Anti‐GM‐CSF therapy in psoriasis
Kim PappMelinda GooderhamRachel E. JenkinsRonald VenderJacek C. SzepietowskiT WagnerBertram HuntB.E. Souberbielle
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Abstract:
Psoriasis is a long‐lasting disease involving inflammation of the skin. In the most common form of this disease ‐ plaque psoriasis ‐ the inflammation is visible as raised, reddened and often scaly areas which may extend widely over the body. Although not generally a life‐threatening condition, psoriasis may increase the risk of other serious disorders (such as cardiovascular disease), and often leads to much reduced quality of life for patients ‐ through physical discomfort (itching, pain), disability, and related emotional trauma. Furthermore, psoriasis occurs worldwide (affecting up to 3% of the populations in various countries) and cannot be completely cured by available treatments. Together, these issues make the disease a serious global burden. Granulocyte‐Macrophage Colony‐Stimulating Factor (GM‐CSF) is made in the body and is important in controlling functions of the body's immune system and the processes involved in inflammation. Therefore, this study was carried out to establish whether blocking the activities of GM‐CSF in patients with moderate or severe plaque psoriasis could result in significant improvement of the disease. In total, 122 patients were enrolled from Canada, Denmark, Germany, Latvia and Poland. The patients were treated over 10 weeks either with namilumab (GM‐CSF blocker) or a placebo (inactive): assessments of their psoriasis were made during this period, and completed after an additional 2 weeks. Notably, throughout the 12‐week study duration no significant improvement was detected for namilumab‐treated patients ‐ in marked contrast to treatment benefit found in a similar study involving patients with rheumatoid arthritis. These findings point to different roles for GM‐CSF in the two diseases, and suggest that blocking GM‐CSF activity alone is not enough for effective treatment of plaque psoriasis.Keywords:
Itching
Сlinical, immunological and genetic differences between patients with early and late onset psoriasis are reported. Comparative studies of clinical characteristics of psoriatic arthritis according to age of psoriasis onset (skin manifestation) are lacking. Aim – to compare the prevalence and clinical characteristics of psoriatic arthritis depending on age of psoriasis onset (skin manifestation) in patients included to the psoriasis patient registry of Russian Society of Dermatovenereologists and Cosmetologists. Materials and methods . Prevalence of psoriatic arthritis in 3,227 patients with psoriasis aged 18 years and older was calculated. Comparison of the clinical characteristics of psoriatic arthritis according to the age of onset of psoriasis was performed on 916 patients with psoriasis and psoriatic arthritis. The U-test was used to compare quantitative variables. To identify the association between qualitative variables, the χ2 test was used; odds ratio and 95% confidence interval were calculated, unadjusted and adjusted for other independent variables. Results . In the majority of patients (73%), psoriasis manifested before the age of 40. Psoriatic arthritis at the time of inclusion to the registry was diagnosed in 31.7% of patients with early onset psoriasis and in 19.5% of patients with late onset psoriasis (p=0.0005). The odds of having psoriatic arthritis were almost two times lower in patients with late onset psoriasis (p=0.0005). When adjusted for sex and age, the odds of having psoriatic arthritis among patients with late onset psoriasis became 4 times lower than in patients with early onset psoriasis (p=0.0005). However, when adjusted for sex and duration of psoriasis, the odds ratio lost its statistical significance. The axial involvement (32.1% vs 20.5%; p=0.003) and the involvement of foot joints (59.7% vs 51.5%; p=0.048) was more likely in patients with early onset psoriasis. The odds ratio for axial involvement was still statistically significant when adjusted for other independent variables. Conclusions . Age of onset of psoriasis before 40 years of age is associated with more frequent axial involvement in psoriatic arthritis.
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Psoriatic arthritis (PsA) is a chronic inflammatory rheumatic disease characterized by arthritis associated with psoriasis.The aim of the study was to determine the prevalence of psoriatic arthritis in a population of patients with psoriasis. According to literature data, its prevalence varies between 1% and 7%, or only exceptionally more.Seventy-two adult patients with psoriasis were examined. Patients came from the north-west part of Croatia, from different towns with the overall population of more than 150,000, thus making a representative epidemiological sample. Some patients were treated by a dermatologist, whereas others were admitted to rheumatology departments for the problems with locomotor system and were diagnosed as psoriatics. All patients were examined, and their data were processed.Statistical analysis showed the two sexes to be equally involved by psoriasis. In most cases psoriasis preceded arthritis. All arthritis patients had their fingernails affected with psoriasis. In the population of patients with psoriasis, the prevalence of arthritis was higher in men (60%) than in women (40%). Arthritis often occurred (37.5%) in patients with psoriasis localized in the inguinal and/or perianal region with toenail involvement, as compared to 8.9% of patients with arthritis without concurrent psoriasis involvement.The prevalence of arthritis in psoriasis patients was 15.3%.
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At the 2012 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) in Stockholm, Sweden, several GRAPPA members led a panel discussion on cardiovascular (CV) comorbidities of psoriasis and psoriatic arthritis (PsA). The panelists discussed the role of insulin resistance in the pathophysiology of psoriasis, the possible effect of tumor necrosis factor inhibitors on CV comorbidities, and the effect of 12/23 monoclonal antibodies on CV outcomes. The panelists also addressed how lessons from CV comorbidity research could be applied to other areas of comorbidity research in psoriasis and PsA and identified future research directions in this area.
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In this study we report on the incidence of the HLA antigens of the histocompatibility system in patients with psoriatic arthritis and psoriasis. We separated from each group an additional subgroup, as follows: (1) a subgroup of patients with psoriasis in whose families the disease occurred (familial psoriasis) and (2) a subgroup of patients who had psoriatic arthritis with affection of the sacroiliac joints and the spine (psoriatic spondylitis).
Patients and Methods
The investigation comprised 60 patients (45 men and 15 women) with symptoms of psoriatic arthritis and 65 patients (36 men and 29 women) with psoriasis. In the first group, the sacroiliac joints and the spine were affected in 19 patients (psoriatic spondylitis) and in the second group, 19 patients came from families in which at least one other member suffered from psoriasis (familial psoriasis). The control group consisted of 302 unrelated persons who showed neither psoriatic arthritis norSpondylitis
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Psoriasis is often associated with other diseases, substantially adding to the patient’s burden of disease. Recent epidemiologic studies have demonstrated an increased cardiovascular morbidity among patients with psoriasis and psoriatic arthritis (PsA), which contributes to their reduced life expectancy. At the meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) adjacent to the International Federation of Psoriasis Associations (IFPA) congress, members discussed the pathogenetic aspects of this association and resulting consequences for the management of patients with psoriasis and PsA. A future research agenda was considered.
Pathogenesis
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Optimal clinical management of psoriasis and psoriatic arthritis (PsA) Optimal clinical management of psoriasis and psoriatic arthritis (PsA) requires understanding of the impact on patients. The NORdic PAtient survey of Psoriasis and PsA (NORPAPP) aimed to obtain current data on disease prevalence and patient perceptions in Sweden, Denmark and Norway. Among 22,050 individuals questioned, the reported prevalence of psoriasis and/or PsA was 9.7% (5.7% physician-diagnosed plus 4.0% self-diagnosed only); prevalence was similar in Sweden (9.4%) and Denmark (9.2%) but significantly higher in Norway (11.9%). Of those reporting a physician?s diagnosis, 74.6% reported psoriasis alone, 10.3% PsA alone and 15.1% both. Patients with PsA perceived their disease to be more severe than those with psoriasis; patients with PsA and psoriasis reported greater disease severity than those with each condition alone. Patient?s perceptions of psoriasis severity correlated weakly (Spearman?s rho 0.42) with clinical severity; both patient perceptions and clinical measures are important in the assessment and management of psoriasis.
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In this study we report on the incidence of the HLA antigens of the histocompatibility system in patients with psoriatic arthritis and psoriasis. We separated from each group an additional subgroup, as follows: (1) a subgroup of patients with psoriasis in whose families the disease occurred (familial psoriasis) and (2) a subgroup of patients who had psoriatic arthritis with affection of the sacroiliac joints and the spine (psoriatic spondylitis).
Patients and Methods
The investigation comprised 60 patients (45 men and 15 women) with symptoms of psoriatic arthritis and 65 patients (36 men and 29 women) with psoriasis. In the first group, the sacroiliac joints and the spine were affected in 19 patients (psoriatic spondylitis) and in the second group, 19 patients came from families in which at least one other member suffered from psoriasis (familial psoriasis). The control group consisted of 302 unrelated persons who showed neither psoriatic arthritis norSpondylitis
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Tumor necrosis factor a (TNF-α)-targeted therapies have expanded the therapeutic options for patients with inflammatory bowel disease (IBD), rheumatoid arthritis (RA), psoriasis, and psoriatic arthritis (PsA) and have significantly improved patients' quality of life. Paradoxically, anti-TNF-α agents may induce psoriatic eruptions or worsen preexisting psoriatic skin disease. Currently, there is no standard approach for the management of TNF inhibitor-induced psoriasis. Here, we conduct a literature review on TNF inhibitor-induced psoriasis and introduce a novel treatment algorithm for maintaining otherwise effective anti-TNF therapy versus switching to a different class as appropriate in the management of patients with IBD, RA, psoriasis, or PsA.
TNF inhibitor
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Given the potential consequences of joint damage for patients with psoriatic arthritis, we believe that the optimization of screening methods and the investigation of arthritis in patients with psoriasis are a medical priority. It is very useful to identify predictors of arthritis in patients with psoriasis. In fact, there is a consensus among doctors that the large gap between the diagnosis of psoriasis and that of psoriatic arthritis should be narrowed. In order to better manage patients with psoriasis, the authors review and discuss recent publications on the evidence of current predictors of arthritis in patients with psoriasis.
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Biomarkers are being recognized that will help identify patients with psoriasis who may be destined to develop psoriatic arthritis (PsA). Recent genome-wide association studies have identified genes that are common to both psoriasis and PsA, as well as differentially expressed in the 2 conditions. Further, biomarkers of inflammation and cartilage can differentiate between patients with PsA and those with psoriasis without arthritis. An overview of these biomarkers was presented at the 2011 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. Additionally, a report was presented from the current database of the International Psoriasis and Psoriatic Arthritis Research Team, a group of dermatologists and rheumatologists with the objective to improve the lives of patients with psoriasis and PsA.
Inflammatory arthritis
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