to synthesize evidence to provide a basis for future immunotherapy.
METHODS
We systematically reviewed the literature during February 2021 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles investigating the relationship between macrophages and urolithiasis, particularly calcium oxalate (CaOx) stones, were extracted from PubMed, MEDLINE, Embase, and Scopus. Study subjects, languages, and publication dates were unrestricted. Two authors searched and screened the publications.
RESULTS
Although several studies have applied mixed modalities, we selected 10, 12, and seven (total, n = 29) of 380 articles that respectively described cultured cells, animal models, and human samples.The investigative trend has shifted to macrophage phenotypes and signaling pathways, including micro (m)-RNAs since the discovery of macrophage involvement in kidney stones in 1999. Earlier studies of mice-associated macrophages with the acceleration and suppression of renal crystal formation. Later studies found that pro-inflammatory M1- and anti-inflammatory M2-macrophages are involved. Studies of human-derived and other macrophages and showed that M2-macrophages (stimulated by CSF-1, IL-4, and IL-13) can phagocytose CaOx crystals, which suppresses stone development. The signaling mechanisms that promote M2-like macrophage polarization toward CaOx nephrocalcinosis, include the NLRP3, PPARγ-miR-23-Irf1/Pknox1, miR-93-TLR4/IRF1, and miR-185-5p/CSF1 pathways.Proteomic findings have indicated that patients who form kidney stones mainly express M1-like macrophage-related proteins, which might be due to CaOx stimulation of the macrophage exosomal pathway.
CONCLUSIONS
This systematic review provides an update regarding the current status of macrophage involvement in CaOx nephrolithiasis. Targeting M2-like macrophage function might offer a therapeutic strategy with which to prevent stones crystal phagocytosis.
Topics: Animals; Calcium Oxalate; Humans; Kidney Calculi; Macrophages; Nephrolithiasis
PubMed: 34108970
DOI: 10.3389/fimmu.2021.673690 -
Actas Urologicas Espanolas 2024Lithiasis in renal graft recipients might be a dangerous condition with a potential risk of organ function impairment. (Review)
Review
INTRODUCTION
Lithiasis in renal graft recipients might be a dangerous condition with a potential risk of organ function impairment.
EVIDENCE ACQUISITION
A systematic literature search was conducted through February 2023. The primary objective was to assess the incidence of lithiasis in kidney transplant (KT) recipients. The secondary objective was to assess the timing of stone formation, localization and composition of stones, possible treatment options, and the incidence of graft loss.
EVIDENCE SYNTHESIS
A total of 41 non-randomized studies comprising 699 patients met our inclusion criteria. The age at lithiasis diagnosis ranged between 29-53 years. Incidence of urolithiasis ranged from 0.1-6.3%, usually diagnosed after 12 months from KT. Most of the stones were diagnosed in the calyces or in the pelvis. Calcium oxalate composition was the most frequent. Different treatment strategies were considered, namely active surveillance, ureteroscopy, percutaneous/combined approach, or open surgery. 15.73% of patients were submitted to extracorporeal shock wave lithotripsy (ESWL), while 26.75% underwent endoscopic lithotripsy or stone extraction. 18.03% of patients underwent percutaneous nephrolithotomy whilst 3.14% to a combined approach. Surgical lithotomy was performed in 5.01% of the cases. Global stone-free rate was around 80%.
CONCLUSIONS
Lithiasis in kidney transplant is a rare condition usually diagnosed after one year after surgery and mostly located in the calyces and renal pelvis, more frequently of calcium oxalate composition. Each of the active treatments is associated with good results in terms of stone-free rate, thus the surgical technique should be chosen according to the patient's characteristics and surgeon preferences.
Topics: Humans; Adult; Middle Aged; Kidney Transplantation; Lithiasis; Calcium Oxalate; Kidney Calculi; Kidney
PubMed: 37574010
DOI: 10.1016/j.acuroe.2023.08.003 -
The British Journal of Dermatology Aug 2019The persistence and effectiveness of systemic therapies for moderate-to-severe psoriasis in current clinical practice are poorly characterized.
BACKGROUND
The persistence and effectiveness of systemic therapies for moderate-to-severe psoriasis in current clinical practice are poorly characterized.
OBJECTIVES
To systematically review observational studies investigating the persistence and effectiveness of acitretin, ciclosporin, fumaric acid esters (FAE) and methotrexate, involving at least 100 adult patients with moderate-to-severe psoriasis, exposed to therapy for ≥ 3 months.
METHODS
MEDLINE, Embase, the Cochrane Library and PubMed were searched from 1 January 2007 to 1 November 2017 for observational studies reporting on persistence (therapy duration or the proportion of patients discontinuing therapy during follow-up) or effectiveness [improvements in Psoriasis Area and Severity Index (PASI) or Physician's Global Assessment (PGA)]. This review was registered with PROSPERO, number CRD42018099771.
RESULTS
Of 411 identified studies, eight involving 4624 patients with psoriasis were included. Variations in the definitions and analyses of persistence and effectiveness outcomes prevented a meta-analysis from being conducted. One prospective multicentre study reported drug survival probabilities of 23% (ciclosporin), 42% (acitretin) and 50% (methotrexate) at 1 year. Effectiveness outcomes were not reported for either acitretin or ciclosporin. The persistence and effectiveness of FAE and methotrexate were better characterized, but mean discontinuation times ranged from 28 to 50 months for FAE and 7·7 to 22·3 months for methotrexate. At 12 months of follow-up, three studies reported that 76% (FAE), 53% (methotrexate) and 59% (methotrexate) of patients achieved ≥ 75% reduction in PASI, and one reported that 76% of FAE-exposed patients achieved a markedly improved or clear PGA.
CONCLUSIONS
The comparative persistence and effectiveness of acitretin, ciclosporin, FAE and methotrexate in real-world clinical practice in the past decade cannot be well described due to the inconsistency of the methods used.
Topics: Acitretin; Adult; Cyclosporine; Dermatologic Agents; Drug Therapy, Combination; Fumarates; Humans; Methotrexate; Multicenter Studies as Topic; Observational Studies as Topic; Psoriasis; Severity of Illness Index; Treatment Outcome
PubMed: 30628069
DOI: 10.1111/bjd.17625