Psoriasis: Kimball AB

Kimball AB, Gladman D, Gelfand JM, Gordon K, Horn EJ, Korman NJ, Korver G, Krueger GG, Strober BE, Lebwohl MG, Anonymous00020. · Department of Dermatology, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts 02114, USA. · J Am Acad Dermatol. · Pubmed #18313171 No free full text.

Abstract: There have been several articles and reports in recent months about comorbidities and risks that affect psoriasis patients in addition to their underlying disease. This piece reviews the current literature and begins to address what should be done with this new information by updating the clinician about what health screening tests, preventative exams, and referrals should be considered in this population.

Kimball AB, Kupper TS. · Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02114, USA. · Clin Dermatol. · Pubmed #18755375 No free full text.

Abstract: Advances in the understanding and treatment of psoriasis in the past several years have been remarkable. New frontiers include better understanding the immunologic pathways that underlie the disease and the development of personalized strategies to maximize the benefit and minimize the risk for patients. Although a cure may not be imminent, there are some strategies under examination that may lead us closer to this goal.

Frangos JE, Kimball AB. · The Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA. · Expert Opin Pharmacother. · Pubmed #18627337 No free full text.

Abstract: BACKGROUND: Topical corticosteroids are the most common treatment modality for patients with psoriasis and atopic dermatitis; however, the efficacy of topical corticosteroids is often hampered by barriers to patient adherence, such as lack of efficacy, side effects and inconvenience. Recently published studies have investigated the safety and efficacy of a novel emollient foam (EF) formulation of clobetasol propionate (CP), a class I topical corticosteroid in psoriasis and atopic dermatitis. OBJECTIVES: To summarize recent literature on CP EF foam, and to evaluate recent Phase II and III clinical trials of CP EF foam in psoriasis and atopic dermatitis. METHODS: The MEDLINE (1950 - January 2008) database was searched using the following terms: 'clobetasol propionate foam', 'topical corticosteroids', 'topical glucocorticoids', 'psoriasis' and 'atopic dermatitis'. Results were evaluated for relevance and quality, and additional references were obtained from bibliographies of selected articles. CONCLUSION: CP EF foam appears to be safe and effective for corticosteroid-responsive dermatoses in adults and children > or = 12 years of age. As compared to its hydroethanolic foam predecessor, CP EF presents a potential advance for patients who are less likely to tolerate alcohol-based foam. As alcohol-based foams can be irritating and cause stinging in non-hair-bearing areas, this new emollient formulation has the potential to widen the use of CP foam to more patients with atopic dermatitis and to more non-scalp body sites in patients with psoriasis.

Boker A, Kimball AB, Rolz-Cruz G. · Brigham and Women's Hospital, Massachusetts General Hospital, Department of Dermatology, Harvard Medical School, 50 Staniford Street #240, Boston, MA 02114, USA. · Curr Opin Investig Drugs. · Pubmed #17979028 No free full text.

Abstract: Psoriasis is a chronic inflammatory skin disorder that can cause substantial disability. The recognition of psoriasis as an immunologically mediated disease led to the development of agents that specifically target key steps in the pathological process. This review focuses on these biological agents, and presents results from phase II and III clinical trials together with the safety profile and approved indications for alefacept, efalizumab, etanercept, infliximab and adalimumab. Preliminary safety and efficacy data for the newer therapeutic agents, such as CNTO-1275 and ABT-874, are also described.

Ciocon DH, Kimball AB. · Division of Dermatology, Albert Einstein College of Medicine, 1400 Pelham Parkway, South Bronx, NY 10461, USA. · Br J Dermatol. · Pubmed #17725671 No free full text.

Abstract: The presence and severity of skin and joint symptoms in patients with psoriasis and psoriatic arthritis frequently do not correspond, a discrepancy that has raised the question of whether they represent two related but different disease processes. The fact that some agents seem to work preferentially in one state over the other reinforces this idea. However, there are also several agents with combined efficacy against cutaneous and articular inflammation that appear to support the existence of a common aetiology. Here we review the clinical, epidemiological and genetic evidence for and against a common pathogenesis for the two diseases. We then discuss the cellular and molecular targets of their selected therapies and how they potentially implicate effector pathways as a common immunopathogenic mechanism. Finally, we examine a recently proposed model of psoriasis pathogenesis involving type 1 interferon-producing plasmacytoid dendritic cells and how it may provide further clues to the aetiological links between psoriasis and psoriatic arthritis.

Kimball AB, Jacobson C, Weiss S, Vreeland MG, Wu Y. · Harvard Medical School, Boston, Massachusetts, USA. · Am J Clin Dermatol. · Pubmed #16343026 No free full text.

Abstract: BACKGROUND: Skin diseases such as psoriasis can profoundly influence a patient's self-image, self-esteem, and sense of well-being. Psoriasis is a multifactorial inflammatory condition with a disease burden that extends beyond the physical symptoms experienced by patients. Psoriasis affects all aspects of quality of life, including physical, psychologic, social, sexual, and occupational elements. OBJECTIVE: The goal of this article was to review the published literature on the impact of psoriasis on quality of life. METHODS: Relevant studies were identified through a comprehensive search of MEDLINE, EMBASE, and the Derwent Drug File databases of English-language articles published between 1993 and 2005 using the terms psoriasis in combination with quality of life, cost, cost-benefit analysis, economic, employment, days lost, healthcare, hospitalization, managed care, outcomes research, occupation, payers, and psychosocial. The reference lists of identified articles were checked for additional studies that might have been missed in the original searches. RESULTS: Data suggest that social stigmatization, high stress levels, physical limitations, depression, employment problems and other psychosocial co-morbidities experienced by patients with psoriasis are not always proportional to, or predicted by, other measurements of disease severity such as body surface area involvement or plaque severity. CONCLUSION: It is essential to include measures of psychosocial morbidity when assessing psoriasis severity and treatment efficacy because of the substantial role that psychosocial burden plays in patient perception of disease severity, quality of life, and disease course.

Reid DC, Kimball AB. · Harvard Medical School, Clinical Unit for Research Trials in Skin, Massachusetts General Hospital, 275 Cambridge Street, Professional Office Building, 402, MA, USA. . · Expert Opin Pharmacother. · Pubmed #16086659 No free full text.

Abstract: Psoriasis is a common, chronic, distressing skin disorder that frequently affects the scalp, skin, nails and joints. Despite treatment, many patients suffer from unremitting disease and decreased quality of life. Scalp-type psoriasis is particularly difficult to treat. Although topical corticosteroids are the mainstay of therapy for moderate-to-severe disease, patients frequently object to the messiness and unfavourable cosmetic appearance of topical treatments. In this context, foam vehicles, which have the advantage of minimal residue and increased ease of application, have emerged as novel alternatives to traditional creams, ointments and solutions. Clobetasol propionate foam 0.05% (OLUX, Connetics Corporation), a high potency topical steroid, has been shown to alleviate symptoms of several dermatological conditions, including scalp and body psoriasis, improve disease severity and increase quality of life. Dose should be limited to 50 g/week, given the risk of adrenal suppression. Because patient preference is an important determinant of medication efficacy in clinical practice, clobetasol foam is a useful new formulation in the treatment of psoriasis and other skin conditions.

Weiss SC, Bergstrom KG, Weiss SA, Kimball AB. · Department of Dermatology, Stanford University Medical Center, Stanford, CA, USA. · Dermatol Nurs. · Pubmed #12751346 No free full text.

Abstract: Psoriasis can have a profound impact on a patient, interfering in all aspects of life. Therefore, measuring the impact of disease and the effects of treatment must include both physiologic measurements as well as health-related quality of life tools. Psychosocial evaluation of patients at risk allows for early interventions that will promote positive patient outcomes and compliance with the treatment pathways.

Kimball AB, Gold MH, Zib B, Davis MW, Anonymous00348. · Clinical Unit for Research Trials in Skin, Massachusetts General and Brigham and Women's Hospitals, Harvard Medical School, Boston, Massachusetts. · J Am Acad Dermatol. · Pubmed #18539358 No free full text.

Abstract: BACKGROUND: Clobetasol propionate 0.05% emulsion foam was recently developed for use on multiple body sites. OBJECTIVE: We sought to evaluate safety and efficacy of clobetasol emulsion foam 0.05% to treat steroid-responsive dermatoses in multiple age groups. METHODS: A phase II open-label study evaluated the effect of clobetasol foam on the hypothalamic-pituitary-adrenal axis in 52 participants aged 6 years or older with mild-to-severe atopic dermatitis (AD). Cosyntropin stimulation test was used to determine the effect of clobetasol foam on hypothalamic-pituitary-adrenal axis, with a normal response considered to be a postinjection serum cortisol level greater than 18 mug/dL. Another phase II open-label pharmacokinetic safety study was conducted in 32 participants aged 12 years or older with mild-to-moderate plaque-type psoriasis. Pharmacokinetic parameters evaluated included maximal plasma concentration of clobetasol propionate, time to achieve maximum concentration, and area under the curve. Two phase III, randomized controlled studies assessed treatment success in participants aged 12 years or older with moderate-to-severe AD (N = 377) or mild-to-moderate plaque-type psoriasis (N = 497). In all studies, participants received study drug for 2 weeks. In the AD study, treatment success was determined using a composite end point requiring an Investigator's Static Global Assessment (ISGA) score of 0 or 1, erythema score of 0 or 1, induration/papulation score of 0 or 1, and improvement in the ISGA score of at least two grades from baseline. Likewise, the study in plaque-type psoriasis used a composite end point requiring an ISGA score of 0 or 1, erythema score of 0 or 1, scaling score of 0 or 1, plaque thickness score of 0, and improvement in the ISGA score of at least two grades from baseline. RESULTS: Significantly more participants achieved treatment success on clobetasol foam than vehicle foam (P < .0001 and P = .0005 for each study). Reversible hypothalamic-pituitary-adrenal axis suppression was observed in 27% of participants aged 18 years or older and 47% in participants aged between 6 and younger than 12 years, but 0% in participants aged between 12 and younger than 18 years. LIMITATIONS: The studies evaluated short-term use only. CONCLUSION: Clobetasol emulsion formulation foam is safe and effective for treatment of moderate-to-severe AD and mild-to-moderate plaque-type psoriasis in patients aged 12 years or older.

Gelfand JM, Kimball AB, Mostow EN, Chiou CF, Patel V, Xia HA, Freundlich B, Stevens SR. · Department of Dermatology and Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA. · Value Health. · Pubmed #18489665 No free full text.

Abstract: OBJECTIVE: The 24-week Etanercept Assessment of Safety and Effectiveness (EASE) study evaluated the effectiveness and tolerability of continuous versus interrupted etanercept treatment in patients with moderate to severe plaque psoriasis. The objective of this analysis was to assess patient-reported outcomes (PROs) and health-care resource utilization (HRU) data from the EASE study. METHODS: Patients received open-label etanercept 50 mg twice weekly for 12 weeks and then received either continued or interrupted (single round of discontinuation and re-treatment with etanercept) etanercept 50 mg once weekly for the second 12 weeks. PROs included the following: 1) the patient global assessments of psoriasis, joint pain, and itching scores; 2) the Dermatology Life Quality Index; 3) the Medical Outcomes Study Short Form 36 vitality domain; 4) the Beck Depression Inventory; 5) the European Quality-of-Life Group Feeling Thermometer; and 6) a patient satisfaction survey. HRU was evaluated using the Economic Implications of Psoriasis patient questionnaire. RESULTS: Continuous treatment with etanercept 50 mg twice weekly for 12 weeks followed by 50 mg once weekly for 12 weeks produced sustained and clinically important improvements in PROs and reductions in HRU. Reductions in some outcome measures after treatment discontinuation at week 12 were observed in the interrupted group; however, most changes did not revert to baseline levels, consistent with some residual clinical effect, and re-treatment produced improvements similar to week 12 levels. CONCLUSIONS: Continuous etanercept treatment provided greater sustained improvements in PROs than interrupted therapy; however, interrupting etanercept therapy, if needed, has predictable and manageable effects.

Leonardi CL, Kimball AB, Papp KA, Yeilding N, Guzzo C, Wang Y, Li S, Dooley LT, Gordon KB, Anonymous00034. · Saint Louis University Medical School, St Louis, MO, USA. · Lancet. · Pubmed #18486739 No free full text.

Abstract: BACKGROUND: Interleukins 12 and 23 have important roles in the pathophysiology of psoriasis. We assessed ustekinumab, a human monoclonal antibody directed against these cytokines, for the treatment of psoriasis. METHODS: In this phase III, parallel, double-blind, placebo-controlled study, 766 patients with moderate-to-severe psoriasis were randomly assigned to receive ustekinumab 45 mg (n=255) or 90 mg (n=256) at weeks 0 and 4 and then every 12 weeks; or placebo (n=255) at weeks 0 and 4, with subsequent crossover to ustekinumab at week 12. Patients who were initially randomised to receive ustekinumab at week 0 who achieved long-term response (at least 75% improvement in psoriasis area and severity index [PASI 75] at weeks 28 and 40) were re-randomised at week 40 to maintenance ustekinumab or withdrawal from treatment until loss of response. Both randomisations were done with a minimisation method via a centralised interactive voice response system. The primary endpoint was the proportion of patients achieving PASI 75 at week 12. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00267969. FINDINGS: All randomised patients were included in the efficacy analysis. 171 (67.1%) patients receiving ustekinumab 45 mg, 170 (66.4%) receiving ustekinumab 90 mg, and eight (3.1%) receiving placebo achieved PASI 75 at week 12 (difference in response rate vs placebo 63.9%, 95% CI 57.8-70.1, p<0.0001 for 45 mg and 63.3%, 57.1-69.4, p<0.0001 for 90 mg). At week 40, long-term response had been achieved by 150 patients in the 45 mg group and 172 patients in the 90 mg group. Of these, 162 patients were randomly assigned to maintenance ustekinumab and 160 to withdrawal. PASI 75 response was better maintained to at least 1 year in those receiving maintenance ustekinumab than in those withdrawn from treatment at week 40 (p<0.0001 by log-rank test). During the placebo-controlled phase, adverse events occurred in 278 (54.5%) of the 510 patients receiving ustekinumab and 123 (48.2%) of the 255 receiving placebo. Serious adverse events occurred in six (1.2%) of 510 patients receiving ustekinumab and in two (0.8%) of 255 receiving placebo in this phase. The pattern of adverse events was much the same in the placebo crossover and randomised withdrawal phases as it was in the placebo-controlled phase. INTERPRETATION: Ustekinumab seems to be efficacious for the treatment of moderate-to-severe psoriasis; dosing every 12 weeks maintains efficacy for at least a year in most patients.

Kimball AB, Gordon KB, Langley RG, Menter A, Chartash EK, Valdes J, Anonymous00301. · Clinical Unit for Research Trials in Skin (CURTIS), Massachusetts General and Brigham and Women's Hospitals, Harvard Medical School, 50 Staniford St, No. 246, Boston, MA 02114, USA. · Arch Dermatol. · Pubmed #18283176 links to  free full text

Abstract: OBJECTIVE: To investigate the efficacy and safety of ABT-874, an interleukin 12/23 monoclonal antibody, in psoriasis. DESIGN: Phase 2, 12-week, multicenter, randomized, double-blind, placebo-controlled trial. SETTING: Outpatient dermatology clinics. Patients One hundred eighty patients with clinically stable moderate to severe chronic plaque psoriasis. Interventions Patients were randomized in groups of 30 to receive 1 of 6 treatments with ABT-874 provided as a subcutaneous injection: one 200-mg dose at week 0; 100 mg every other week for 12 weeks; 200 mg weekly for 4 weeks; 200 mg every other week for 12 weeks; 200 mg weekly for 12 weeks; or placebo. Main Outcome Measure At least a 75% reduction in the Psoriasis Area and Severity Index. RESULTS: The percentage of patients achieving a 75% reduction in the Psoriasis Area and Severity Index at week 12 was statistically significantly greater in all of the ABT-874 treatment groups than in the placebo group (200 mg once, 63% [19 of 30]; 100 mg every other week for 12 weeks, 93% [28 of 30]; 200 mg weekly for 4 weeks, 90% [27 of 30]; 200 mg every other week for 12 weeks, 93% [28 of 30]; 200 mg weekly for 12 weeks, 90% [27 of 30]; placebo, 3% [1 of 30]; P < .001). Treatment with ABT-874 was well tolerated. The most common adverse event was injection-site reaction, and the most common infectious adverse events were nasopharyngitis and upper respiratory tract infection. There were no serious infectious adverse events. CONCLUSIONS: ABT-874, an interleukin 12/23 monoclonal antibody, was highly effective and well tolerated in the treatment of psoriasis. Longer-term studies are required to confirm these findings.

Revicki DA, Willian MK, Menter A, Gordon KB, Kimball AB, Leonardi CL, Langley RG, Kimel M, Okun M. · Center for Health Outcomes Research, United BioSource Corporation, 7101 Wisconsin Avenue, Bethesda, MD 20814, USA. · J Dermatolog Treat. · Pubmed #18058494 No free full text.

Abstract: OBJECTIVE: The effect of adalimumab on patient-reported outcomes (PROs) was evaluated in patients with moderate to severe psoriasis during the initial 16-week, double-blind period of a 52-week, Phase III, multicenter trial. METHODS: Patients were randomized to placebo or adalimumab 80 mg at Week 0 and 40 mg every other week from Week 1 to Week 15. PROs were evaluated throughout the study and included the Dermatology Life Quality Index (DLQI), the Short Form 36 Health Survey (SF-36), the Work Productivity and Activity Impairment Questionnaire-Specific Health Problem (WPAI-SHP), and several patient-rated symptom scales. RESULTS: The adalimumab-treated group reported significantly greater improvements in DLQI total score (p<0.001), SF-36 Physical Component Summary score (p<0.001), and Mental Component Summary score (p<0.001) compared with the placebo-treated group over 16 weeks. Significant differences, favoring adalimumab, were also seen for the DLQI subscale scores (p < 0.001); SF-36 scale scores (p<0.001); WPAI-SHP work impairment (p<0.001), activity limitation (p<0.001), and overall work impairment scores (p<0.001); patient's global assessment of disease severity (p<0.001), psoriasis pain (p<0.001), and psoriasis-related pruritus (p = 0.002). CONCLUSION: Adalimumab was efficacious in improving dermatology-specific and general health-related quality of life, work and activity limitations, and psoriasis-related symptoms in patients with moderate to severe psoriasis over a 16-week period.

Menter A, Tyring SK, Gordon K, Kimball AB, Leonardi CL, Langley RG, Strober BE, Kaul M, Gu Y, Okun M, Papp K. · Division of Dermatology, Baylor Research Institute, University of Texas Southwestern Medical School, 3900 Junius St, 125, Dallas, TX 75246-1613, USA. · J Am Acad Dermatol. · Pubmed #17936411 No free full text.

Abstract: BACKGROUND: Adalimumab is a fully human monoclonal antibody that binds tumor necrosis factor, a key proinflammatory cytokine involved in the pathogenesis of psoriasis. OBJECTIVE: We sought to evaluate clinical efficacy and safety of adalimumab for moderate to severe psoriasis and investigate continuous versus interrupted therapy. METHODS: We conducted a 52-week, multicenter study of 1212 patients randomized to receive adalimumab (40 mg) or placebo every other week for the first 15 weeks. At least 75% improvement in the Psoriasis Area and Severity Index (PASI) score was the criterion for advancement through this multiphase study. RESULTS: At week 16, 71% (578 of 814) of adalimumab- and 7% (26 of 398) of placebo-treated patients achieved greater than or equal to 75% improvement in the PASI score. During weeks 33 to 52, the percentage of patients rerandomized to placebo who lost adequate response (defined as <50% improvement in the PASI response relative to baseline and at least a 6-point increase in PASI score from week 33) was 28% compared with 5% of patients treated continuously with adalimumab. LIMITATIONS: Lack of an active comparator and evaluation of maintenance of response beyond week 52 are limitations. CONCLUSION: Adalimumab is efficacious and well-tolerated in the treatment of chronic plaque psoriasis. TRIAL REGISTRATION: Clinical trials.gov. NCT00237887.

Kimball AB, Jackson JM, Sobell JM, Boh EE, Grekin S, Pharmd EB, Woolley JM, Xia HA, Chiou CF, Stevens SR. · Massachusetts General and Brigham and Women's Hospitals, Harvard Medical School, Boston, MA 02114, USA. · J Drugs Dermatol. · Pubmed #17373192 No free full text.

Abstract: The Experience Diagnosing, Understanding Care, and Treatment with Enbrel (EDUCATE) trial is a phase IV, 24-week, multicenter, open-label study of etanercept 50 mg weekly in the treatment of psoriatic arthritis (PsA) in community dermatology clinics. In this study, patients with active PsA and moderate to severe plaque psoriasis have measurable uses of healthcare resources at baseline, reflecting a burden of illness. Etanercept significantly reduced healthcare resource utilization, absenteeism, and caregiver assistance in PsA patients after 24 weeks of treatment. These results could translate into savings on both direct and indirect costs and improvements in health-related quality of life for patients with PsA.

Feldman SR, Kimball AB, Krueger GG, Woolley JM, Lalla D, Jahreis A. · Wake Forest University School of Medicine, Winston Salem, North Carolina 27157-1071, USA. · J Am Acad Dermatol. · Pubmed #16243150 No free full text.

Abstract: 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.

Bergstrom KG, Arambula K, Kimball AB. · Department of Dermatology, Stanford University, California 94305-5334, USA. · Cutis. · Pubmed #14655784 No free full text.

Abstract: For topical medications commonly used to treat dermatologic conditions, outcomes may be affected by the choice of delivery vehicles. The aim of this study was to compare quality of life (QOL), effectiveness, user satisfaction, and cost-effectiveness of 2 clobetasol regimens for the treatment of psoriasis over 14 days. In a single-blind design, 32 patients randomized into 2 groups applied either clobetasol foam 0.05% to the skin and scalp or combination clobetasol cream 0.05% to the skin and clobetasol solution 0.05% to the scalp. Psoriasis severity was measured using the standardized Psoriasis Area and Severity Index (PASI) and self-administered PASI (SAPASI). QOL was assessed via the EuroQoL-5D (EQ-5D) questionnaire and Dermatology Life Quality Index (DLQI). Cost-effectiveness was measured by the amount of medication used per body surface area (BSA) treated and by cost per point improvement in PASI score. In this study, a foam formulation performed better than a cream/solution combination by several measures. A greater absolute improvement in psoriasis severity was seen in the group using the foam than in the group using the cream/solution (mean decrease in PASI=5.0 vs 3.3, P=.05). The PASI score in the foam group decreased by 41% versus 35% in the cream/solution group (P=.17). In scalp psoriasis, the group using the foam had greater improvement in both absolute (P=.03) and percentage (P=.03) terms and than the solution group. When measuring global QOL, foam users had a significantly greater increase in EQ-5D than those using the cream/solution in absolute (P=.05, P=.02) and percentage (P=.04, P=.02) terms (first and second survey components, respectively). Differences in improvement of skin-specific QOL, quantified by DLQI scores between groups, were suggested but not statistically significant. Patients using foam spent less time applying medication compared with previous topical medications (P<.001). No significant difference in cost was appreciated between foam and cream/solution over the period after controlling for BSA (8.18 dollars vs 7.05 dollars per percentage BSA affected, P=.30).

Kimball AB, Kawamura T, Tejura K, Boss C, Hancox AR, Vogel JC, Steinberg SM, Turner ML, Blauvelt A. · Dermatology Branch, National Cancer Institute, Bethesda, MD 20892-1908, USA. · Arch Dermatol. · Pubmed #12374540 links to  free full text

Abstract: BACKGROUND: In several open-label studies, recombinant human interleukin 10 (rhIL-10), a type 2 anti-inflammatory cytokine, has been reported to improve psoriasis, a disease characterized by type 1 cytokine inflammation. OBJECTIVE: To evaluate the safety, efficacy, and immunologic parameters in individuals with psoriasis treated with rhIL-10. DESIGN AND INTERVENTION: Patients received rhIL-10 (20 micro g/kg) or placebo subcutaneously 3 times weekly for 12 weeks in a randomized, double-blind manner. SETTING AND PATIENTS: National Institutes of Health Clinical Center in Bethesda. Twenty-eight patients with moderate-to-severe psoriasis as defined by a Psoriasis Area Severity Index (PASI) score of 10 or higher. MAIN OUTCOME MEASURE: The primary clinical end point was the mean percentage change in the PASI score comparing baseline and week 12 scores. Intracellular cytokine production by peripheral blood mononuclear cells (PBMCs) was measured by flow cytometry. RESULTS: There was no significant difference in the mean percentage change in the PASI score from baseline to week 12 between the rhIL-10-treated group and control patients (17% vs 13% improvement, respectively; P =.69), although a modest trend toward improvement in patients receiving rhIL-10 was documented at both the 6- and 8-week points. Interestingly, proinflammatory and type 1 cytokine production by PBMCs progressively declined in the rhIL-10-treated patients during the entire 12-week study period. CONCLUSIONS: Treatment with rhIL-10 resulted in only temporary clinical improvement in psoriasis, despite sustained systemic decreases in proinflammatory and type 1 cytokine production. These data suggest that immunotherapy that decreases the ratio of systemic type 1 and type 2 cytokine production does not necessarily lead to improvement of type 1 cytokine-mediated disease.

Horn EJ, Chambers CD, Menter A, Kimball AB, Anonymous00039. · International Psoriasis Council, Dallas, Texas, USA. · J Am Acad Dermatol. · Pubmed #19615534 No free full text.

This publication has no abstract.

Lima XT, Abuabara K, Kimball AB, Lima HC. · Massachusetts General Hospital - Harvard Medical School, Boston, MA 02114, USA. · Expert Opin Biol Ther. · Pubmed #19569977 No free full text.

Abstract: BACKGROUND: Psoriasis is a chronic, autoimmune, T-cell mediated, inflammatory disease. An improved understanding of the pathogenesis of the autoimmune response has led to the development of targeted biologic therapies. Briakinumab is a human monocolonal antibody that blocks the activity of the cytokines IL-12 and IL-23. Immune dysregulation has been implicated in multiple inflammatory disorders and briakinumab has been investigated for the treatment of psoriasis, rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis. OBJECTIVES: This review focuses on briakinumab and its use in chronic plaque-type psoriasis. METHODS: A literature review was performed, searching Medline and the clinicaltrials.gov database for all articles with the keywords ABT-874, IL-12/IL-23 and psoriasis. CONCLUSIONS: Although limited by small sample sizes, length of follow-up, and a lack of direct comparisons with other psoriasis treatments, initial data regarding the safety and efficacy of briakinumab for the treatment of psoriasis is promising. Ongoing Phase III trials may provide additional information regarding the relative efficacy and safety of briakinumab.

Weiss SC, Rehmus W, Kimball AB. · No affiliation provided · Ther Clin Risk Manag. · Pubmed #18360608 links to  free full text

Abstract: OBJECTIVE: Recently a number of new therapies have been introduced to treat psoriasis, but concerns have been expressed about their high cost. The purpose of this study was to determine whether most psoriasis treatments lie within the accepted range of cost-utility. METHODOLOGY: 32 patients with moderate to severe psoriasis were administered the Euro-Qol 5 Dimension (EQ-5D) survey to calculate their health state utility. Economic modeling was performed with a range of therapeutic costs applying the calculated utility score. Paired t-tests were used to calculate significance. RESULTS: At the conclusion of 2 weeks of therapy, the mean psoriasis area and severity index (PASI) improved 35% to 7.2 (p<0.001). The mean health state utility score on the EQ-5D improved 11.5% from 77.7 units before therapy to 86.7 units after therapy (p=0.007). CONCLUSION: A therapy that achieves at least a PASI 35 would be considered cost-effective by conventional standards if it does not exceed $33 600 in cost.

Kimball AB, Robinson D, Wu Y, Guzzo C, Yeilding N, Paramore C, Fraeman K, Bala M. · Harvard Medical School, Boston, Massachussettes, USA. · Dermatology. · Pubmed #18349542 links to  free full text

Abstract: BACKGROUND: Cardiovascular diseases or risk factors (CVDR) seem to be more common in psoriasis patients than in the general population. OBJECTIVE: We assessed the relationship of psoriasis with CVDR by analysis of healthcare claims data using a cross-sectional, prevalence-based study design. PATIENTS AND MeTHODS: The IMS Health and MarketScan claims databases were used to identify adults with psoriasis diagnostic codes. Non-psoriasis controls were matched 3:1 based on age, gender, census region and previous medical insurance coverage. Odds ratios evaluated the relative prevalence of CVDR, and Mantel-Haenszel confidence intervals were estimated. RESULTS: CVDR prevalence was generally higher in psoriasis patients than controls in both datasets. Odds ratios for atherosclerosis, congestive heart failure, type 2 diabetes, and peripheral vascular disease were >or=1.20 for psoriasis patients. Elevated disease severity was associated with a higher rate of CVDR, but varied somewhat by dataset and condition. Conclusions: Elevated CVDR rates were found in psoriasis patients compared with controls. This pattern merits further examination.

Ciocon DH, Horn EJ, Kimball AB. · Department of Dermatology, Albert Einstein College of Medicine, Bronx, New York, USA. · Am J Clin Dermatol. · Pubmed #18284265 No free full text.

Abstract: INTRODUCTION: Five to forty percent of patients with cutaneous psoriasis develop an inflammatory, oligoarticular spondyloarthropathy known as psoriatic arthritis. OBJECTIVE: To compare health-related quality of life (QOL) between cutaneous psoriatic patients with and without psoriatic arthritis. METHOD: Secondary cross-sectional analysis of data obtained from the 2005 Spring US National Psoriasis Foundation Quality of Life Telephone/Internet Survey. 426 patients with psoriasis and/or psoriatic arthritis were included in the 2005 survey. Among these respondents, the self-reported disease histories of 140 patients with cutaneous psoriasis and psoriatic arthritis were compared with those of 278 patients with cutaneous psoriasis only. Both groups were compared with respect to demographics, skin disease severity, treatment history and satisfaction, and QOL using previously validated assessment scales. RESULTS: Compared with those with skin psoriasis only, respondents with cutaneous psoriasis and psoriatic arthritis were slightly older, more likely to be female and members of the National Psoriasis Foundation, and more likely to report a younger age of disease onset. They were also more likely to be unemployed, to report their job was affected by their condition, and to report a higher mean estimate of lost annual wages. On both univariate and multivariate analysis, however, no significant differences between groups were detected in skin disease severity, overall QOL, and satisfaction with current treatment options. At the same time, individuals with skin psoriasis and psoriatic arthritis were more likely to be taking systemic agents. They also reported higher mean scores for pain, while those with cutaneous psoriasis reported higher mean scores for self-consciousness only. CONCLUSION: In contrast to previous reports that did not control for skin disease severity, this study demonstrates that patients with cutaneous psoriasis and psoriatic arthritis do not report significantly worse health-related QOL compared with patients with cutaneous psoriasis only. Nor do they report significantly greater dissatisfaction with current treatment options. These findings may reflect the intrinsic inadequacy of the QOL instruments used in this study for capturing the additional burden of joint disease. Alternatively, these findings may reflect the existence of a threshold of joint disease in patients with skin psoriasis and psoriatic arthritis below which joint symptoms are perceived as negligible relative to cutaneous disease.

Lebwohl M, Bagel J, Gelfand JM, Gladman D, Gordon KB, Hsu S, Kalb RE, Kimball AB, Korman NJ, Krueger GG, Mease P, Morison WL, Paller A, Pariser DM, Ritchlin C, Strober B, Van Voorhees A, Weinstein GD, Young M, Horn L. · Department of Dermatology, Mount Sinai School of Medicine, New York, New York, USA. · J Am Acad Dermatol. · Pubmed #17980456 No free full text.

Abstract: BACKGROUND: Biologics are widely used in the treatment of psoriasis and psoriatic arthritis. OBJECTIVE: Our aim was to arrive at a consensus on the kind of monitoring and the vaccinations that should be performed before and during biologic therapy. METHODS: Medical literature and data presented at meetings were reviewed and a consensus conference was held by members of the Medical Board of the National Psoriasis Foundation. RESULTS: Consensus was established on monitoring and vaccination practices that included discussion and recognition of variations in those practices. History, physical examination, chemistry screen with liver function tests, complete blood cell count, and platelet count and tuberculosis testing are widely obtained at baseline and with variable frequencies thereafter. Patients treated with efalizumab have platelet counts checked more often; liver function tests are repeated more frequently in patients treated with infliximab; patients taking tumor necrosis factor blockers undergo tuberculosis testing more often; and patients treated with alefacept have CD4 counts checked approximately every 2 weeks. Avoidance of live vaccines during biologic therapy and administration of essential vaccines before biologic therapy were discussed, although vaccination is performed only to a variable degree. There was no consistency in the measurement of antinuclear antibodies among the experts. LIMITATIONS: There are few evidence-based studies on monitoring practices for patients with psoriasis taking biologic therapies. CONCLUSIONS: In patients taking biologic therapies for psoriasis, monitoring of blood chemistries, blood counts, CD4 counts, antinuclear antibodies, tuberculin skin tests, history, and physical examination may be warranted depending on the particular therapy and the particular patient. Vaccination practices are also addressed.

Chan JR, Blumenschein W, Murphy E, Diveu C, Wiekowski M, Abbondanzo S, Lucian L, Geissler R, Brodie S, Kimball AB, Gorman DM, Smith K, de Waal Malefyt R, Kastelein RA, McClanahan TK, Bowman EP. · Discovery Research, Schering-Plough Biopharma (formerly DNAX Research, Inc.), Palo Alto, CA 94304, USA. · J Exp Med. · Pubmed #17074928 links to  free full text

Abstract: Aberrant cytokine expression has been proposed as an underlying cause of psoriasis, although it is unclear which cytokines play critical roles. Interleukin (IL)-23 is expressed in human psoriasis and may be a master regulator cytokine. Direct intradermal administration of IL-23 in mouse skin, but not IL-12, initiates a tumor necrosis factor-dependent, but IL-17A-independent, cascade of events resulting in erythema, mixed dermal infiltrate, and epidermal hyperplasia associated with parakeratosis. IL-23 induced IL-19 and IL-24 expression in mouse skin, and both genes were also elevated in human psoriasis. IL-23-dependent epidermal hyperplasia was observed in IL-19-/- and IL-24-/- mice, but was inhibited in IL-20R2-/- mice. These data implicate IL-23 in the pathogenesis of psoriasis and support IL-20R2 as a novel therapeutic target.