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Comparative efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy for active rheumatoid arthritis.
Ho Lee, Y, Gyu Song, G
Journal of clinical pharmacy and therapeutics. 2020;(4):674-681
Abstract
WHAT IS KNOWN AND OBJECTIVE Several clinical trials have attempted to evaluate the efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy in patients with active rheumatoid arthritis (RA), but their relative efficacy and safety as monotherapy remain unclear due to the lack of data from head-to-head comparison trials. The relative efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy for rheumatoid arthritis (RA) were assessed. METHODS We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) and examine the efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy relative to placebo in patients with RA. RESULTS AND DISCUSSION Five RCTs comprising 1547 patients met the inclusion criteria. Compared with placebo, tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy showed a significantly higher American College of Rheumatology 20% (ACR20) response rate. Peficitinib 150 mg monotherapy showed the highest ACR20 response rate (odds ratio, 17.24.39; 95% credible interval, 6.57-51.80). The ranking probability based on the surface under the cumulative ranking curve indicated that peficitinib 150 mg had the highest probability of being the best treatment for achieving the ACR20 response rate, followed by peficitinib 100 mg, filgotinib 200 mg, filgotinib 100 mg, tofacitinib 5 mg, upadacitinib 15 mg, baricitinib 4 mg and placebo. However, the number of patients who experienced serious adverse events did not differ significantly between the JAK inhibitors, except for tofacitinib 5 mg, and placebo. WHAT IS NEW AND CONCLUSION All five JAK inhibitors-tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib-were efficacious monotherapy interventions for active RA, and differences were noted in their efficacy and safety in monotherapy.
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Risk of Stroke in Chronic Heart Failure Patients Without Atrial Fibrillation: Analysis of the Controlled Rosuvastatin in Multinational Trial Heart Failure (CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca-Heart Failure (GISSI-HF) Trials.
Abdul-Rahim, AH, Perez, AC, Fulton, RL, Jhund, PS, Latini, R, Tognoni, G, Wikstrand, J, Kjekshus, J, Lip, GY, Maggioni, AP, et al
Circulation. 2015;(17):1486-94; discussion 1494
Abstract
BACKGROUND Our aim was to describe the incidence and predictors of stroke in patients who have heart failure without atrial fibrillation (AF). METHODS AND RESULTS We pooled 2 contemporary heart failure trials, the Controlled Rosuvastatin in Multinational Trial Heart Failure (CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza cardiaca-Heart Failure trial (GISSI-HF). Of the 9585 total patients, 6054 did not have AF. Stroke occurred in 165 patients (4.7%) with AF and in 206 patients (3.4%) without AF (rates 16.8/1000 patient-years and 11.1/1000 patient-years, respectively). Using Cox proportional-hazards models, we identified the following independent predictors of stroke in patients without AF (ranked by χ(2) value): age (hazard ratio, 1.34; 95% confidence interval, 1.18-1.63 per 10 years), New York Heart Association class (1.60, 1.21-2.12 class III/IV versus II), diabetes mellitus treated with insulin (1.87, 1.22-2.88), body mass index (0.74, 0.60-0.91 per 5 kg/m(2) up to 30), and previous stroke (1.81, 1.19-2.74). N-terminal pro B-type natriuretic peptide (available in 2632 patients) was also an independent predictor of stroke (hazard ratio, 1.31; 1.11-1.57 per log unit) when added to this model. With the use of a risk score formulated from these predictors, we found that patients in the upper third of risk had a rate of stroke that approximated the risk in patients with AF. CONCLUSIONS A small number of demographic and clinical variables identified a subset of patients who have heart failure without AF at a high risk of stroke.
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Rosuvastatin Treatment for Preventing Contrast-Induced Acute Kidney Injury After Cardiac Catheterization: A Meta-Analysis of Randomized Controlled Trials.
Yang, Y, Wu, YX, Hu, YZ
Medicine. 2015;(30):e1226
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Abstract
We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the protective effects of rosuvastatin on contrast-induced acute kidney injury (CI-AKI) and major adverse cardiovascular events (MACEs) in patients undergoing cardiac catherization.PubMed, MEDLINE, Web of Science, EMBASE, ClinicalTrials.gov, and the Cochrane Central RCTs were searched for RCTs from inception to May 2015, to compare rosuvastatin for preventing CI-AKI with placebo treatment in patients undergoing cardiac catherization.Five RCTs with a total of 4045 patients involving 2020 patients pretreated with rosuvastatin and 2025 control patients were identified and analyzed. Patients treated with rosuvastatin had a 51% lower risk of CI-AKI compared with the control group based on a fixed-effect model (OR = 0.49, 95% CI = 0.37-0.66, P < 0.001), and showed a trend toward a reduced risk of MACEs (OR = 0.62, 95% CI = 0.36-1.07, P = 0.08). A subgroup analysis showed that studies with Jadad score ≥3 showed a significant reduction of CI-AKI (OR = 0.53, 95% CI, 0.38-0.73, P < 0.001). However, the risk of CI-AKI did not significantly differ in the studies with Jadad score <3 (OR = 0.54, 95% CI, 0.13-2.24, P = 0.40). In addition, the rosuvastatin treatment showed no effect for preventing CI-AKI in patients with chronic kidney disease (CKD) undergoing elective cardiac catherization (I = 0%, OR = 0.81, 95% CI = 0.41-1.61, P = 0.55).This updated meta-analysis demonstrated that preprocedural rosuvastatin treatment could significantly reduce the incidence of CI-AKI, with a trend toward a reduced risk of MACEs in patients undergoing cardiac catheterization. However, rosuvastatin treatment did not seem to be effective for preventing CI-AKI in CKD patients undergoing elective cardiac catheterization.
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Lipid-lowering efficacy of rosuvastatin.
Adams, SP, Sekhon, SS, Wright, JM
The Cochrane database of systematic reviews. 2014;(11):CD010254
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Abstract
BACKGROUND Rosuvastatin is one of the most potent statins and is currently widely prescribed. It is therefore important to know the dose-related magnitude of effect of rosuvastatin on blood lipids. OBJECTIVES Primary objective To quantify the effects of various doses of rosuvastatin on serum total cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, non-HDL-cholesterol and triglycerides in participants with and without evidence of cardiovascular disease. Secondary objectives To quantify the variability of the effect of various doses of rosuvastatin.To quantify withdrawals due to adverse effects (WDAEs) in the randomized placebo-controlled trials. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 10 of 12, 2014 in The Cochrane Library, MEDLINE (1946 to October week 5 2014), EMBASE (1980 to 2014 week 44), Web of Science Core Collection (1970 to 5 November 2014) and BIOSIS Citation Index (1969 to 31 October 2014). No language restrictions were applied. SELECTION CRITERIA Randomized controlled and uncontrolled before-and-after trials evaluating the dose response of different fixed doses of rosuvastatin on blood lipids over a duration of three to 12 weeks. DATA COLLECTION AND ANALYSIS Two review authors independently assessed eligibility criteria for studies to be included and extracted data. WDAEs information was collected from the placebo-controlled trials. MAIN RESULTS One-hundred and eight trials (18 placebo-controlled and 90 before-and-after) evaluated the dose-related efficacy of rosuvastatin in 19,596 participants. Rosuvastatin 10 to 40 mg/day caused LDL-cholesterol decreases of 46% to 55%, when all the trials were combined using the generic inverse variance method. The quality of evidence for these effects is high. Log dose-response data over doses of 1 to 80 mg, revealed strong linear dose-related effects on blood total cholesterol, LDL-cholesterol and non-HDL-cholesterol. When compared to atorvastatin, rosuvastatin was about three-fold more potent at reducing LDL-cholesterol. There was no dose-related effect of rosuvastatin on blood HDL-cholesterol, but overall, rosuvastatin increased HDL by 7%. There is a high risk of bias for the trials in this review, which would affect WDAEs, but unlikely to affect the lipid measurements. WDAEs were not statistically different between rosuvastatin and placebo in 10 of 18 of these short-term trials (risk ratio 0.84; 95% confidence interval 0.48 to 1.47). AUTHORS' CONCLUSIONS The total blood total cholesterol, LDL-cholesterol and non-HDL-cholesterol-lowering effect of rosuvastatin was linearly dependent on dose. Rosuvastatin log dose-response data were linear over the commonly prescribed dose range. Based on an informal comparison with atorvastatin, this represents a three-fold greater potency. This review did not provide a good estimate of the incidence of harms associated with rosuvastatin because of the short duration of the trials and the lack of reporting of adverse effects in 44% of the placebo-controlled trials.
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Risk of gastrointestinal events with sorafenib, sunitinib and pazopanib in patients with solid tumors: a systematic review and meta-analysis of clinical trials.
Santoni, M, Conti, A, De Giorgi, U, Iacovelli, R, Pantano, F, Burattini, L, Muzzonigro, G, Berardi, R, Santini, D, Cascinu, S
International journal of cancer. 2014;(4):763-73
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Gastrointestinal (GI) events have been described with sorafenib, sunitinib and pazopanib in cancer patients. We performed an up-to-date meta-analysis to determine the incidence and relative risk (RR) in patients with cancer treated with these agents. PubMed databases were searched for articles published till May 2013. Eligible studies were selected according to PRISMA statement. Summary incidence, RR, and 95% CIs were calculated using random-effects or fixed-effects models based on the heterogeneity of selected studies. A total of 6,447 patients were available for the meta-analysis; 2,260 had renal cell carcinoma (RCC) and 4,187, 1,691 non-small cell lung cancers, 599 hepatocellular cancers, 1,066 breast cancers, 165 neuroendocrine tumors, 304 gastrointestinal stromal tumors and 362 soft tissue sarcomas. Diarrhea was the most common GI event. When stratified by tumor type (RCC vs. non-RCC), the difference among the incidences of GI events was significant for diarrhea (p < 0.001) and vomiting (p = 0.006), that resulted higher in RCC patients. In RCC patients, sorafenib registered the lower incidence and RR of all grades GI events. The difference was statistically significant for sorafenib versus sunitinib-related all and high-grade events (p < 0.001) and for sorafenib versus pazopanib all grades GI events (p < 0.001) and high-grade anorexia (p < 0.001). Treatment with VEGFR TKIs sorafenib, sunitinib and pazopanib is associated with a significant increase in the risk of GI events in patients with cancer, and frequent clinical monitoring should be emphasized when managing these three and newer VEGFR TKIs.
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A meta-analysis of randomized head-to-head trials for effects of rosuvastatin versus atorvastatin on apolipoprotein profiles.
Takagi, H, Umemoto, T, ,
The American journal of cardiology. 2014;(2):292-301
Abstract
To determine which statin will better improve the apolipoprotein (Apo) profiles (ApoA-I levels, ApoB levels, and ApoB/A-I ratios), we performed a meta-analysis of randomized head-to-head trials of rosuvastatin versus atorvastatin therapy. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched through December 2012 using Web-based search engines (PubMed and OVID). The search terms included "apolipoprotein," "rosuvastatin," "atorvastatin," "randomized," "randomly," and "randomization." Of 42 potentially relevant studies initially screened, 25 reports of randomized trials enrolling 14,283 patients were included. A pooled analysis for the percentage of changes in ApoA-I demonstrated a benefit of rosuvastatin versus atorvastatin in the comparison of all rosuvastatin/atorvastatin dose ratios (mean difference 2.97%, 3.39%, 5.77%, and 6.25%). For the percentage of changes in ApoB, a benefit was seen for rosuvastatin versus atorvastatin in the 1/1 (-6.06%) and 1/2 dose ratio (-1.80%). However, a benefit was seen for atorvastatin versus rosuvastatin in the 1/4 (2.38%) and 1/8 dose ratio (6.59%). The pooled analysis for the percentage of changes in the Apo B/A-I ratios demonstrated a benefit for rosuvastatin versus atorvastatin in the 1/1 (-7.22%) and 1/2 dose ratio (-3.51%), with no difference in the 1/4 dose ratio. In contrast, a benefit was seen for atorvastatin versus rosuvastatin in the 1/8 dose ratio (4.03%). In conclusion, rosuvastatin might increase Apo A-I levels at all dose ratios and decrease ApoB levels and ApoB/A-I ratios in the 1/1 and 1/2 dose ratio versus atorvastatin. Only higher dose atorvastatin appeared to be more effective for the reduction in ApoB levels (1/4 and 1/8 dose ratio) and Apo B/A-I ratios (1/8 dose ratio).
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[Impact on the carotid intima-medial thickness and safety of rosuvastatin in Chinese patients with carotid atherosclerosis: a meta-analysis].
Feng, X, Zhang, J, Liu, M, Li, X
Zhonghua xin xue guan bing za zhi. 2014;(3):247-53
Abstract
OBJECTIVE To evaluate the efficacy and safety of rosuvastatin in Chinese patients with carotid atherosclerosis. METHOD A systematic search of Pubmed, EMBase, CENTRAL, CBMdisc, CNKI and WANFANG databases up to January 2013 was performed to identify studies comparing rosuvastatin with a placebo or other statins on carotid intima-medial thickness (IMT) with a minimum follow-up of 6 months in Chinese patients. Meta-analysis was performed by using RevMan 5.0 software after the strict evaluation of the methodological quality of the included studies independently by two reviewers. RESULTS Twenty-eight studies involving 1 392 individuals were included in this review. The pooled weighted mean difference (WMD) between rosuvastatin and placebo or control on IMT was 0.28 mm (95%CI 0.14-0.42, P < 0.01), with 0.31 mm (95%CI 0.14-0.49, P < 0.01) on 6-8 months and 0.16 mm (95%CI 0.05-0.27, P = 0.005) on 12 months, respectively. Analysis on studies in core journals showed the WMD between rosuvastatin and placebo or control on IMT was 0.18 mm (95%CI 0.09-0.27, P < 0.01). The WMD between rosuvastatin and other statins on IMT was 0.06 mm (95%CI 0.04-0.08, P < 0.01). The WMD between rosuvastatin and placebo or control on plaque score was 0.89 (95%CI 0.78-0.99, P < 0.01). The WMD between rosuvastatin and placebo or control on plaque area was 1.46 (95%CI 0.67-2.25, P < 0.01).Reports of adverse effect were elevated liver enzyme (2.30%, 19/825), elevated muscle enzyme (0.73%, 6/825), muscle aches (0.61%, 5/825). CONCLUSIONS Rosuvastatin therapy is effective and safe to decrease IMT in Chinese patients with carotid atherosclerosis.
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Achievement of 2011 European low-density lipoprotein cholesterol (LDL-C) goals of either <70 mg/dl or ≥ 50% reduction in high-risk patients: results from VOYAGER.
Karlson, BW, Nicholls, SJ, Lundman, P, Palmer, MK, Barter, PJ
Atherosclerosis. 2013;(1):265-9
Abstract
OBJECTIVE Guidelines published in 2011 by the European Atherosclerosis Society and the European Society of Cardiology recommend a goal of either low-density lipoprotein cholesterol (LDL-C) <70 mg/dl (~1.8 mmol/l) or ≥ 50% reduction in LDL-C for patients at very high cardiovascular risk. The aim of this study was to determine the percentage of high-risk patients from the VOYAGER individual patient data meta-analysis treated with rosuvastatin 10-40 mg, atorvastatin 10-80 mg or simvastatin 10-80 mg who achieved this goal. METHODS We analysed 25,075 patient exposures from high-risk patients. Paired comparisons were made between each rosuvastatin dose and an equal or higher dose of either atorvastatin or simvastatin, with a series of meta-analyses that included only randomised studies that directly compared rosuvastatin and its comparator treatments. RESULTS As statin dose increased, higher percentages of patients achieved LDL-C <70 mg/dl or ≥ 50% LDL-C reduction. A greater percentage achieved this goal with rosuvastatin 10-40 mg (43.8-79.0%) than with equal or double milligram doses of atorvastatin (16.1-65.2%) or simvastatin (0-39.7%). Paired comparisons showed statistically significant differences for: rosuvastatin 10 mg vs. atorvastatin 10-20 mg and simvastatin 10-20 mg; rosuvastatin 20 mg vs. atorvastatin 20-40 mg and simvastatin 20-80 mg; and rosuvastatin 40 mg vs. atorvastatin 40-80 mg and simvastatin 40-80 mg (all p < 0.001). CONCLUSION These data from VOYAGER highlight the importance of an effective statin at an appropriate dose to achieve treatment goals for LDL-C in patients with very high cardiovascular risk.
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Efficacy, safety and tolerability of tofacitinib in patients with an inadequate response to disease modifying anti-rheumatic drugs: a meta-analysis of randomized double-blind controlled studies.
Berhan, A
BMC musculoskeletal disorders. 2013;:332
Abstract
BACKGROUND This meta-analysis was conducted to determine the efficacy, safety and tolerability of tofacitinib in the treatment of rheumatoid arthritis in patients with an inadequate response or intolerance to at least one of the nonbiologic or biologic disease-modifying antirheumatic drugs (DMARDs). METHODS Electronic based literature search was conducted in the databases of HINARI (Health InterNetwork Access to Research Initiative), MEDLINE and Cochrane library. The studies included in the meta-analysis were double-blind randomized clinical trials that were conducted in treatment-refractory or intolerant patients with rheumatoid arthritis. The odds ratios (OR), standardized mean differences (SMD) and the 95% confidence intervals (95% CI) were determined by using the random effects model. Heterogeneity among the included studies was evaluated by I² statistics. RESULTS The odds of tofacitinib treated patients who met the criteria for an at least a 20% improvement in the American College of Rheumatology scale (ACR 20) was more than 4 times higher than placebo treated patients (overall OR = 4.15; 95% CI, 3.23 to 5.32). Even though the discontinuation rate due to adverse events was not different from placebo groups, tofacitinib was associated with infections (overall SMD = 1.96, 95% CI = 1.428 to 2.676), reduction in neutrophil counts (overall SMD = -0.34, 95% CI = -0.450 to -0.223) and elevated levels of LDL cholesterol and liver enzymes. CONCLUSIONS Tofacitinib was effective in the treatment of active rheumatoid arthritis in patients with an inadequate response or intolerance to at least one DMARDs. However, treatment with tofacitinib was associated with infections and laboratory abnormalities.
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Preventive effects of rosuvastatin on atrial fibrillation: a meta-analysis of randomized controlled trials.
Liu, T, Korantzopoulos, P, Li, L, Li, G
International journal of cardiology. 2013;(6):3058-60