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Biomedical subjects

Gerald G Krueger

Publications and source records attributed to Gerald G Krueger.

At least 19 recordsLinked to original sources
PubMed2006

Effect of infliximab therapy on employment, time lost from work, and productivity in patients with psoriatic arthritis.

OBJECTIVE: To examine the effect of infliximab on employment status, time lost from work, and productivity in a double-blind, placebo-controlled study of patients with active psoriatic arthritis (PsA). METHODS: Two hundred adult patients with PsA were randomized to intravenous infusions of either infliximab 5 mg/kg or placebo at Weeks 0, 2, 6, 14, and 22, with early escape at Week 16. Employment status, workdays missed, and productivity were assessed at baseline and at Week 14. The effect of PsA on daily productivity was assessed using a visual analog scale. RESULTS: At baseline, similar percentages of patients in both treatment groups were employed and similar percentages missed workdays; the mean productivity score at baseline was similar between groups (roughly 3 on a scale of 0 to 10). At Week 14, median productivity increased significantly in the infliximab group compared with the placebo group (67.5% vs 9.2%; p < 0.0001). Compared with the placebo group, higher proportions of patients in the infliximab group improved employment status from unemployed at baseline to employed at Week 14 (11.5% vs 0%; p = 0.084) and from part-time to full-time employment (30.0% vs 10.0%; p = 0.582). Among patients employed at baseline and Week 14, a lower proportion of patients in the infliximab group than in the placebo group had missed workdays in the 4 weeks prior to Week 14 (p = 0.138). CONCLUSION: After 14 weeks of treatment, infliximab improved productivity in patients with active PsA. There was also a trend toward increased employment and reduced time lost from work for patients treated with infliximab.

Adult↗
PubMed2006

Observations of psoriasis in the absence of therapeutic intervention identifies two unappreciated morphologic variants, thin-plaque and thick-plaque psoriasis, and their associated phenotypes.

Psoriatic plaque thickness is a clinical measure of psoriasis severity. We have observed that patients tend to revert to a baseline thickness of psoriatic plaques when in an untreated state, and hypothesized that other features of psoriasis could associate with this trait. Data prospectively collected on 500 participants in the Utah Psoriasis Initiative were used for the study. In response to a question assessing plaque thickness when disease was at its worst, 144 (28.8%) reported thick plaques, 123 (24.6%) reported thin plaques, and 233 (46.6%) reported intermediate thickness. For patients with "worst-ever" disease at enrollment (n=122), there was significant correlation of thickness between assessment by the patient and the physician (r=0.448, P-value 0.01). Thick plaques associated with male gender, increased body mass index, nail disease, psoriatic arthritis, larger plaques, more body sites, and greater total body surface area affected. Thin plaques associated with eczema, guttate psoriasis, and skin cancer. We suggest that this is preliminary evidence that plaque thickness is an easily measured trait that associates with other clinical features of psoriasis, and that stratification on this phenotype may be useful in further defining the genetic basis of this disease.

Adult↗
PubMed2006

An analysis of select pathogenic messages in lesional and non-lesional psoriatic skin using non-invasive tape harvesting.

We report the use of non-invasive tape stripping to sample psoriatic lesional and non-lesional skin in 96 patients. The procedure was well tolerated with any discomfort described as mild; we did not observe any cases of Koebner phenomena at any non-lesional tape-stripped sites. Tape-harvested epidermis was extracted for RNA, which was profiled by semiquantitative reverse transcriptase-PCR. This analysis revealed that mRNAs for tumor necrosis factor alpha, IFNgamma, Krt-16, CD2, IL-23A, IL-12B, and vascular endothelial growth factor are overexpressed in the "average" psoriatic lesion in a majority of patients. In addition, 10 of these patients were biopsied at lesional and non-lesional sites and the expression data compared to tape-stripping data. This comparison shows that five of seven mRNA are more highly expressed in cells captured by tape stripping than biopsy, suggesting that the upper aspect of a lesion contains cells very active in the disease. The tape-harvesting data reveal that approximately 46% of lesions have at least one pathogenic mRNA within non-lesional skin limits. Data demonstrate that tape stripping reveals mRNA markers not detected in biopsy samples and thus the method may be a useful supplement to biopsy.

Biopsy↗
PubMed2006

Patients with psoriasis respond to continuous open-label etanercept treatment after initial incomplete response in a randomized, placebo-controlled trial.

BACKGROUND: Etanercept provides rapid, significant improvement in psoriatic symptoms and disease. OBJECTIVE: The effectiveness of continued etanercept treatment beyond 24 weeks in patients who initially did not achieve at least a 50% improvement from baseline in the Psoriasis Area and Severity Index (PASI 50) was assessed. METHODS: Patients with moderate to severe plaque psoriasis received 50 mg open-label, subcutaneous etanercept per week after completing blinded therapy with placebo or 1 of 3 doses of etanercept. The PASI was measured. RESULTS: Irrespective of prior dosing regimens, 43% of 157 patients who did not attain PASI 50 responses at week 24 achieved PASI 50 responses at week 36; 55% achieved PASI 50 responses at week 60. Etanercept was safe and well tolerated. LIMITATIONS: Interpretation of these results is limited by the open-label design of the analysis. CONCLUSION: More than half of patients who initially had an inadequate response to treatment achieved satisfactory responses with continued etanercept therapy. The safety profile of etanercept in these patients and in patients who had more immediate responses was similar.

Adult↗
PubMed2005

Impact of obesity and smoking on psoriasis presentation and management.

OBJECTIVE: To study the impact of obesity and smoking on psoriasis. DESIGN: Cross-sectional study. SETTING: University of Utah Department of Dermatology clinics. PATIENTS: A case series of patients with psoriasis enrolled in the prospective Utah Psoriasis Initiative (UPI) (which carefully performs phenotyping of patients with psoriasis) was compared with 3 population databases: the Behavioral Risk Factor Surveillance System of the Utah population, the 1998 patient-member survey from the National Psoriasis Foundation, and 500 adult patients who attend our clinics and do not have psoriasis (non-psoriatic population). RESULTS: The prevalence of obesity in patients within the UPI population was higher than that in the general Utah population (34% vs 18%; P<.001) and higher than that in the non-psoriatic population attending our clinics. Assessment of body image perception with a standardized diagram in the UPI group resulted in the median body image score of normal weight at 18 years of age and the onset of psoriasis, but it changed to overweight at the time of enrollment in the UPI. Thus, obesity appears to be the consequence of psoriasis and not a risk factor for onset of disease. We did not observe an increased risk for psoriatic arthritis in patients with obesity; furthermore, obesity did not positively or negatively affect the response or the adverse effects of topical corticosteroids, light-based treatments, and systemic medications. The prevalence of smoking in the UPI population was higher than in the general Utah population (37% vs 13%; P<.001) and higher than in the non-psoriatic population (37% vs 25%; P<.001). We found a higher prevalence of smokers in the obese population within the UPI than in the obese population within the Utah population (25% vs 9%; P<.001). CONCLUSIONS: Patients with psoriasis attending the University of Utah Dermatology Clinics were more likely to be obese and to smoke compared with non-psoriatic patients and more likely to be obese compared with other large cohorts with psoriasis. Smoking appears to have a role in the onset of psoriasis, but obesity does not. The high prevalence of obesity and smoking in a psoriasis cohort has not been previously noted; if confirmed, it supports the prediction that a significant portion of patients with psoriasis will have the comorbid conditions and public health issues of those with obesity and smoke.

Adrenal Cortex Hormones↗
PubMed2005

An integrated analysis of thirteen trials summarizing the long-term safety of alefacept in psoriasis patients who have received up to nine courses of therapy.

BACKGROUND: Information on longer-term safety and tolerability is needed to confidently prescribe alefacept therapy for chronic plaque psoriasis beyond 1 or 2 courses. OBJECTIVE: The aim of this work was to further examine the safety profile of alefacept by integrating data from clinical trials involving patients with chronic plaque psoriasis who received up to 9 courses of therapy over a 5-year period. METHODS: Data from 13 clinical trials conducted in patients with plaque psoriasis were integrated because they had similar inclusion/exclusion criteria and assessments. Patients who enrolled in the analyzed trials were aged > or =15 years with chronic plaque psoriasis for > or =12 months that involved > or =10% of body surface area, and CD4+ T lymphocyte counts above the lower limit of normal (>404 cells/microL). The incidences of adverse events (AEs), serious AEs, discontinuations for AEs, infections, serious infections, malignancies, and anti-alefacept antibodies were summarized for each course of alefacept. The incidence of infections was stratified according to CD4+ T lymphocyte counts (<250 cells/microL vs > or =250 cells/microL). RESULTS: Data from 13 clinical trials of alefacept were integrated and summarized (multicenter, randomized, double-blind studies, n = 6; multicenter, open-label studies, n = 5; other, n = 2). The analyzed population (n = 1869) included 1291 (69.1%) men and 578 (30.9%) women, between the ages of 15 and 84 years (mean, 44.8 years), of whom 1648 (88.2%) were white. Weights ranged from 40 kg to 206 kg (mean, 90.0 kg). A total of 1369 of these patients had been included in a previous analysis. Among the most commonly reported AEs in each treatment course were headache (0%-14.2%), nasopharyngitis (7.7%-25.0%), influenza (0%-8.1%), upper respiratory tract infection (0%-12.5%), and pruritus (0%-7.5%). The rates of discontinuations due to AEs (0%-4.8%), serious AEs (0%-4.8%), serious infections (0%-0.9%), or malignancies (0%-4.8%) did not appear to increase with repeated exposure. Fewer than 1 % of patients in each course developed a serious infection. No opportunistic infections or infection-related deaths were reported. The incidence of infections appeared to be unrelated to CD4+ T lymphocyte counts. Fewer than 2.5% of patients tested positive for anti-alefacept antibodies during any course of therapy. CONCLUSIONS: This integrated analysis of data from 13 trials with 1869 patients supports the safety and tolerability of alefacept for longer-term treatment of psoriasis.

Adolescent↗
PubMed2005

A multicenter, randomized, double-blind trial of tazarotene 0.1% cream in the treatment of photodamage.

BACKGROUND: Previous studies indicate that tazarotene is efficacious in reducing signs of photodamage. Objective We sought to confirm the efficacy and tolerability of tazarotene 0.1% cream in the treatment of facial photodamage. METHODS: A total of 568 patients with at least moderate fine wrinkling or mottled hyperpigmentation applied tazarotene 0.1% cream or vehicle cream to their face once daily for 24 weeks. RESULTS: Tazarotene cream was significantly more effective than vehicle in reducing fine wrinkles, mottled hyperpigmentation, lentigines, irregular depigmentation, apparent pore size, elastosis, tactile roughness, and an overall integrated assessment of photodamage. Significance was achieved as early as week 2 for some parameters and had not plateaued by week 24. The majority of patients reported improvements in their photodamage as early as week 4. Adverse events were predominantly mild or moderate signs or symptoms of skin irritation. CONCLUSION: Once-daily tazarotene 0.1% cream is effective in ameliorating multiple signs of facial photodamage.

Adult↗
PubMed2005

Etanercept improves the health-related quality of life of patients with psoriasis: results of a phase III randomized clinical trial.

In this randomized, double-blind, phase III trial, patients with psoriasis received etanercept for 24 weeks or placebo for 12 weeks followed by etanercept for 12 weeks. At week 12, improvement in Dermatology Life Quality Index was 47% to 61% with etanercept compared with 11% with placebo (P < .0001). Etanercept rapidly and substantially improved patients' health-related quality of life.

Adult↗
PubMed2004

The remittive effects of alefacept.

The duration of response to treatment with alefacept has been assessed in patients with moderate to severe chronic plaque psoriasis who responded to alefacept therapy in phase 2 and phase 3 clinical studies. In a phase 2 trial, duration of response was based on time to retreatment with alefacept. In two phase 3 studies, the more objective measure of maintenance of a > or =50% reduction from baseline Psoriasis Area and Severity Index (PASI 50) was used. Two patient subsets were analyzed: (1) those who achieved a PASI 75 at any time during the trials and (2) those who achieved a Physician Global Assessment of "clear" or "almost clear" at any time during the trials. Regardless of the criterion used or the route of alefacept administration (intravenous or intramuscular), the median duration of response to alefacept therapy ranged from 7 to 10 months across the three studies. Alefacept is a remittive therapy for psoriasis.

Alefacept↗
PubMed2004

Current concepts and review of alefacept in the treatment of psoriasis.

Alefacept is a novel biologic agent that selectively targets the memory T-cell population involved in the pathogenesis of psoriasis. Alefacept, administered by intramuscular (IM)or intravenous (IV) bolus injection, is safe and efficacious and improves quality of life ina broad spectrum of psoriasis patients. Disease remissions last approximately 7 months in responders following either IM or IV administration without further treatment. In clinical studies, treatment of patients with psoriasis with up to six courses of alefacept demonstrates the following: no evidence of an increased risk for infection or malignancy;no correlation between rates of infection, malignancy, and circulating CD4+ /CD8+ T-cell counts; and low immunogenicity. A preliminary study evaluating the use of alefacept for the treatment of active psoriatic arthritis parallels the psoriasis experience and supports the premise of targeting T cells as an intervention for this disease. Research continues to examine the use of alefacept in combination with other systemic psoriasis therapies and phototherapy and its potential as a treatment for other T-cell-mediated diseases, such as psoriatic arthritis, alopecia areata, and rheumatoid arthritis.

Alefacept↗
PubMed2004

A 50% reduction in the Psoriasis Area and Severity Index (PASI 50) is a clinically significant endpoint in the assessment of psoriasis.

A 75% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI 75) is the current benchmark of primary endpoints for most clinical trials of psoriasis. Many consider this endpoint to be too stringent as it places potentially useful therapies at risk of failing to demonstrate efficacy. We hypothesized that a 50% reduction in the PASI score (PASI 50) represents a meaningful change in a person's life and thus is a better primary endpoint. To test this hypothesis, we analyzed PASI scores, quality of life (QoL) data, and desired re-treatment scores from a number of clinical trials in addition to studying individual elements that make up the PASI. This analysis shows (1). the PASI score is not linearly reflective of psoriasis severity (eg, a reduction in area of 95% without a change in redness, scaliness, and induration translates to only a 66% reduction in PASI); conversely, a drop in erythema, scale, and induration from an average of 3 to 1 would not lead to a 75% reduction in PASI; (2). treatment with methotrexate, an effective psoriasis therapy, more frequently reaches PASI 50 than PASI 75 as evidenced by a recent open trial in which 63% of patients achieved PASI 50 versus 26% achieving PASI 75; (3). improvement in QoL exists at PASI 50, using the Dermatology Quality of Life Index, as documented in several recently completed large clinical trials; (4). patients achieving PASI 75 frequently defer therapy until they are well below PASI 50; a clinical trial where retreatment was patient initiated showed patients did not re-treat until their PASI dropped to an average of 20% improvement from baseline; and (5). effective, meaningful therapies are consistently differentiated from placebo at PASI 50 as evidenced by histologic and photographic parameters of clinical trials of alefacept, efalizumab, and etanercept. We conclude that PASI 50 equates to a clinically meaningful improvement in psoriasis and represents a discerning primary endpoint.

Humans↗
PubMed2004

FGF-7 expression enhances the performance of bioengineered skin.

To improve the performance of bioengineered skin, we used a recombinant retrovirus encoding FGF-7 to modify diploid human keratinocytes genetically. Control or FGF-7-expressing keratinocytes were seeded onto acellular human dermis to form bioengineered skin. Gene-modified skin secreted significant levels of FGF-7 and formed a thicker and hyperproliferative epidermis with about four times the number of cells per square centimeter. Secretion of an endogenous trophic factor, VEGF, was increased approximately 5-fold. Migration of FGF-7-expressing keratinocytes was stimulated as was the self-healing of bioengineered skin expressing FGF-7. When tested in a bacterial infection model, the antimicrobial properties of FGF-7-expressing skin were increased >500-fold against both gram-negative and gram-positive bacteria. After transplantation to full-thickness wounds on athymic mice, skin expressing FGF-7 was revascularized more rapidly. These results demonstrate that genetic modification can be used to enhance performance and that expression of FGF-7 augments several properties important to the wound-healing properties of bioengineered skin.

Animals↗
PubMed2004

Seborrheic keratoses: a study comparing the standard cryosurgery with topical calcipotriene, topical tazarotene, and topical imiquimod.

BACKGROUND: Patients with seborrheic keratoses frequently desire an effective topical therapy for seborrheic keratoses. OBJECTIVE: To compare topical calcipotriene, topical tazarotene, and topical imiquimod with standard cryosurgery in the treatment of seborrheic keratoses. METHODS: Fifteen patients with numerous seborrheic keratoses were enrolled in an open-label study comparing cryosurgery with topical agents. Eight separate seborrheic keratoses were selected to be treated with topical medications. One lesion was treated with cryosurgery. RESULTS: One treatment with cryosurgery led to clinical and histological improvement of all lesions treated. Neither scarring nor recurrence resulted in cryosurgery. In seven of 15 patients, tazarotene 0.1% cream applied BID caused clinical improvement in lesions within 16 weeks. CONCLUSION: Cryosurgery produces clinical and histological improvement of seborrheic keratoses. The result with cryosurgery was cosmetically acceptable to all patients. Responders to tazarotene cream 0.1% found it cosmetically acceptable.

Adjuvants, Immunologic↗
PubMed2004

Alefacept: a novel biologic in the treatment of psoriasis.

Recognition of psoriasis as a T-cell-mediated immune disease has led to the development of various therapeutic approaches directed against the T cell and T-cell processes such as activation, trafficking and cytokine release. The novel and selective biologic agent alefacept, with an effect of selective apoptotic reduction in memory-effector T cells, has been given FDA approval for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy. The clinical profile of this novel biologic agent is presented here. Two pivotal multicenter, randomized, placebo-controlled, double-blind studies enrolling 1060 patients were designed to support the efficacy and safety of alefacept in the treatment of moderate to severe chronic plaque psoriasis. With either intramuscular or intravenous administration, well over half of patients treated with a single course of alefacept achieved a 50% reduction in PASI (Psoriasis Area and Severity Index), and a second course of therapy provided further benefit by increasing response rates and providing long-lasting off-treatment responses regardless of the route of administration. In all studies, alefacept was well tolerated. There was no evidence of an increased risk of infections or malignancies and no opportunistic infections were reported. Consistent with its composition as a fully human fusion protein, alefacept had a low incidence of immunogenicity and no evidence of an increased rate of antibody development over time. There was no evidence that primary or secondary responses to a new antigen or memory response to a recall antigen were blunted in patients treated with alefacept. In conclusion, alefacept is the first biologic therapy to demonstrate positive effects in an immune-mediated disease while maintaining immune responses to novel and recall antigens. This selective effect on the immune system distinguishes alefacept from immunosuppressive therapies that are nonselective.

Alefacept↗
PubMed2003

A randomized trial of etanercept as monotherapy for psoriasis.

OBJECTIVE: To determine safety and efficacy of monotherapy with etanercept. DESIGN: Randomized, double-blind, placebo-controlled, multicenter study. SETTING: Outpatient, ambulatory; private practice and university dermatology research centers. PATIENTS: Patients aged at least 18 years, with plaque psoriasis involving 10% or more of body surface area; 148 were screened and 112 were randomly assigned to treatment groups and received study drug. INTERVENTIONS: Patients received placebo or etanercept, 25 mg, subcutaneously twice a week for 24 weeks. Other psoriasis therapies were limited during the study. MAIN OUTCOME MEASURES: Safety measurements included tracking of adverse events and laboratory values. Efficacy was evaluated using the Psoriasis Area and Severity Index (PASI); the primary end point was a 75% improvement in PASI. Other efficacy measurements included patient and physician global assessments and quality-of-life measures. RESULTS: After 12 weeks of treatment, 17 (30%) of the 57 etanercept-treated patients and 1 (2%) of the 55 placebo-treated patients had achieved PASI 75%, and after 24 weeks, 32 (56%) of etanercept-treated patients and 3 (5%) of placebo-treated patients had reached this level (P<.001 for both time points). By 24 weeks, psoriasis was clear or minimal by physician's global assessment in more than 50% of patients who received etanercept. Treatment failure (PASI response <50) occurred in 23% of patients at week 24. All other measures confirmed the efficacy of etanercept. Adverse events were similar among etanercept and placebo groups. CONCLUSION: Etanercept monotherapy provided significant benefit to patients with psoriasis and had a favorable safety profile.

Adolescent↗
PubMed2003

Efficacy of acitretin and commercial tanning bed therapy for psoriasis.

OBJECTIVE: To assess the efficacy of acitretin and commercial tanning bed therapy for the treatment of moderate to severe chronic plaque-type psoriasis. DESIGN: Retrospective medical record review and telephone survey of subjects and prospective open-label trial. SETTING: University dermatology clinic. PATIENTS: The study population comprised 26 subjects in the retrospective study and 17 subjects in the prospective study, all with moderate to severe plaque-type psoriasis. INTERVENTION: Twelve weeks of daily oral acitretin (25 mg) therapy and commercial tanning bed UV exposure (mean UV-B output of 4.7%) for 4 to 5 days per week. RESULTS: In the retrospective review, 19 (83%) of 23 subjects had clearance or near clearance, 2 (9%) of 23 had moderate improvement, and 2 (9%) of 23 had no improvement. Patients reported a high degree of satisfaction with the treatment. In the prospective trial, the Psoriasis Area and Severity Index (PASI) and National Psoriasis Foundation scores decreased an average of 78.6% and 79.0% from baseline, respectively. A reduction from baseline in the PASI score of 50% and 75% (PASI 50 and PASI 75) was achieved by 13 (76%) and 10 (59%) patients, respectively. Adverse events were generally mild to moderate. CONCLUSIONS: Acitretin use in combination with commercial tanning bed therapy appears to be effective and useful for psoriasis in areas without access to physician-directed phototherapy. The variability of tanning salon light and quality mandates caution when using this therapy.

Acitretin↗