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Superior Efficacy (superior + efficacy)

Distribution by Scientific Domains

Medical Sciences	100%

Distribution within Medical Sciences

Oncology & Radiotherapy	18%
Dermatology	12%

Selected Abstracts

Superior efficacy of a Cremophor-free albumin-bound paclitaxel compared with solvent-based paclitaxel in Chinese patients with metastatic breast cancer

ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 3 2009
Zhong-Zhen GUAN
Abstract Aim: In a previous study, a 130-nm nanoparticle albumin-bound paclitaxel (nab -paclitaxel) demonstrated improved efficacy and safety profile compared with solvent-based paclitaxel (sb-paclitaxel) in Caucasian patients with metastatic breast cancer (MBC). The aim of the present randomized study was to compare the response rates and safety profile of nab -paclitaxel with sb-paclitaxel in Chinese patients with MBC. Methods: In the present open-label, multicenter study, 210 patients with MBC were randomly assigned to receive nab -paclitaxel 260 mg/m2 intravenously (i.v.) over 30 min every 3 weeks (q3w) with no premedication or sb-paclitaxel 175 mg/m2 i.v. over 3 h q3w with standard premedication. Results: The overall response rate was 54 and 29% in patients treated with nab -paclitaxel and sb-paclitaxel, respectively (P < 0.001). nab -paclitaxel induced a higher response rate in patients who were <65 years old, patients who were receiving first-line therapy, patients who had no prior anthracycline therapy, patients who had , or >3 metastatic lesions, and patients who had visceral disease. The progression-free survival (PFS) period was 7.6 months for nab -paclitaxel and 6.2 months for sb-paclitaxel (P = 0.118). Despite the 49% higher paclitaxel dose in patients receiving nab -paclitaxel compared with patients receiving sb-paclitaxel, the safety profile was similar in both treatment groups. The most common grades 3 and 4 adverse event (AE) in both arms was neutropenia. The most common grade 3 nonhematologic AE was peripheral neuropathy, and no grade 4 peripheral neuropathy was observed. Conclusion: Compared with sb-paclitaxel, nab -paclitaxel demonstrated superior efficacy, an acceptable safety profile, and a trend toward increased PFS in patients with MBC. [source]

Diversity of effective treatments of panic attacks: what do they have in common?,

DEPRESSION AND ANXIETY, Issue 1 2010
Walton T. Roth M.D.
Abstract By comparing efficacious psychological therapies of different kinds, inferences about common effective treatment mechanisms can be made. We selected six therapies for review on the basis of the diversity of their theoretical rationales and evidence for superior efficacy: psychoanalytic psychotherapy, hypercapnic breathing training, hypocapnic breathing training, reprocessing with and without eye-movement desensitization, muscle relaxation, and cognitive behavior therapy. The likely common element of all these therapies is that they reduce the immediate expectancy of a panic attack, disrupting the vicious circle of fearing fear. Modifying expectation is usually regarded as a placebo mechanism in psychotherapy, but may be a specific treatment mechanism for panic. The fact that this is seldom the rationale communicated to the patient creates a moral dilemma: Is it ethical for therapists to mislead patients to help them? Pragmatic justification of a successful practice is a way out of this dilemma. Therapies should be evaluated that deal with expectations directly by promoting positive thinking or by fostering non-expectancy. Depression and Anxiety, 2010. Published 2009 Wiley-Liss, Inc. [source]

Achieving remission with venlafaxine and fluoxetine in major depression: its relationship to anxiety symptoms

DEPRESSION AND ANXIETY, Issue 1 2002
Jonathan R.T. Davidson M.D., M.B.A.
Abstract Venlafaxine, a serotonin and norepinephrine reuptake inhibitor (SNRI), produces significantly higher remission rates in depressed patients than do the selective serotonin reuptake inhibitors (SSRIs). In this analysis of pooled data, we explored the relationship between differences in treatment efficacy, early improvement of symptoms, and severity of baseline anxiety in depressed patients treated with either venlafaxine or fluoxetine. A pooled analysis was performed on data from 1,454 outpatients with major depression from five double-blind, randomized studies comparing the 6-week efficacy of venlafaxine (542 patients) with fluoxetine (555 patients). The Hamilton rating scale for depression (HAM-D) total and item scores were analyzed at different treatment times up to 6 weeks. Venlafaxine and fluoxetine both produced statistically significant higher response and remission rates compared with placebo starting from week 2 for response and weeks 3 to 4 for remission. Venlafaxine was statistically significantly superior to fluoxetine from week 3 until week 6 in respect of response rate, and from week 2 until week 6 for remission rate. After 1 week of treatment, greater improvement in individual symptoms was observed in the depressed mood, suicide, and psychic anxiety items of the HAM-D scale for both venlafaxine- and fluoxetine-treated patients compared with placebo. Improvement in psychic anxiety was statistically significantly greater with venlafaxine than with fluoxetine. The presence of baseline psychic anxiety correlated significantly to treatment outcome when analyzing the remission rates. In depressed patients with moderate anxiety (HAM-D psychic anxiety score ,2), venlafaxine statistically significantly increased remission rates compared with placebo from week 4 until week 6, while a significant effect of fluoxetine on remission rates was observed starting at week 6. Remission rates in the severely anxious depressed patients (score >2) were statistically significantly higher with venlafaxine than placebo starting from week 3 until the end of the study period, but no difference could be observed between fluoxetine and placebo. Baseline severity of psychic anxiety had a significant impact on remission rates after treatment of patients diagnosed with depression. Venlafaxine's superior remission rates in the more severely anxious patients and its ability to improve psychic anxiety as early as week 1 compared with fluoxetine suggest that venlafaxine's early efficacy on anxiety symptoms may be the basis for its superior efficacy in depression. Depression and Anxiety 16:4,13, 2002. © 2002 Wiley-Liss, Inc. [source]

Vildagliptin plus metformin combination therapy provides superior glycaemic control to individual monotherapy in treatment-naive patients with type 2 diabetes mellitus

DIABETES OBESITY & METABOLISM, Issue 5 2009
E. Bosi
Aim:, To compare the efficacy and safety of vildagliptin and metformin initial combination therapy with individual monotherapies in treatment-naive patients with type 2 diabetes mellitus (T2DM). Methods:, This was a 24-week, randomized, double-blind, active-controlled study. Treatment-naive patients with T2DM who had a glycated haemoglobin (HbA1c) of 7.5,11% (N = 1179) were randomized equally to receive vildagliptin plus high-dose metformin combination therapy (50 mg + 1000 mg twice daily), vildagliptin plus low-dose metformin combination therapy (50 mg + 500 mg twice daily), vildagliptin monotherapy (50 mg twice daily) or high-dose metformin monotherapy (1000 mg twice daily). The primary objective was to demonstrate that HbA1c reduction from baseline with either combination therapy is superior to both monotherapies at the week 24 endpoint. Patients who failed glycaemic-screening criteria [HbA1c >11% or fasting plasma glucose (FPG) >15 mmol/l (270 mg/dl)] could enter a 24-week, single-arm substudy. These patients (N = 94) received open-label vildagliptin plus high-dose metformin combination therapy (100 mg + 1000 mg twice daily). Results:, From comparable baseline values (8.6,8.7%), HbA1c decreased in all four treatment groups, to the greatest extent with vildagliptin plus high-dose metformin combination therapy. Mean (SE) HbA1c change from baseline was ,1.8% (0.06%), ,1.6% (0.06%), ,1.1% (0.06%) and ,1.4% (0.06%) with vildagliptin plus high-dose metformin combination therapy, vildagliptin plus low-dose metformin combination therapy, and vildagliptin and metformin monotherapies respectively. The between-group difference was superior with vildagliptin plus high-dose metformin combination therapy (p < 0.001 vs. both monotherapies) and vildagliptin plus low-dose metformin combination therapy (p < 0.001 and p = 0.004, vs. vildagliptin and metformin monotherapies, respectively). Higher baseline HbA1c values were linked to greater HbA1c reductions, with changes of ,3.2% (0.22%), ,2.7% (0.22%), ,1.5% (0.24%) and ,2.6% (0.26%) respectively, occurring in patients with baseline HbA1c,10%. Reductions in FPG were superior with vildagliptin plus high-dose metformin combination therapy [change from baseline ,2.63 (0.13) mmol/l] compared with both monotherapies [,1.26 (0.13) mmol/l and ,1.92 (0.13) mmol/l, respectively; p < 0.001]. There was no incidence of hypoglycaemia or severe hypoglycaemia with either combination therapy, and neither was associated with weight gain. All treatments were well tolerated and displayed a comparable incidence of adverse events overall. Despite superior HbA1c lowering, the vildagliptin plus low-dose metformin combination therapy group demonstrated a favourable gastrointestinal (GI) tolerability profile compared with metformin monotherapy. Conclusions:, In treatment-naive patients, combinations of vildagliptin and both high-dose and low-dose metformin provide superior efficacy to monotherapy treatments with a comparable overall tolerability profile and low risk of hypoglycaemia. The potential dose-sparing effect of adding vildagliptin to low-dose metformin in preference to the up-titration of metformin may allow patients to achieve equivalent or superior HbA1c lowering without the GI tolerability issues associated with higher doses of metformin. [source]

Active immunization with IL-1 displayed on virus-like particles protects from autoimmune arthritis

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2008
Gunther Spohn
Abstract IL-1 is an important mediator of inflammation and a major cause of tissue damage in rheumatoid arthritis (RA). Therapeutic administration of recombinant IL-1 receptor antagonist (IL-1Ra) is efficacious in reducing clinical symptoms of disease, but suffers from several drawbacks, including the need for frequent administrations of large amounts. Here, we show that immunization of mice with either IL-1, or IL-1, chemically cross-linked to virus-like particles (VLP) of the bacteriophage Q, elicited a rapid and long-lasting autoantibody response. The induced Ab efficiently neutralized the binding of the respective IL-1 molecules to their receptors in vitro and their pro-inflammatory activities in vivo. In the collagen-induced arthritis model, both vaccines strongly protected mice from inflammation and degradation of bone and cartilage. Moreover, immunization with either vaccine showed superior efficacy than daily administrations of high amounts of IL-1Ra. In the T and B cell-independent collagen Ab transfer model, immunization with the IL-1, vaccine strongly protected from arthritis, whereas immunization with the IL-1, vaccine had no effect. Our results suggest that active immunization with IL-1,, and especially IL-1, conjugated to Q, VLP, might become an efficacious and cost-effective new treatment option for RA and other systemic IL-1-dependent inflammatory disorders. [source]

Subcutaneous histamine versus sodium valproate in migraine prophylaxis: a randomized, controlled, double-blind study

EUROPEAN JOURNAL OF NEUROLOGY, Issue 10 2007
R. O. Millán-Guerrero
Histamine has a selective affinity for H3-receptors and it may specifically inhibit the neurogenic edema response involved in migraine pathophysiology. The objective of this study was to evaluate the therapeutic potential of subcutaneous administration of histamine in migraine prophylaxis, compared with oral administration of sodium valproate, in an open clinical trial. Ninety-two patients with migraine were selected under criteria established by the International Headache Society and enrolled in a 12-week double-blind controlled clinical trial to evaluate the efficacy of subcutaneous administration of histamine (1,10 ng twice a week; n = 46) compared with oral administration of sodium valproate (500 mg daily dose; n = 46). The variables studied were headache intensity, frequency, duration, analgesic intake and migraine disability assessment (MIDAS). Two-tailed Student's t - test was used to compare means and the Mann,Whitney U and anova tests were used. The data collected during the 4th, 8th and 12th weeks of treatment revealed that histamine caused a significantly greater reduction (P < 0.001) in intensity and duration of migraine attacks as well as in analgesic intake. No difference was detected in the frequency of attacks or in MIDAS. The present study provides evidence of the superior efficacy of histamine applied subcutaneously in migraine prophylaxis when compared with sodium valproate taken orally. Subcutaneously applied histamine may represent a novel and effective therapeutic alternative in resistant migraine patients. [source]

The 40-mg dose of eletriptan: comparative efficacy and tolerability versus sumatriptan 100 mg

EUROPEAN JOURNAL OF NEUROLOGY, Issue 2 2004
Hans-Christoph Diener
Meta-analysis provides valuable information regarding relative efficacies of triptans, but head-to-head comparator studies remain the gold standard. Three similar head-to-head trials comparing eletriptan 40 mg (E40) with sumatriptan 100 mg (S100) provide a rare opportunity and sufficient power, for robust comparisons of efficacy. Data were combined from three double-blind, placebo-controlled, first-dose, first-attack acute migraine treatment studies comparing E40 (n = 1132), S100 (n = 1129), and placebo (n = 645). The primary outcome was headache response at 2 h. Secondary outcomes included headache response at 1 h, pain-free and functional responses, and sustained headache and pain-free responses. Odds ratios were calculated for summary estimates of probability of response. There were higher headache response rates with eletriptan versus sumatriptan at 2 h (67% vs. 57%; P < 0.0001) and 1 h (34% vs. 26%; P < 0.0001). Eletriptan also had higher 2 h pain-free (35% vs. 25%; P < 0.0001) and functional responses (67% vs. 58%; P < 0.0001). Sustained headache (42%) and pain-free (22%) response rates were higher for eletriptan versus sumatriptan (34%, P < 0.0001; 15%, P < 0.0001). The probability of response for eletriptan versus sumatriptan ranged from 36% higher (relief of nausea) to 64% higher (sustained pain-free rate). Combined analysis demonstrates that E40 has superior efficacy versus S100 across all clinically relevant outcomes. [source]

Sequential methods and group sequential designs for comparative clinical trials

FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 5 2003
Véronique Sébille
Abstract Comparative clinical trials are performed to assess whether a new treatment has superior efficacy than a placebo or a standard treatment (one-sided formulation) or whether two active treatments have different efficacies (two-sided formulation) in a given population. The reference approach is the single-stage design and the statistical test is performed after inclusion and evaluation of a predetermined sample size. In practice, the single-stage design is sometimes difficult to implement because of ethical concerns and/or economic reasons. Thus, specific early termination procedures have been developed to allow repeated statistical analyses to be performed on accumulating data and stop the trial as soon as the information is sufficient to conclude. Two main different approaches can be used. The first one is derived from strictly sequential methods and includes the sequential probability ratio test and the triangular test. The second one is derived from group sequential designs and includes Peto, Pocock, and O'Brien and Fleming methods, , and , spending functions, and one-parameter boundaries. We review all these methods and describe the bases on which they rely as well as their statistical properties. We also compare these methods and comment on their advantages and drawbacks. We present software packages which are available for the planning, monitoring and analysis of comparative clinical trials with these methods and discuss the practical problems encountered when using them. The latest versions of all these methods can offer substantial sample size reductions when compared with the single-stage design not only in the case of clear efficacy but also in the case of complete lack of efficacy of the new treatment. The software packages make their use quite simple. However, it has to be stressed that using these methods requires efficient logistics with real-time data monitoring and, apart from survival studies or long-term clinical trials with censored endpoints, is most appropriate when the endpoint is obtained quickly when compared with the recruitment rate. [source]

Soy extract phytoestrogens with high dose of isoflavones for menopausal symptoms

JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 6 2009
Augusto Ferrari
Abstract Aim:, The aim of the present study was to assess the efficacy and safety of a standardized compound based on an extract of soy phytoestrogens, with high doses of isoflavones in the management of menopausal hot flushes. Methods:, A total of 180 women aged 40,65 years with a minimum of five moderate-to-severe hot flushes in the last 7 days at baseline and absence of menstruation for at least 6 months participated in a 12-week prospective, randomized, double-blind, placebo-controlled multicenter trial. After a 2-week run-in period, women received one tablet a day of 80 mg isoflavones (corresponding to 60 mg of genistein) or a matching placebo. Results:, The mean daily number of moderate-to-severe hot flushes decreased in both study groups, but the reduction was greater in the isoflavones arm at 6 (36.2%) and 12 weeks (41.2%) than in the placebo arm (24.0% at 6 weeks, 29.3% at 12 weeks), with a difference of 1.1 (95% CI [,2.0 to ,0.06]) (P = 0.038) at 6 weeks and 1.1 (95% CI [,2.05 to ,0.15]) (P = 0.023) at 12 weeks. Similar findings were obtained for hot flushes of any intensity. The Kupperman index decreased in both study groups. Relief of hot flushes was greater when time to menopause was ,12 months and in cases of BMI ,27 kg/m2. Conclusion:, In daily practice conditions, high doses of isoflavones, particularly genistein, can be used for the management of hot flushes in postmenopausal women not treated with hormone replacement therapy due to their superior efficacy to placebo and very good safety profile. [source]

Virological, serological and biochemical outcomes through 3 years of entecavir treatment in nucleoside-naive Chinese chronic hepatitis B patients

JOURNAL OF VIRAL HEPATITIS, Issue 2010
G. B. Yao
Summary., Hepatitis B virus (HBV) infection has a high prevalence in China. Entecavir has shown superior efficacy over lamivudine in Chinese nucleoside-naive chronic hepatitis B (CHB) patients over 48 weeks, with continued clinical benefit to 96 weeks. The present study evaluates the long-term efficacy of entecavir in Chinese CHB patients who continued entecavir treatment for 144 weeks. Patients receiving either entecavir 0.5 mg/day (n = 258) or lamivudine 100 mg/day (n = 261) entered the initial 96-week randomized, double-blind, controlled efficacy study. Patients who did not achieve a consolidated response [HBV DNA <0.7 MEq/mL; alanine aminotransferase (ALT) <1.25 × upper limit of normal; and if hepatitis B e antigen (HBeAg) positive at baseline, loss of HBeAg for ,24 weeks] or who experienced viral breakthrough or relapse entered a 48-week entecavir rollover study. A total of 160 patients received continuous entecavir for 144 weeks; of these, 89% had undetectable serum HBV DNA, 86% showed ALT normalization, 20% reported HBeAg loss and 8% experienced HBeAg seroconversion. The cumulative rates of HBeAg loss and seroconversion were 36% and 27% at Week 144, respectively. The development of resistance was low, with three patients up to Week 96 and an additional two patients in Weeks 96,144 showing evidence of associated genotypic mutations. Entecavir was well tolerated. Adverse event rates were similar to those in lamivudine-treated patients, but patients receiving entecavir experienced fewer ALT flares. This study demonstrates that entecavir provides durable, long-term suppression of HBV DNA and ALT normalization in Chinese CHB patients, and is associated with low rates of emerging resistance. The results are consistent with the findings using entecavir globally and in Japan. [source]

(204) Rofecoxib Was More Effective than Codeine with Acetaminophen in the Treatment of Acute Pain

PAIN MEDICINE, Issue 3 2001
David J. Chang
Rofecoxib (VIOXX®) is a selective inhibitor of cyclo-oxygenase-2 and is indicated for the treatment of acute pain. Prior acute pain studies showed similar analgesic efficacy of rofecoxib 50 mg compared with analgesics doses of non-selective NSAIDs. We performed a randomized, double-blind trial to evaluate the efficacy and safety of rofecoxib, a standard fixed formulation of codeine with acetaminophen, and placebo in the treatment of acute pain. Three-hundred ninety-three patients with moderate or severe pain after surgical extraction of at least two 3rd molars were randomized to receive a single dose of rofecoxib 50 mg (n = 182), codeine 60 mg with acetaminophen 600 mg (n = 180), or placebo (n = 31). Efficacy was assessed at 11 pre-specified time points after dosing by pain relief and pain intensity scores. Patient global assessment of study medication was also performed. Baseline characteristics were similar among the groups. The mean age was 21 years; 69.0% were female; and 78.6% had a pain intensity score of "moderate." For the primary endpoint, total pain relief over 6 hours, rofecoxib was more effective than codeine/acetaminophen (p < 0.001) and placebo (p < 0.001). Proportion of patients who rated the study medication as good, very good, or excellent at 6 hours was 64.6% on rofecoxib, 36.4% on codeine/acetaminophen, and 10.3% on placebo (rofecoxib> codeine/acetaminophen; p < 0.001). The time to rescue medication was longer for rofecoxib compared to codeine/acetaminophen (p < 0.001). More patients on codeine/acetaminophen experienced clinical adverse events than rofecoxib (p < 0.05). Patients receiving codeine/acetaminophen versus rofecoxib had higher incidences of nausea (25.0% vs 6.0%; p < 0.001) and vomiting (18.3% vs 3.8%; p < 0.001). In this study, rofecoxib had superior efficacy and gastrointestinal safety compared to codeine/acetaminophen, which provides support for the use of rofecoxib as an alternative option to opioid analgesics in the treatment of acute post-surgical pain. [source]

Superior efficacy of a Cremophor-free albumin-bound paclitaxel compared with solvent-based paclitaxel in Chinese patients with metastatic breast cancer

Comparison of fesoterodine and tolterodine extended release for the treatment of overactive bladder: a head-to-head placebo-controlled trial

BJU INTERNATIONAL, Issue 1 2010
Sender Herschorn
Study Type , Therapy (RCT) Level of Evidence 1b OBJECTIVE To compare the efficacy and tolerability of fesoterodine 8 mg with tolterodine extended-release (ER) 4 mg and placebo in a randomized clinical trial of patients with an overactive bladder (OAB). PATIENTS AND METHODS In this 12-week double-blind, double-dummy, placebo-controlled, randomized clinical trial, eligible patients reported OAB symptoms for ,3 months and recorded ,8 voids and ,1 urgency urinary incontinence (UUI) episode per 24 h in 3-day bladder diaries at baseline. Patients were randomized in a 2:2:1 ratio to fesoterodine (4 mg for 1 week then 8 mg for 11 weeks); tolterodine ER 4 mg; or placebo (with sham dose escalation for tolterodine ER and placebo). Endpoints were changes from baseline to week 12 in UUI episodes (primary endpoint), total and nocturnal voids, urgency episodes, severe urgency episodes, and frequency-urgency sum per 24 h; mean voided volume per void (MVV); and the OAB questionnaire (OAB-q), Patient Perception of Bladder Condition (PPBC), and Urgency Perception Scale (UPS). Safety and tolerability were assessed and summarized over the 12-week study period. RESULTS Fesoterodine (636 patients) significantly improved UUI episodes at week 12 (primary endpoint) compared with tolterodine ER (641 patients; P = 0.017) and placebo (313 patients; P < 0.001). Fesoterodine also produced significantly greater improvements than tolterodine ER in MVV (P = 0.005). Fesoterodine significantly improved all diary endpoints compared with placebo (P < 0.001), except for nocturnal voids (P = 0.327). Tolterodine ER significantly improved all diary endpoints vs placebo (P < 0.001), except for nocturnal voids (P = 0.506) and MVV (P = 0.103). Diary dry rates (the proportion of patients reporting no UUI episodes at endpoint among those with one or more UUI episodes at baseline) were significantly higher with fesoterodine (64%) than with tolterodine ER (57%; P = 0.015) and placebo (45%; P < 0.001). Improvements in PPBC, UPS and OAB-q scale and domain scores at week 12 were all significantly better with fesoterodine than placebo (all P < 0.001) and tolterodine ER (all P < 0.05) except for the OAB-q Sleep domain vs tolterodine ER (P = 0.081). Dry mouth and constipation rates were 28% and 5% in the fesoterodine group, 16% and 4% in the tolterodine ER group, and 6% and 3% with placebo, respectively. Discontinuations due to treatment-emergent adverse events were 6%, 4% and 2% in the fesoterodine, tolterodine ER, and placebo groups, respectively. CONCLUSION In patients with OAB, fesoterodine 8 mg showed superior efficacy over tolterodine ER 4 mg and placebo in reducing UUI episodes (primary endpoint) and in improving most patient-reported outcome measures. Both active treatments were well tolerated. [source]

Efficacy and safety results from the randomized controlled comparative study of adalimumab vs. methotrexate vs. placebo in patients with psoriasis (CHAMPION)

BRITISH JOURNAL OF DERMATOLOGY, Issue 3 2008
J.-H. Saurat
Summary Background, Biologic therapies such as adalimumab, a tumour necrosis factor antagonist, are safe and effective in the treatment of moderate to severe chronic plaque psoriasis. Objectives, To compare a biologic agent with methotrexate, a traditional systemic agent, to define clearly the role of biologics in psoriasis. Methods, Patients with moderate to severe plaque psoriasis were randomized to adalimumab (80 mg subcutaneously at week 0, then 40 mg every other week, n = 108), methotrexate (7·5 mg orally, increased as needed and as tolerated to 25 mg weekly; n = 110) or placebo (n = 53) for 16 weeks. The primary efficacy endpoint was the proportion of patients achieving at least a 75% improvement in the Psoriasis Area and Severity Index (PASI 75) after 16 weeks. Safety was assessed at all visits through week 16. Results, After 16 weeks, 79·6% of adalimumab-treated patients achieved PASI 75, compared with 35·5% for methotrexate (P < 0·001 vs. adalimumab) and 18·9% for placebo (P < 0·001 vs. adalimumab). Statistically significantly more adalimumab-treated patients (16·7%) than methotrexate-treated patients (7·3%) or placebo-treated patients (1·9%) achieved complete clearance of disease. The response to adalimumab was rapid, with a 57% improvement in mean PASI observed at week 4. Adverse events were similar across treatment groups. Adverse events leading to study discontinuation were greatest in the methotrexate group, primarily because of hepatic-related adverse events. Conclusions, After 16 weeks, adalimumab demonstrated significantly superior efficacy and more rapid improvements in psoriasis compared with either methotrexate or placebo. [source]

DJ-927, a novel oral taxane, overcomes P-glycoprotein-mediated multidrug resistance in vitro and in vivo

CANCER SCIENCE, Issue 5 2003
Motoko Shionoya
DJ-927 is a novel taxane, which was selected for high solubility, non-neurotoxicity, oral bioavailability, and potent antitumor activity. In this study, we compared the in vitro and in vivo efficacy of DJ-927 with those of paclitaxel and docetaxel. DJ-927 exhibited stronger cytotoxicity than paclitaxel and docetaxel in various tumor cell lines, especially against P-glycoprotein (P-gp)-expressing cells. The cytotoxicity of DJ-927, unlike those of other taxanes, was not affected by the P-gp expression level in tumor cells, or by the co-presence of a P-gp modulator. When intracellular accumulation of the three compounds was compared, intracellular amounts of DJ-927 were much higher than those of paclitaxel or docetaxel, particularly in P-gp-positive cells. In vivo, DJ-927 showed potent antitumor effects against two human solid tumors in male BALB/c- nu/nu mice, and yielded significant life-prolongation in a murine liver metastasis model with male C57BL/6 mice, in which neither paclitaxel nor docetaxel was effective. The results demonstrate the superior efficacy of orally administered DJ-927 over intravenously administered paclitaxel or docetaxel against P-gp-expressing tumors, probably due to higher intracellular accumulation. A phase I clinical trials of DJ-927 is currently ongoing in the US. (Cancer Sci 2003; 94: 459,466) [source]

Methotrexate for psoriasis in the era of biological therapy

CLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 5 2008
R. B. Warren
Summary Methotrexate's traditional role as a first line agent for moderate to severe psoriasis is being challenged by the rapid and growing use of biological therapies. A recent study comparing adalimumab with methotrexate showed significantly superior efficacy of adalimumab over methotrexate over 16 weeks. Although it is inexpensive, the future use of methotrexate may be compromised by its unpredictable response and toxicity, and by the introduction of newer, more effective biological therapies. However, recent advances in the screening of liver fibrosis by monitoring serum levels of the aminoterminal peptide fragment of type III procollagen have reduced the need for liver biopsy. Furthermore, the potential for personalized methotrexate use by application of modern pharmacogenetics and pharmacokinetics may ensure its place as a first-line agent for the treatment of psoriasis for the foreseeable future. [source]