Psoriasis: Reich K

Nast A, Kopp IB, Augustin M, Banditt KB, Boehncke WH, Follmann M, Friedrich M, Huber M, Kahl C, Klaus J, Koza J, Kreiselmaier I, Mohr J, Mrowietz U, Ockenfels HM, Orzechowski HD, Prinz J, Reich K, Rosenbach T, Rosumeck S, Schlaeger M, Schmid-Ott G, Sebastian M, Streit V, Weberschock T, Rzany B, Anonymous00272, Anonymous00273. · Division of Evidence Based Medicine (dEBM), Klinik für Dermatologie, Venerologie und Allergologie, Charité-Universitätsmedizin Berlin, Germany. · J Dtsch Dermatol Ges. · Pubmed #17615051 No free full text.

Abstract: Psoriasis vulgaris is a common and often chronic inflammatory skin disease. The incidence of psoriasis in Western industrialized countries ranges from 1 to 2%. Patients afflicted with severe psoriasis vulgaris may experience a significant reduction in quality of life. Despite the large variety of treatment options available, patient surveys have revealed lack of satisfaction with the efficacy of available treatments and a high rate of non-compliance. To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft (DDG) and the Berufsverband Deutscher Dermatologen (BVDD) initiated a project to develop evidence-based guidelines for the management of psoriasis. These resulting Guidelines focus on induction therapy in cases of mild, moderate, and severe plaquetype psoriasis in adults. The Guidelines include evidence-based evaluation of the efficacy of all currently available therapeutic options in Germany. In addition, they offer detailed information on how best to administer the various treatments and give information on contraindications, adverse drug reactions, and drug interactions as well as estimates of practicability and cost. The Guidelines were developed following the recommendations of the Arbeitsgemeinschaft wissenschaftlicher medizinischer Fachgesellschaften (AWMF). The therapeutic recommendations were developed by an expert group and finalized during interdisciplinary consensus conferences.

Nast A, Kopp I, Augustin M, Banditt KB, Boehncke WH, Follmann M, Friedrich M, Huber M, Kahl C, Klaus J, Koza J, Kreiselmaier I, Mohr J, Mrowietz U, Ockenfels HM, Orzechowski HD, Prinz J, Reich K, Rosenbach T, Rosumeck S, Schlaeger M, Schmid-Ott G, Sebastian M, Streit V, Weberschock T, Rzany B. · Division of Evidence Based Medicine, Klinik für Dermatologie, Venerologie, Allergologie, Charité-Universitätsmedizin Berlin, Schumannstrasse 20/21, Berlin, Germany. · Arch Dermatol Res. · Pubmed #17497162 links to  free full text

Abstract: Psoriasis vulgaris is a common and chronic inflammatory skin disease which has the potential to significantly reduce the quality of life in severely affected patients. The incidence of psoriasis in Western industrialized countries ranges from 1.5 to 2%. Despite the large variety of treatment options available, patient surveys have revealed insufficient satisfaction with the efficacy of available treatments and a high rate of medication non-compliance. To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the management of psoriasis. The guidelines focus on induction therapy in cases of mild, moderate, and severe plaque-type psoriasis in adults. The short version of the guidelines reported here consist of a series of therapeutic recommendations that are based on a systematic literature search and subsequent discussion with experts in the field; they have been approved by a team of dermatology experts. In addition to the therapeutic recommendations provided in this short version, the full version of the guidelines includes information on contraindications, adverse events, drug interactions, practicality, and costs as well as detailed information on how best to apply the treatments described (for full version, please see Nast et al., JDDG, Suppl 2:S1-S126, 2006; or http://www.psoriasis-leitlinie.de ).

Nast A, Kopp IB, Augustin M, Banditt KB, Boehncke WH, Follmann M, Friedrich M, Huber M, Kahl C, Klaus J, Koza J, Kreiselmaier I, Mohr J, Mrowietz U, Ockenfels HM, Orzechowski HD, Prinz J, Reich K, Rosenbach T, Rosumeck S, Schlaeger M, Schmid-Ott G, Sebastian M, Streit V, Weberschock T, Rzany B, Anonymous00487. · Division of Evidence Based Medicine (dEBM), Klinik für Dermatologie, Venerologie und Allergologie, Charité-Universitätsmedizin Berlin. · J Dtsch Dermatol Ges. · Pubmed #17187649 No free full text.

This publication has no abstract.

Mrowietz U, Barth J, Boehncke WH, Reich K, Rosenbach T, Streit V, Wozel G. · Universitäts-Hauklinik Kiel. · J Dtsch Dermatol Ges. · Pubmed #16734844 No free full text.

This publication has no abstract.

Augustin M, Reich K, Reusch M, Luger T, Franzke N, Schafer I, Rustenbach SJ, Radtke MA. · No affiliation provided · Dermatology. · Pubmed #19270443 No free full text.

This publication has no abstract.

Reich K, Griffiths CE. · Dermatologikum Hamburg, Stephansplatz 5, 20354 Hamburg, Germany. · Arch Dermatol Res. · Pubmed #18784934 No free full text.

Abstract: The physical presentation of psoriasis and its impact on health-related quality of life (HRQoL) varies greatly between patients as well as over the course of the disease. A number of instruments have been developed for evaluating disease severity and its impact on HRQoL, the best known being the Psoriasis Area and Severity Index (PASI). HRQoL is most commonly evaluated using the Dermatology Life Quality Index (DLQI) and/or the Short-Form-36 Health Survey (SF-36). The exact correlation between the reduction of skin symptoms upon therapy and changes of HRQoL is not known. Since improvement of HRQoL is being established as an independent goal of psoriasis therapy, a better understanding of the relationship between skin symptoms and HRQoL during treatment will likely influence not only disease concepts but also physicians treatment decisions. Based on a selective review of the literature, this paper focuses on recent insight obtained from clinical trials with infliximab on the correlation between skin clearance and changes of HRQoL in psoriasis and compares these findings with results from studies with other biologics. Together these data indicate that despite the lack of a direct correlation between absolute PASI and DLQI values, significant reductions of PASI are likely to correlate with significant improvements of HRQoL. There is also evidence, that large improvements of HRQoL as currently discussed as treatment goals in psoriasis are primarily achieved in patients with an at least 75% reduction of their PASI.

Mössner R, Schön MP, Reich K. · Department of Dermatology, Georg-August University, von-Siebold-Str. 3, 37075 Göttingen, Germany. · Clin Dermatol. · Pubmed #18755367 No free full text.

Abstract: The identification of new pathophysiological mechanisms in chronic inflammatory diseases and the development of techniques that allow production of antibodies and fusion proteins that antagonize target molecules with high specificity has not only revolutionized the treatment of rheumatoid arthritis and chronic inflammatory bowel disease, but it also has revolutionized the treatment of psoriasis in recent years. Two different classes of so-called biological therapies (biologics) have become available to treat psoriasis: tumor necrosis factor (TNF) antagonists and T-cell modulators. TNF antagonists that have been studied with psoriasis include the antibodies infliximab and adalimumab and the fusion protein etanercept. These treatments differ in their capacity to reduce the skin symptoms of psoriasis and other important characteristics of the drug profile. This article summarizes the important aspects of efficacy, safety, and practicability of TNF antagonists in the treatment of psoriasis. This article may be helpful for the daily routine when selecting the right therapy for a patient and managing the TNF antagonist during maintenance therapy.

Reich K, Sinclair R, Roberts G, Griffiths CE, Tabberer M, Barker J. · Dermatologikum Hamburg, Hamburg, Germany. · Curr Med Res Opin. · Pubmed #18355421 No free full text.

Abstract: BACKGROUND: The comparative effects of biological response modifiers (BRMs) on the severity of psoriasis and its effects on health-related quality of life (HRQoL) have not been evaluated. OBJECTIVE: To conduct a meta-analysis to assess the effects of available biological agents on the severity of psoriasis, as well as to provide data on the effects of these agents on HRQoL. METHODS: Medline and other databases were searched for randomized controlled trials (>or= 10 weeks' duration in adults) comparing biological therapies for moderate-to-severe psoriasis with placebo. A Mantel-Haenszel fixed-effects model was employed to estimate the pooled relative risks (RR) of patients achieving >or= 75% reduction of baseline Psoriasis Area and Severity Index (PASI 75) after >or= 10 weeks of treatment. Similar analyses were also conducted on PASI 50 and PASI 90. Using a random-effects model, we estimated the likelihood of achieving PASI 50, PASI 75, and PASI 90 at 10-12 weeks and 24 weeks. Data on the effects of different BRMs (vs. placebo) on HRQoL were also presented. Numbers (%) of patients discontinuing treatment were presented as a general index of drug tolerability. RESULTS: Patients receiving infliximab 5 mg/kg intravenously at weeks 0, 2, and 6, then every 8 weeks, had the highest RR of achieving PASI 75, with a pooled RR value of 25.48 (95% confidence interval [CI], 14.04-46.23); followed by etanercept 50 mg administered subcutaneously (SC) twice weekly with RR = 11.92 (95% CI, 8.17-17.39); etanercept 25 mg SC twice weekly with RR = 10.68 (95% CI, 6.15-18.57); efalizumab 1-2 mg/kg SC per week with RR = 7.47 (95% CI, 5.20-10.73); and alefacept administered weekly (various doses) with RR = 3.37 (95% CI, 2.18-5.23). (All RR values were estimated vs. placebo.) Similar findings were observed with regard to proportions of patients achieving PASI 50 and PASI 90. The random-effects analysis suggested that infliximab significantly increased the likelihood of achieving PASI 50, PASI 75, and PASI 90 compared with placebo at 10-12 weeks; however, there were no significant differences between biological treatments at 24 weeks. Each BRM improved HRQoL compared with placebo according to findings from the Dermatology Life Quality Index. Proportions of patients discontinuing treatment were similar in active-treatment and placebo groups. CONCLUSIONS: Infliximab significantly reduced disease severity by both fixed- and random-effects models. All biological therapies improved HRQoL compared with placebo, and proportions of patients discontinuing treatment were similar in active-treatment and placebo groups. The analysis is potentially limited by statistical factors and did not systematically account for different toxicity profiles, but the findings establish a foundation for head-to-head comparative trials.

Reich K, Mrowietz U. · Dermatologikum Hamburg, Germany. · J Dtsch Dermatol Ges. · Pubmed #17610606 No free full text.

Abstract: The introduction of biologics has not only broadened the therapeutic armamentarium for psoriasis but also stimulated discussion about the treatment of this common skin condition. The recently presented German S3 psoriasis guideline contains detailed information on the efficacy of the different products and describes important safety and practical aspects of psoriasis treatments. Patient surveys and recent studies in Germany indicate a relatively high mean severity of skin symptoms and low quality of life among affected patients. One possible explanation is that the conventional traditional and new treatment options are not being used consistently. In this paper, minimum treatment goals for psoriasis that should be achieved by an individually selected treatment regimen are presented. If, after a defined period of time, an at least 50 % reduction of the baseline Psoriasis Area and Severity Index (PASI) and a Dermatology Life Quality Index of ( not less-than 5 is not reached, patients should be switched to another therapy, after a balanced discussion. Whenever necessary, a continuous maintenance therapy should be instituted with special attention to these goals. Patients should carefully be monitored for the presence of psoriatic arthritis and comorbidities because these may need to be integrated in the planning of treatment goals on an interdisciplinary basis.

Mössner R, Reich K. · Abteilung Dermatologie und Venerologie, Georg-August-Universität Göttingen. · Hautarzt. · Pubmed #16133635 No free full text.

Abstract: Psoriasis is one of the immune-mediated inflammatory diseases (IMIDs), in whose pathogenesis Th1-mediated immune responses are considered crucial. Infliximab is a chimeric monoclonal antibody directed against the Th1-cytokine TNF-alpha that has already been approved for the therapy of psoriatic arthritis (in combination with methotrexate). In clinical studies, infliximab has proved safe and effective in treating plaque-type psoriasis. In 80% of treated patients, the Psoriasis Area and Severity Index (PASI) decreased after 10 weeks by > or =75%. Infliximab is expected to be approved as second-line therapy in Germany this year for the treatment of psoriasis vulgaris.

Papp KA, Langley RG, Lebwohl M, Krueger GG, Szapary P, Yeilding N, Guzzo C, Hsu MC, Wang Y, Li S, Dooley LT, Reich K, Anonymous00035. · Probity Medical Research, Waterloo and University of Western Ontario, London, ON, Canada. · Lancet. · Pubmed #18486740 No free full text.

Abstract: BACKGROUND: Ustekinumab, a human monoclonal antibody against interleukins 12 and 23, has shown therapeutic potential for psoriasis. This study assessed the efficacy and safety of ustekinumab in psoriasis patients and assessed dosing intensification in partial responders. METHODS: In this multicentre, phase III, double-blind, placebo-controlled study, 1230 patients with moderate-to-severe psoriasis (defined by a psoriasis area and severity index [PASI] score > or =12, and at least 10% total body surface area involvement) were randomly assigned to receive ustekinumab 45 mg (n=409) or 90 mg (n=411) at weeks 0 and 4, then every 12 weeks, or placebo (n=410). Partial responders (ie, patients achieving > or =50% but <75% improvement from baseline in PASI) were re-randomised at week 28 to continue dosing every 12 weeks or escalate to dosing every 8 weeks. Both randomisations were done with a minimisation method via a centralised interactive voice response. The primary endpoint was the proportion of patients achieving at least 75% improvement in PASI (PASI 75) at week 12. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00307437. FINDINGS: All randomised patients were included in the efficacy analysis. 273 (66.7%) patients receiving ustekinumab 45 mg, 311 (75.7%) receiving ustekinumab 90 mg, and 15 (3.7%) receiving placebo achieved the primary endpoint (difference in response rate 63.1%, 95% CI 58.2-68.0, p<0.0001 for the 45 mg group vs placebo and 72.0%, 67.5-76.5, p<0.0001 for the 90 mg group vs placebo). More partial responders at week 28 who received ustekinumab 90 mg every 8 weeks achieved PASI 75 at week 52 than did those who continued to receive the same dose every 12 weeks (22 [68.8%] vs 11 [33.3%]; difference in response rate 35.4%, 95% CI 12.7-58.1, p=0.004). There was no such response to changes in dosing intensity in partial responders treated with ustekinumab 45 mg. During the placebo-controlled phase, 217 (53.1%) patients in the 45 mg group, 197 (47.9%) in the 90 mg group, and 204 (49.8%) in the placebo group experienced adverse events; serious adverse events were seen in eight (2.0%) patients in the 45 mg group, five (1.2%) in the 90 mg group, and eight (2.0%) in the placebo group. INTERPRETATION: Although treatment with ustekinumab every 12 weeks is effective for most patients with moderate-to-severe psoriasis, intensification of dosing to once every 8 weeks with ustekinumab 90 mg might be necessary to elicit a full response in patients who only partially respond to the initial regimen.

Rich P, Griffiths CE, Reich K, Nestle FO, Scher RK, Li S, Xu S, Hsu MC, Guzzo C. · Oregon Health Sciences University, Dermatology and Clinical Research, Portland, Oregon 97210, USA. · J Am Acad Dermatol. · Pubmed #18083272 No free full text.

Abstract: BACKGROUND: Although nail psoriasis occurs frequently in patients with psoriatic skin lesions, effective treatments are limited. OBJECTIVE: Occurrence of nail psoriasis by type and incidence of nail clearance using the Nail Psoriasis Severity Index were evaluated. METHODS: This was a 50-week, phase III study in which 378 patients with moderate to severe psoriasis were randomized 4:1 to infliximab (5 mg/kg) or placebo at weeks 0, 2, 6, and every 8 weeks through week 46, with placebo crossover to infliximab at week 24. RESULTS: Of the 373 evaluated patients, 305 (81.8%) had baseline nail psoriasis. The right thumbnail was most often the worst involved nail, and pitting and onycholysis were the most common lesions. Among patients with baseline nail psoriasis, 6.9%, 26.2%, and 44.7% in the infliximab group had nail disease clearance at weeks 10, 24, and 50, respectively, versus 5.1% in the placebo group at week 24 (P < .001). Mean percent improvements in Nail Psoriasis Severity Index score at weeks 10 and 24 were 26.8% and 57.2%, respectively, in the infliximab group versus -7.7% and -4.1%, respectively, in the placebo group (both P < .001). At week 24, mean percent improvements in nail matrix and nail bed features were 52.9% and 69.2%, respectively (vs -1.9% and 18.4% for placebo; P < .001). LIMITATIONS: The study did not evaluate nail response beyond 1 year. CONCLUSIONS: Patients with psoriasis receiving infliximab experienced marked and sustained nail improvement.

Reich K, Nestle FO, Papp K, Ortonne JP, Wu Y, Bala M, Evans R, Guzzo C, Li S, Dooley LT, Griffiths CE. · Department of Dermatology, Georg-August University, Göttingen, Germany. · Br J Dermatol. · Pubmed #16704649 No free full text.

Abstract: BACKGROUND: Psoriasis has a well-documented, markedly negative effect on patient quality of life. OBJECTIVES: To evaluate the impact of long-term infliximab maintenance therapy on health-related quality of life (HRQoL) in patients with psoriasis. METHODS: The Dermatology Life Quality Index (DLQI) and 36-item Short Form Health Survey (SF-36) were administered as part of the pivotal double-blind, placebo-controlled efficacy and safety EXPRESS study of infliximab in chronic plaque psoriasis. In total, 378 patients with moderate-to-severe psoriasis were enrolled at 32 centres in Europe and Canada. Patients were randomized to receive either placebo or infliximab 5 mg kg(-1) induction at weeks 0, 2 and 6 followed by maintenance every 8 weeks; placebo patients crossed over at week 24 to receive the infliximab induction and maintenance regimen. RESULTS: At week 10, infliximab-treated patients had significantly greater improvement in DLQI scores (P < 0.001) and SF-36 physical and mental component summary scores (P < 0.001) than placebo-treated patients. Significant improvement (P < 0.001) was also seen in all eight SF-36 subscales, and was greatest for the "Bodily Pain" and "Social Functioning" scales. Significant improvement in HRQoL persisted with maintenance infliximab treatment at week 24 (P < 0.001), with patients achieving a Psoriasis Area and Severity Index score of 0 reporting the greatest benefit. Treatment-related HRQoL improvement remained substantial at week 50. CONCLUSIONS: Infliximab induction and maintenance regimens resulted in rapid, substantial, sustained and clinically meaningful improvement in both dermatology-specific and general quality of life indices in patients with psoriasis, with total clearance resulting in maximum improvement.

Reich K, Nestle FO, Papp K, Ortonne JP, Evans R, Guzzo C, Li S, Dooley LT, Griffiths CE, Anonymous00095. · Department of Dermatology, Georg-August University, Göttingen, Germany. · Lancet. · Pubmed #16226614 No free full text.

Abstract: BACKGROUND: Tumour necrosis factor alpha (TNFalpha) is thought to play a part in the pathogenesis of psoriasis. We assessed the efficacy and safety of continuous treatment with infliximab, a monoclonal antibody that binds to and neutralises the activity of TNFalpha, in patients with psoriasis. METHODS: In this phase III, multicentre, double-blind trial, 378 patients with moderate-to-severe plaque psoriasis were allocated in a 4:1 ratio to receive infusions of either infliximab 5 mg/kg or placebo at weeks 0, 2, and 6, then every 8 weeks to week 46. At week 24, placebo-treated patients crossed over to infliximab treatment. Skin and nail signs of psoriasis were assessed using the psoriasis area and severity index (PASI) and nail psoriasis severity index (NAPSI), respectively. The primary endpoint, analysed on an intention-to-treat-basis, was the proportion of patients achieving at least a 75% improvement in PASI from baseline to week 10. FINDINGS: At week 10, 80% (242/301) of patients treated with infliximab achieved at least a 75% improvement from their baseline PASI (PASI 75) and 57% (172/301) achieved at least a 90% improvement (PASI 90), compared with 3% and 1% in the placebo group, respectively (p<0.0001). At week 24, PASI 75 (82% for infliximab vs 4% for placebo) and PASI 90 (58%vs 1%) were maintained (p<0.0001). At week 50, 61% achieved PASI 75 and 45% achieved PASI 90 in the infliximab group. Infliximab was generally well tolerated in most patients. INTERPRETATION: Infliximab is effective in both an induction and maintenance regimen for the treatment of moderate-to-severe psoriasis, with a high percentage of patients achieving sustained PASI 75 and PASI 90 improvement through 1 year.

Reich K, Garbe C, Blaschke V, Maurer C, Middel P, Westphal G, Lippert U, Neumann C. · Department of Dermatology, Georg-August-University, Von-Siebold-Strasse 3, 37075 Göttingen, Germany. · J Invest Dermatol. · Pubmed #11180010 links to  free full text

Abstract: Psoriasis is a chronic inflammatory skin disease in which epidermal hyperplasia results from the release of cytokines by infiltrating type 1 T cells. Up- regulation of endogenous interleukin-10 controls type 1 skin responses in animal models; however, interleukin-10 production is low in psoriatic lesions. Consistent with an important role of interleukin-10 in psoriasis, we and colleagues have recently demonstrated clinical efficacy of subcutaneous administration of recombinant interleukin-10 to affected patients. Here, we studied the effects of interleukin-10 on disease-related inflammatory pathways. Patients were treated with recombinant interleukin-10 over 6 wk in an open-label phase II clinical trial. Tissue was obtained before and after therapy and examined by histology/immunohistochemistry, in situ hybridization, and quantitative real-time reverse transcription-polymerase chain reaction. Ten of 14 patients showed a marked reduction of the clinical disease activity. The clinical response was associated with a significant decrease of cutaneous T cell infiltration and the lesional expression of type 1 cytokines interferon-gamma and tumor necrosis factor-alpha. Interleukin-10 inhibited the epidermal interleukin-8 pathway by downregulating the expression of interleukin-8, its receptor CXCR2, and its inducer interleukin-17, and partially reversed the aberrant keratinocyte maturation defining psoriatic epidermal pathology. Remarkably, there was evidence that genetic factors are involved in the response to interleukin-10 as individual variations in the downregulation of tumor necrosis factor-alpha were related to the presence of polymorphisms in the tumor necrosis factor-alpha promoter. These data suggest that excessive production of type 1 cytokines in human skin disease can be counter-regulated by the administration of recombinant interleukin-10. Genotypic analysis may help to identify patients that will preferentially respond to interleukin-10 therapy.

Mrowietz U, Reich K. · Psoriasis-Zentrum, Abteilung Dermatologie, Venerologie und Allergologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Schittenhelmstr. 7, 24105 Kiel, Germany. · Dtsch Arztebl Int. · Pubmed #19564982 links to  free full text

Abstract: BACKGROUND: Psoriasis is one of the most prevalent chronic inflammatory diseases, affecting approximately 2 million people in Germany. METHODS: Selective literature review taking into account the German S1 and S3 guidelines for the treatment of this condition. RESULTS AND CONCLUSIONS: Psoriasis is a very troublesome disease with a high economic impact. The disease often persists for life, and the patient has an increased risk of cardiovascular diseases and their complications. One out of five patients develops psoriatic arthritis. The clinical picture of psoriasis is highly variable with regard to lesional characteristics and the severity of disease. To improve the management of psoriasis the guidelines must be followed and all appropriate topical and systemic treatment options must be tried, with clearly defined treatment goals. The spectrum of established systemic treatments for psoriasis has been extended by the biologics. These can be used to achieve a good skin status and a clear-cut improvement in quality of life even in patients who do not--or no longer--respond adequately to conventional therapies.

Reich K, Thaci D, Mrowietz U, Kamps A, Neureither M, Luger T. · Dermatologikum Hamburg, Hamburg, Germany. · J Dtsch Dermatol Ges. · Pubmed #19459898 No free full text.

Abstract: BACKGROUND: This study collected data on the safety and efficacy of fumaric acid esters (FAE; Fumaderm) in the long-term treatment of psoriasis. PATIENTS AND METHODS: Patients were included at 163 dermatological centers if they either had been treated continuously with FAE for at least 24 months, or for 36 months with interruptions of no longer than 6 months. Data were reported from baseline, after 3, 6, 12, 24, and 36 or more months of therapy. Safety parameters were monitored and the severity of skin symptoms was assessed by "Physician's Global Assessment" (PGA) and "Psoriasis Area and Severity Index" (PASI). RESULTS: 984 patients were included with a mean duration of 44 months of continuous treatment. The percentage of patients documented as markedly improved or clear was 67 % after six months, 78 % after 24 months, and 82 % after 36 months of therapy. Improvement was similar in patients with moderate and severe disease. Changes of laboratory parameters were usually insignificant and did not require a modification of FAE treatment in more than 90 % of the cases. CONCLUSIONS: In the long-term treatment of patients with moderate and severe psoriasis FAE show a good and sustained clinical efficacy combined with a favorable safety profile.

Radtke MA, Reich K, Blome C, Rustenbach S, Augustin M. · German Center for Health Services Research in Dermatology, Health Economics and QoL Research Group, Department of Dermatology, University Clinics of Hamburg, Hamburg, Germany. · J Eur Acad Dermatol Venereol. · Pubmed #19309433 No free full text.

Abstract: BACKGROUND: Psoriatic arthritis (PsA) is a chronic, systemic, inflammatory disorder characterized by the association of arthritis with psoriasis. Patients with PsA may have a heterogeneous and variable clinical course. Evidence that affected patients can have significant radiographic joint damage, functional impairment, reduced quality of life and long-term work disability is increasing. OBJECTIVES: This study aims to determine the prevalence and clinical features of psoriatic arthritis and joint complaints in patients with psoriasis examined in a German national survey. METHODS: This study is a non-interventional, cross-sectional analysis on 2009 patients with psoriasis from 13 dermatological hospitals and 129 dermatological private practices and outpatient clinics in Germany. Patients showing rheumatological symptoms were further recorded with respect to active arthritis and PsA symptoms according to Group for Research and Assessment of Psoriasis and Psoriatic Arthritis criteria. RESULTS: Nineteen per cent of the patients had PsA, including 14.8% previously confirmed and 4.2% newly diagnosed disease. Another 7.7% had intermittent but clinically unspecific joint symptoms, which could not be clearly attributed to PsA. About half (49.7%) of the patients with PsA had at least 1 swollen joint and 84.9% (n = 287) suffered from joint pain. Patients suffering from pain marked an average of 8.7 joints on a diagram as painful out of a possible 28. The mean number of swollen joints among the affected patients amounted to an average of 6.8. CONCLUSION: Our results show that there is still a significant number of patients suspected of having joint involvement without ever having been diagnosed with PsA. Recently published data indicate that progression of joint damage and functional disability can be prevented if adequate treatment is started promptly. Early diagnosis and interdisciplinary care are thus crucial.

Reich K, Krüger K, Mössner R, Augustin M. · Dermatologikum Hamburg, Stephansplatz 5, 20354 Hamburg, Germany. · Br J Dermatol. · Pubmed #19210498 No free full text.

Abstract: BACKGROUND: Because psoriatic arthritis (PsA) usually develops years after the first manifestation of skin symptoms, in many cases the initial diagnosis of PsA depends on the dermatologist. OBJECTIVES: To investigate the prevalence and clinical pattern of PsA in a daily practice population of patients with psoriasis. METHODS: Patients were enrolled in an observational prospective cross-sectional cohort study at 48 community and academic centres. Demographic and medical parameters were recorded, including severity of skin symptoms (Psoriasis Area and Severity Index, PASI), previous and current treatments, concomitant diseases, and the impact of psoriasis on productivity and health-related quality of life (Dermatology Life Quality Index, DLQI). Patients with joint symptoms were referred to a rheumatologist for diagnosis and to record the activity and pattern of arthritis. RESULTS: Among 1511 patients 20.6% had PsA; in 85% of the cases PsA was newly diagnosed. Of these patients more than 95% had active arthritis and 53.0% had five or more joints affected. Polyarthritis (58.7%) was the most common manifestation pattern, followed by oligoarthritis (31.6%) and arthritis mutilans (4.9%). Distal interphalangeal involvement was present in 41.0% and dactylitis in 23.7% of the patients. Compared with patients without arthritis, patients with PsA had more severe skin symptoms (mean PASI 14.3 vs. 11.5), a lower quality of life (mean DLQI 11.6 vs. 7.7) and greater impairment of productivity parameters. CONCLUSIONS: The findings are consistent with a high prevalence of undiagnosed cases of active PsA among patients with psoriasis seen by dermatologists. As many of these patients also have significant skin symptoms, treatment strategies are required that are equally effective in the control of skin and joint symptoms of psoriasis.

Menter A, Reich K, Gottlieb AB, Bala M, Li S, Hsu MC, Guzzo C, Diels J, Gelfand JM. · Psoriasis Research Unit, Baylor Research Institute, Dallas,TX, USA. · J Drugs Dermatol. · Pubmed #19137767 No free full text.

Abstract: INTRODUCTION: Infliximab is indicated for severe plaque psoriasis (PsO). The investigators compared safety event rates in infliximab PsO trials with those of the general United States and PsO populations. METHODS: Integrated data (n=1373 patients) were compared with external databases. RESULTS: The analyses reported here are based on 1106 patient years and 116 patient years of follow-up in the infliximab group and the placebo group, respectively. The standardized mortality ratio in infliximab-treated patients (0.17 [95% confidence interval [CI]: 0.00-0.92], 1 patient died) was lower than that of the general PsO population. No death occurred in the placebo group. Comparing with the psoriasis population, the standardized incidence ratios (SIRs) for hospitalization were 1.16 (95% CI: 0.92-1.43) in infliximab-treated patients and 1.07 (95% CI: 0.46-2.11) in placebo-treated patients. For serious infection, the SIRs were 1.28 (95% CI: 0.78-1.97) in infliximab-treated patients and 1.47 (95% CI: 0.18-5.32) in placebo patients. The incidence of tuberculosis (TB) among infliximab-treated patients was 0.18 per 100 patient-years (95% CI: 0.02-0.65). No TB occurred in the placebo group. Standardized incidence ratio for malignancy (excluding nonmelanoma skin cancers) was 0.39 (95% CI: 0.05-1.42; 2 malignancies) in infliximab-treated patients. No malignancy occurred in the placebo group. LIMITATIONS: Exclusion criteria in clinical studies may bias selection of subjects who are healthier than the general population. Additionally, the limited number of patients followed over a maximum of 1 year can limit the ability to detect infrequent events or those events that require prolonged follow-up to detect. Nonmelanoma skin cancers were excluded from the analysis. Finally, populations and adverse event definitions may have differed in external databases and studies. CONCLUSION: Based on the data from external databases, mortality, hospitalization, and serious infection rates in infliximab-treated patients were generally comparable to or less than that of the PsO population. Internal malignancy rates were similar to that expected in the general US population. However, the limitations of these data must be considered when compared with the totality of the safety profile of infliximab generated across all indications.

van de Kerkhof PC, Hoffmann V, Anstey A, Barnes L, Bolduc C, Reich K, Saari S, Segaert S, Vaillant L. · Department of Dermatology, University Hospital Nijmegen, Centrum St Radboud, Postbus 9101, 6525 GL Nijmegen, The Netherlands. · Br J Dermatol. · Pubmed #19067709 No free full text.

Abstract: BACKGROUND: There is a need for new treatments for scalp psoriasis, as many topical treatments are cosmetically unacceptable and difficult to apply, resulting in poor compliance. OBJECTIVES: To compare the efficacy and safety of a new, once-daily, two-compound scalp formulation (Xamiol; LEO Pharma A/S, Ballerup, Denmark) containing calcipotriol 50 microg g(-1) plus betamethasone 0.5 mg g(-1) (as dipropionate), with the active ingredients as single compounds in the same vehicle. METHODS: This 8-week, multicentre, double-blind, parallel-group study, randomized adult patients with scalp psoriasis involving > 10% of the scalp to the two-compound scalp formulation (n = 568), betamethasone dipropionate 0.5 mg g(-1) (n = 563), or calcipotriol 50 microg g(-1) (n = 286). The primary efficacy measure was the proportion of patients with 'absence of disease' or 'very mild disease' according to investigators' assessments at week 8. RESULTS: The proportion of patients with 'absence of disease' or 'very mild disease' at week 8 was significantly higher in the two-compound group (68.4%) than the betamethasone dipropionate (61.0%, P = 0.0079) or calcipotriol (43.4%, P < 0.0001) groups. The proportion of patients rating their scalp psoriasis as 'clear' or 'almost clear' was significantly higher for the two-compound scalp formulation (69.6%) than for betamethasone dipropionate (59.9%, P = 0.0006) or calcipotriol (44.7%, P < 0.0001). The incidence of lesional/perilesional adverse events was lower in the two-compound and betamethasone dipropionate groups than the calcipotriol group. CONCLUSIONS: The two-compound scalp formulation was well tolerated and more effective in the treatment of scalp psoriasis than either of its individual components in the same vehicle.

Mease PJ, Reich K, Anonymous00097. · Seattle Rheumatology Associates, Division of Rheumatology Research, Swedish Medical Center, Seattle, Washington, USA. · J Am Acad Dermatol. · Pubmed #19028407 No free full text.

Abstract: BACKGROUND: A single course of alefacept intramuscularly in combination with methotrexate (MTX) was effective in treating both psoriasis and psoriatic arthritis (PsA). OBJECTIVE: We sought to determine the efficacy and safety of an additional course of alefacept intramuscularly in combination with MTX in patients with PsA. METHODS: In this open-label extension study, patients with PsA on stable doses of MTX were treated with an additional 12 weekly intramuscular injections of alefacept followed by 12 weeks of observation. Efficacy of PsA treatment was measured as 20% reduction in American College of Rheumatology criteria (ACR20). RESULTS: At the end of the open-label extension phase, 86 of 160 (54%) patients achieved ACR20, of which 28 of 55 had received placebo plus MTX and 58 of 105 received alefacept plus MTX in the prior double-blind phase. Although there was no increase in the proportion of patients achieving ACR20 after a second course of alefacept plus MTX, those achieving ACR50 and ACR70 increased from 17% and 7%, respectively, in the double-blind phase to 32% and 12%, respectively, in the open-label extension phase. LIMITATIONS: In this open-label extension phase of the study there was no control group and the effect on psoriasis in these patients was not measured. CONCLUSIONS: Patients with psoriasis and PsA on stable doses of MTX derive benefit for both conditions from one or more courses of alefacept, with further benefit in PsA apparent after a second course of treatment. No additional toxicity was observed.

Mössner R, Stiens G, König IR, Schmidt D, Platzer A, Krüger U, Reich K. · Department of Dermatology, Georg-August-University, Von-Siebold-Strasse 3, Göttingen 37075, Germany. · Arch Dermatol Res. · Pubmed #18979110 links to  free full text

Abstract: Serotonin is a monoamine acting as a neuromediator in the central and peripheral nervous system. Recently, serotonin has also been shown to influence T- and B-cell function. The serotonin transporter is central in the regulation of the serotonergic system and widely expressed on cells of the immune system. A functional length polymorphism in the promoter of the serotonin transporter gene (5-HTTLPR) has been implicated in the genetic background of depression. Psoriasis is a complex disease with a polygenetic inheritance. In light of the role of T-cell mediated inflammation in psoriasis and the increased prevalence of depression in psoriatic patients, we analyzed the 5-HTTLPR polymorphism in 309 patients with psoriasis vulgaris and 315 healthy control individuals. No significant differences in genotype distribution and allele frequencies were found. There was also no difference in the score of the Hamilton Rating Scale for Depression in patients with psoriasis (n = 137) characterized by carriage of different 5-HTTLPR genotypes. These findings argue against a major contribution of the 5-HTTLPR polymorphism to psoriasis susceptibility and the occurrence of depressive symptoms among psoriatic patients.

Augustin M, Reich K, Reich C, Purwins S, Jeff Rustenbach S, Schäfer I, Radtke M. · CVderm, Department of Dermatology and Venereology, University Clinics Hamburg-Eppendorf, Germany. · J Dtsch Dermatol Ges. · Pubmed #18801145 No free full text.

Abstract: BACKGROUND: Many different forms of treatment are available for psoriasis. The German standard is the national AWMF S3 guideline. A national survey on psoriasis care in 2005 indicated deficits in psoriasis care in Germany. AIM: Assessment of the health care situation of patients with psoriasis in Germany. METHODS: Nation-wide cross-sectional study, in 142 dermatological practices and clinics. The following data were documented: a) Doctor Questionnaire: Treatment, illnesses, clinical characteristics and severity (PASI). b) Patient Questionnaire: Quality of life (QoL), patient relevant therapeutic benefits and satisfaction with the quality of the care. A panel of experts developed and analyzed 8 criteria as indicators of the quality of care. RESULTS: Of the 2009 evaluated patients, 11.6% suffered from severe psoriasis (PASI > 20) and 27.4% from moderate psoriasis (PASI 10-20). The average PASI value was 10.1, and the DLQI 7.5. 32.2% of patients had a serious reduction in their QoL (DLQI > 10). The share of patients with preceding systemic therapy was 47.3%, in severe psoriasis 62.1%, while 20.1% of the patients had received inpatient treatment. The average number of days absent from work was 3.4. Compared to 2005, all 8 indicators improved. CONCLUSION: Significant numbers of psoriasis patients show serious quality of life reductions and high grades of clinical severity. In comparison to 2005, there has been a notable, nation-wide improvement in psoriasis care.

Hüffmeier U, Lascorz J, Böhm B, Lohmann J, Wendler J, Mössner R, Reich K, Traupe H, Kurrat W, Burkhardt H, Reis A. · Institute of Human Genetics, University Hospital Erlangen, University Erlangen-Nuremberg, Erlangen, Germany. · J Invest Dermatol. · Pubmed #18800148 No free full text.

Abstract: Variants in two genes of the IL-23 receptor (R) pathway have recently been shown to be associated with psoriasis vulgaris (PV). We were interested whether the risk conferred by these variants differs between psoriatic skin and joint disease. Four variants of the IL12B and IL23R genes were analyzed in 1,114 PV patients, 748 patients with psoriatic arthritis (PA) and 937 healthy controls before and after stratification for the major psoriasis risk allele at psoriasis susceptibility locus 1 (PSORS1). For both PA and PV, we detected the strongest association with two IL12B single-nucleotide polymorphisms and the corresponding haplotype as reflected by minimal P-values of 10(-7) and highest odds ratios of 1.50 (1.28-1.75) for rs6887695 in PA patients and 1.50 (1.27-1.76) for rs3212227 in the PV cohort, respectively. For IL23R, only rs11209026 showed an association. The results remained significant after correction for multiple testing. No difference was observed after stratification for the PSORS1 risk allele. While confirming recent reports on variants of the IL-23R pathway as susceptibility factors for PV, our study is the first to extend analysis of both genes to PA. However, our results indicate that these variants are not specific risk factors for arthritis, but relevant for susceptibility to psoriasis in general.