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A B Gottlieb

Publications and source records attributed to A B Gottlieb.

At least 19 recordsLinked to original sources
PubMed2007

Comparison of clinical and pharmacokinetic profiles of etanercept 25 mg twice weekly and 50 mg once weekly in patients with psoriasis.

BACKGROUND: Etanercept is a tumour necrosis factor antagonist that is approved in the U.S.A., Canada and Europe for treating adult patients with chronic moderate to severe plaque psoriasis. OBJECTIVES: To assess whether clinical efficacy, safety and pharmacokinetic (PK) profiles of etanercept 50 mg once weekly are comparable to etanercept 25 mg twice weekly. METHODS: Patients from a U.S. phase 3 study and a global phase 3 study were subsequently enrolled in an open-label extension study (extension study) where they all received etanercept at a dose of 50 mg once weekly for an initial 12 weeks. Patients who had received at least 24 weeks of etanercept 25 mg twice weekly in the global phase 3 study and were enrolled in the extension study (n = 265) were assessed for efficacy and safety at extension study baseline and after 12 weeks of etanercept 50 mg once weekly. Efficacy endpoints included the Psoriasis Area and Severity Index (PASI), the Dermatology Life Quality Index and the Physician's Global Assessment of psoriasis. In addition, PK profiles from patients in the U.S. phase 3 study were compared with PK profiles from another set of patients in the extension study. Comparison was made between a subset of patients receiving etanercept 25 mg twice weekly dosing in the U.S. phase 3 study (n = 13) and those receiving etanercept 50 mg once weekly in the extension study (n = 84). RESULTS: The mean PASI score was 5.77 at extension study baseline after treatment with etanercept 25 mg twice weekly, which was sustained at 5.82 after 12 weeks of etanercept 50 mg once weekly. Similar results were observed in other efficacy endpoints. Etanercept 50 mg once weekly was generally well tolerated. No new safety findings were reported. PK profiles overlapped extensively between the two dosing regimens. CONCLUSIONS: In this report, we demonstrate that efficacy, safety and PK profiles were comparable between etanercept 25 mg twice weekly and 50 mg once weekly in patients who had received at least 24 weeks of etanercept 25 mg twice weekly prior to receiving etanercept 50 mg once weekly in the extension study.

Adult↗
PubMed2005

Infliximab treatment results in significant improvement in the quality of life of patients with severe psoriasis: a double-blind placebo-controlled trial.

BACKGROUND: Psoriasis is a chronic disease that significantly diminishes the health-related quality of life (HRQOL). Infliximab is a chimeric, tumour necrosis factor alpha monoclonal antibody that has been shown to improve the signs and symptoms of plaque psoriasis. OBJECTIVES: The objective of this study was to evaluate the effect of infliximab induction therapy on the HRQOL of patients with severe plaque psoriasis. METHODS: In this double-blind, placebo-controlled trial, 249 patients were randomly assigned to receive intravenous infusions of 3 or 5 mg kg(-1) of infliximab or placebo and were treated at weeks 0, 2 and 6. Patients completed the Dermatology Life Quality Index (DLQI) at baseline and week 10. RESULTS: Infliximab induction therapy resulted in a substantial improvement in HRQOL. At week 10, patients in the infliximab 3- and 5-mg kg(-1) groups showed a median percentage improvement in DLQI scores of 84.0% and 91.0%, respectively, compared with 0% in the placebo group (P < 0.001). The median decrease from baseline in DLQI score at week 10 was 8.0 and 10.0 for the 3 and 5 mg kg(-1) infliximab groups, respectively, compared with 0 in the placebo group (P < 0.001). Thirty-three per cent and 40% of patients in the 3 and 5 mg kg(-1) infliximab groups, respectively, had a DLQI score of 0 at week 10, compared with 2% in the placebo group (P < 0.001). There was a strong correlation between the percentage change from baseline at week 10 in Psoriasis Area and Severity Index (PASI) scores and the percentage change in DLQI scores during the same period (Spearman's correlation, 0.61, P < 0.001). When the infliximab and placebo treatment groups were combined, patients with at least 75% improvement in PASI scores between baseline and week 10 had a greater mean improvement in DLQI scores (81%) than those with 50-75% improvement in PASI during the same period (60%). CONCLUSIONS: Infliximab induction therapy resulted in significant improvement in HRQOL in patients with severe psoriasis.

Adult↗
PubMed2005

Oral pimecrolimus in the treatment of moderate to severe chronic plaque-type psoriasis: a double-blind, multicentre, randomized, dose-finding trial.

BACKGROUND: There is a need for safe and effective alternative treatments for patients with moderate to severe psoriasis. OBJECTIVES: Pimecrolimus is a calcineurin inhibitor that is being investigated in oral form for the treatment of psoriasis. PATIENTS AND METHODS: A double-blind, randomized, parallel-group, dose-finding study was performed. Healthy adult outpatients with moderate to severe chronic plaque-type psoriasis (n = 143) were randomized to receive oral placebo or pimecrolimus 10 mg, 20 mg or 30 mg twice daily (b.d.) for 12 weeks. MAIN OUTCOME MEASURES: The Psoriasis Area and Severity Index (PASI) was used to assess clinical severity of psoriasis. Results were analysed at weeks 7 (primary endpoint) and 13. Safety was assessed by monitoring all adverse events, laboratory investigations (blood chemistry, urinalysis, haematology) and physical examinations. RESULTS: The change from baseline in PASI at week 7 showed a dose-dependent effect. The differences between each of the two higher doses of pimecrolimus and placebo were statistically significant (P < 0.001; ANOVA). The mean percentage decreases from baseline in PASI in the placebo group and pimecrolimus 10 mg, 20 mg and 30 mg b.d. groups at week 7 were 3.1%, 22.2%, 51.3% and 54.0%, respectively. Most adverse events were of mild or moderate severity. The only adverse event to show a dose-response relationship was a transient feeling of warmth. No clinically relevant effects on laboratory parameters were observed, and no increase in skin infection with pimecrolimus was seen. CONCLUSIONS: Oral pimecrolimus produces a dose-dependent reduction in psoriasis severity, with doses of 20 mg and 30 mg b.d. being the most effective and well tolerated.

Abdominal Pain↗
PubMed2005

Alefacept for psoriasis and psoriatic arthritis.

Alefacept is a bioengineered fusion protein of soluble lymphocyte function antigen (LFA-3) with Fc fragments of IgG1. It is marketed in many countries for the treatment of moderate to severe psoriasis. This paper reviews the data supporting the use of alefacept in psoriasis and psoriatic arthritis.

Alefacept↗
PubMed2003

Etanercept therapy in patients with autoimmunity and hepatitis C.

Accumulated data suggest that etanercept may be a therapeutic option in patients with hepatitis C and coexisting autoimmune disorders such as rheumatoid arthritis, psoriasis, psoriatic arthritis and ankylosing spondylitis. Additionally, etanercept may actually be of benefit, when used in combination with standard treatments, for hepatitis C.

Animals↗
PubMed2003

Clinical research helps elucidate the role of tumor necrosis factor-alpha in the pathogenesis of T1-mediated immune disorders: use of targeted immunotherapeutics as pathogenic probes.

Psoriasis is a life-disabling disorder in which 8-10% of patients aged 18-54 actively contemplate suicide because of their disease. Owing to the toxicity and/or inconvenience of current, FDA-approved treatments far moderate-to-severe psoriasis, they are generally used intermittently so that patients experience cycles of remission-flare-remission-flare, etc. The challenge to drug development for moderate-to-severe psoriasis is to provide safe and effective long-term management. Immunobiologics offer the hope for safe, long-term control of psoriasis because they lack targeted organ toxicity. Thus the treatment paradigm may shift from one of intermittent treatment limited by toxicity with resultant flares of disease, to one similar to that seen in diabetes or hypertension in which disease is controlled continuously. Additionally, immunobiologics may alter the natural history of psoriasis. Etanercept, which targets TNF-alpha, controls signs and symptoms and halts joint destruction in patients with psoriatic arthritis. The long-lived remissions observed after cessation of alefacept or infliximab (anti-TNF-alpha monoclonal antibody) treatment lead this author to speculate that these immunobiologics may actually alter the natural history of the cutaneous manifestations of psoriasis.

Antibodies, Monoclonal↗
PubMed2001

Betamethasone valerate foam for treatment of nonscalp psoriasis.

BACKGROUND: Although betamethasone valerate (BMV) foam, 0.12% (Luxiq, Connectics Corporation, Palo Alto, CA) is approved by the Food and Drug Administration for the treatment of corticosteroid-responsive scalp dermatoses, no data are available for its use on nonscalp psoriasis. OBJECTIVE: We evaluated the safety and efficacy of BMV foam in treating psoriatic lesions at nonscalp sites. METHODS: We conducted a randomized, double-blind, placebo-controlled, paired-comparison, split-body study of 40 patients with mild to moderate plaque-type psoriasis. Patients applied BMV foam and placebo foam twice daily for 12 weeks. RESULTS: At the end of the treatment period, 70% of patients had greater than 50% improvement of lesions on their active foam-treated side compared with 24% of patients with similar improvement on their placebo foam-treated side. Adverse effects were limited to temporary stinging, burning, or itching in several patients. Three patients (7.5%) withdrew because of stinging or itching. CONCLUSIONS: The results indicate that BMV foam is effective against nonscalp psoriasis. Twice-daily applications are well tolerated, compliance exceeds 90%, cosmetic characteristics are acceptable, and the medication may reduce the need for multiple prescriptions.

Administration, Topical↗
PubMed2001

Efficacy and safety of infliximab monotherapy for plaque-type psoriasis: a randomised trial.

BACKGROUND: Currently available treatments for moderate to severe psoriasis are either incompletely effective in some patients, or are associated with toxic effects. Since tumour necrosis factor alpha (TNF-alpha) is thought to have a role in the pathogenesis of psoriasis, we did a double-blind, randomised trial to assess the clinical benefit and safety of infliximab-a monoclonal antibody against TNF-alpha. METHODS: 33 patients with moderate to severe plaque psoriasis were randomly assigned intravenous placebo (n=11), infliximab 5 mg/kg (n=11), or infliximab 10 mg/kg (n=11) at weeks 0, 2, and 6. Patients were assessed at week 10 for the primary endpoint (score on the physician's global assessment [PGA]). Analysis was by intention to treat. FINDINGS: Of the 33 patients enrolled, three dropped out. Nine of 11 (82%) patients in the infliximab 5 mg/kg group were responders (good, excellent, or clear rating on PGA), compared with two of 11 (18%) in the placebo group (difference 64% [95% CI 20-89], p=0.0089), and ten of 11 (91%) patients in the infliximab 10 mg/kg group were responders (difference from placebo 73% [30-94], p=0.0019). The median time to response was 4 weeks for patients in both infliximab groups. There were no serious adverse events, and infliximab was well tolerated. INTERPRETATION: In this controlled trial, patients receiving the anti-TNF-alpha agent infliximab as monotherapy experienced a high degree of clinical benefit and rapid time to response in the treatment of moderate to severe plaque psoriasis compared with patients who received placebo. These findings suggest that TNF-alpha has a pivotal role in the pathogenesis of psoriasis.

Adult↗
PubMed2001

Psoriasis. Immunopathology and immunomodulation.

Biologics in development for the treatment of moderate to severe plaque-type psoriasis are discussed in this article. Immunomodulators used as therapeutic, pathogenic probes will continue to identify targets that play primary roles in the pathogenesis of psoriasis.

Antibodies, Monoclonal↗
PubMed2001

Consensus conference: acitretin in combination with UVB or PUVA in the treatment of psoriasis.

Although adjunctive treatment with retinoids in concert with either psoralen-ultraviolet A (PUVA) or ultraviolet B (UVB) phototherapy has been a treatment option for chronic, moderate to severe plaque psoriasis for nearly two decades, acitretin-UV therapy is an underutilized therapeutic modality. According to a recent member survey by the National Psoriasis Foundation, many psoriasis patients are frustrated with available treatment options, which they perceive as ineffective, inconvenient, and/or excessively conservative. Treatment of psoriasis with acitretin in concert with UVB or PUVA is emerging as a viable clinical strategy. Compared with either acitretin or UV light monotherapy alone, the combination regimen enhances efficacy and limits treatment frequency, duration, and cumulative doses. These effects translate into care that is more effective, better tolerated, more convenient, less costly, and, perhaps, safer during long-term treatment than phototherapy alone. Drawing from an extensive literature search and the expertise of its participants, this consensus conference advances clinical recommendations as well as "clinical pearls" for health providers who treat patients with chronic, moderate to severe plaque psoriasis and suggests avenues for future research.

Acitretin↗
PubMed2000

Treatment with anti-tumor necrosis factor alpha (TNF-alpha) monoclonal antibody dramatically decreases the clinical activity of psoriasis lesions.

We treated a 57-year-old woman for refractory inflammatory bowel disease with a humanized anti-tumor necrosis factor alpha monoclonal antibody (Infliximab). The patient also had a 15-year history of Crohn's disease and a 20-year history of moderate to severe psoriasis. She received a single infusion of Infliximab (5 mg/kg). Two weeks after the infusion her psoriasis had dramatically improved in appearance. To our knowledge, our case is the first reported instance of successful anti-tumor necrosis factor alpha therapy in psoriasis.

Antibodies, Monoclonal↗
PubMed2000

Two considerations for patients with psoriasis and their clinicians: what defines mild, moderate, and severe psoriasis? What constitutes a clinically significant improvement when treating psoriasis?

The definitions of psoriasis severity and clinically significant improvement in psoriasis are used to classify treatments, obtain Food and Drug Administration approval, and determine product labeling and reimbursement. The Medical Advisory Board of the National Psoriasis Foundation has addressed these issues because of their importance in the clinical trials that are conducted to gain FDA approval of indications. Narrow indications, which are without a sound rational basis, will-in this era of constant oversight by third party payers-affect physicians' ability to manage patients with psoriasis. Body surface area (BSA) is usually used to define severity for clinical trials. It is not optimal for defining psoriasis severity because there are some patients with low BSA involvement who have very severe psoriasis and some patients with high BSA involvement who have mild psoriasis. We conclude that a quality of life (QOL) standard is better than BSA measurement for identifying patients with severe psoriasis. The second issue is what defines clinically significant improvement for patients with psoriasis. Setting an arbitrarily high criterion of clinical efficacy for new psoriasis treatments will likely limit the development and approval of useful treatments. To maximize the availability of useful psoriasis treatments, it is our thesis that psoriasis treatments should be approved when they have been shown to produce a statistically significant level of improvement in well-designed clinical trials.

Humans↗
PubMed2000

Successful in vivo blockade of CD25 (high-affinity interleukin 2 receptor) on T cells by administration of humanized anti-Tac antibody to patients with psoriasis.

BACKGROUND: Daclizumab is a humanized antibody to the alpha-subunit (CD25) of the interleukin 2 (IL-2) receptor that blocks normal IL-2 binding to this receptor. Because IL-2 is a major stimulus for T-cell growth, blockade of the IL-2 receptor could be useful in treating T-cell-mediated (autoimmune) diseases. OBJECTIVE: Our purpose was to determine whether adequate concentrations of antibody were achieved in circulating blood and in psoriatic skin lesions to saturate CD25 receptors. We also intended to measure clinical effect and safety of this agent when used alone (without other immunosuppressive drugs) in psoriasis. METHODS: Nineteen patients with psoriasis in two centers received daclizumab at an initial dose of 2 mg/kg, then 1 mg/kg at weeks 2, 4, 8, and 12. To determine whether CD25 was blocked in vivo, flow cytometric studies measured (1) expression of CD25 on CD3(+) T cells derived from blood and (2) immuno-histochemistry measures of CD25(+) cells done on pretreatment and posttreatment biopsy specimens. Patients were followed up clinically with photographs and Psoriasis Area and Severity Index scores. RESULTS: This study showed a consistent blockade of CD25 in peripheral blood and tissue during the first 4 weeks of therapy while the dosing was every 2 weeks. Variable desaturation of receptors began after 4 weeks, which correlated with a reversal in disease improvement. Patients with a pretreatment Psoriasis Area and Severity Index score of less than 36 showed a mean reduction in severity by 30% at 8 weeks (P =.02). During the 16 weeks of treatment, a 44.8% decrease in expression of the IL-2 receptor alpha-subunit was found. The absolute T-cell counts were calculated and showed no significant changes during the course of the study. No significant adverse events were produced by daclizumab during this study. CONCLUSION: We therefore conclude that daclizumab is a well-tolerated agent that blocks CD25 expression in peripheral blood and skin. Furthermore, it may be useful in treating psoriasis in some patients.

Adult↗
PubMed2000

Anti-CD4 monoclonal antibody treatment of moderate to severe psoriasis vulgaris: results of a pilot, multicenter, multiple-dose, placebo-controlled study.

BACKGROUND: OKTcdr4a (IMUCLONE) is a humanized anti-CD4 IgG4 monoclonal antibody that retains the binding and in vitro immunosuppressive properties of the parent murine antibody. Psoriasis is a chronic disease for which treatment with multiple doses of monoclonal antibodies is likely to be required for adequate control. OBJECTIVE: This study was performed to test the efficacy and safety of OKTcdr4a, given in sequential courses over a period of several weeks, in the treatment of moderate to severe psoriasis vulgaris. METHODS: Twenty-eight patients (45.6 +/- 10.1 years of age) were studied, with a mean pretreatment Psoriasis Area and Severity Index (PASI) score of 18.3. In the first double-blind phase of the study, patients were randomized to receive OKTcdr4a as a 225 mg/course (low dose), 750 mg/course (high dose), or placebo divided into 3 identical infusions over a 5-day period. After 42 days, patients who met the criteria for re-treatment with OKTcdr4a were re-treated with the 750 mg/course in an open phase of the study. RESULTS: After the double-blind course of treatment, the mean PASI decreased by 11% in the placebo group, by 4% in the low-dose group, and by 17% in the high-dose group at 15 days. Twenty patients met the criteria for re-treatment (ie, did not experience a decrease in PASI score of 50% at 42 days). They were re-treated with OKTcdr4a at 43 days with the 750 mg/course in the open phase of the study. By day 99, the mean PASI score decreased from 19.9 at baseline to 17 in those patients who had received either placebo or low-dose OKTcdr4a followed by high-dose OKTcdr4a. In contrast, the mean PASI score decreased from 17.4 at baseline to only 7.7 in those patients who had received high-dose OKTcdr4a for both courses. Sustained CD4 saturation was not necessary for sustained clinical response. No patients had significant changes in circulating CD4(+) T-cell counts. The infusions were well tolerated. CONCLUSION: Targeting CD4 using sequential treatments with a humanized monoclonal antibody (OKTcdr4a) may offer another therapeutic option for the treatment of moderate to severe psoriasis.

Adult↗
PubMed2000

Concomitant administration of vitamin E does not change the side effects of isotretinoin as used in acne vulgaris: a randomized trial.

BACKGROUND: Isotretinoin treatment is frequently associated with reversible, dose-related side effects. Recent studies claimed that combining vitamin E with high-dose isotretinoin ameliorated isotretinoin-induced side effects. OBJECTIVE: The purpose of this double-blind, randomized study was to determine the effects of a fixed dose of vitamin E on the side effects of isotretinoin for treatment-resistant acne vulgaris. METHODS: One hundred forty subjects were randomly assigned to one of two treatment programs with isotretinoin (1 mg/kg) together with either vitamin E (800 IU/day) or a vitamin E placebo for 20 weeks. The incidence, severity, and duration of the side effects (eg, dry eyes, dry lips) were assessed. RESULTS: A fixed 800 IU/day dose of vitamin E did not improve the incidence, severity, or duration of side effects associated with isotretinoin (1 mg/kg per day). CONCLUSION: Vitamin E did not significantly ameliorate retinoid side effects when combined with 1 mg/kg of isotretinoin in the treatment of acne.

Acne Vulgaris↗
PubMed1998

Staphylococcal scalded skin syndrome in an immunocompetent adult: possible implication of low-dosage prednisone.

Staphylococcal scalded skin syndrome (SSSS) mainly affects infants and young children. Very few cases of adult SSSS have been reported. Adult SSSS is usually associated with immunosuppression, overwhelming sepsis, and kidney failure. We report the case of an immunocompetent 51-year-old woman without renal failure who sustained SSSS after a 7-day course of oral prednisone administered postoperatively.

Administration, Oral↗