Related ArticlesAre the classification criteria for psoriatic arthritis better than existing criteria for diagnosing psoriatic arthritis? Comment on the article by Taylor et al.
Arthritis Rheum. 2007 Jan 30;56(2):699-700
Authors: McGonagle D, Lyn Tan A
PMID: 17265515 [PubMed - as supplied by publisher]
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Related ArticlesAdalimumab for long-term treatment of psoriatic arthritis: Forty-eight week data from the adalimumab effectiveness in psoriatic arthritis trial.
Arthritis Rheum. 2007 Jan 30;56(2):476-488
Authors: Gladman DD, Mease PJ, Ritchlin CT, Choy EH, Sharp JT, Ory PA, Perdok RJ, Sasso EH
OBJECTIVE: To evaluate the efficacy and safety of treatment with adalimumab, a fully human anti-tumor necrosis factor (anti-TNF) monoclonal antibody, over 48 weeks in patients with moderate to severe psoriatic arthritis (PsA). METHODS: Patients who completed the Adalimumab Effectiveness in Psoriatic Arthritis Trial (ADEPT), a 24-week, double-blind study of adalimumab versus placebo in PsA, could elect to receive open-label adalimumab, 40 mg subcutaneously every other week after week 24. Radiographs were obtained at week 48 and were read with radiographs obtained previously. Clinical and radiographic efficacy data were analyzed overall and in patient subsets. Safety data were collected over 48 weeks. RESULTS: At week 48, patients from the adalimumab arm of ADEPT (n = 151) had achieved American College of Rheumatology 20% improvement (ACR20), ACR50, and ACR70 response rates of 56%, 44%, and 30%, respectively. Among those evaluated with the Psoriasis Area and Severity Index (PASI) (n = 69), PASI50, PASI75, PASI90, and PASI100 response rates (>/=50%, >/=75%, >/=90%, and 100% reduction in PASI scores, respectively) were 67%, 58%, 46%, and 33%, respectively (ACR and PASI response rates were analyzed using nonresponder imputation). Improvements in disability, as measured by the Disability Index of the Health Assessment Questionnaire (mean change in score -0.4) were sustained from week 24 to week 48. At week 24 and week 48, the mean changes from baseline in the modified total Sharp score were -0.1 and 0.1, respectively, for patients who received adalimumab for 48 weeks (n = 133), and 0.9 and 1.0, respectively, for patients who received placebo for 24 weeks followed by adalimumab for 24 weeks (n = 141). Adalimumab demonstrated clinical and radiographic efficacy regardless of whether patients were receiving methotrexate (MTX) at baseline. Adalimumab was generally safe and well tolerated through week 48. CONCLUSION: Adalimumab improved joint and skin manifestations, reduced disability, and inhibited radiographic progression over 48 weeks in patients with PsA who were participants in ADEPT. MTX use at baseline was not required for clinical or radiographic efficacy. Adalimumab had a good safety profile through week 48.
PMID: 17265483 [PubMed - as supplied by publisher]
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Related ArticlesTechnical and Diagnostic Performance of 6 Assays for the Measurement of Citrullinated Protein/Peptide Antibodies in the Diagnosis of Rheumatoid Arthritis.
Clin Chem. 2007 Jan 26;
Authors: Coenen D, Verschueren P, Westhovens R, Bossuyt X
BACKGROUND: Several anticitrullinated protein/peptide antibodies (ACPA) assays have been reported to be of diagnostic value for rheumatoid arthritis (RA). We evaluated the technical performance and diagnostic accuracy of 6 ELISAs for the detection of antibodies to citrullinated protein/peptide antigens. METHODS: ACPA were determined in 298 serum samples using 6 commercially available ACPA assays. One hundred two samples were from RA patients, including patients with early and established RA, and 196 were from controls, including patients with psoriatic arthritis, connective tissue diseases, organ-specific autoimmune diseases, and a group of consecutive patients for whom a rheumatologist ordered anticyclic citrullinated peptide (CCP) antibodies. The ELISA reagent sets under study were Citrullinated Protein Antibodies (Genesis), Anti-MCV (Orgentec), Immunoscan RA (Euro-Diagnostica), Anti-CCP ELISA (IgG; Euroimmun), EliA(TM) CCP (Phadia), and Quanta Lite(TM) CCP3 IgG ELISA (Inova). Technical performance (imprecision, linearity, correlation, and agreement) and diagnostic accuracy (sensitivity and specificity) were compared. RESULTS: Variable technical performance was noted among the different ACPA assays, with some assays displaying poor reproducibility and bad linearity. ACPA results were well correlated among assays with the same antigen specificity, but the numerical values reported for each assay differed widely. Using cutoff values proposed by the manufacturer, diagnostic sensitivities ranged between 69.6% and 77.5% and specificities between 87.8% and 96.4%. The areas under the ROC curves were comparable among the different assays. CONCLUSIONS: Overall diagnostic performance of ACPA assays is comparable among the different assays, but standardization is needed. For some assays, analytical characteristics could be improved.
PMID: 17259232 [PubMed - as supplied by publisher]
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Related ArticlesThe PTPN22 C1858T functional polymorphism and autoimmune diseases–a meta-analysis.
Rheumatology (Oxford). 2007 Jan;46(1):49-56
Authors: Lee YH, Rho YH, Choi SJ, Ji JD, Song GG, Nath SK, Harley JB
OBJECTIVE: To assess whether combined evidence shows the association between the protein tyrosine phosphatase non-receptor 22 (PTPN22) C1858T polymorphism and autoimmune diseases, and to summarize the effect size of the polymorphism associated with susceptibility of autoimmune diseases. METHODS: We surveyed studies on the PTPN22 C1858T polymorphism and autoimmune diseases using comprehensive Medline search and review of the references. Meta-analysis was performed for genotypes T/T (recessive effect), T/T + C/T (dominant effect) and T-allele in random effects models. RESULTS: Twenty-nine studies with 43 comparisons including 13 rheumatoid arthritis (RA), six systemic lupus erythematosus (SLE), six type-1 DM (T1D), three Grave’s disease (GD), four inflammatory bowel diseases (IBD), three juvenile idiopathic arthritis (JIA), two psoriasis, two multiple sclerosis, two Addison’s disease and two Celiac disease were available for the meta-analysis. The overall odds ratios (ORS) for T-allele, T/T and T/T + C/T genotypes were significantly increased in RA, SLE, GD and T1D (OR for T-allele = 1.58, 1.49, 1.85, 1.61, respectively, P
PMID: 16760194 [PubMed - in process]
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Related ArticlesLoss-of-Function Variants of the Filaggrin Gene Are Not Major Susceptibility Factors for Psoriasis Vulgaris or Psoriatic Arthritis in German Patients.
J Invest Dermatol. 2007 Jan 25;
Authors: Hüffmeier U, Traupe H, Oji V, Lascorz J, Ständer M, Lohmann J, Wendler J, Burkhardt H, Reis A
Psoriasis vulgaris and atopic dermatitis share a number of features such as chronic cutaneous inflammation and disturbed epidermal barrier function. Genome-wide scans have revealed a conspicuous overlap of susceptibility loci for both diseases involving chromosomal regions 1q21, 3q21, 17q25, and 20p12. Recently, two loss-of-function variants in the gene encoding filaggrin at 1q21 were shown to be strongly associated with atopic dermatitis. In view of a possible genetic overlap of the two skin diseases, we investigated 375 patients suffering from psoriasis vulgaris, 375 patients with psoriatic arthritis, and 376 control probands. Moreover we directly studied expression of filaggrin in 10 patients suffering from psoriasis vulgaris. Our immunohistochemical analysis revealed a checkered pattern with alternating positive broadened or almost absent filaggrin expression. However, no association was found for the two variants of filaggrin (FLG). We conclude that despite a markedly altered filaggrin expression in psoriatic skin, loss-of-function variants of the FLG gene are neither associated with psoriasis vulgaris nor with psoriatic arthritis. The abnormal staining might reflect the altered epidermal differentiation. Our findings imply that the genetic background underlying the epidermal barrier defect in psoriasis is distinct from that found in atopic dermatitis.Journal of Investigative Dermatology advance online publication, 25 January 2007; doi:10.1038/sj.jid.5700720.
PMID: 17255953 [PubMed - as supplied by publisher]
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Related ArticlesPrediction of major clinical response (ACR50) to infliximab in psoriatic arthritis refractory to methotrexate.
Ann Rheum Dis. 2007 Jan 25;
Authors: Gratacòs J, Casado E, Real J, Torre-Alonso JC
OBJECTIVES: To determine the predictive factors of clinical response to infliximab in patients with refractory psoriatic polyarthritis. METHODS: Multicenter open study which included 69 patients with psoriatic polyarthritis refractory to methotrexate (15 mg/week at least for 8 weeks). Patients were treated with infliximab 5mg/Kg every 8 weeks in addiction to their stable doses of methotrexate. A major clinical response was defined by the ACR 50 at week 38. Logistic regression analysis was performed to analyze which of the following parameters at the start of treatment were associated with an ACR50 response: demographic and clinical characteristics, duration of disease, tender and swollen joint counts, involvement of large joints (knee and/or hip), ESR, CRP, HAQ disability index, axial involvement and presence of erosions at baseline. RESULTS: In an intention-to-treat analysis 44% of patients achieved an ACR50 response. In the univariate analysis both the presence of large joints involvement and severe disability were associated with a poor clinical response. In a multivariate logistic regression analysis high CRP values was independently associated to a good therapeutical response (OR=18.7; 95% CI = 1.8- 181.6, p=0.011). In contrast, large joint involvement and severe disability were associated with a poor response, although only for large joint involvement reached statistical significance (OR=29.3; 95% CI= 3.2- 266.3, p=0.003). CONCLUSION: A lower disability and mainly the lack of large join involvement and higher CRP serum levels at the start of the infliximab treatment seem to be factors that influence the probability to achieve a good therapeutical response in psoriatic arthritis patients.
PMID: 17179176 [PubMed - as supplied by publisher]
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Related ArticlesVEGF/VEGFR signalling as a target for inhibiting angiogenesis.
Expert Opin Investig Drugs. 2007 Jan;16(1):83-107
Authors: Kiselyov A, Balakin KV, Tkachenko SE
VEGFs and a respective family of tyrosine kinases receptors (VEGFRs) are key proteins modulating angiogenesis, the formation of new vasculature from an existing vascular network. There has been considerable evidence in vivo, including clinical observations, that abnormal angiogenesis is implicated in a number of disease conditions, which include rheumatoid arthritis, inflammation, cancer, psoriasis, degenerative eye conditions and others. Antiangiogenic therapies based on inhibition of VEGF/VEGFR signalling were reported to be powerful clinical strategies in oncology and ophthalmology. Current efforts have yielded promising clinical data for several antiangiogenic therapeutics. In this review, the authors elucidate key aspects of VEGFR signalling, as well as clinically relevant strategies for the inhibition of VEGF-induced angiogenesis, with an emphasis on small-molecule VEGFR inhibitors.
PMID: 17155856 [PubMed - indexed for MEDLINE]
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Related ArticlesHLA-Cw6 and HLA-DRB1*07 together are associated with less severe joint disease in psoriatic arthritis.
Ann Rheum Dis. 2007 Jan 12;
Authors: Ho PY, Barton A, Worthington J, Thomson W, Silman AJ, Bruce IN
OBJECTIVE: HLA genes predict disease severity in psoriasis (HLA-Cw6) and rheumatoid arthritis (shared epitope (SE)), but the situation is unclear for psoriatic arthritis (PsA). The aim of this study was to determine the association of the HLA-Cw6 and HLA-DRB1 gene with disease severity in a large UK PsA cohort. METHODS: Genotyping of the HLA-Cw and HLA-DRB1 loci was undertaken in DNA samples from PsA patients (n=480). Stratification and regression analysis were used within the PsA cases to determine whether HLA-Cw6, HLA-DRB1 or the presence of the SE alleles predicted disease severity as measured by the health assessment questionnaire (HAQ) score, the total number of damaged or involved joints adjusted for disease duration and disease modifying antirheumatic treatments. RESULTS: HLA-Cw6 was found to be in linkage disequilibrium with HLA-DRB1*07 (r2 = 0.46). PsA patients who carried both HLA-Cw6 and HLA-DRB1*07 had fewer damaged or involved joints [41% fewer damaged (95% CI 23 to 55%, p=0.02) and 31% fewer involved joints (95% CI 16 to 44%, p
PMID: 17223660 [PubMed - as supplied by publisher]
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Related ArticlesEctopic lymphoid neogenesis in psoriatic arthritis.
Ann Rheum Dis. 2007 Jan 12;
Authors: Cañete JD, Santiago B, Cantaert T, Sanmartí R, Palacín A, Celis R, Graell E, Gil-Torregrosa B, Baeten D, Pablos JL
OBJECTIVE: Ectopic lymphoid neogenesis (LN) occurs in rheumatoid synovium where it is postulated to drive local antigen-dependent B cell development and autoantibody production. This process involves the expression of specific homing chemokines and the development of high endothelial venules (HEV). We aimed to investigate whether these phenomena occur in psoriatic arthritis (PsA) synovium, where autoantibodies have not been described and the organization and function of B cells is not clear, and to analyze their clinical correlates. METHODS: Arthroscopic synovial biopsies from PsA patients before and after TNF-[alpha] blockade were characterized by immunohistochemistry for T/B cell segregation, peripheral lymph node addressin (PNAd)- positive HEV, and CXCL13, CCL21 and CXCL12 chemokines expression in relationship to the size of lymphoid aggregates. RESULTS: Lymphoid aggregates of variable size were observed in 25 of 27 PsA synovial tissues. T/B cell segregation was often observed and correlated with the size of lymphoid aggregates. A close relationship between the presence of large and highly organized aggregates, the development of PNAd+ HEV, and the expression of CXCL13 and CCL21 was found. Large organized aggregates with all LN features were found in 13 of 27 tissues. LN in PsA synovitis was not related to the duration, pattern, or severity of the disease. The synovial LN pattern remained stable over time in persistent synovitis, but a complete response to therapy was associated with a regression of the LN features. CONCLUSIONS: LN occurs frequently in inflamed PsA synovial tissues. Highly organized follicles display the characteristic features of PNAd+ HEV and CXCL13 and CCL21 expression, demonstrating that the microanatomical bases for germinal center formation are present in PsA. The regression of LN upon effective treatment indicates that the pathogenic and clinical relevance of these structures in PsA merits further investigation.
PMID: 17223654 [PubMed - as supplied by publisher]
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Related ArticlesCoexistence of psoriatic arthritis and systemic lupus erythematosus.
Isr Med Assoc J. 2007 Jan;9(1):48-9
Authors: Avriel A, Zeller L, Flusser D, Abu Shakra M, Halevy S, Sukenik S
PMID: 17274359 [PubMed - in process]
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