Psoriasis: Bos JD

Lecluse LL, Piskin G, Mekkes JR, Bos JD, de Rie MA. · Department of Dermatology, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands. · Br J Dermatol. · Pubmed #18627374 No free full text.

Abstract: Infliximab (Remicade; Schering-Plough, Kenilworth, NJ, U.S.A.) is a chimeric monoclonal antibody that acts as a tumour necrosis factor-alpha inhibitor. Infliximab is registered for the treatment of rheumatoid arthritis, psoriatic arthritis, Crohn disease, ulcerative colitis, ankylosing spondylitis and plaque-type psoriasis. Like other foreign protein-derived agents, infliximab may lead to infusion reactions during and after infusion. Infusion reactions occur in 3-22% of patients with psoriasis treated with infliximab. Most of these reactions are mild or moderate and only few are severe. Nevertheless, they may lead to discontinuation of treatment. As infliximab for psoriasis is prescribed as a last resort and is in most cases very effective, discontinuation of treatment is undesirable. With proper care and prevention of the infusion reactions the need to discontinue treatment with infliximab can be diminished. The objective of this article is to present a guideline for the management of infliximab-related infusion reactions, based on the best available evidence. This guideline can be used in patients with psoriasis as well as in dermatology patients receiving infliximab for off-label indications such as hidradenitis suppurativa or pyoderma gangrenosum.

Bos JD, Spuls PI. · Department of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands. · Clin Dermatol. · Pubmed #18755361 No free full text.

Abstract: Topical therapy in psoriasis is of use in mild cases. It is also applied as an adjunct to phototherapy and systemic treatments in moderate to severe cases. Long-established pharmaceuticals such as cignolin, tar preparations, and glucocorticoids are still in use. Newer topical agents such as vitamin A and D derivatives are gradually replacing them. Combining a vitamin D derivative and a strong glucocorticoid now seems to be the most efficient way to treat psoriasis when topical agents are indicated. There is a growing list of "alternative" treatment options, where evidence is generally absent. Rewarding investments should perhaps be directed at intervening with molecules of innate immunity. Superfluous activation of natural immune system cascades is now in view as the major culprit in psoriasis, replacing the T-cell hypothesis of the disease. Agents directed at tumor necrosis factor alpha, Toll-like receptors, and neutrophils may have great impact in future topical therapy of psoriasis. Finally, innovations in the development of more targeted glucocorticoids and vitamin A and D derivatives, where desired effects are better separated from undesired side effects, may lead to an increased benefit/risk ratio of these nuclear receptor-directed therapies.

Bos JD. · Department of Dermatology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. · J Am Acad Dermatol. · Pubmed #17317489 No free full text.

Abstract: Recently, emphasis has shifted from T cells to innate (natural) immunity as the possible major culprit in psoriasis. All known elements of innate immune responses are up-regulated in psoriasis lesions, which must have a polygenetic origin. We hypothesize that urbanized populations have been under evolutionary pressure that selects for increased innate immunity responses because those offer relative but immediate protection from epidemic infections. That would have resulted in a changing gene pool, in which alleles of polymorphisms associated with increased innate immunity responses have amplified in these populations. Having too many of these genes together in one individual would result in a relatively low number of infections. On the other hand, it would also result in a higher prevalence of diseases related to increased innate immunity, such as psoriasis, and perhaps also multiple sclerosis and rheumatoid arthritis. Indeed, in indigenous people (Inuit, Aborigines, Ami) who have not been under this selection pressure, morbidity due to infections is high and the prevalence of psoriasis is low or even absent.

Menter A, Leonardi CL, Sterry W, Bos JD, Papp KA. · Baylor University Medical Center, Dallas, Texas, USA. · J Am Acad Dermatol. · Pubmed #16488340 No free full text.

This publication has no abstract.

Bos JD, de Rie MA, Teunissen MB, Piskin G. · Department of Dermatology, Academic Medical Center, University of Amsterdam, P.O.Box 22700, 1100 DE Amsterdam, the Netherlands. · Br J Dermatol. · Pubmed #15948970 No free full text.

Abstract: The current understanding of the function of natural killer (NK) T cells in innate immunity and their potential to control acquired specific immunity, as well as the remarkable efficacy of antitumour necrosis factor-alpha biological treatments in psoriasis, forces us to refine the current T-cell hypothesis of psoriasis pathogenesis, and to give credit to the role of innate immunity. Psoriasis might be envisioned to be a genetically determined triggered state of otherwise dormant innate immunity. This aggravated state of innate immunity is represented by the activity of NK T cells, dendritic cells, neutrophils and keratinocytes, leading to the recruitment and activation of preferentially type 1 T cells, possibly in an antigen-independent way. Keratinocytes in psoriasis then are sensitive to the effects of T-cell activation and cytokine production, interferon (IFN)-gamma, by responding with psoriasiform hyperplasia. The chronic inflammation of psoriatic lesions suggests that this might be due to a deficiency in downregulation processes (e.g. a defect in the regulatory T-cell repertoire) and/or the persistence of an unknown trigger resulting in an exaggerated innate immune response.

de Rie MA, Goedkoop AY, Bos JD. · Department of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · Dermatol Ther. · Pubmed #15379769 No free full text.

Abstract: Psoriasis is a chronic disease that affects the skin and joints. Clinical hallmarks comprise erythematous plaques covered by silvery scaling and a chronic recurrent course. Histologically, psoriasis is characterized by the hyperproliferation of the epidermis, elongated and prominent blood vessels and a thick perivascular lymphocytic infiltrate. Psoriasis is now considered an auto-immune disease. Although many different therapies are available, there is clearly a need for new treatments. Our improvement of understanding of the pathogenesis of psoriasis together with the possibility to develop bioactive proteins ("biologicals") targeted at specific steps in the pathogenesis of psoriasis, have opened a new field of promising future treatments. In the development and assessment of new therapeutical modalities for psoriasis, a clear definition of a patient's psoriasis severity is essential. The impact of a given therapy can only then be evaluated, based on the changes in the severity score during and after application of the treatment.

Sterry W, Barker J, Boehncke WH, Bos JD, Chimenti S, Christophers E, De La Brassinne M, Ferrandiz C, Griffiths C, Katsambas A, Kragballe K, Lynde C, Menter A, Ortonne JP, Papp K, Prinz J, Rzany B, Ronnevig J, Saurat JH, Stahle M, Stengel FM, Van De Kerkhof P, Voorhees J. · Department of Dermatology and Allergy, University Hospital Charité, Berlin, Germany. · Br J Dermatol. · Pubmed #15265063 No free full text.

Abstract: Psoriasis is a chronic, immune-mediated disorder that usually requires long-term treatment for control. Approximately 25% of patients have moderate to severe disease and require phototherapy, systemic therapy or both. Despite the availability of numerous therapeutic options, the long-term management of psoriasis can be complicated by treatment-related limitations. With advances in molecular research and technology, several biological therapies are in various stages of development and approval for psoriasis. Biological therapies are designed to modulate key steps in the pathogenesis of psoriasis. Collectively, biologicals have been evaluated in thousands of patients with psoriasis and have demonstrated significant benefit with favourable safety and tolerability profiles. The limitations of current psoriasis therapies, the value of biological therapies for psoriasis, and guidance regarding the incorporation of biological therapies into clinical practice are discussed.

de Korte J, Sprangers MA, Mombers FM, Bos JD. · Department of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · J Investig Dermatol Symp Proc. · Pubmed #15083781 No free full text.

Abstract: Data on physical, psychological, and social functioning of patients with psoriasis have been presented in many studies. The introduction of quality-of-life questionnaires has made it possible to systematically compare these data across studies. The aim of this study was to present an overview of quality-of-life data and to describe the relationship between demographic and clinical variables and quality of life in patients with psoriasis. Computerized bibliographic databases were screened for publications from January 1966 to April 2000. Predefined selection criteria were used to identify quality-of-life studies in psoriasis. Two investigators independently assessed and, subsequently, agreed on inclusion. Data were extracted on the objectives, methods, sample characteristics, and results of the studies. A total of 118 publications were found. Seventeen studies met the inclusion criteria. Patients with psoriasis reported physical discomfort, impaired emotional functioning, a negative body and self-image, and limitations in daily activities, social contacts and (skin-exposing) activities, and work. More severe psoriasis was associated with lower levels of quality of life. There was a tendency that higher age was associated with slightly lower levels of physical functioning and slightly higher levels of psychological functioning and overall quality of life. Sex and quality of life were found to be unrelated.

Spuls PI, Witkamp L, Bossuyt PM, Bos JD. · Departments of Dermatology and Epidemiology and Biostatistics, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands. · Arch Dermatol. · Pubmed #15023777 No free full text.

Abstract: OBJECTIVE: To determine the outcome in placebo-treated patients with plaque-type psoriasis. DATA SOURCES: Online search of MEDLINE and EMBASE until January 2001 and the Cochrane Library (2001, issue 1), supplemented by references, reviews, guidelines, and textbooks. STUDY SELECTION: Randomized controlled induction of remission trials of patients with chronic plaque-type psoriasis with systemic treatments with a placebo group not treated with antipsoriatic medication. Identified studies were examined by 2 independent reviewers. Through MEDLINE, 290 studies could be identified. Twenty-seven placebo-controlled studies were included (488 patients). DATA EXTRACTION: Two independent reviewers extracted data on first author, year of publication, design, comparison, placebo treatment, number of patients, treatment duration, type of psoriasis and baseline severity in the placebo group, mean relative change in outcome measures, and/or percentage of patients with worsening of psoriasis; no change; minimal, moderate, or good improvement; or complete clearance. DATA SYNTHESIS: Owing to substantial heterogeneity and differences in the way outcomes were reported, no summary estimates could be obtained. The outcome of placebo treatment was poor in most studies. Some reported a mean relative change of 11% to 47%. The highest percentages of patients ended up in the worsening, no change, or minimal improvement categories. Also, complete clearance was possible. No explanation for the differences in outcome between placebo groups could be found. Description of placebo groups was often insufficient. CONCLUSIONS: The effect of treatment in placebo groups varied across studies in an unpredictable way. To evaluate the variability, improvement of the standardization of study designs, entry criteria, and outcome measures is necessary in psoriasis trials.

Gottlieb AB, Bos JD. · Clinical Research Center, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick 08901, USA. · Clin Immunol. · Pubmed #12482385 No free full text.

Abstract: Psoriasis is a chronic, inflammatory disease with lesions that produce considerable physical discomfort and often lead to substantial disruption in patients' daily activities. The use of currently available, nonspecific, systemic immunosuppressive therapies for patients with moderate to severe psoriasis is limited by an inability to maintain disease remission safely. Advances in recombinant DNA technology paralleled with increased understanding of the immunopathology of psoriasis have led to the development of numerous biologic agents for the treatment of this disease. These new biologic therapies target specific steps in psoriasis pathology, including direct effects on T cells, T cell activation, T cell migration, and cellular production and secretion of cytokines. By selectively targeting the activities of T cells that are directly involved in psoriasis pathogenesis, these novel agents offer improved safety profiles and enhanced efficacy. In this article, the mechanisms of T cell pathogenicity that guided the development of these new biologic therapies are reviewed along with clinical data on the progress of these agents.

De Korte J, Mombers FM, Sprangers MA, Bos JD. · Department of Dermatology, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands. · Arch Dermatol. · Pubmed #12224984 No free full text.

Abstract: OBJECTIVE: To critically appraise the suitability of current quality-of-life (QOL) questionnaires for psoriasis research. DATA SOURCES: Computerized searches of 5 bibliographic databases. QUESTIONNAIRE SELECTION: Predefined criteria were used to identify QOL questionnaires in dermatologic studies. Two investigators independently assessed and agreed on multidimensional generic, dermatology-specific, and psoriasis-specific QOL questionnaires for inclusion. DATA EXTRACTION: Data were extracted on the internal structure, reliability, and validity of the included questionnaires. DATA SYNTHESIS: Three generic, 3 dermatology-specific, and none of the psoriasis-specific questionnaires met the inclusion criteria: the Nottingham Health Profile (NHP), the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), the Sickness Impact Profile (SIP), the Dermatology Quality of Life Scales (DQOLS), the Dermatology-Specific Quality of Life Instrument (DSQL), and the Skindex-29. The generic NHP, SF-36 and SIP are well established, reliable, and valid. Although the data are not conclusive, the SF-36 was useful to assess effects of psoriasis on its component scales. The dermatology-specific DQOLS, DSQL, and Skindex-29 are relatively new and, therefore, less widely tested. Available psychometric data demonstrated the reliability and validity of all 3 dermatology-specific questionnaires. The Skindex-29 was also useful to assess change. CONCLUSIONS: None of the identified psoriasis-specific questionnaires met the inclusion criteria. Data on the suitability of the included questionnaires for psoriasis research were relatively sparse. The included generic questionnaires allow comparisons with nondermatologic diseases but do not allow assessment of relevant dermatology-specific aspects and are not sensitive to subtle effects of psoriasis on QOL. On the basis of the psychometric data of the present review, we find the Skindex-29 to be the most valuable dermatology-specific questionnaire for psoriasis research. Combination of the Skindex-29 with the generic SF-36 combines the merits of both types of questionnaires and we therefore recommend this combination.

Heydendael VM, Spuls PI, Ten Berge IJ, Opmeer BC, Bos JD, de Rie MA. · Department of Dermatology, Academic Medical Center, University of Amsterdam, PO Box 22660, the Netherlands. · Br J Dermatol. · Pubmed #12100194 No free full text.

Abstract: BACKGROUND: Cyclosporin is an effective treatment for severe plaque psoriasis. Unfortunately, its use may be limited by time- and dose-related nephrotoxicity. Serum trough levels may be useful for monitoring the risk of nephrotoxicity. OBJECTIVES: To determine whether monitoring of trough levels is necessary in psoriasis patients undergoing short-term treatment with cyclosporin. METHODS: A computerized and manual literature search identified studies on adults with plaque-type psoriasis treated with cyclosporin < or = 5 mg kg-1 daily, in which trough levels were measured in whole blood. Number of patients, treatment duration, formulation and dosage, renal function tests and trough levels were extracted. The association between renal function and trough levels was investigated. Additionally, in a randomized controlled trial on cyclosporin vs. methotrexate in moderate to severe psoriasis, cyclosporin trough levels were measured frequently in 20 patients during 12 weeks of treatment. The Pearson correlation coefficient between serum creatinine and cyclosporin trough levels was calculated. RESULTS: Fifty-six articles were found concerning cyclosporin trough level measurements in psoriasis patients, of which eight were analysed. Many studies were excluded due to inappropriate cyclosporin dosages used. As data were heterogeneous and lacked various key parameters, a correlation study and a meta-analysis could not be performed. Instead, a quantitative description of the literature was given. No high mean trough levels or elevations of serum creatinine were described. In our clinical study, all the mean trough levels in 17 patients treated with cyclosporin 3 mg kg-1 daily were within the therapeutic range (< 200 ng mL-1). Elevated trough levels were found in two of three patients treated with cyclosporin 3-5 mg kg-1 daily. No signs of renal dysfunction were seen. CONCLUSIONS: The literature does not provide a definitive answer on whether monitoring cyclosporin trough levels in patients with psoriasis should be standard practice. Our own data show no need for cyclosporin trough level monitoring during short-term treatment with cyclosporin 3 mg kg-1 daily. However, when cyclosporin doses are > 3 mg kg-1 daily, monitoring may be indicated.

Bos JD, De Rie MA. · Dept of Dermatology, Academic Medical Center, University of Amsterdam, The Netherlands. · Immunol Today. · Pubmed #10081229 No free full text.

This publication has no abstract.

Dubertret L, Sterry W, Bos JD, Chimenti S, Shumack S, Larsen CG, Shear NH, Papp KA, Anonymous00197. · Hôpital Saint Louis, Paris, France, and University Hospital Charite, Berlin, Germany. · Br J Dermatol. · Pubmed #16792770 No free full text.

Abstract: BACKGROUND: Efalizumab (anti-CD11a), a humanized monoclonal antibody, blocks multiple T-cell-dependent functions implicated in the pathogenesis of psoriasis, including T-cell activation, migration to the skin, reactivation in psoriatic skin and interactions with keratinocytes. OBJECTIVES: This multinational, randomized, double-blind, placebo-controlled, parallel-group trial was designed to evaluate the safety and efficacy of subcutaneous efalizumab 1.0 mg kg-1 once weekly for 12 weeks compared with placebo in a population that included high-need patients, defined as those for whom at least two systemic therapies were unsuitable because of lack of efficacy, intolerance or contraindication. PATIENTS/METHODS: Patients with moderate-to-severe plaque psoriasis [involvement of >or=10% of total body surface area and Psoriasis Area and Severity Index (PASI)>or=12.0 at screening] were randomized in a 2:1 ratio to receive efalizumab or placebo. The primary efficacy endpoint was the proportion of patients achieving >or=75% PASI improvement (PASI-75 response) at week 12 in the intention-to-treat population; secondary endpoints included changes in PASI, static Physician's Global Assessment, Physician's Global Assessment of change from baseline and percentage of body surface area affected. Results We enrolled 793 patients (529 received efalizumab and 264 placebo), including 526 high-need patients (342 received efalizumab and 184 placebo). Week 12 PASI-75 rates were 29.5% for efalizumab compared with 2.7% for placebo among high-need patients (P<0.0001) and 31.4% for efalizumab compared with 4.2% for placebo in the full study population (P<0.0001). RESULTS: for all secondary efficacy endpoints showed superiority of efalizumab over placebo in both the high-need and the full populations. Efalizumab demonstrated a favourable safety profile, without evidence of systemic toxicity, in both the high-need group and the overall study population. CONCLUSIONS: The efficacy and safety of efalizumab therapy were comparable between high-need patients and the more general moderate-to-severe psoriasis patient population. In view of its demonstrated efficacy and safety profile, efalizumab represents a valuable option for the treatment of adult patients with moderate-to-severe plaque psoriasis, including high-need patients.

Opmeer BC, Heydendael VM, De Borgie CA, Spuls PI, Bossuyt PM, Bos JD, De Rie MA. · Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, University of Amsterdam, The Netherlands. · Arch Dermatol. · Pubmed #15210458 links to  free full text

Abstract: OBJECTIVES: To document and compare the costs of treatment of psoriasis with 2 established systemic agents that differ substantially in their unit costs: methotrexate vs cyclosporine. DESIGN: Cost-minimization analysis within a randomized controlled trial. SETTING: Outpatient dermatology department at an academic hospital. PATIENTS: Adults with moderate to severe plaque psoriasis, with no previous methotrexate or cyclosporine treatment. INTERVENTION: Sixteen weeks of treatment with methotrexate or cyclosporine and an additional 36 weeks of follow-up. MAIN OUTCOME MEASURES: Direct and indirect medical and nonmedical costs associated with resource utilization during treatment and follow-up. RESULTS: Average cumulative total costs associated with 16 weeks of treatment were 1593 US dollars for methotrexate and 2114 US dollars for cyclosporine (521 US dollars less for methotrexate); during 36 weeks of follow-up, these costs were 2418 US dollars and 2306 US dollars, respectively. The overall difference in cumulative 1-year costs was 409 US dollars, or approximately 10% of the total costs. CONCLUSIONS: After 1 year, the overall difference in total costs between methotrexate and cyclosporine for 16 weeks of treatment and follow-up is relatively small. Systemic medication costs are only a fraction of the costs directly and indirectly generated by utilization of health care resources and associated with individual patients rather than with methotrexate or cyclosporine. Economic arguments can be supportive of but not decisive for individual patient decisions and guidelines for systemic therapy. Rational decision making for the treatment of psoriasis may include costs only within a long-term horizon and may consider the societal and patient benefits of different alternatives.

Goedkoop AY, Kraan MC, Teunissen MB, Picavet DI, de Rie MA, Bos JD, Tak PP. · Division of Clinical Immunology and Rheumatology, Academic Medical Centre/University of Amsterdam, Meibergdreef 9, NL-1105 AZ Amsterdam, The Netherlands. · Ann Rheum Dis. · Pubmed #15194570 links to  free full text

Abstract: BACKGROUND: Tumour necrosis factor alpha (TNFalpha) blockade using infliximab, a chimeric anti-TNFalpha antibody, is an effective treatment for both psoriasis and psoriatic arthritis (PsA). OBJECTIVE: To analyse the early effects of infliximab treatment on serial skin and synovial tissue biopsy samples. METHODS: Twelve patients with both active psoriasis and PsA received a single infusion of either infliximab (3 mg/kg) (n = 6) or placebo (n = 6) intravenously. Synovial tissue and lesional skin biopsy specimens were obtained at baseline and 48 hours after treatment. Immunohistochemical analysis was performed to analyse the inflammatory infiltrate. In situ detection of apoptotic cells was performed by TUNEL assay and by immunohistochemical staining with anti-caspase-3 antibodies. Stained tissue sections were evaluated by digital image analysis. RESULTS: A significant reduction in mean (SEM) T cell numbers was found in both lesional epidermis (baseline 37 (11) cells/mm, 48 hours 26 (11), p = 0.028) and synovial tissue (67 (56) cells/mm(2)v 32 (30), p = 0.043) after infliximab treatment, but not after placebo treatment (epidermis 18 (8) v 43 (20), NS; synovium 110 (62) v 46 (21), NS). Similarly, the number of macrophages in the synovial sublining was significantly reduced after anti-TNFalpha treatment (100 (73) v 10 (8), p = 0.043). The changes in cell numbers could not be explained by induction of apoptosis at the site of inflammation. CONCLUSIONS: The effects of anti-TNFalpha therapy in psoriasis and psoriatic arthritis may be explained by decreased cell infiltration in lesional skin and inflamed synovial tissue early after initiation of treatment.

Heydendael VM, de Borgie CA, Spuls PI, Bossuyt PM, Bos JD, de Rie MA. · Department of Dermatology, Academic Medical Center, University of Amsterdam, The Netherlands. · J Investig Dermatol Symp Proc. · Pubmed #15083779 No free full text.

Abstract: Psoriasis is a chronic scaling and inflammatory skin disease that can affect patients' quality of life and daily functioning. We studied the scores of 85 patients suffering from moderate to severe plaque-type psoriasis, participating in a randomized controlled trial. We compared their scores on a generic quality-of-life instrument with data from two reference populations. We examined associations between clinical severity, as measured by the components of the Psoriasis Area and Severity Index (PASI), and the respective quality-of-life subdimensions, measured by the Medical Outcome Survey Short Form 36 (SF-36), to find out what elements of disease activity are related with impaired quality of life. Compared to the reference population, quality of life was impaired in terms of bodily pain and social functioning. There were no significant correlations between overall disease severity, as measured by PASI, and the SF-36 subdimensions. When examining the PASI components, we found significant correlations between desquamation on the upper limbs and mental health and bodily pain (r = -0.23 and r = -0.28, respectively) and between desquamation on the scalp and mental health (r = -0.29). In conclusion, we found that psoriasis patients had a lower quality of life than a reference population, without a significant relation between disease severity or disease area and quality of life. Yet psoriasis lesions located on visible body parts are significantly correlated with aspects of quality of life.

Goedkoop AY, de Rie MA, Picavet DI, Kraan MC, Dinant HJ, van Kuijk AW, Tak PP, Bos JD, Teunissen MB. · Department of Dermatology, Academic Medical Center, University of Amsterdam, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands. · Arch Dermatol Res. · Pubmed #14968366 No free full text.

Abstract: Alefacept, a LFA-3/IgG1 fusion protein, interferes with the activation and proliferation of T cells by binding to the CD2 receptor on their surfaces. The clinical efficacy of this drug has been demonstrated in chronic plaque psoriasis. We performed a single-center, open-label study to investigate the immunohistochemical effects in psoriatic lesional skin. A group of 11 patients with plaque psoriasis all received 12 weekly doses of 7.5 mg alefacept intravenously. Skin biopsies were obtained at baseline and on days 8, 43 and 92, and were evaluated by digital image analysis after immunohistochemical staining. After completion of treatment, 8 out of the 11 patients experienced a reduction in PASI of 50% or more compared to baseline. Immunohistochemical analysis displayed a gradual decrease in the number of cutaneous T cells during therapy, with a significant reduction in epidermal CD8+ cells and dermal CD4+ cells on day 92. Patients with a reduction in PASI of 50% or more after therapy had a clearance of effector/memory T cells from the epidermis, in contrast to patients with a reduction in PASI of less than 50%. These findings support the hypothesis that effector/memory T cells play a prominent role in the pathogenesis of psoriasis, and that alefacept is capable of reducing these cells in lesional psoriatic skin.

Heydendael VM, Spuls PI, Opmeer BC, de Borgie CA, Reitsma JB, Goldschmidt WF, Bossuyt PM, Bos JD, de Rie MA. · Department of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · N Engl J Med. · Pubmed #12917302 links to  free full text

Abstract: BACKGROUND: Methotrexate and cyclosporine are well-known systemic therapies for moderate-to-severe chronic plaque psoriasis. We conducted a randomized, controlled trial comparing methotrexate and cyclosporine in terms of effectiveness, side effects, and the quality of life. METHODS: A total of 88 patients with moderate-to-severe psoriasis were randomly assigned to treatment for 16 weeks with either methotrexate (44 patients; initial dose, 15 mg per week) or cyclosporine (44 patients; initial dose, 3 mg per kilogram of body weight per day) and were followed for another 36 weeks. The primary outcome was the difference between groups in the psoriasis area-and-severity index after 16 weeks of treatment, after adjustment for base-line values; scores were determined in a blinded fashion by trained observers. RESULTS: Two patients were excluded from the analysis after randomization because they were found to be ineligible, and one patient withdrew his consent. Twelve patients in the methotrexate group had to discontinue treatment because of reversible elevations in liver-enzyme levels, and 1 patient in the cyclosporine group had to do so because of an elevation in the bilirubin level, but all 13 were included in the analysis. After 16 weeks of treatment, the mean (+/-SE) score for the psoriasis area-and-severity index decreased from 13.4+/-3.6 at base line to 5.0+/-0.7 among 43 patients treated with methotrexate, whereas the score decreased from 14.0+/-6.6 to 3.8+/-0.5 among 42 patients treated with cyclosporine. After adjustment for base-line values, the mean absolute difference in values at 16 weeks was 1.3 (95 percent confidence interval, -0.2 to 2.8; P=0.09). The physician's global assessment of the extent of psoriasis, the time to and the rates of remission, and the quality of life were similar in the two groups. CONCLUSIONS: No significant differences in efficacy were found between methotrexate and cyclosporine for the treatment of moderate-to-severe psoriasis.

Piskin G, Heydendael VM, de Rie MA, Bos JD, Teunissen MB. · Department of Dermatology, Room L3-359, Academic Medical Center, University of Amsterdam, P.O. Box: 22700, The Netherlands. · Arch Dermatol Res. · Pubmed #12624782 No free full text.

This publication has no abstract.

Kraan MC, van Kuijk AW, Dinant HJ, Goedkoop AY, Smeets TJ, de Rie MA, Dijkmans BA, Vaishnaw AK, Bos JD, Tak PP. · Division of Clinical Immunology and Rheumatology F4-218, Academic Medical Center/University of Amsterdam, Meibergdreef 9, NL-1105 AZ Amsterdam, The Netherlands. · Arthritis Rheum. · Pubmed #12384938 links to  free full text

Abstract: OBJECTIVE: To investigate whether alefacept (a fully human lymphocyte function-associated antigen 3 [LFA-3]/IgG1 fusion protein that blocks the LFA-3/CD2 interaction) is able to reduce the signs and symptoms of joint inflammation in patients with active psoriatic arthritis (PsA). METHODS: Eleven patients with active PsA were treated with alefacept for 12 weeks in an open-label and explorative study. Clinical joint assessment and laboratory assessments were performed at baseline and after 4, 9, 12, and 16 weeks of treatment. Serial synovial tissue (ST) biopsy specimens from an inflamed index joint (knee, ankle, wrist, or metacarpophalangeal joint) were obtained by arthroscopy at baseline and after 4 and 12 weeks of treatment. RESULTS: At the completion of treatment, 6 of 11 patients (55%) fulfilled the Disease Activity Score (DAS) response criteria. Nine patients (82%) fulfilled the DAS response criteria at any point during the study. There was a statistically significant reduction in CD4+ lymphocytes (P < 0.05), CD8+ lymphocytes (P = 0.05), and CD68+ macrophages (P < 0.02) in the ST after 12 weeks of treatment compared with baseline. The ST and peripheral blood of those patients fulfilling the DAS response criteria contained more CD45RO+ cells at baseline and displayed a significant reduction in these cells compared with nonresponding patients. CONCLUSION: The changes in ST, together with the improvement in clinical joint scores, after treatment with alefacept support the hypothesis that T cell activation plays an important role in this chronic inflammatory disease. Furthermore, since alefacept, a T cell-specific agent, led to decreased macrophage infiltration, the data indicate that T cells are highly involved in synovial inflammation in PsA.

Brands S, Brakman M, Bos JD, de Rie MA. · Department of Dermatology, Academic Medical Centre, University of Amsterdam, and the Department of Dermatology, Reinier de Graaf Gasthuis, Delft, The Netherlands. · J Am Acad Dermatol. · Pubmed #10570386 No free full text.

Abstract: BACKGROUND: Broad-band UVB phototherapy has appeared to be effective in clearing psoriatic lesions. After the advent of calcipotriol ointment, promising results have been obtained by combining these two therapeutic modalities. Also, an additional effect of narrow-band UVB phototherapy on treatment with calcipotriol ointment has been demonstrated. OBJECTIVE: Our purpose was to compare treatment with low-dose narrow-band UVB phototherapy both with and without calcipotriol ointment. METHODS: We included 53 patients suffering from plaque-type psoriasis. All patients underwent low-dose narrow-band UVB phototherapy. Nearly half of the patients were randomized to apply calcipotriol ointment (50 microg/g) twice daily on the affected skin. The Psoriasis Area and Severity Index (PASI) was used to evaluate psoriatic lesions. RESULTS: In this study we showed that low-dose narrow-band UVB phototherapy is effective in the treatment of psoriasis and that calcipotriol ointment does not improve treatment outcome. CONCLUSION: Calcipotriol ointment does not improve treatment with low-dose narrow-band UVB phototherapy.

de Groot M, Teunissen MB, Ortonne JP, Lambert JR, Naeyaert JM, Picavet DI, Arreaza MG, Simon JS, Kraan M, Bos JD, de Rie MA. · Department of Dermatology, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands, · Arch Dermatol Res. · Pubmed #17647003 links to  free full text

Abstract: Several reports have indicated that the chemokine receptor CCR5 and its ligands, especially CCL5 (formerly known as RANTES), may play a role in the pathogenesis of psoriasis. The purpose of this investigation was to examine the expression of CCR5 and its ligands in chronic plaque psoriasis and to evaluate the clinical and immunohistochemical effect of a CCR5 receptor inhibitor. Immunohistochemical analysis showed low but significant increased total numbers of CCR5 positive cells in epidermis and dermis of lesional skin in comparison to non-lesional skin. However, relative expression of CCR5 proportional to the cells observed revealed that the difference between lesional and non-lesional skin was only statistically significant in the epidermis for CD3 positive cells and in the dermis for CD68 positive cells. Quantification of mRNA by reverse transcriptase-polymerase chain reaction only showed an increased expression of CCL5 (RANTES) in lesional skin. A randomized placebo-controlled clinical trial in 32 psoriasis patients revealed no significant clinical effect and no changes at the immunohistochemical level comparing patients treated with placebo or a CCR5 inhibitor SCH351125. We conclude that although CCR5 expression is increased in psoriatic lesions, this receptor does not play a crucial role in the pathogenesis of psoriasis.

Opmeer BC, Heydendael VM, deBorgie CA, Spuls PI, Bossuyt PM, Bos JD, de Rie MA. · Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, P.O. Box 22660, 1100 DD, Amsterdam, The Netherlands. · J Clin Epidemiol. · Pubmed #17573985 No free full text.

Abstract: OBJECTIVE: The importance of validly identifying and incorporating patients' views for improving health care is generally acknowledged. Common approaches to assess patients' preferences are based on the quality adjusted life year (QALY) framework, but this ignores a number of aspects that may be relevant. As an alternative, we assessed patients' treatment preferences and trade-offs for five common systemic therapies for psoriasis. STUDY DESIGN AND SETTING: Twenty-nine patients with moderate-to-severe psoriasis expressed treatment preferences for five oral and phototherapies and indicated the relative importance of various treatment attributes, such as adverse effects, discomforts, and safety measures. In a structured interview, they were presented with clinical scenarios that contained descriptions of process and outcome characteristics and illustrations of the anticipated treatment benefit. RESULTS: Over all paired comparisons, methotrexate (33%), cyclosporin (30%), acitretin (15%), UV-B (14%), and PUVA (8%) were preferred to the other treatment. Patients were willing to trade-off their initial preference for more improvement of psoriasis. CONCLUSIONS: Psoriasis patients generally prefer oral to phototherapies and consider most adverse effects and several discomforts important for selecting treatment. Our scenario-based structured interview approach to treatment preferences allowed us to incorporate a broad spectrum of potentially relevant decision components in a clinically meaningful way.

de Groot M, Appelman M, Spuls PI, de Rie MA, Bos JD. · Department of Dermatology A0-252, Academic Medical Centre, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, the Netherlands. · Br J Dermatol. · Pubmed #16965432 No free full text.

Abstract: BACKGROUND: Etanercept and efalizumab recently became available and reimbursed for routine use in severe psoriasis in the Netherlands. The criteria for reimbursement are Psoriasis Area and Severity Index (PASI) > or = 10 (or Skindex-29 > or = 35 if PASI > or = 8 and < 10) and ineffectiveness of ultraviolet (UV) B/psoralen plus UVA, methotrexate and ciclosporin, or a contraindication to or serious side-effect(s) during these treatments. OBJECTIVES: We hypothesized: (i) that efficacy would be lower than that obtained in published phase II and III studies because (a) resistance to all conventional therapies as a reimbursement condition would select for more resistant cases and (b) inclusion would be more restricted to severe cases (higher PASI), and (ii) that efficacy would be lower in obese patients due to the possible role of adipose tissue in tumour necrosis factor (TNF)-alpha homeostasis. METHODS: We treated 50 patients (38 men, 12 women; mean PASI 15.8) with etanercept 25 mg or 50 mg twice weekly and evaluated in a retrospective analysis the efficacy and safety in comparison with data from published trials. Additionally, we related the clinical effect to the body mass index (BMI), for adipose tissue is thought to have a possible role in TNF-alpha homeostasis. RESULTS: Based on the literature, 30% and 49% of the patients treated with etanercept 25 mg and 50 mg twice weekly, respectively, should have achieved 75% or more improvement in PASI compared with baseline (PASI 75), and 10% and 21%, respectively, should have achieved 90% or more improvement (PASI 90). Our data showed that 21% in the 2 x 25 mg group and 23% in the 2 x 50 mg group achieved PASI 75. PASI 90 was only attained in 7% of patients treated with 2 x 25 mg and 6% of those treated with 2 x 50 mg. Contrary to our hypothesis, the mean initial PASI was comparable with the mean PASI mentioned in the phase II and III clinical trials. Although fatigue is not identified as a side-effect of etanercept, 10% of our patients reported fatigue as an adverse event during etanercept treatment. High BMI, indicating overweight or obesity, was found both in patients with little efficacy and in patients achieving PASI 75 or better. CONCLUSIONS: Use of etanercept in real practice gives impressive results, but these are generally less favourable than those published in clinical trial reports. This is probably due to the stringent conditions for reimbursement, which select for more treatment-resistant patients. Fatigue as a possible side-effect of etanercept should also be an issue for further investigation. Finally, the BMI does not seem to influence the patients' response to etanercept, although further investigations would be needed to confirm this.