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Receiving Placebo (receiving + placebo)
Selected AbstractsP43 Acute urticaria to infliximabCONTACT DERMATITIS, Issue 3 2004Ana Giménez-Arnau Infliximab is a chimeric antitumor necrosis factor-alpha monoclonal antibody used to treat Crohn's disease and rheumatoid arthritis. Acute infusion reactions, headache, fever, chills, urticaria and chest pain were seen in 17% of patients with infliximab compared with 7% of those receiving placebo. Other adverse cutaneous reactions are fungal dermatitis, eczema, seborrhoea, hordeolum, bullous eruption, furunculosis, periorbital oedema, hyperkeratosis, rosacea, verruca, skin pigmentation, alopecia, leukocytoclastic vasculitis, lichenoid drug eruption, erythema multiforme, perniosis-like eruption, granuloma annulare and acute folliculitis. Any pathogenic mechanism has been suggested. Patch test with infliximab can induce flare-up of lesions, nausea and malaise and suggest a percutaneous absortion. A sixty years-old man with atopy background and rheumatoid arthritis treated with Remicare®, infliximab who developed a severe acute urticaria with angioedema is presented. The lesions appearance after previous endovenous administrations and the worsening spreading wheals days after the injection clinically suggested an hypersensitivity mechanism. The protocolized study drug hypersensitivity performed showed only the Prick Test positivity with infliximab at 30/60 minutes. Patch test with infliximab was negative and any adverse event was reported. Actually the patient is treated with etanercept and this drug is well tolerated. This result suggested a type I hypersensitivity mediated reaction. Urticaria could be induced as immunologic reaction of the host against the murine part of infliximab, just as it hapens with other antichimeric antibodies. [source] Emergency Department Treatment of Viral Gastritis Using Intravenous Ondansetron or Dexamethasone in ChildrenACADEMIC EMERGENCY MEDICINE, Issue 10 2006Christine M. Stork PharmD Abstract Objectives To compare the efficacy of intravenous ondansetron or dexamethasone compared with intravenous fluid therapy alone in children presenting to the emergency department with refractory vomiting from viral gastritis who had failed attempts at oral hydration. Methods This double-blind, randomized, controlled trial was performed in a tertiary care pediatric emergency department. Children aged 6 months to 12 years presenting with more than three episodes of vomiting in the past 24 hours, mild/moderate dehydration, and failed oral hydration were included. Patients with other medical causes were excluded. Subjects were randomized to dexamethasone 1 mg/kg (15 mg maximum), ondansetron 0.15 mg/kg, or placebo (normal saline [NS], 10 mL). All subjects also received intravenous NS at 10,20 mL/kg/hr. Oral fluid tolerance was evaluated at two and four hours. Those not tolerating oral fluids at four hours were admitted. Discharged patients were evaluated at 24 and 72 hours for vomiting and repeat health care visits. The primary study outcome was hospitalization rates between the groups. Data were analyzed using chi-square test, Kruskal,Wallis test, Mantel,Haenszel test, and analysis of variance, with p < 0.05 considered significant. Results A total of 166 subjects were enrolled; data for analysis were available for 44 NS-treated patients, 46 ondansetron-treated patients, and 47 dexamethasone-treated patients. Hospital admission occurred in nine patients (20.5%) receiving placebo (NS alone), two patients (4.4%) receiving ondansetron, and seven patients (14.9%) receiving dexamethasone, with ondansetron significantly different from placebo (p = 0.02). Similarly, at two hours, more ondansetron-treated patients (39 [86.6%]) tolerated oral hydration than NS-treated patients (29 [67.4%]; relative risk, 1.28; 95% confidence interval = 1.02 to 1.68). There were no differences in number of mean episodes of vomiting or repeat visits to health care at 24 and 72 hours in the ondansetron, dexamethasone, or NS groups. Conclusions In children with dehydration secondary to vomiting from acute viral gastritis, ondansetron with intravenous rehydration improves tolerance of oral fluids after two hours and reduces the hospital admission rate when compared with intravenous rehydration with or without dexamethasone. [source] Original Article: Treatment: Dose-dependent effects of the once-daily GLP-1 receptor agonist lixisenatide in patients with Type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled trialDIABETIC MEDICINE, Issue 9 2010R. E. Ratner Diabet. Med. 27, 1024,1032 (2010) Abstract Aims, To evaluate the dose,response relationship of lixisenatide (AVE0010), a glucagon-like peptide-1 (GLP-1) receptor agonist, in metformin-treated patients with Type 2 diabetes. Methods, Randomized, double-blind, placebo-controlled, parallel-group, 13 week study of 542 patients with Type 2 diabetes inadequately controlled [glycated haemoglobin (HbA1c) , 7.0 and < 9.0% (, 53 and < 75 mmol/mol)] on metformin (, 1000 mg/day) treated with subcutaneous lixisenatide doses of 5, 10, 20 or 30 ,g once daily or twice daily or placebo. The primary end-point was change in HbA1c from baseline to 13 weeks in the intent-to-treat population. Results, Lixisenatide significantly improved mean HbA1c from a baseline of 7.55% (59.0 mmol/mol); respective mean reductions for 5, 10, 20 and 30 ,g doses were 0.47, 0.50, 0.69 and 0.76% (5.1, 5.5, 7.5 and 8.3 mmol/mol), on once-daily and 0.65, 0.78, 0.75 and 0.87% (7.1, 8.5, 8.2 and 9.5 mmol/mol) on twice-daily administrations vs. 0.18% (2.0 mmol/mol) with placebo (all P < 0.01 vs. placebo). Target HbA1c < 7.0% (53 mmol/mol) at study end was achieved in 68% of patients receiving 20 and 30 ,g once-daily lixisenatide vs. 32% receiving placebo (P < 0.0001). Dose-dependent improvements were observed for fasting, postprandial and average self-monitored seven-point blood glucose levels. Weight changes ranged from ,2.0 to ,3.9 kg with lixisenatide vs. ,1.9 kg with placebo. The most frequent adverse event was mild-to-moderate nausea. Conclusions, Lixisenatide significantly improved glycaemic control in mildly hyperglycaemic patients with Type 2 diabetes on metformin. Dose,response relationships were seen for once- and twice-daily regimens, with similar efficacy levels, with a 20 ,g once-daily dose of lixisenatide demonstrating the best efficacy-to-tolerability ratio. This new, once-daily GLP-1 receptor agonist shows promise in the management of Type 2 diabetes to be defined further by ongoing long-term studies. [source] Randomized controlled trial of dexamphetamine maintenance for the treatment of methamphetamine dependenceADDICTION, Issue 1 2010Marie Longo ABSTRACT Aim To investigate the safety and efficacy of once-daily supervised oral administration of sustained-release dexamphetamine in people dependent on methamphetamine. Design Randomized, double-blind, placebo-controlled trial. Participants Forty-nine methamphetamine-dependent drug users from Drug and Alcohol Services South Australia (DASSA) clinics. Intervention Participants were assigned randomly to receive up to 110 mg/day sustained-release dexamphetamine (n = 23) or placebo (n = 26) for a maximum of 12 weeks, with gradual reduction of the study medication over an additional 4 weeks. Medication was taken daily under pharmacist supervision. Measurements Primary outcome measures included treatment retention, measures of methamphetamine consumption (self-report and hair analysis), degree of methamphetamine dependence and severity of methamphetamine withdrawal. Hair samples were analysed for methamphetamine using liquid chromatography-mass spectrometry. Findings Treatment retention was significantly different between groups, with those who received dexamphetamine remaining in treatment for an average of 86.3 days compared with 48.6 days for those receiving placebo (P = 0.014). There were significant reductions in self-reported methamphetamine use between baseline and follow-up within each group (P < 0.0001), with a trend to a greater reduction among the dexamphetamine group (P = 0.086). Based on hair analysis, there was a significant decrease in methamphetamine concentration for both groups (P < 0.0001). At follow-up, degree of methamphetamine dependence was significantly lower in the dexamphetamine group (P = 0.042). Dexamphetamine maintenance was not associated with serious adverse events. Conclusions The results of this preliminary study have demonstrated that a maintenance pharmacotherapy programme of daily sustained-release amphetamine dispensing under pharmacist supervision is both feasible and safe. The increased retention in the dexamphetamine group, together with the general decreases in methamphetamine use, degree of dependence and withdrawal symptom severity, provide preliminary evidence that this may be an efficacious treatment option for methamphetamine dependence. [source] Almotriptan Increases Pain-Free Status in Patients With Acute Migraine Treated in Placebo-Controlled Clinical TrialsHEADACHE, Issue 2002FRCP(C), Ninan T. Mathew MD Objectives.,Evaluate the efficacy of a single oral dose of almotriptan in achieving pain-free status during treatment of acute migraine attacks. Methods.,This pooled analysis (N=1321) used data from two randomized, placebo-controlled, phase III trials (studies A and B) to determine the proportion of patients with migraine achieving pain-free status 2 hours after a single oral dose of study medication (almotriptan or placebo). Pain was assessed using a 4-point integer scale (0=no headache, 3=severe headache), and recorded in a patient self-assessment booklet. Results.,The proportion of patients pain-free at 2 hours after study medication was significantly greater with almotriptan 6.25 mg (both studies P,.002) and almotriptan 12.5 mg (both studies P,.001) than with placebo. In study A, 11.6% of patients taking almotriptan 12.5 mg versus 2.5% of patients receiving placebo were pain-free at 1 hour (P=.016). At 1.5 hours, 26.8% of patients taking almotriptan 12.5 mg versus 8.8% receiving placebo (P=.001) were pain-free, and at 2 hours, 38.4% on almotriptan versus 11.3% on placebo were pain-free (P<.001). In study B, 23.8% of patients taking almotriptan 12.5 mg were free from pain at 1.5 hours versus 10.2% receiving placebo (P<.001). At 2 hours, 39.2% taking almotriptan 12.5 mg versus 15.3% receiving placebo were pain-free (P<.001). Increases in pain-free status with almotriptan generally occurred in a dose-dependent manner. Conclusion.,Compared with placebo, almotriptan 12.5 mg significantly increases the proportion of patients who are pain-free by as early as 1 hour, and consistently by 1.5 hours, after a single dose. [source] Safety and efficacy of oral entecavir given for 28 days in patients with chronic hepatitis B virus infectionHEPATOLOGY, Issue 3 2001Ph.D., Robert A. de Man M.D. Entecavir is an oral antiviral drug with selective activity against hepatitis B virus (HBV). We conducted a randomized, placebo-controlled, dose-escalating study in patients with chronic hepatitis B infection in which we evaluated the efficacy and safety of entecavir given for 28 days. Follow-up was 24 weeks. All doses of entecavir (0.05 mg, 0.1 mg, 0.5 mg, and 1.0 mg) showed a pronounced suppression of replication of the HBV with a 2.21, 2.29, 2.81, and 2.55 mean log10 reduction of viral load, respectively. Approximately 25% of patients on entecavir showed a decline of HBV DNA below the limit of detection of the Chiron HBV-DNA assay (<0.7 MEq/mL). In the postdosing follow-up period patients who were treated with 0.5 and 1.0 mg of entecavir showed a considerably slower return in their HBV DNA levels to baseline compared with those patients treated with lower dosages (P < .05). All doses of entecavir were well tolerated with no significant difference between treated patients and those receiving placebo. No significant changes in alanine transaminase (ALT) levels within the dose groups and the placebo group between baseline and the end of treatment were observed. Three patients (9%) (1 each in the 0.05-, 0.1-, and 0.5-mg groups) experienced asymptomatic hepatitis flares 16 weeks (2 patients) and 24 weeks (1 patient) after withdrawal of entecavir. In conclusion, in this 28-day study of entecavir a pronounced decrease of HBV DNA was observed and there were no significant side effects in entecavir patients in comparison with placebo-treated patients. (HEPATOLOGY 2001;34:578-582.) [source] Safety of efalizumab in adults with chronic moderate to severe plaque psoriasis: A phase IIIb, randomized, controlled trialINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 5 2006Kim A. Papp MD Background, To provide safety data for efalizumab, a recombinant humanized monoclonal IgG1 antibody, in adults with chronic plaque psoriasis. Methods, A 12-week, Phase IIIb, randomized, double-blind, parallel-group, placebo-controlled trial. At 58 study sites in the USA and Canada, 686 patients with moderate to severe chronic plaque psoriasis received an initial conditioning dose of efalizumab 0.7 mg/kg subcutaneously (SC) followed by either 11 weekly doses of efalizumab 1 mg/kg SC or matching placebo. Main outcome measures were safety and tolerability outcomes (primary) and efficacy outcomes (secondary). Results, During 12 weeks of therapy with efalizumab or placebo, the incidence of clinical adverse events was 82.2% and 72.9%, respectively; the incidence of serious adverse events was 1.8% and 3.4%, respectively; and the incidence of nonserious adverse events leading to withdrawal was 1.8% and 1.7%, respectively. In the efalizumab group, there were no clinically significant changes in vital signs or laboratory parameters and no evidence of end-organ toxicities. A significantly higher proportion of patients receiving efalizumab than those receiving placebo achieved , 75% improvement in the Psoriasis Area and Severity Index (PASI) (P < 0.001), , 50% improvement in PASI (P < 0.001), and a static Physician's Global Assessment rating of Minimal or Clear (P < 0.001). The mean improvement in the Psoriasis Symptom Assessment was significantly greater in the efalizumab group (P < 0.001). Conclusions, Efalizumab treatment SC for 12 weeks was safe, well tolerated, and effective in patients with moderate to severe chronic plaque psoriasis. [source] Randomized, Placebo-Controlled Trial of the Cognitive Effect, Safety, and Tolerability of Oral Extended-Release Oxybutynin in Cognitively Impaired Nursing Home Residents with Urge Urinary IncontinenceJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 5 2008Thomas E. Lackner PharmD OBJECTIVES: Determine the cognitive effect, safety, and tolerability of oral extended-release oxybutynin in cognitively impaired older nursing home residents with urge urinary incontinence. DESIGN: Randomized, double-blinded, placebo-controlled trial. SETTING: Twelve skilled nursing homes. PARTICIPANTS: Fifty women aged 65 and older with urge incontinence and cognitive impairment. INTERVENTION: Four-week treatment with once-daily oral extended-release oxybutynin 5 mg or placebo. MEASUREMENTS: Withdrawal rates and delirium or change in cognition from baseline at 1, 3, 7, 14, 21, and 28 days after starting treatment using the Confusion Assessment Method (CAM), Mini-Mental State Examination (MMSE), and Severe Impairment Battery (SIB). The Brief Agitation Rating Scale, adverse events, falls incidence, and serum anticholinergic activity change with treatment were also assessed. RESULTS: Participants' mean age ±standard deviation was 88.6±6.2, and MMSE baseline score was 14.5±4.3. Ninety-six percent of subjects receiving oxybutynin (n=26) and 92% receiving placebo (n=24) completed treatment (P=.50). The differences in mean change in CAM score from baseline to all time points were equivalent between the oxybutynin and placebo groups. Delirium did not occur in either group. One participant receiving oxybutynin was withdrawn because of urinary retention, which resolved without treatment. Mild adverse events occurred in 38.5% of participants receiving oxybutynin and 37.5% receiving placebo (P=.94). CONCLUSION: Short-term treatment using oral extended-release oxybutynin 5 mg once daily was safe and well tolerated, with no delirium, in older female nursing home participants with mild to severe dementia. Future research should investigate different dosages and long-term treatment. [source] The Role of Benzodiazepines in the Treatment of InsomniaJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 6 2001Meta-Analysis of Benzodiazepine Use in the Treatment of Insomnia PURPOSE: To obtain a precise estimate of the efficacy and common adverse effects of benzodiazepines for the treatment of insomnia compared with those of placebo and other treatments. BACKGROUND: Insomnia, also referred to as disorder of initiating or maintaining sleep, is a common problem and its prevalence among older people is estimated to be 23% to 34%.1 The total direct cost in the United States for insomnia in 1995 was estimated to be $13.9 billion.2 The complaint of insomnia in older people is associated with chronic medical conditions; psychiatric problems, mainly depression, chronic pain, and poor perceived general condition;1,3,4 and use of sleep medications.5 Thus in most cases, insomnia is due to some other underlying problem and is not just a consequence of aging.6 Accordingly, the management of insomnia should focus on addressing the primary problem and not just short-term treatment of the insomnia. Benzodiazepines belong to the drug class of choice for the symptomatic treatment of primary insomnia.7 This abstract will appraise a meta-analysis that compared the effect of benzodiazepines for short-term treatment of primary insomnia with placebo or other treatment. DATA SOURCES: Data sources included articles listed in Medline from 1966 to December 1998 and the Cochrane Controlled Trials Registry. The medical subject heading (MeSH) search terms used were "benzodiazepine" (exploded) or "benzodiazepine tranquillizers" (exploded) or "clonazepam,""drug therapy,""randomized controlled trial" or "random allocation" or "all random,""human," and "English language." In addition, bibliographies of retrieved articles were scanned for additional articles and manufacturers of brand-name benzodiazepines were asked for reports of early trials not published in the literature. STUDY SELECTION CRITERIA: Reports of randomized controlled trials of benzodiazepine therapy for primary insomnia were considered for the meta-analysis if they compared a benzodiazepine with a placebo or an alternative active drug. DATA EXTRACTION: Data were abstracted from 45 randomized controlled trials representing 2,672 patients, 47% of whom were women. Fifteen studies included patients age 65 and older and four studies involved exclusively older patients. Twenty-five studies were based in the community and nine involved inpatients. The duration of the studies ranged from 1 day to 6 weeks, with a mean of 12.2 days and median of 7.5 days. The primary outcome measures analyzed were sleep latency and total sleep duration after a sleep study, subjects' estimates of sleep latency and sleep duration, and subjects' report of adverse effects. Interrater reliability was checked through duplicate, independent abstraction of the first 21 articles. Overall agreement was between 95% and 98% (kappa value of 0.90 and 0.95 accordingly) for classification of the studies and validity of therapy, and 76% (kappa value of 0.51) for study of harmful effects. A scale of 0 to 5 was used to rate the individual reports, taking into account the quality of randomization, blinding, follow-up, and control for baseline differences between groups. Tests for homogeneity were applied across the individual studies and, when studies were found to be heterogeneous, subgroup analysis according to a predefined group was performed. MAIN RESULTS: The drugs used in the meta-analysis included triazolam in 16 studies; flurazepam in 14 studies; temazepam in 13 studies; midazolam in five studies; nitrazepam in four studies; and estazolam, lorazepam, and diazepam in two studies each. Alternative drug therapies included zopiclone in 13 studies and diphenhydramine, glutethimide, and promethazine in one study each. Only one article reported on a nonpharmacological treatment (behavioral therapy). The mean age of patients was reported in 33 of the 45 studies and ranged between 29 and 82. SLEEP LATENCY: In four studies involving 159 subjects, there was sleep-record latency (time to fall asleep) data for analysis. The pooled difference indicated that the latency to sleep for patients receiving a benzodiazepine was 4.2 minutes (95% CI = (,0.7) (,9.2)) shorter than for those receiving placebo. Patient's estimates of sleep latency examined in eight studies showed a difference of 14.3 minutes (95% CI = 10.6,18.0) in favor of benzodiazepines over placebo. TOTAL SLEEP DURATION: Analysis of two studies involving 35 patients in which total sleep duration using sleep-record results was compared indicated that patients in the benzodiazepine groups slept for an average of 61.8 minutes (95% CI = 37.4,86.2) longer than those in the placebo groups. Patient's estimates of sleep duration from eight studies (566 points) showed total sleep duration to be 48.4 minutes (95% CI = 39.6,57.1) longer for patients taking benzodiazepines than for those on placebo. ADVERSE EFFECTS: Analysis of eight studies (889 subjects) showed that those in the benzodiazepine groups were more likely than those in the placebo groups to complain of daytime drowsiness (odds ratio (OR) 2.4, 95% confidence interval (CI) = 1.8,3.4). Analysis of four studies (326 subjects) also showed that subjects in the benzodiazepine groups were more likely to complain of dizziness or lightheadedness than the placebo groups. (OR 2.6, 95% CI = 0.7,10.3). Despite the increased reported side effects in the benzodiazepine groups, drop-out rates were similar in the benzodiazepine and placebo groups. For patient reported outcome, there was no strong correlation found for sleep latency data, (r = 0.4, 95% CI = (,0.3) (,0.9)) or for sleep duration (r = 0.2, 95% CI = ,0.8,0.4) between benzodiazepine dose and outcome. COMPARISON WITH OTHER DRUGS AND TREATMENTS: In three trials with 96 subjects, meta-analysis of the results comparing benzodiazepines with zopiclone, did not show significant difference in sleep latency in the benzodiazepine and placebo groups, but the benzodiazepine groups had increased total sleep duration (23.1 min. 95% CI = 5.6,40.6). In four trials with 252 subjects, the side effect profile did not show a statistically significant difference (OR 1.5, CI 0.8,2.9). There was only one study comparing the effect of behavioral therapy with triazolam. The result showed that triazolam was more effective than behavioral therapy in decreasing sleep latency, but its efficacy declined by the second week of treatment. Behavioral therapy remained effective throughout the 9-week follow-up period. There were four small trials that involved older patients exclusively, with three of the studies having less than 2 weeks of follow-up. The results were mixed regarding benefits and adverse effects were poorly reported. CONCLUSION: The result of the meta-analysis shows that the use of benzodiazepines results in a decrease in sleep latency and a significant increase in total sleep time as compared with placebo. There was also a report of significantly increased side effects, but this did not result in increased discontinuation rate. There was no dose-response relationship for beneficial effect seen with the use of benzodiazepines, although the data are scant. Zopiclone was the only alternative pharmacological therapy that could be studied with any precision. There was no significant difference in the outcome when benzodiazepines were compared with zopiclone. There was only one study that compared the effect of benzodiazepines with nonpharmacological therapy; thus available data are insufficient to comment. [source] Serum TRACP 5b Is a Useful Marker for Monitoring Alendronate Treatment: Comparison With Other Markers of Bone Turnover,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2005Arja Nenonen MSc Abstract We studied clinical performance of serum TRACP 5b and other bone turnover markers, including S-CTX, U-DPD, S-PINP, S-BALP, and S-OC, for monitoring alendronate treatment. TRACP 5b had higher clinical sensitivity, area under the ROC curve, and signal-to-noise ratio than the other markers. Introduction: The purpose of this study was to compare the clinical performance of serum TRACP 5b (S-TRACP5b) with that of other markers of bone turnover in the monitoring of alendronate treatment. Materials and Methods: This double-blinded study included 148 healthy postmenopausal women that were randomly assigned into two groups: one receiving 5 mg alendronate daily (n = 75) and the other receiving placebo (n = 73) for 12 months. All individuals in both groups received calcium and vitamin D daily. The bone resorption markers S-TRACP5b, serum C-terminal cross-linked telopeptides of type I collagen (S-CTX), and total urinary deoxypyridinoline (U-DPD), and the serum markers of bone formation procollagen I N-terminal propeptide (S-PINP), bone-specific alkaline phosphatase (S-BALP), and total osteocalcin (S-OC) were assessed at baseline and at 3, 6, and 12 months after initiation of treatment. Lumbar spine BMD (LBMD) was measured at baseline and 12 months. Results: Compared with the placebo group, LBMD increased, and all bone markers decreased significantly more in the alendronate group (p < 0.001 for each parameter). The decrease of S-TRACP5b after first 3 months of alendronate treatment correlated significantly with the changes of all other markers except S-OC, the best correlation being with S-CTX (r = 0.60, p < 0.0001). The changes of LBMD at 12 months only correlated significantly with the changes of S-TRACP5b (r = ,0.32, p = 0.005) and S-CTX (r = ,0.24, p = 0.037) at 3 months. Based on clinical sensitivity, receiver operating characteristic (ROC) curves, and signal-to-noise ratio, S-TRACP5b, S-CTX, and S-PINP were the best markers for monitoring alendronate treatment. Clinical sensitivity, area under the ROC curve, and signal-to-noise ratio were higher for S-TRACP5b than for the other markers. Conclusion: These results show that S-TRACP5b, S-CTX, and S-PINP are useful markers for monitoring alendronate treatment. [source] Relationships Between Bone Mineral Density and Incident Vertebral Fracture Risk with Raloxifene Therapy,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2002Somnath Sarkar Ph.D. Abstract Although low absolute values of bone mineral density (BMD) predict increased fracture risk in osteoporosis, it is not certain how well increases in BMD with antiresorptive therapy predict observed reductions in fracture risk. This work examines the relationships between changes in BMD after 1 year or 3 years of raloxifene or placebo therapy and the risk for new vertebral fractures at 3 years. In the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, 7705 postmenopausal women with osteoporosis were randomized to placebo or raloxifene 60 mg/day or 120 mg/day. Relationships between baseline BMD and changes in BMD from baseline with the risk of new vertebral fractures were analyzed in this cohort using logistic regression models with the raloxifene doses pooled. As has been observed in other populations, women with the lowest baseline lumbar spine or femoral neck BMD in the MORE cohort had the greatest risk for vertebral fractures. Furthermore, for any percentage change, either increase or decrease in femoral neck or lumbar spine BMD at 1 year or 3 years, raloxifene-treated patients had a statistically significantly lower vertebral fracture risk compared with placebo-treated patients. The decrease in fracture risk with raloxifene was similar across the range of percentage change in femoral neck BMD observed at 3 years; patients receiving raloxifene had a 36% lower risk of vertebral fracture compared with those receiving placebo. At any percentage change in femoral neck and lumbar spine BMD observed at 1 year, raloxifene treatment decreased the risks of new vertebral fractures at 3 years by 38% and 41%, respectively. The logistic regression model showed that the percentage changes in BMD with raloxifene treatment accounted for 4% of the observed vertebral fracture risk reduction, and the other 96% of the risk reduction remains unexplained. The present data show that the measured BMD changes observed with raloxifene therapy are poor predictors of vertebral fracture risk reduction with raloxifene therapy. [source] CB1 Receptor Blockade and its Impact on Cardiometabolic Risk Factors: Overview of the RIO Programme with RimonabantJOURNAL OF NEUROENDOCRINOLOGY, Issue 2008A. J. Scheen Rimonabant, the first selective CB1 receptor antagonist in clinical use, has been extensively investigated in the Rimonabant in Obesity (RIO) programme, comprising four 1,2 year placebo-controlled randomised clinical trials recruiting more than 6600 overweight/obese patients with or without co-morbidities. Rimonabant 20 mg daily consistently reduced body weight, waist circumference, triglycerides, blood pressure, insulin resistance and C-reactive protein levels, and increased HDL cholesterol concentrations in both non-diabetic and type-2 diabetic overweight/obese patients. Adiponectin levels were increased, an effect that correlated with HDL cholesterol augmentation, while small dense LDL cholesterol levels were decreased in patients receiving rimonabant 20 mg compared with those receiving placebo in RIO Lipids. Furthermore, in RIO Diabetes, a 0.7% reduction in glycated haemoglobin (HbA1c) levels was observed in metformin- or sulphonylurea-treated patients with type-2 diabetes, an effect recently confirmed in the 6-month SERENADE (Study Evaluating Rimonabant Efficacy in drug-NAïve DiabEtic patients) trial in drug-naïve diabetic patients. Almost half of metabolic changes occurred beyond weight loss, in agreement with direct peripheral effects. The positive effects observed after 1 year were maintained after 2 years. Rimonabant was generally well-tolerated, but with a slightly higher incidence of depressed mood disorders, anxiety, nausea and dizziness compared with placebo. In clinical practice, rimonabant has to be prescribed to the right patient, i.e. overweight/obese subjects with cardiometabolic risk factors and with no major depressive illness and/or ongoing antidepressive treatment, in order to both maximise efficacy and minimise safety issues. New trials are supposed to confirm the potential role of rimonabant in patients with abdominal adiposity, atherogenic dyslipidaemia and/or type-2 diabetes, i.e. at high cardiometabolic risk. [source] Possibility that certain hypnotics might cause cancer in skinJOURNAL OF SLEEP RESEARCH, Issue 3 2008DANIEL F. KRIPKE Summary Fifteen epidemiologic studies have associated hypnotic drugs with excess mortality, especially excess cancer deaths. Until recently, insufficient controlled trials were available to demonstrate whether hypnotics actually cause any cancers. The US Food and Drug Administration (FDA) Approval History and Documents were accessed for zaleplon, eszopiclone and ramelteon. Since zolpidem was used as a comparison drug in zaleplon trials, some zolpidem data were also available. Incident cancers occurring during randomized hypnotics administration or placebo administration were tabulated. Combining controlled trials for the four drugs, there were 6190 participants given hypnotics and 2535 given placebo in parallel. There were eight mentions of incident non-melanoma skin cancers among participants receiving hypnotics but no comparable mentions of cancers among those receiving placebo (P = 0.064, one-tailed). There were also four mentions of incident tumors of uncertain malignancy among those receiving hypnotics but none among those receiving placebo, so combining uncertain and definite malignancies yielded a more significant contrast (P = 0.016). FDA files revealed that all four of the new hypnotics were associated with cancers in rodents. Three had been shown to be clastogenic. Together with the epidemiologic data and laboratory studies, the available evidence signals that new hypnotics may increase cancer risk. Due to limitations in available data, confirmatory research is needed. [source] Naltrexone and Cue Exposure With Coping and Communication Skills Training for Alcoholics: Treatment Process and 1-Year OutcomesALCOHOLISM, Issue 11 2001Peter M. Monti Background: Promising treatments for alcoholics include naltrexone (NTX), cue exposure combined with urge-specific coping skills training (CET), and communication skills training (CST). This study investigated the effects of combining these elements as treatment adjuncts. Methods: A 2 × 2 design investigated the effects of CET combined with CST, as compared with an education and relaxation control treatment, during a 2-week partial hospital program (n= 165) followed by 12 weeks of NTX (50 mg/day) or placebo during aftercare (n= 128). Drinking outcomes were assessed at 3, 6, and 12 months after discharge from the partial hospital. Process measures included urge, self-efficacy (confidence about staying abstinent in risky situations), and self-reported coping skills. Medically eligible alcohol-dependent patients were recruited. Results: Among those compliant with medication on at least 70% of days, those who received NTX had significantly fewer heavy drinking days and fewer drinks on days that they drank than those receiving placebo during the medication phase but not during the subsequent 9 months. CET/CST-condition patients were significantly less likely to report a relapse day and reported fewer heavy drinking days at the 6- and 12-month follow-ups than patients in the control treatment. Interactions of medication with behavioral treatments were not significant. Process measures showed that NTX resulted in lower weekly urge ratings, and those in CET/CST used more of the prescribed coping skills after treatment, reported fewer cue-elicited urges, and reported more self-efficacy in a posttest role-play test. Drinking reductions at 3, 6, and 12 months correlated with more use of coping skills, lower urge, and higher self-efficacy. Conclusions: The results suggest the probable value of keeping alcoholics on NTX for longer periods of time and the importance of increasing compliance with NTX. They also support the earlier promising effects of CET and CST as adjuncts to treatment programs for alcoholics by maintaining treatment gains over at least a year. The value of the urge-specific and general coping skills and of self-efficacy and urge constructs was demonstrated in their association with drinking outcomes. [source] Clinical trial: esomeprazole for moderate-to-severe nighttime heartburn and gastro-oesophageal reflux disease-related sleep disturbancesALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2010D. Johnson Aliment Pharmacol Ther 2010; 32: 182,190 Summary Background, Nighttime heartburn, common among patients with gastro-oesophageal reflux disease (GERD), is associated with substantial clinical effects. GERD-related sleep disturbances are underappreciated and undertreated. Aim, To evaluate the efficacy of esomeprazole on GERD-related nighttime heartburn and associated sleep disturbances. Methods, In this multicentre, randomized, double-blind, placebo-controlled study, patients with moderate-to-severe nighttime heartburn and GERD-related sleep disturbances (endoscopies not required) received esomeprazole 20 mg or placebo each morning for 4 weeks. Heartburn symptoms and GERD-related sleep disturbances were evaluated using the validated Pittsburgh Sleep Quality Index and validated Work Productivity and Activity Impairment Questionnaire. Results, The analysis included 262 patients (esomeprazole, n = 137; placebo, n = 125). Significantly more patients receiving esomeprazole achieved nighttime heartburn relief (primary end point) than those receiving placebo (34.3% vs. 10.4%; P < 0.0001). Secondary end points such as relief of GERD-related sleep disturbances (P = 0.006), days without GERD-related sleep disturbances (P = 0.0003) and complete resolution of sleep disturbances (P < 0.0001) favoured esomeprazole over placebo. Sleep quality, work productivity and regular daily activities also improved significantly with esomeprazole vs. placebo. Conclusions, Esomeprazole 20 mg is effective for patients with moderate-to-severe nighttime heartburn and GERD-related sleep disturbances, improving heartburn symptoms, sleep quality, work productivity and functionality. [source] Targeting T-cell subsets to achieve remissionJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 2003E Christophers ABSTRACT Patients with psoriasis have an increase in pathogenic CD45RO+ memory-effector T cells during active disease. The genetically engineered fully human fusion protein alefacept has been developed to selectively target this subset of T cells. Alefacept binds to memory-effector CD45RO+ T cells, inhibiting their activation and inducing T-cell apoptosis. The selectivity of alefacept for memory-effector CD45RO+ T cells was evaluated in 229 patients with chronic psoriasis in a randomized, placebo-controlled, double-blind study conducted at 22 centres in the USA. Patients received alefacept intravenously at doses of 0.025 mg/kg, 0.075 mg/kg, or 0.150 mg/kg, or placebo once weekly for 12 weeks. Two weeks after completing treatment, patients receiving alefacept showed significant improvement in the Psoriasis Area and Severity Index (PASI) compared with those receiving placebo. Mean reductions in the PASI score were up to 53% lower than baseline scores in the alefacept treatment group, compared with a 21% decline from baseline in the placebo group (P < 0.001). In addition to the significant improvement in psoriasis, treatment with alefacept produced long-term remission in some patients. Twelve weeks after completion of therapy, 28 patients became clear or almost clear. The therapy was well tolerated and nonimmunogenic. Importantly, during treatment, there was a correlation between improvement in psoriasis and a dose-dependent reduction in peripheral blood CD45RO+ memory-effector T cells, but not in CD45RA+ naive T cells. This correlation indicates a relationship between a specific T-cell subset reduction (CD45RO+) and clinical outcome in psoriasis. [source] Efficacy of Ronidazole for Treatment of Feline Tritrichomonas foetus InfectionJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2006Jody L. Gookin Objectives: To determine the efficacy of ronidazole (RDZ), tinidazole (TDZ), and metronidazole (MDZ) against Tritrichomonas foetus in vitro and of RDZ for treatment of feline naturally occurring or experimentally induced T foetus infection. Animals: A cat naturally infected with T foetus infection and diarrhea. Ten specific-pathogen-free (SPF) kittens. Procedure: RDZ, TDZ, and MDZ were tested for activity against 3 different feline isolates of T foetus in vitro. RDZ then was administered to a naturally infected cat at 10 mg/kg PO q24h for 10 days. SPF kittens were infected orogastrically with feline T foetus and treated with either placebo or RDZ (10 mg/kg PO q12h for 14 days). Cats with relapsing infection or those receiving placebo were treated subsequently with RDZ (either 30 or 50 mg/kg PO q12h for 14 days). Feces were examined for T foetus by direct microscopy, culture, and polymerase chain reaction (PCR) testing weekly. Results: Both RDZ and TDZ killed T foetus at concentrations >0.1 ,g/mL in vitro. In the naturally infected cat, RDZ abolished diarrhea and T foetus infection for 85 days after treatment, at which time infection and diarrhea relapsed. Retreatment with RDZ eradicated diarrhea and T foetus infection for over 407 days. In experimentally induced infection, RDZ at 10 mg/kg caused initial improvement, but infection relapsed in all 5 cats 2 to 20 weeks after treatment. At 30 or 50 mg/kg, 10/10 cats were negative for T foetus infection for follow-up durations of 21 to 30 weeks after treatment. Conclusions and Clinical Relevance: Oral administration of RDZ at 30 to 50 mg/kg q12h for 14 days resolved diarrhea and eradicated infection (on the basis of polymerase chain reaction [PCR] testing) in 1 naturally infected cat and 10 experimentally inoculated cats receiving a different isolate of T foetus. [source] Lactobacillus reuteri therapy to reduce side-effects during anti- Helicobacter pylori treatment in children: a randomized placebo controlled trialALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2006E. LIONETTI Summary Background Helicobacter pylori eradication fails in about 25,30% of children, particularly because of the occurrence of resistance to antibiotics and side-effects. Aim To determine whether adding the Lactobacillus reuteri to an anti- H. pylori regimen could help to prevent or minimize the gastrointestinal side-effects burden in children. Methods Forty H. pylori -positive children (21 males; median age: 12.3 years) were consecutively treated with 10-day sequential therapy [omeprazole + amoxycillin for 5 days, and omeprazole + clarithromycin + tinidazole for other 5 days] and blindly randomized to receive either L. reuteri ATCC 55730 (108 CFU) or placebo. All children completed the Gastrointestinal Symptom Rating Scale (GSRS) at entry, during and after treatment. H. pylori status was assessed after 8 weeks by 13C-urea breath test. Results Overall, in all probiotic supplemented children when compared with those receiving placebo there was a significant reduction of GSRS score during eradication therapy (4.1 ± 2 vs. 6.2 ± 3; P < 0.01) and at the end of follow-up (3.2 ± 2 vs. 5.8 ± 3.4; P < 0.009). Overall, children receiving L. reuteri report less symptoms than those receiving placebo. Conclusion L. reuteri is capable of reducing frequency and intensity of antibiotic-associated side-effects during eradication therapy for H. pylori. [source] The efficacy of sublingual immunotherapy for house dust mites respiratory allergy: results of a GA²LEN meta-analysisALLERGY, Issue 11 2009E. Compalati Recent meta-analyses documented the efficacy and safety of sublingual immunotherapy (SLIT) in patients with allergic rhinitis (AR) and asthma (AA). Although SLIT appeared globally effective, the sub-analyses for single allergens provided uncertain results. This study is aimed to investigate the efficacy of SLIT with house dust mite (HDM) extracts in AR and AA through an updated reassessment of randomized controlled trials. Electronic databases were searched up to March 31, 2008, for randomized DBPC trials, assessing the efficacy of SLIT in AR and AA due to HDM sensitization. Outcomes were symptom scores and rescue medications use. For AR, eight studies fulfilled the selection criteria. A significant reduction in symptoms of AR (SMD ,0.95; CI 95%,1.77 to ,0.14 P = 0.02) was found in 194 patients (adults and children) receiving SLIT compared to 188 receiving placebo. For AA, with nine studies, similar results were found for symptoms (SMD ,0.95; CI 95%,1.74 to ,0.15 P = 0.02) in 243 patients (adults and children) receiving SLIT compared to 209 receiving placebo. A reduction in rescue medication use was found for AR (SMD ,1.88; CI 95%,3.65 to ,0.12 P = 0.04) in 89 patients, and AA (SMD ,1.48; CI 95%,2.70 to ,0.26 P = 0.02) in 202 patients. A relevant inter-study heterogeneity was detected. Promising evidence of efficacy for SLIT, using mite extract in allergic patients suffering from AR and AA, are herein shown. These findings suggest that more data are needed, derived from large-population-based high quality studies, and corroborated by objective outcomes, mainly for AA. [source] The size of the disease relevant IgE antibody fraction in relation to ,total-IgE' predicts the efficacy of anti-IgE (Xolair®) treatmentALLERGY, Issue 10 2009S. G. O. Johansson Background:, Some patients with allergic asthma treated with anti-IgE (Xolair®) do not become symptom free. Better criteria for response assessment than allergy skin tests or IgE determination are needed. The impact of the size of the disease relevant allergen-specific IgE antibody fraction, i.e. the percentage of IgE antibody of total IgE, was evaluated in cat allergic patients treated with the recommended doses of Xolair®. Results were measured as changes in basophil allergen threshold sensitivity (CD-sens). Methods:, In a double-blind placebo controlled trial 20 patients with a high (>3.8%) and 18 with a low (<1%) percentage of IgE antibodies to cat were given Xolair® for 16 weeks and the change in CD-sens was compared to 11 and 10 patients, respectively, in each group receiving placebo. Results:, The CD-sens dropped significantly in both the high (P < 0.001) and low (P < 0.001) group on Xolair® but did not change significantly after placebo. For Xolair® -treated patients, at the end of the trial there was a highly significant (P < 0.001) difference in CD-sens between the high group, where no patients, and the low group, where 13/18 patients, had become negative. Conclusions:, The currently recommended doses of Xolair® very efficiently eliminate IgE antibodies if the IgE antibody fraction is <1% of total IgE but has not enough effect on allergen sensitivity if the fraction is >3,4%. Further studies will show if increased doses of Xolair® would help also these patients, who seem to represent about 1/3 of the patient population. [source] Cost-effectiveness of the oral adsorbent AST-120 versus placebo for chronic kidney diseaseNEPHROLOGY, Issue 5 2008TOMOHIKO TAKAHASHI SUMMARY: Aim: This study was designed to evaluate the cost-effectiveness of AST-120, an oral adsorbent that attenuates the progression of chronic kidney disease. Methods: We developed a Markov model with six health states, including four levels of serum creatinine, haemodialysis and death, using data from a randomized clinical trial conducted in Japan. Direct costs relevant to chronic kidney disease were calculated from a Japanese reimbursement perspective. Projected quality-adjusted life years (QALY) and costs were compared between the AST-120 and placebo groups. The target population was nondiabetic patients with serum creatinine levels from 5.0 to 8.0 mg/dL (442,707 µmol/L) at baseline. Probabilistic sensitivity analysis was performed to evaluate the stability of the results. Results: At 3 years, mean total costs per patient were estimated at ¥6.67 million (US$56 982) in the AST-120 group and ¥9.38 million (US$80 196) in the placebo group. Mean total costs were ¥2.72 million (US$23 205) lower among patients receiving AST-120. QALY per patient were 0.295 (approximately 3.5 months) greater for patients receiving AST-120 than for those receiving placebo over 3 years. The finding that treatment with AST-120 dominated placebo (i.e. was less costly and resulted in more QALY) was upheld in sensitivity analyses. Conclusion: The use of AST-120 in patients with advanced chronic kidney disease may help to slow the rate of growth in expenditures for kidney disease. [source] Women with Pain due to Osteoarthritis: The Efficacy and Safety of a Once-Daily Formulation of TramadolPAIN MEDICINE, Issue 6 2009FRCP, Walter F. Kean MB ChB ABSTRACT Objective., This analysis assesses the efficacy and safety of treatment with a once-daily oral formulation of tramadol for up to 12 weeks compared with placebo in women with moderate-to-severe pain due to osteoarthritis of the knee. Design., Two parallel, placebo-controlled phase III clinical trials were analyzed; patients were randomized to a fixed dosage of Tramadol Contramid® once a day (OAD) 100, 200, and 300 mg daily, or placebo. Outcome Measures., The primary efficacy end points were the percentage difference from baseline of the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) subscale scores for pain and physical function, and the patient global rating of pain relief after 12 weeks of maintenance therapy. Results., The analysis included 405 women receiving tramadol and 280 receiving placebo. At week 12, 179 of 204 women (87.7%) receiving tramadol rated their overall pain relief as effective or very effective compared with 134 of 177 (75.7%) receiving placebo. A time-weighted analysis revealed statistically significant improvements over placebo for all the WOMAC subscale scores across all three dosages. The percentage improvements from baseline of the WOMAC pain scores were significantly better than placebo for the 100-mg (58.8 ± 37.1%, P = 0.018) and 300-mg (58.9 ± 38.8%, P = 0.023) treatment arms; however, the 200-mg dosage was not significant (53.0 ± 38.5%, P = 0.175). The WOMAC physical function scores showed significant improvement for the 100 (56.9 ± 36.4%, P = 0.009), 200 (54.0 ± 33.8%, P = 0.034), and 300 mg (53.4 ± 41.4%, P = 0.043) daily dosages. Conclusion., For moderate-to-severe pain due to osteoarthritis of the knee, women experience significant analgesia and improvement of physical function over time with treatment with Tramadol Contramid® OAD. [source] Duloxetine for the Management of Diabetic Peripheral Neuropathic Pain: Response ProfilePAIN MEDICINE, Issue 5 2007Yili L. Pritchett PhD ABSTRACT Objective., The current analysis examines the response profile in patients receiving duloxetine for the management of diabetic peripheral neuropathic pain (DPNP). Patients/Design., Data were pooled from three double-blind, randomized, placebo-controlled 12-week acute therapy trials of patients with DPNP of at least 6 months' duration. Study 1 (N = 457) had treatment groups of duloxetine 20 mg once daily (QD), 60 mg QD, 60 mg twice daily (BID), and placebo; Studies 2 (N = 334) and 3 (N = 348) compared duloxetine 60 mg QD and 60 mg BID with placebo. The primary efficacy measure in each study was the weekly mean score of the 24-hour average pain severity. Treatment response was defined as a 30% reduction in pain severity, although some analyses were repeated using alternative response criteria (50% reduction, or 2-point reduction, in pain severity). Results., Consistently across the three studies, response rates at endpoint were significantly higher among patients receiving duloxetine (60 mg QD or 60 mg BID) than among those receiving placebo, regardless of the chosen response criterion (30% reduction, 50% reduction, or 2-point reduction in weekly mean of 24-hour average pain severity). The proportion of patients achieving pain relief in the duloxetine treatment groups was significantly greater than that in the placebo group at Week 1 and at all subsequent study visits to the end of acute phase therapy. Using diary data (24-hour average pain severity) from the first 7 days of treatment, the first significant separation from placebo in pain severity reduction for duloxetine 60 mg QD occurred at Day 1 (Study 1), Day 2 (Study 2), and Day 4 (Study 3), while significant separation in response rates first occurred at Day 3 when using pooled data. Conclusions., Patients with DPNP receiving duloxetine 60 mg QD or 60 mg BID had significantly higher rates of treatment response, when compared with patients receiving placebo, regardless of the chosen response criterion. Response to duloxetine treatment tended to occur early in therapy. [source] Combination antibiotics as a treatment for chronic Chlamydia -induced reactive arthritis: A double-blind, placebo-controlled, prospective trial,ARTHRITIS & RHEUMATISM, Issue 5 2010J. D. Carter Objective Chlamydia trachomatis and Chlamydophila (Chlamydia) pneumoniae are known triggers of reactive arthritis (ReA) and exist in a persistent metabolically active infection state in the synovium, suggesting that they may be susceptible to antimicrobial agents. The goal of this study was to investigate whether a 6-month course of combination antibiotics is an effective treatment for patients with chronic Chlamydia- induced ReA. Methods This study was a 9-month, prospective, double-blind, triple-placebo trial assessing a 6-month course of combination antibiotics as a treatment for Chlamydia -induced ReA. Eligible patients had to be positive for C trachomatis or C pneumoniae by polymerase chain reaction (PCR). Groups received 1) doxycycline and rifampin plus placebo instead of azithromycin; 2) azithromycin and rifampin plus placebo instead of doxycycline; or 3) placebos instead of azithromycin, doxycycline, and rifampin. The primary end point was the number of patients who improved by 20% or more in at least 4 of 6 variables without worsening in any 1 variable in both combination antibiotic groups combined and in the placebo group at month 6 compared with baseline. Results The primary end point was achieved in 17 of 27 patients (63%) receiving combination antibiotics and in 3 of 15 patients (20%) receiving placebo. Secondary efficacy end points showed similar results. Six of 27 patients (22%) randomized to combination antibiotics believed that their disease went into complete remission during the trial, whereas no patient in the placebo arm achieved remission. Significantly more patients in the active treatment group became negative for C trachomatis or C pneumoniae by PCR at month 6. Adverse events were mild, with no significant differences between the groups. Conclusion These data suggest that a 6-month course of combination antibiotics is an effective treatment for chronic Chlamydia -induced ReA. [source] Golimumab, a new human anti,tumor necrosis factor , antibody, administered intravenously in patients with active rheumatoid arthritis: Forty-eight,week efficacy and safety results of a phase III randomized, double-blind, placebo-controlled study ,ARTHRITIS & RHEUMATISM, Issue 4 2010Joel Kremer Objective To assess the efficacy and safety of intravenous administration of golimumab in patients with rheumatoid arthritis (RA). Methods Adult patients with RA in whom disease activity was persistent despite treatment with methotrexate (MTX) at a dosage of 15,25 mg/week for ,4 weeks were randomized to receive intravenous infusions of placebo plus MTX or intravenous infusions of golimumab at a dose of 2 mg/kg or 4 mg/kg, with or without MTX, every 12 weeks through week 48. Patients with <20% improvement in the swollen and tender joint counts could enter early escape and receive additional active treatment (week 16) or could have their dose regimen adjusted (week 24). The primary end point was the proportion of patients achieving a 50% response according to the American College of Rheumatology improvement criteria (ACR50) at week 14. Results The primary study end point was not met (at week 14, an ACR50 response was observed in 21% of the patients treated with golimumab plus MTX compared with 13% of the patients treated with placebo plus MTX [P = 0.051]). By week 24, significantly more patients treated with golimumab plus MTX had achieved an ACR50 response. Differences in the proportion of patients achieving an ACR50 response between the group receiving golimumab monotherapy and the group receiving placebo plus MTX were not significant at either week 14 (16% versus 13%) or week 24 (10% versus 9%). At week 48, the proportions of patients achieving ACR20 and ACR50 responses were highest among those who had received golimumab 4 mg/kg plus MTX (70% and 48%, respectively). Concomitant treatment with MTX was associated with a lower incidence of antibodies to golimumab. The most commonly reported adverse events through week 48 were infections (48% of patients treated with golimumab with or without MTX and 41% of patients receiving placebo plus MTX). Conclusion The primary end point was not met. However, intravenously administered golimumab plus MTX appears to have benefit in the longer-term reduction of RA signs/symptoms in MTX-resistant patients, with no unexpected safety concerns. [source] Efficacy, pharmacodynamics, and safety of VX-702, a novel p38 MAPK inhibitor, in rheumatoid arthritis: Results of two randomized, double-blind, placebo-controlled clinical studies,ARTHRITIS & RHEUMATISM, Issue 5 2009Nemanja Damjanov Objective To assess the efficacy and safety of VX-702, a p38 MAPK inhibitor, in patients with active, moderate-to-severe rheumatoid arthritis (RA). Methods Two 12-week, double-blind, placebo-controlled studies of VX-702 were conducted in patients with active, moderate-to-severe RA. In the VeRA study, 313 patients received placebo or 2 daily doses of VX-702. In Study 304, 117 patients received placebo, daily VX-702, or twice weekly VX-702 in addition to concomitant methotrexate (MTX). Study end points included the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (an ACR20 response), ACR50 and ACR70 responses, changes in the serum levels of biomarkers of inflammation, and safety assessments. Results The numerically superior ACR20 response rates among patients receiving VX-702 compared with those receiving placebo in both studies did not reach pairwise statistical significance at the highest doses in either study. At week 12 in the VeRA study, ACR20 response rates were 40%, 36%, and 28% among patients receiving 10 mg of VX-702, 5 mg of VX-702, and placebo, respectively. In Study 304, the response rates were 40%, 44%, and 22% for patients receiving 10 mg VX-702 daily plus MTX, 10 mg VX-702 twice weekly plus MTX, and placebo, respectively. Reductions in the levels of C-reactive protein, soluble tumor necrosis factor receptor p55, and serum amyloid A were observed as early as week 1 in both studies, but these levels rapidly returned to baseline values by week 4. The overall frequency of adverse events was similar between the VX-702 and placebo groups. In the VeRA study, serious infections were more frequent in the VX-702 groups compared with the placebo group (2.4% versus 0%) but not in Study 304 (2.6% versus 4.9%). Conclusion The modest clinical efficacy plus the transient suppression of biomarkers of inflammation observed in this study suggest that p38 MAPK inhibition may not provide meaningful, sustained suppression of the chronic inflammation seen in RA. [source] Terazosin for treating symptomatic benign prostatic obstruction: a systematic review of efficacy and adverse effectsBJU INTERNATIONAL, Issue 3 2002T.J. Wilt Objective To systematically review and evaluate the effectiveness and adverse effects of the ,-antagonist, terazosin, for treating urinary symptoms associated with benign prostatic obstruction (BPO). Methods Studies were sought and included in the review if they were randomized trials of at least 1 month duration, involved men with symptomatic BPO and compared terazosin with placebo or active controls. The study, patient characteristics and outcome data were extracted in duplicate onto standardized forms using a prospectively developed protocol. Results Seventeen studies involving 5151 men met the inclusion criteria, i.e. placebo-controlled (10), ,-blockers (seven), finasteride alone or combined with terazosin and placebo (one), and microwave therapy (one). The study duration was 4,52 weeks; the mean age of the men was 65 years and 82% were white. Baseline urological symptom scale scores and flow rates showed that men had moderate BPO. Efficacy outcomes were rarely reported in a way that allowed for data pooling, but indicated that terazosin improved symptom scores and flow rates more than did placebo or finasteride, and similarly to other ,-antagonists. The pooled mean percentage improvement for the Boyarsky symptom score was 37% for terazosin and 15% for placebo (four studies). The mean percentage improvement for the American Urological Association symptom score was 38%, compared with 17% and 20% for placebo and finasteride, respectively (two studies). The pooled mean improvement in the International Prostate Symptom Score of 40% was similar to that with tamsulosin (43%). Peak urinary flow rates improved more with terazosin (22%) than with placebo (11%) and finasteride (15%), but did not differ significantly from the other ,-antagonists. The percentage of men discontinuing terazosin was comparable with those receiving placebo and finasteride, but greater than with other ,-antagonists. Adverse effects were greater than with placebo and included dizziness, asthenia, headache and postural hypotension. Conclusions The available evidence indicates that terazosin improves the symptoms and flow rates associated with BPO; it was more effective than placebo or finasteride and similar to other ,-antagonists. Adverse effects were generally mild but more frequent than with other ,-antagonists and associated with a two- to four-fold increase in treatment discontinuation. [source] | |||||||||||||||||||||||||