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Biomedical subjects

Alan Menter

Publications and source records attributed to Alan Menter.

At least 19 recordsLinked to original sources
PubMed2006

A randomized comparison of continuous vs. intermittent infliximab maintenance regimens over 1 year in the treatment of moderate-to-severe plaque psoriasis.

BACKGROUND: Previous studies of infliximab in psoriasis have demonstrated rapid improvement with induction therapy and sustained response with regularly administered maintenance therapy. OBJECTIVE: The efficacy and safety of continuous (every-8-week) and intermittent (as-needed) maintenance regimens were compared. METHODS: Patients with moderate-to-severe psoriasis (n = 835) were randomized to induction therapy (weeks 0, 2, and 6) with infliximab 3 mg/kg or 5 mg/kg or placebo. Infliximab-treated patients were randomized again at week 14 to continuous or intermittent maintenance regimens at their induction dose. RESULTS: At week 10, 75.5% and 70.3% of patients in the infliximab 5 mg/kg and 3 mg/kg groups, respectively, achieved PASI 75; 45.2% and 37.1% achieved PASI 90 (vs 1.9% [PASI 75] and 0.5% [PASI 90] for placebo; P < .001). Through week 50, PASI responses were better maintained with continuous compared with intermittent therapy within each dose, and with 5 mg/kg compared with 3 mg/kg continuous therapy. LIMITATIONS: Longer term (>1 year) maintenance therapy and further study of infliximab serum concentrations over this period, in both PASI 75 responders and non-responders, would be preferable. CONCLUSIONS: Through week 50, response was best maintained with continuous infliximab therapy. Infliximab was generally well-tolerated in most patients.

Adult↗
PubMed2006

Relapse, rebound, and psoriasis adverse events: an advisory group report.

Psoriasis is a chronic disease, the severity of which varies among patients and changes unpredictably over time in individual patients. Psoriasis can be exacerbated during treatment by infection, endocrine factors, hypocalcemia, medications, psychologic stress, skin trauma, or other factors. Patients who discontinue treatments may experience a return of disease--relapse--or worsening of disease--rebound. The National Psoriasis Foundation (NPF) proposed standardized definitions of relapse and rebound. Efalizumab, a recombinant humanized immunoglobulin G-1 monoclonal antibody, is approved for the management of psoriasis. During efalizumab clinical trials, a small percentage of patients experienced protocol-defined adverse events related to psoriasis. After publication of the NPF definition of rebound, post hoc exploratory analyses of the efalizumab clinical trial data were performed. The efalizumab clinical trial investigators discussed their observations, the analyses, and their individual approaches to the treatment of patients receiving or discontinuing efalizumab therapy, the conclusions of which are described herein.

Antibodies, Monoclonal↗
PubMed2006

Tazarotene versus tazarotene plus hydroquinone in the treatment of photodamaged facial skin: a multicenter, double-blind, randomized study.

OBJECTIVES: To compare the efficacy and tolerability of tazarotene plus hydroquinone versus tazarotene alone in the treatment of facial photodamage. METHODS: Patients with facial mottled hyperpigmentation of at least moderate severity and an overall integrated assessment of photodamage score of at least moderate applied tazarotene 0.1% cream each evening and either hydroquinone 4% cream or placebo cream each morning for up to 24 weeks. RESULTS: Among 131 patients enrolled, 114/124 (92%) with exit data completed. Both regimens were highly effective in reducing photodamage, with tazarotene plus hydroquinone showing superiority over tazarotene alone for some efficacy measures. The incidence of >or=1-grade improvement from baseline (on a scale of none, minimal, mild, moderate, or severe) was significantly greater with tazarotene plus hydroquinone than with tazarotene alone for lentigines (weeks 12-24, p or=50% global improvement was also significantly superior with the combination regimen as early as week 8 (p<or=0.01). Both regimens were associated with good tolerability and high patient satisfaction (no significant between-group differences). CONCLUSIONS: The adjunctive use of hydroquinone can enhance the efficacy of tazarotene in reducing dyspigmentation associated with photodamage.

Administration, Topical↗
PubMed2006

Safety of efalizumab in adults with chronic moderate to severe plaque psoriasis: a phase IIIb, randomized, controlled trial.

BACKGROUND: To provide safety data for efalizumab, a recombinant humanized monoclonal IgG(1) 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 > or = 75% improvement in the Psoriasis Area and Severity Index (PASI) (P < 0.001), > or = 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.

Adolescent↗
PubMed2006

A review of malignancies observed during efalizumab (Raptiva) clinical trials for plaque psoriasis.

BACKGROUND: Psoriasis is a chronic, incurable immune-mediated disease. Most therapies used for moderate to severe psoriasis are immunosuppressive. Agents that depress immune function, including traditional psoriasis therapies, have been associated with an increased incidence of malignancies. Efalizumab is a recombinant monoclonal immunoglobulin G1 (IgG1) antibody approved for use in psoriasis patients. OBJECTIVES: To evaluate the incidence of malignancy in patients receiving efalizumab during clinical trials compared with placebo-treated patients, psoriasis patients from external cohorts and the general US population. METHODS: Patient data were pooled from multiple phase III placebo-controlled, open-label efalizumab clinical trials, and the incidence rate of reported malignancies was calculated as a function of patient years of observation. The results for the efalizumab-treated patients were compared with the data on psoriasis patients from insurance claims databases and a registry of events in the general population. RESULTS: The efalizumab- and placebo-treated patients had similar incidence rates of malignancy, including lymphoproliferative disease, solid tumor, malignant melanoma and nonmelanoma skin cancer. The incidence of nonmelanoma skin cancers, including basal cell carcinoma and squamous cell carcinoma, in patients receiving efalizumab or placebo was elevated relative to the external databases. CONCLUSIONS: These results suggest that efalizumab treatment does not increase a patient's risk for malignancy. The difference observed with nonmelanoma skin cancer may be due to biases introduced by the clinical trial methodology. Additional patient observation is necessary to ascertain whether a link exists between efalizumab therapy and nonmelanoma skin cancer above that normally observed in psoriasis patients.

Antibodies, Monoclonal↗
PubMed2005

Localization of PSORS1 to a haplotype block harboring HLA-C and distinct from corneodesmosin and HCR.

Psoriasis is a complex inflammatory disease of the skin affecting 1-2% of the Caucasian population. Associations with alleles from the HLA class I region (now known as PSORS1), particularly HLA-Cw*0602, were described over 20 years ago. However, extensive linkage disequilibrium (LD) within this region has made it difficult to identify the true susceptibility allele from this region. A variety of genes and regions from a 238-kb interval extending from HLA-B to corneodesmosin (CDSN) have been proposed to harbor PSORS1. In order to identify the minimum block of LD in the MHC class I region associated with psoriasis we performed a comprehensive case/control and family-based association study on 242 Northern European psoriasis families and two separate European control populations. High resolution HLA typing of HLA-A, -B and -C alleles was performed, in addition to the genotyping of 18 polymorphic microsatellites and 36 SNPs from a 772-kb segment of the HLA class I region harboring the previously described interval. This corresponded on average to one SNP every 7 kb in the candidate 238 kb region. With all tests, the association was the strongest with single markers and haplotypes from a block of LD harboring HLA-C and SNP n.9. Logistic regression analyses indicated that association seen with candidate genes from the interval such as CDSN and HCR was entirely dependent on association with HLA-Cw*0602 and SNP n.9-G alleles. The previously reported association with CDSN and HCR was observed to be due to the existence of the associated alleles lying on the most commonly over-transmitted haplotype. Rare over-transmitted haplotypes also harbored HLA-Cw*12 alleles. HLA-Cw*12 family members are closely related to HLA Cw*0602, sharing identical sequences in their alpha-2 domains, peptide-binding pockets A, D and E and all 3' introns. The introduction of a potential binding site for the RUNX/AML family of transcription factors in intron 7, is also specific to these HLA-C alleles. These variants need to be investigated further for their role as PSORS1.

Case-Control Studies↗
PubMed2005

Efficacy and safety observed during 24 weeks of efalizumab therapy in patients with moderate to severe plaque psoriasis.

OBJECTIVE: To assess the efficacy and safety of a 24-week course of efalizumab. DESIGN: Phase 3, randomized, double-blind, parallel-group, placebo-controlled 12-week study followed by a 12-week open-label study. SETTING: Outpatient dermatology clinics. Patients A total of 556 patients with moderate to severe chronic plaque psoriasis who were seeing an outpatient dermatologist were included in the study. Intervention For weeks 1 to 12, the 556 patients were randomized to receive 1 mg/kg of efalizumab weekly or placebo subcutaneously. For weeks 13 to 24, 516 of these patients received 1 mg/kg of efalizumab weekly. MAIN OUTCOME MEASURES: Proportion of patients with a 75% or greater improvement in Psoriasis Area and Severity Index (PASI-75), a 50% or greater improvement in PASI (PASI-50), static Physician's Global Assessment (sPGA) rating of minimal or clear, and improvements in Dermatology Life Quality Index (DLQI), itching scale, and Psoriasis Symptom Assessment (PSA) frequency and severity scores at weeks 12 and 24. Safety was evaluated by reviewing adverse events, laboratory parameters, vital signs, and anti-efalizumab antibodies. RESULTS: At week 12, 26.6% of efalizumab-treated patients achieved PASI-75 and 58.5% achieved PASI-50. After 24 weeks of continuous efalizumab therapy, PASI responses increased: 43.8% of patients achieved PASI-75 and 66.6% achieved PASI-50. The percentage of patients who achieved an sPGA rating of minimal or clear increased from 25.7% to 35.9%. The mean percentage of improvement in all patient-reported outcomes (DLQI, itching scale, and PSA frequency and severity scores) at week 12 was maintained at week 24 (DLQI, 49.2%; itching scale, 42.2%; PSA frequency, 47.6%; PSA severity, 47.3%). There was a decline in overall reported adverse events from weeks 1 to 12 (80.4%) to weeks 13 to 24 (63.2%) without evidence of cumulative toxic effects. Conclusion Extending efalizumab treatment from 12 to 24 weeks leads to improved efficacy and maintenance of quality of life with no evidence of cumulative toxic effects noted in patients with moderate to severe chronic plaque psoriasis.

Adult↗
PubMed2005

Extended efalizumab therapy improves chronic plaque psoriasis: results from a randomized phase III trial.

BACKGROUND: Efalizumab inhibits multiple T-cell-mediated processes. OBJECTIVE: To evaluate 12- and 24-week efalizumab therapy for psoriasis. METHODS: In this phase III, randomized, double-blind trial, 498 patients received subcutaneous 1 or 2 mg/kg/wk efalizumab or placebo for 12 weeks. Efalizumab-treated patients who achieved <75% Psoriasis Area and Severity Index improvement (PASI-75) were re-randomized to a second 12-week course of treatment. Results At week 12, 39% and 27% of efalizumab-treated patients (1 and 2 mg/kg, respectively) achieved PASI-75 (vs 2% placebo; P < .001, both dose groups). At week 24, an additional 20% of efalizumab-treated patients achieved PASI-75 (vs placebo 7%, P = .018). Efalizumab was well tolerated. CONCLUSION: Twelve-week efalizumab treatment resulted in significant improvement; extension of therapy to 24 weeks resulted in additional improvement in patients who initially had not achieved PASI-75. There were no significant changes in safety profile during weeks 13-24.

Adult↗
PubMed2005

Decision points for the initiation of systemic treatment for psoriasis.

Psoriasis has a tremendous effect on health-related quality of life. Phototherapy and systemic treatments are used for patients with more debilitating (physically and emotionally) forms of the disease. These treatments can be extremely effective but can also have potentially significant adverse effects. The decision to undertake systemic treatment of psoriasis is a complex one that requires both experience and judgment. With the recent advent of new biologic systemic drugs for moderate to severe psoriasis, the need to clarify patient candidates for systemic therapy has become very important. Here, we present a diagnostic algorithm and a formal measure, the Koo-Menter Psoriasis Instrument (KMPI), to aid in identifying patients that would benefit from systemic therapy. In addition, the KMPI can be used to document and justify treatment decisions for health care payers. While the decision to undertake systemic treatment and the choice of specific treatment plan must ultimately be made mutually by the patient and physician, these tools are designed to provide information that will be valuable in these determinations.

Algorithms↗
PubMed2005

Combining traditional agents and biologics for the treatment of psoriasis.

Psoriasis patients deserve long-term control of their disease with optimal safety. Traditional agents (methotrexate, cyclosporine, retinoids, and photochemotherapy [PUVS]), although providing excellent short-term control, may produce acute or chronic toxicities, thus limiting their usage. Dermatologists are well versed in combination and rotational therapies for psoriasis, using these and other agents. With the advent of biologic therapies (three currently approved, and others pending), the potential for safer long-term psoriasis control is being realized. A review of the literature, plus our personal experience in using combinations of traditional agents and biologics, is presented.

Acitretin↗
PubMed2005

Efalizumab: continuous therapy for chronic psoriasis.

Efalizumab is a humanised monoclonal antibody targeting the CD11a subunit of lymphocyte function-associated antigen-1, specifically developed for psoriasis. Indicated for patients with moderate-to-severe plaque psoriasis, efalizumab is FDA-approved in the US for patients aged > or = 18, as well as being approved in several other European countries. Clinical studies have proven the efficacy of efalizumab for a majority of patients, improving quality of life with continuous maintenance therapy by means of weekly subcutaneous self-injections. Controlled trials have demonstrated the safety and tolerability of efalizumab. Clinical trials have established that approximately 30% of patients can achieve a PASI-75 response within 12 weeks of initiating treatment, with further clinical benefit noted with continued therapy up to 24 and even 36 months of therapy. Efalizumab may thus potentially offer patients a safe option for long-term safe control in managing their disease.

Antibodies, Monoclonal↗
PubMed2004

The effect of psoriasis on patients' quality of life and improvements associated with alefacept therapy.

Patients with psoriasis may experience impaired psychosocial mental status regardless of their objectively defined disease severity. The objective clinical measures of disease that are commonly used to evaluate a patient's psoriasis fail to take into account the effect of psoriasis on patients' quality of life (QOL). As a result, a significant number of patients are dissatisfied with conventional treatments and are searching for new options. A high unmet need for effective and safe long-term therapies that can also improve patients' QOL exists in psoriasis. Alefacept, a selective biologic agent specifically designed for the treatment of psoriasis, provides improvement in both the physical (as measured by the Psoriasis Area and Severity Index) and mental (as measured by the Dermatology Life Quality Index) aspects of the disease. Additionally, alefacept is extremely well tolerated, with no negative effect on QOL, and the improvement in QOL are maintained off-treatment, which is consistent with its remittive effects on the disease. Alefacept helps fulfill the needs of psoriasis patients by providing efficacy, safety, off-treatment remissions, and improvement in QOL.

Alefacept↗
PubMed2004

Evaluation of safety and clinical activity of multiple doses of the anti-CD80 monoclonal antibody, galiximab, in patients with moderate to severe plaque psoriasis.

BACKGROUND: Reduction in lesional, activated T cells induces improvement in psoriatic plaques. Galiximab (IDEC-114), an IgG(1) anti-CD80 antibody, binds to CD80, a costimulatory molecule involved in T-cell activation. OBJECTIVE: A Phase I/II, multidose, multischedule, dose-finding study of galiximab to evaluate safety, pharmacokinetics, and clinical activity was conducted in 35 patients with moderate to severe plaque psoriasis. METHODS: Seven cohorts of five patients received galiximab intravenously on three different schedules at different dose levels. RESULTS: Adverse events (AEs) commonly occurred as mild and self-limiting. Improvements were observed in most cohorts without evidence of a dose response in Psoriasis Area and Severity Index (50% or greater reduction in PASI score in 40% of patients), Physician's Global Psoriasis Assessment (PGA rating of Good or above in 57% of patients), and Psoriasis Severity Scale (PSS, baseline mean of 7.6 decreased by Study Day 127 to 5.0). An association was observed between reduction in CD3(+) cell count in histologic studies and reduction in PASI score. No antibodies to galiximab were detected. CONCLUSION: Galiximab appears to be safe and well tolerated with preliminary evidence of clinical and histologic response.

Adult↗
PubMed2004

Psoriasis and its treatment with infliximab-mediated tumor necrosis factor alpha blockade.

The pathogenesis of psoriasis, a chronic immune-mediated inflammatory skin disease,involves increased concentrations and activity of several proinflammatory cytokines,including tumor necrosis factor alpha (TNF-alpha). Infliximab is a chimeric human-murine TNF-alpha antibody that selectively blocks the activity of TNF-alpha. In controlled clinical trials, infliximab treatment has produced rapid and sustained improvements in psoriasis lesions and psoriatic joint involvement, with a favorable short-term safety and tolerability profile. Treatment with infliximab may be associated with an increased risk of infection or infusion reaction: however, the side-effect profile of infliximab in patients with psoriasis remains to be fully characterized, and assessment of infliximab in this population is currently ongoing in phase 3 studies. Comprehensive evaluation in controlled trials may allow infliximab to take its place among the expanding group of biologic drugs for the treatment of moderate to severe psoriasis.

Antibodies, Monoclonal↗