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Selected AbstractsTreatment of erythrodermic psoriasis in HCV+ patient with adalimumabDERMATOLOGIC THERAPY, Issue 2009Antonio Giovanni Richetta ABSTRACT Erythrodermic psoriasis is a severe and disabling variant of psoriasis. The authors present the case of a 48-year-old man with psoriasis and hemophilia presented with a history of hepatitis C virus (HCV) infection treated with pegylated interferon alpha-2a and ribavirin therapy. At the end of antiviral therapy, skin manifestation progressively worsened, becoming erythrodermic, with lack of efficacy of steroid therapy. The authors decided to start biological therapy with induction dose of adalimumab (Humira, Abbott Laboratories, Abbott Park, Chicago, IL) 80 mg at Week 0 and 40 mg weekly. In our case, this resulted in a highly effective and safe treatment. [source] DMARD combination therapy in rheumatoid arthritis: 5-year follow-up results in a daily practice settingINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 1 2006Fereydoun DAVATCHI Abstract Aim:, To evaluate the overall effect of disease modifying anti-rheumatic drug (DMARD) combination therapy in daily practice. Methods:, In a retrospective study, 161 consecutive files of patients who attended regular follow-up sessions, seen from 1998, were analysed. Their data were extracted at baseline, 6 months, 1, 2, 3, 4 and 5 years. American College of Rheumatology ACR70 criteria was chosen for the evaluation of the global result. DMARD combination was methotrexate (7.5,15 mg weekly) and chloroquine (150 mg daily), with low-dose prednisolone (less than 10 mg daily). In cases of remission, methotrexate was gradually tapered, then prednisolone. Chloroquine was discontinued after 1 year if no recurrence occurred at low-dose (150 mg every other day). In cases of recurrence at any stage, the treatment scheme was stepped back. Results:, The data of 161 patients were analysed. One hundred and six were rheumatoid factor positive (RF+) (66%). ACR 70 for all patients at 6 months follow-up was 72.5% (95% CI = 7.0); at 1 year, 75.8% (95% CI = 6.7); at 2 years, 72.2% (95% CI = 7.2); at 3 years, 78.9% (95% CI = 6.6); at 4 years, 78.4% (95% CI = 6.9); and at 5 years, 70.6% (95% CI = 8.5). Conclusion:, The classical DMARD combination therapy, when used with adequate low-dose prednisolone, gave an ACR70 response from 71,79%. The efficacy of the treatment did not fade over time. RF, patients did better than RF+ patients, but the difference was not statistically significant. [source] Adalimumab sustains clinical remission and overall clinical benefit after 2 years of therapy for Crohn's diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2010R. PANACCIONE Aliment Pharmacol Ther,31, 1296,1309 Summary Background, In the randomized, double-blind, placebo-controlled CHARM trial, adalimumab was more effective than placebo in maintaining clinical remission for patients with moderate-to-severe Crohn's disease (CD) through 56 weeks. Aim, To substantiate the long-term safety and clinical benefits of adalimumab through 2 years of therapy in CHARM and its open-label extension (ADHERE). Methods, Patients entering ADHERE on blinded therapy received adalimumab 40 mg every other week (eow). Patients who had already moved to open-label adalimumab eow or weekly in CHARM continued their regimens. Data were analysed by originally randomized treatment group at CHARM baseline (adalimumab 40 mg eow, adalimumab 40 mg weekly, or placebo), regardless of whether patients entered ADHERE or received open-label adalimumab (eow or weekly). Results, After up to 2 years of therapy, 37.6%, 41.9% and 49.8% of patients originally randomized to placebo, adalimumab eow and adalimumab weekly, respectively, were in clinical remission. All groups experienced sustained improvements on the Inflammatory Bowel Disease Questionnaire. Decreasing hazard rates for both all-cause and CD-related hospitalizations were observed over time. Over a 2-year period, the rates of serious adverse events and malignancies (33.3 and 1.1 events/100-patient-years respectively) were similar to those observed during the overall adalimumab CD clinical development programme. Conclusions, Adalimumab demonstrated sustained maintenance of clinical remission, improvements in quality of life and reductions in hospitalization during long-term treatment for CD, with no new safety concerns identified. [source] Disease remission and sustained halting of radiographic progression with combination etanercept and methotrexate in patients with rheumatoid arthritis,ARTHRITIS & RHEUMATISM, Issue 12 2007D. van der Heijde Objective The Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes (TEMPO) is a 3-year, double-blind, multicenter study evaluating the efficacy and safety of etanercept, methotrexate, and the combination of etanercept plus methotrexate in patients with active rheumatoid arthritis (RA). The results after 1 and 2 years of the study have been previously reported. Here we provide the 3-year clinical and radiographic outcomes and safety of etanercept, methotrexate, and the combination in patients with RA. Methods In this randomized, double-blind, multicenter TEMPO study, 682 patients received etanercept 25 mg twice weekly, methotrexate ,20 mg weekly, or the combination. Key efficacy assessments included the Disease Activity Score (DAS) and the DAS in 28 joints. Results Combination therapy resulted in significantly greater improvement in the DAS and in more patients with disease in remission than either monotherapy. This finding was confirmed by longitudinal analysis; patients receiving combination therapy were more than twice as likely to have disease in remission than those receiving either monotherapy. Independent predictors of remission included male sex, lower disease activity, lower level of joint destruction, and/or better physical function. Combination and etanercept therapy both resulted in significantly less radiographic progression than did methotrexate (P < 0.05). Etanercept and combination treatment were well tolerated, with no new safety findings. Conclusion Etanercept plus methotrexate showed sustained efficacy through 3 years and remained more effective than either monotherapy, even after adjustment for patient withdrawal. Combination therapy for 3 years led to disease remission and inhibition of radiographic progression, 2 key goals for treatment of patients with RA. [source] Comparison of etanercept and methotrexate, alone and combined, in the treatment of rheumatoid arthritis: Two-year clinical and radiographic results from the TEMPO study, a double-blind, randomized trialARTHRITIS & RHEUMATISM, Issue 4 2006Désirée van der Heijde Objective To evaluate the efficacy, including radiographic changes, and safety of etanercept and methotrexate (MTX), used in combination and alone, in patients with rheumatoid arthritis (RA) in whom previous treatment with a disease-modifying antirheumatic drug other than MTX had failed. Methods Patients with RA were treated with etanercept (25 mg subcutaneously twice weekly), oral MTX (up to 20 mg weekly), or combination therapy with etanercept plus MTX through a second year, in a double-blinded manner. Clinical response was assessed using American College of Rheumatology (ACR) criteria and the Disease Activity Score (DAS), in a modified intent-to-treat analysis with the last observation carried forward (LOCF) and in a population of completers. Radiographs of the hands, wrists, and forefeet were scored for erosions and joint space narrowing at annual intervals. Results A total of 503 of 686 patients continued into year 2 of the study. During the 2 years, significantly fewer patients receiving combination therapy withdrew from the study (29% of the combination therapy group, 39% of the etanercept group, and 48% of the MTX group). Both the LOCF and the completer analyses yielded similar results. The ACR 20% improvement (ACR20), ACR50, and ACR70 responses and the remission rates (based on a DAS of <1.6) were significantly higher with combination therapy than with either monotherapy (P < 0.01). Similarly, improvement in disability (based on the Health Assessment Questionnaire) was greater with combination therapy (P < 0.01). The combination therapy group showed significantly less radiographic progression than did either group receiving monotherapy (P < 0.05); moreover, radiographic progression was significantly lower in the etanercept group compared with the MTX group (P < 0.05). For the second consecutive year, overall disease progression in the combination therapy group was negative, with the 95% confidence interval less than zero. Adverse events were similar in the 3 treatment groups. Conclusion Etanercept in combination with MTX reduced disease activity, slowed radiographic progression, and improved function more effectively than did either monotherapy over a 2-year period. No increase in toxicity was associated with combination treatment with etanercept plus MTX. [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 2008J.-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] A case report of Hailey,Hailey disease treated with alefacept (Amevive®)BRITISH JOURNAL OF DERMATOLOGY, Issue 2 2008D.S. Hurd Summary Hailey,Hailey disease (chronic benign familial pemphigus) is a chronic, recurrent blistering disorder characterized clinically by erosions occurring primarily in intertriginous regions and histologically by suprabasilar acantholysis. We report a case of Hailey,Hailey disease initially unresponsive to multiple topical corticosteroids, tetracycline, dapsone, ciclosporin, isotretinoin, prednisone, methotrexate, topical ciclopirox, tazarotene cream, pimecrolimus cream and tacrolimus ointment. Partial response of this patient's perineal disease was achieved with Amevive® 15 mg weekly for 12 weeks, intramuscularly. To our knowledge, this case represents the first such published report of successful treatment of Hailey,Hailey disease using alefacept. [source] An open-label, dose-ranging study of methotrexate for moderate-to-severe adult atopic eczemaBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2007S.C. Weatherhead Summary Background, Treatment options for moderate-to-severe atopic eczema are limited. Although methotrexate (MTX) is a widely used and effective treatment for psoriasis, there have been no previous prospective trials of its use in refractory atopic eczema, despite a few small, retrospective reports suggesting that it is a well-tolerated and effective treatment. Objectives, We have assessed the safety and efficacy of oral MTX in 12 adults with moderate-to-severe atopic eczema in an open-label, dose-ranging, prospective trial using objective outcome measures. Methods, All patients had previously received other second-line therapies and had disease only partially responsive to potent topical steroids and emollients. During the 24-week MTX treatment period, unrestricted use of standard topical therapy was permitted. We used an incremental MTX dose regime, starting at 10 mg per week (following a 5-mg test dose) and increasing by 2·5 mg weekly until response was achieved or treatment was limited by toxicity. Disease activity [six area six sign atopic dermatitis (SASSAD) score] was assessed every 4 weeks during treatment and 12 weeks after stopping MTX. The primary endpoint was 24-week change in disease activity. Results, On average, disease activity improved by 52% from baseline (95% confidence interval 45,60%). There were significant improvements in quality of life, body surface area affected and loss of sleep and itch scores. Global response was rated as ,marked improvement' in five of 12 and six of 12 patients, by investigators and patients, respectively. In all patients, the majority of improvement in disease activity was seen by week 12, and, interestingly, patients who had not responded well over this period despite reaching a dose of 15 mg weekly failed to improve with further dose escalation. Only one patient withdrew due to minor adverse effects. MTX was well tolerated by the remaining 11 patients, all of whom completed treatment, achieving a median dose of 15 mg weekly. Importantly, eight of nine patients had a persistent improvement 12 weeks after stopping MTX, with mean disease activity remaining 34% below baseline. Conclusions, We have shown that MTX is an effective, well-tolerated treatment for moderate-to-severe atopic eczema, and response appears to compare favourably with other second-line therapies. A randomized, controlled trial is now warranted. [source] A phase I/II study of weekly high-dose erlotinib in previously treated patients with nonsmall cell lung cancer,CANCER, Issue 5 2006Daniel T. Milton MD Abstract BACKGROUND. Preclinical studies have suggested that erlotinib at high doses may inhibit additional sites downstream of the epidermal growth factor receptor (EGFR), resulting in greater antitumor efficacy. The objective of this study was to determine the tolerability and efficacy of high-dose erlotinib administered on a weekly schedule to patients with advanced nonsmall cell lung cancer (NSCLC). METHODS. The authors conducted a Phase I/II trial of weekly erlotinib in patients with progressive NSCLC who had received previous chemotherapy. In the Phase I portion, patients were enrolled in 3-patient cohorts at erlotinib dose levels of 1200 mg, 1600 mg, and 2000 mg once weekly. The Phase II portion was designed to determine the major objective response rate of the dose identified in the Phase I portion of the trial. RESULTS. Twenty-seven patients were enrolled. No dose-limiting toxicity was observed. Grade 1 and 2 rash and diarrhea were the principle toxicities, and each occurred in 92% of patients. Among 21 patients who were treated at the Phase II dose of 2000 mg weekly, a single objective response was identified, yielding a response rate of 5% (95% confidence interval, 0.2,22%). For this cohort, the median survival was 9.5 months. The sole radiographic response occurred in a patient whose pretreatment tumor specimen harbored an EGFR exon 19 deletion. CONCLUSIONS. Erlotinib at a dose of 2000 mg administered weekly was tolerated well by these patients with advanced NSCLC. The 5% objective response rate did not reach the stated objective at the interim efficacy analysis, prompting the closure of the study. Cancer 2006. © 2006 American Cancer Society. [source] Three years' experience with infliximab in recalcitrant psoriasisCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 5 2006K. Ahmad Summary Background., In this retrospective study, we report our experience with infliximab for recalcitrant psoriasis. Methods., Twelve patients were treated between September 2001 and April 2005. Infliximab 5 mg/kg was given at 0, 2 and 6 weeks followed by 5 mg/kg at 8-week intervals. When two patients developed resistance to treatment, methotrexate was added at a dose of 5,7.5 mg weekly for all patients. Response to treatment was assessed with physician global assessment with a score of excellent, good, moderate, poor and failure. Ten patients had chronic plaque psoriasis, one had pustular palmoplantar psoriasis and one had acrodermatitis continua of Hallopeau. Results., Nine patients, including the patient with acrodermatitis continua, showed an excellent response. Two patients initially showed good response but became resistant to treatment. One patient failed to respond, and treatment was discontinued. With time, six patients with excellent response and two with good response developed side-effects that necessitated stopping treatment. Conclusions., We have found infliximab to be very impressive, both in efficacy and speed of action, in severe psoriasis. Its use, however, is limited, as it requires hospital admission and by the need for concomitant methotrexate. Because of its powerful immunosuppressive action, the possibility of activating tuberculosis and inducing lymphoma remains a concern. [source] Effects of TNF-alpha antagonism on E-selectin in obese subjects with metabolic dysregulationCLINICAL ENDOCRINOLOGY, Issue 1 2010Markella V. Zanni Summary Objective, Endothelial adhesion molecules like E-selectin play an important role in leukocyte recruitment and development of atherosclerotic plaque. E-selectin is increased in obesity, yet little is known regarding the specific factors contributing to elevated E-selectin in obesity and whether tumour necrosis factor alpha (TNF-alpha) increases E-selectin in vivo in this population. The objectives of this study were to: (1) determine the body composition, metabolic and inflammatory factors associated with increased E-selectin and (2) determine the role of TNF-alpha in the physiological regulation of E-selectin by antagonism of TNF-alpha with etanercept among obese subjects. Methods, E-selectin levels, body composition, metabolic parameters and inflammatory cytokines were assessed in 51 obese subjects and 37 non-obese healthy controls. Obese subjects were randomized to etanercept 50 mg weekly or placebo for 4 weeks. Changes in E-selectin were compared between treatment groups. Results, Obese subjects had higher E-selectin than non-obese controls (47·4 [32·7,58·8] vs. 27·2 [20·3,42·1] ng/ml, obese vs. non-obese, P < 0·0001). E-selectin was significantly associated with multiple body composition measures and metabolic parameters, along with specific measures of TNF-alpha activation, including soluble tumour necrosis factor receptors 1 (P = 0·03) and 2 (P = 0·02). In multivariate modelling, visceral adipose tissue, but not other measures of body composition, remained significantly associated with E-selectin. Among obese subjects, treatment with etanercept significantly decreased E-selectin (,5·7 ± 8·7 vs. 0·5 ± 6·0 ng/ml, etanercept vs. placebo, P = 0·005). Conclusions, E-selectin is increased in obesity, in relationship to increased visceral adiposity and markers of TNF-alpha activation. TNF-alpha antagonism with etanercept reduces E-selectin in obese subjects, providing evidence that the systemic circulatory release of E-selectin is regulated at least in part by TNF-alpha in obesity. [source] | ||||||||||||||||||||||