Literature on Psoriatic Arthritis

Related ArticlesProblems encountered during anti-tumour necrosis factor therapy.

Best Pract Res Clin Rheumatol. 2006 Aug;20(4):757-90

Authors: Desai SB, Furst DE

Worldwide, over 400,000 patients have been treated with tumour necrosis factor (TNF)-alpha antagonists for indications that include rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory bowel disease, psoriatic arthritis and ankylosing spondylitis. Since their approval, concerns regarding safety have been raised. There is a risk of re-activation of granulomatous diseases, especially tuberculosis, and measures should be taken for detection and treatment of latent tuberculosis infections. Preliminary data suggest that anti-TNF therapy may be safe in chronic hepatitis C. However, TNF-alpha antagonists have resulted in re-activation of chronic hepatitis B if not given concurrently with antiviral therapy. Solid tumours do not appear to be increased with anti-TNF therapy. Variable rates of increased lymphoma risk have been described with anti-TNF therapy compared with the general population, although no increased risk was found compared with a rheumatoid arthritis population. Large phase II and III trials with TNF-alpha antagonists in advanced heart failure have shown trends towards a worse prognosis, and should therefore be avoided in this population. Both etanercept and infliximab are associated with the formation of autoantibodies, and these autoantibodies are rarely associated with any specific clinical syndrome. Rare cases of aplastic anaemia, pancytopenia, vasculitis and demyelination have been described with anti-TNF therapy. This chapter will discuss the safety profile and adverse events of the three commercially available TNF-alpha antagonists: etanercept, infliximab and adalimumab. The data presented in this review have been collected from published data, individual case reports or series, package inserts, the Food and Drug Administration postmarketing adverse events surveillance system, and abstracts from the American College of Rheumatology and European Congress of Rheumatology meetings for 2005.

PMID: 16979537 [PubMed - indexed for MEDLINE]

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Related ArticlesEmerging peptide therapeutics for inflammatory diseases.

Curr Pharm Biotechnol. 2006 Aug;7(4):241-6

Authors: Vally M, Seenu S, Pillarisetti S

Steroids are the best known anti-inflammatory drugs and have been in use for more than 50 years. Their chronic use however was limited by safety concerns. Non-steroidal anti-inflammatory drugs (NSAIDs) including COX-2 inhibitors although devoid of steroid side effects often possess gastrointestinal side effects. In addition recent data suggest that chronic use of some Cox inhibitors is associated with cardiovascular risk. Currently biologics represent the best option for many inflammatory diseases where TNFalpha is the main culprit. These include rheumatoid arthritis, ulcerative colitis, inflammatory bowel disease and psoriasis. A wealth of information is now available on the role of different cytokines and adhesion molecules in the origin and progression of inflammatory diseases. With the success of protein therapeutics such as Etanercept (Enbrel), which binds TNFalpha and inhibits its activity, research has been focused on developing small peptides that can interfere with cytokines or specific cell surface molecules and inhibit the inflammatory reactions. Here we review these peptides that are in discovery and development phases and their potential in the treatment of inflammatory diseases.

PMID: 16918401 [PubMed - indexed for MEDLINE]

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Related ArticlesSafety of etanercept in psoriasis: a critical review.

Drug Saf. 2006;29(8):675-85

Authors: Sánchez Carazo JL, Mahiques Santos L, Oliver Martinez V

Conventional systemic treatments for patients with psoriasis are associated with multiple adverse effects that require continuous monitoring. The introduction of new biological agents such as etanercept, a fully human fusion protein, has permitted individualisation of patients’ treatment according to disease stage. The drug is a competitive inhibitor of tumour necrosis factor-alpha (TNFalpha) that prevents interaction between this cytokine and its cell surface receptors. Etanercept also modulates the activity of other inflammatory cytokines and does not induce complement-mediated cell lysis in vitro. The main source of information regarding etanercept safety comes from studies in patients with rheumatoid arthritis. The most common adverse effect during drug administration is mild injection site reactions. There is no increase in the overall incidence of infections compared with placebo, although there have been several reports of infections caused by intracellular organisms (Mycobacterium tuberculosis, Listeria monocytogenes, and Mycobacterium avium intracellulare). Therefore, combination of this drug with corticosteroids must be carefully monitored and should be avoided in patients with established sepsis. There are no data showing that treatment with etanercept results in an increase in the occurrence of malignant neoplasms. However, caution is recommended in use of etanercept in patients with a current or past history of demyelinating disease. Etanercept must be used with extreme caution in patients with heart failure because of several reports indicating a worsening or de novo occurrence of congestive heart failure while receiving the drug. Monitoring of autoantibodies is not currently considered necessary as they do not predict response, toxicity or autoimmune events. The presence of non-neutralising antibodies to the TNF receptor fragment or other protein components of etanercept has not been related to a decrease in drug response or adverse reactions. Etanercept does not generally modify the course of inflammatory bowel disease. When combined with other systemic therapies for psoriasis, current data do not show an increase in adverse events. In patients with hepatitis C viral infection, etanercept does not increase transaminase levels or viral load and in some instances has allowed the concomitant use of interferon which had previously been discontinued because of a worsening of psoriasis. Etanercept is rated as a US FDA category B drug in pregnancy. However, its use is not recommended in pregnant women unless the benefit-risk ratio greatly favours its use. Etanercept is not recommended for use in lactating women. Etanercept represents a relevant treatment for psoriasis, efficacious over many weeks and safe but special care should be taken to avoid the potential risks.

PMID: 16872241 [PubMed - indexed for MEDLINE]

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Related ArticlesModulating TNF-alpha signaling with natural products.

Drug Discov Today. 2006 Aug;11(15-16):725-32

Authors: Paul AT, Gohil VM, Bhutani KK

Natural products have been, and continue to be, a major source of pharmacologically active substances from which drugs can be developed. Currently, tumor necrosis factor-alpha (TNF-alpha) inhibitors from natural origins are being advanced for the treatment of inflammatory disorders. Elevated TNF-alpha synthesis has been associated with the development of diabetes, septic shock, tumorigenesis, rheumatoid arthritis, psoriatic arthritis and inflammatory bowel disease. Currently, only protein-based drugs are available for the clinical inhibition of TNF-alpha activity. Small-molecule drugs that can regulate TNF-alpha levels or activity might provide a cost-effective alternative to protein-based therapeutics. This review briefly highlights the physiological and pathological roles of TNF-alpha, and covers those natural compounds capable of interfering with TNF-alpha activity.

PMID: 16846800 [PubMed - indexed for MEDLINE]

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Related ArticlesCirculating cytokines in Norwegian patients with psoriatic arthritis determined by a multiplex cytokine array system.

Rheumatology (Oxford). 2006 Aug 27;

Authors: Szodoray P, Alex P, Chappell-Woodward CM, Madland TM, Knowlton N, Dozmorov I, Zeher M, Jarvis JN, Nakken B, Brun JG, Centola M

Objectives. Serum cytokines play an important role in the pathogenesis of psoriatic arthritis (PsA) by initiating and perpetuating various cellular and humoral autoimmune processes. The aim of this study was to describe a broad spectrum of T- and B-cell cytokines, growth factors and chemokines in patients with PsA and healthy individuals. Methods. A novel protein array system, denoted as multiplex cytokine assay was utilized to measure simultaneously the levels of 23 circulating cytokines of patients with PsA and healthy individuals. Additionally, correlational clustering and discriminant function analysis (DFA), two multivariate, supervised analysis methods were employed to identify a subset of biomarkers in order to describe potential functional inter-relationships among these pathological cytokines and identify biomarkers with prognostic and diagnostic utility. Results. Univariate analysis demonstrated that serum levels of a complex set of immune and inflammatory modulating cytokines are significantly up-regulated in patients with PsA relative to unaffected controls including interleukin (IL)-10, IL-13, interferen (IFN)-alpha, epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), fibroblast growth factor [CCL3 macrophage inflammatory protein (MIP)-1alpha], CCL4 (MIP-1beta) and CCL11 (Eotaxin), while granulocyte-colony stimulating factor was significantly reduced in PsA patients. Correlational clustering was able to discriminate among, and hence subclassify, patients with varying levels of disease activity, which may prove useful in guiding therapy in these apparently phenotypically distinct disease subsets. DFA identified EGF, IFN-alpha, VEGF, CCL3 (MIP-1alpha) and IL-12p40 as analytes with the strongest discriminatory power among various PsA patients and controls. Conclusions. Our findings suggest that these factors modulate PsA pathology and the articular involvement in a synergistic manner. Identifying factors could be used in the development of clinical diagnostic tests, which are valuable to guide evidence-based diagnosis and disease management of PsA.

PMID: 16936328 [PubMed - as supplied by publisher]

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Related ArticlesSpinal pseudoarthrosis: a rare complication in psoriatic arthritis.

J Formos Med Assoc. 2006 Aug;105(8):685-8

Authors: Li KJ, Yu CL, Hsu CY, Hsieh SC, Hsu PN

Discovertebral erosion with pseudoarthrosis is a well-known complication in ankylosing spondylitis but it is seldom mentioned in psoriatic arthritis. We report a 53-year-old woman with an 8-year history of psoriatic arthritis who developed severe low back pain followed by sudden onset of numbness in the lower limbs, weakness and dysesthesia. Abnormal contour of L1 and L2 vertebrae and intervertebral disc space was noted during radiologic examination. Pseudoarthrosis was suspected based on extensive osseous resorption and reactive sclerosis about the discovertebral junction on magnetic resonance imaging study. She underwent emergency operation due to spinal instability with neurologic deficit. Pseudoarthrosis was confirmed intraoperatively. No evidence of infection or neoplasms was found. This case shows that pseudoarthrosis can be complicated in patients with psoriatic arthritis, and this possibility should be considered in patients with previously quiescent disease.

PMID: 16935772 [PubMed - in process]

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Related ArticlesInfliximab treatment in two patients with psoriatic arthritis and secondary IgA nephropathy.

Clin Rheumatol. 2006 Aug 19;

Authors: Sakellariou GT, Vounotrypidis P, Berberidis C

PMID: 16924391 [PubMed - as supplied by publisher]

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Related ArticlesPredictors for radiological damage in psoriatic arthritis: Results from a single centre.

Ann Rheum Dis. 2006 Aug 17;

Authors: Bond SJ, Farewell VT, Schentag CT, Gladman DD

We have previously reported on the predictors for the development of clinical damage in psoriatic arthritis. The aim of the current investigation was to identify predictors for radiological damage in psoriatic arthritis. METHODS: Patients followed prospectively according to a standard protocol at The University of Toronto between 1978 and 2004 were included. The principal outcome was the change between visits in the number of damaged joints both clinically and radiologically. Explanatory variables considered included: gender, age, arthritis duration at first visit, time in clinic, number of tender swollen joints, functional class, ESR, level of medication, and, to adjust for within patient correlation, the number of clinically damaged joints at the first of the two visits over which change was observed. RESULTS: At the time of this analysis there were 625 patients recorded in the database. Multivariate analysis of predictors for both clinical and radiological damage show that age, time in clinic, initial ESR, number of tender and swollen joints at previous visit, and number of deformed joints at previous visit, were related to both clinical and radiological damage. CONCLUSIONS: The number of actively inflamed joints, particularly the number of swollen joints was associated with progression of radiological damage. The higher number of previously damaged joints the higher the risk for progression of damage. Thus patients with PsA need to be treated even in the presence of damage as long as there is evidence of inflammation, to prevent progression of damage.

PMID: 16916855 [PubMed - as supplied by publisher]

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Related ArticlesClassification criteria for psoriatic arthritis: development of new criteria from a large international study.

Arthritis Rheum. 2006 Aug;54(8):2665-73

Authors: Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H,

OBJECTIVE: To compare the accuracy of existing classification criteria for the diagnosis of psoriatic arthritis (PsA) and to construct new criteria from observed data. METHODS: Data were collected prospectively from consecutive clinic attendees with PsA and other inflammatory arthropathies. Subjects were classified by each of 7 criteria. Sensitivity and specificity were compared using conditional logistic regression analysis. Latent class analysis was used to calculate criteria accuracy in order to confirm the validity of clinical diagnosis as the gold standard definition of “case”-ness. Classification and Regression Trees methodology and logistic regression were used to identify items for new criteria, which were then constructed using a receiver operating characteristic curve. RESULTS: Data were collected on 588 cases and 536 controls with rheumatoid arthritis (n = 384), ankylosing spondylitis (n = 72), undifferentiated arthritis (n = 38), connective tissue disorders (n = 14), and other diseases (n = 28). The specificity of each set of criteria was high. The sensitivity of the Vasey and Espinoza method (0.97) was similar to that of the method of McGonagle et al (0.98) and greater than that of the methods of Bennett (0.44), Moll and Wright (0.91), the European Spondylarthropathy Study Group (0.74), and Gladman et al (0.91). The CASPAR (ClASsification criteria for Psoriatic ARthritis) criteria consisted of established inflammatory articular disease with at least 3 points from the following features: current psoriasis (assigned a score of 2; all other features were assigned a score of 1), a history of psoriasis (unless current psoriasis was present), a family history of psoriasis (unless current psoriasis was present or there was a history of psoriasis), dactylitis, juxtaarticular new bone formation, rheumatoid factor negativity, and nail dystrophy. These criteria were more specific (0.987 versus 0.960) but less sensitive (0.914 versus 0.972) than those of Vasey and Espinoza. CONCLUSION: The CASPAR criteria are simple and highly specific but less sensitive than the Vasey and Espinoza criteria.

PMID: 16871531 [PubMed - in process]

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Related ArticlesPsoriatic arthritis and rheumatoid arthritis: findings in contrast-enhanced MRI.

AJR Am J Roentgenol. 2006 Aug;187(2):351-7

Authors: Schoellnast H, Deutschmann HA, Hermann J, Schaffler GJ, Reittner P, Kammerhuber F, Szolar DH, Preidler KW

OBJECTIVE: Our objective was to define typical MRI findings of the wrist and the hand in patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA). MATERIALS AND METHODS: Eighteen PsA and 21 RA patients with arthralgia of the wrist or hand joints underwent gadolinium-enhanced MRI of the wrist and hand. Two experienced radiologists interpreted abnormalities in consensus with respect to periarticular soft-tissue swelling, synovitis with or without effusion, periostitis, bone edema, bone erosions, bone cysts, and tenosynovitis. The distribution of the abnormalities also was evaluated. RESULTS: Erosions were statistically more frequent in patients with RA (p 0.05). The radiocarpal joint, the midcarpal joints, the carpometacarpal joints, and the metacarpophalangeal joints were significantly affected more frequently in patients with RA than in patients with PsA (p

PMID: 16861537 [PubMed - indexed for MEDLINE]

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