scholarly journals Soluble Biomarkers of Cartilage and Bone Metabolism in Early Proof of Concept Trials in Psoriatic Arthritis: Effects of Adalimumab Versus Placebo

PLoS ONE ◽  
2010 ◽  
Vol 5 (9) ◽  
pp. e12556 ◽  
Author(s):  
Arno W. R. van Kuijk ◽  
Jeroen DeGroot ◽  
Rishma C. Koeman ◽  
Nico Sakkee ◽  
Dominique L. Baeten ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Bone Metabolism ◽  
Proof Of Concept ◽  
Early Proof

scholarly journals High-resolution MRI assessment of dactylitis in psoriatic arthritis shows flexor tendon pulley and sheath-related enthesitis

2014 ◽  
Vol 74 (1) ◽  
pp. 185-189 ◽  
Author(s):  
Ai Lyn Tan ◽  
Eiji Fukuba ◽  
Nicola Ann Halliday ◽  
Steven F Tanner ◽  
Paul Emery ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
High Resolution ◽  
Flexor Tendon ◽  
Extensor Tendon ◽  
Proof Of Concept ◽  
Collateral Ligament ◽  
High Resolution Mri ◽  
Signal Changes ◽  
Flexor Tenosynovitis ◽  
Normal Controls

ObjectiveDactylitis is a hallmark of psoriatic arthritis (PsA) where flexor tenosynovitis is common. This study explored the microanatomical basis of dactylitis using high-resolution MRI (hrMRI) to visualise the small entheses around the digits.MethodsTwelve patients with psoriatic dactylitis (4 fingers, 8 toes), and 10 healthy volunteers (6 fingers, 4 toes) had hrMRI of the digits using a ‘microscopy’ coil and contrast enhancement. All structures were evaluated including the tendons and ligaments, related enthesis organs, pulleys, volar/plantar plates and tendon sheaths.ResultsIn dactylitis, collateral ligament enthesitis was seen in nine digits (75%), extensor tendon enthesitis in six digits (50%), functional enthesitis (5 digits, 42%), abnormal enhancement at the volar plates (2/5 joints, 40%) and the plantar plate (1/5 joints, 20%). Nine cases (75%) demonstrated flexor tenosynovitis, with flexor tendon pulley/flexor sheath microenthesopathy observed in 50% of all cases. Less abnormalities which were milder was observed in the normal controls, none of whom had any signal changes in the tendon pulleys or fibrous sheaths.ConclusionsThis study provides proof of concept for a link between dactylitis and ‘digital polyenthesitis’ including disease of the miniature enthesis pulleys of the flexor tendons, further affirming the concept of enthesitis in PsA.

scholarly journals Evaluation of serum markers of the immune response and bone metabolism facilitates early detection of psoriatic arthritis in patients with psoriasis

2020 ◽  
Vol 49 ◽  
Author(s):  
K. M. Koreshkova ◽  
Z. R. Khismatullina
Keyword(s):  
Immune Response ◽  
Parathyroid Hormone ◽  
Psoriatic Arthritis ◽  
Bone Metabolism ◽  
Matrix Protein ◽  
Clinical Chemistry ◽  
Past History ◽  
Human Leukocyte ◽  
Control Group ◽  
Open Label

Relevance: Psoriatic arthritis (PA) is a severe complication of psoriasis, leading to progressive damage to the musculoskeletal system, a decrease in the quality of life and early disability. CASPAR criteria, widely used for PA diagnosis, are highly sensitive and specific. However, some patients with psoriasis score ≥ 3 with CASPAR criteria without an established PA diagnosis. At present, there is a search for PA biomarkers, which could mirror the stages of pathogenesis of joint and enthesis destruction in this disease.Aim: To identify the most significant changes in biochemical parameters in patients with PA, that would be pathophysiologically associated with the disease.Materials and methods: We performed an open label comparative parallel group study in 60 patients with PA and 40 patients with psoriasis without PA. Clinical assessments included filling in the questionnaires, past history, dermatologist consultation, severity of psoriasis by PASI, and PA activity. Clinical chemistry examination included the levels of antibodies to citrullinated peptide, erythrocyte sedimentation rate, C-reactive protein (CRP), human leukocyte antigen HLA B27, immunoglobulins A, M, and G, complement system components C3, C4, circulating immune complexes (CIC), as well as bone metabolism parameters (calcium, phosphorus, magnesium, seromucoid, alkaline phosphatase (AP), osteocalcin, parathyroid hormone, vitamin D, matrix metalloproteinases MMP-1, MMP-3, MMP-8, and cartilage oligomeric matrix protein (СОМР).Results: Psoriasis was diagnosed in 86.6% (n = 52) of the patients with PA. Family history of psoriasis was confirmed in 55.0% (n = 22) of the patients with psoriasis without PA and in 60.0% (n = 36) of the patients with PA (p = 0.681). Compared to the patients with psoriasis without PA, the patients with PA had higher prevalence of psoriatic onychodystrophy (71.6%, n = 43, vs. 35.0%, n = 14, p = 0.0004), dactylitis (28.3%, n = 17, vs. 5.0%, n = 2, p = 0.004), extra-articular bone proliferation signs (26.6%, n = 16, vs. 5.0%, n = 2, p = 0.006). In the patients with PA, compared to those without PA, there was a significant increase in CRP levels (27.4 vs. 9.5 mg/l, p = 0.002), more than 2-fold increase in IgM and IgG (IgM, 2.35 vs. 1.2 g/l, p = 0.023; IgG, 17.7 vs. 8.45 g/l, p < 0.0001), and CIC (89.3 vs. 29.5 mU/ml, p = 0.0003). Serum phosphorus and magnesium levels in the patients with PA were lower than in the psoriasis patients without PA (phosphorus 0.8 vs. 1.6 mmol/l, respectively, p = 0.045, magnesium 0.5 vs. 1.0 mmol/l, respectively, p = 0.001), with somewhat higher parathyroid hormone levels (67.3 vs. 25.1 ng/ml, respectively, p = 0.013). Osteocalcin levels in the PA patients were by 37.3% lower than in the patients with psoriasis without PA (17.57 vs. 24.13 ng/ml, respectively, p = 0.004). MMP-1 levels in the PA group were 12.3-fold higher than in the non-PA group (37.68 vs. 3.05 ng/ml, respectively, p < 0.0001), and MMP-3 levels were 3.7-fold higher (42.35 vs. 11.36 ng/ml, respectively, p = 0.022). In the patients with PA, AP levels were 2.52-fold higher than in the control group (150.2 vs. 59.5 U/ml, respectively, p = 0.007), and COMP levels were 2.08-fold higher (415.2 vs. 199.5 ng/ml, respectively, p = 0.006).Conclusion: The patients with PA have higher serum CRP, IgM, IgG, CIC, MMP-1, MMP-3, AP, and COMP levels and lower osteocalcin, phosphorus, and magnesium concentrations, than the patients with psoriasis. These parameters are not PA-specific; however, the search for the most sensitive biomarkers of the systemic immune response and bone remodeling seems to be a promising area of research, since identification of such markers would allow for timely prediction and detection of PA in patients with psoriasis.

scholarly journals Mechanisms of progressive fibrosis in connective tissue disease (CTD)-associated interstitial lung diseases (ILDs)

2020 ◽  
pp. annrheumdis-2020-217230 ◽  
Author(s):  
Paolo Spagnolo ◽  
Oliver Distler ◽  
Christopher J Ryerson ◽  
Argyris Tzouvelekis ◽  
Joyce S Lee ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Connective Tissue Disease ◽  
Lung Diseases ◽  
Kinase Inhibitor ◽  
Target Population ◽  
Interstitial Lung Diseases ◽  
Proof Of Concept ◽  
Phase Ii Studies ◽  
Early Proof ◽  
Genetic Mechanisms

Interstitial lung diseases (ILDs), which can arise from a broad spectrum of distinct aetiologies, can manifest as a pulmonary complication of an underlying autoimmune and connective tissue disease (CTD-ILD), such as rheumatoid arthritis-ILD and systemic sclerosis (SSc-ILD). Patients with clinically distinct ILDs, whether CTD-related or not, can exhibit a pattern of common clinical disease behaviour (declining lung function, worsening respiratory symptoms and higher mortality), attributable to progressive fibrosis in the lungs. In recent years, the tyrosine kinase inhibitor nintedanib has demonstrated efficacy and safety in idiopathic pulmonary fibrosis (IPF), SSc-ILD and a broad range of other fibrosing ILDs with a progressive phenotype, including those associated with CTDs. Data from phase II studies also suggest that pirfenidone, which has a different—yet largely unknown—mechanism of action, may also have activity in other fibrosing ILDs with a progressive phenotype, in addition to its known efficacy in IPF. Collectively, these studies add weight to the hypothesis that, irrespective of the original clinical diagnosis of ILD, a progressive fibrosing phenotype may arise from common, underlying pathophysiological mechanisms of fibrosis involving pathways associated with the targets of nintedanib and, potentially, pirfenidone. However, despite the early proof of concept provided by these clinical studies, very little is known about the mechanistic commonalities and differences between ILDs with a progressive phenotype. In this review, we explore the biological and genetic mechanisms that drive fibrosis, and identify the missing evidence needed to provide the rationale for further studies that use the progressive phenotype as a target population.

scholarly journals Objective markers of drug effects on brain function from recordings of scalp potential in healthy volunteers

2002 ◽  
Vol 4 (4) ◽  
pp. 388-394
Keyword(s):  
Healthy Volunteers ◽  
Brain Function ◽  
Cholinergic System ◽  
Drug Effects ◽  
Event Related Potential ◽  
Aging Brain ◽  
Pharmacological Effects ◽  
Proof Of Concept ◽  
Pharmacological Challenge ◽  
Early Proof

In order to stress the importance of P300 responses in drug development, we describe the spatiotemporal characteristics of this objective, evoked event-related potential. These brain activations reflect mnemonic function, in which limbic structures play a role. It is demonstrated that a pharmacological challenge concerning, for example, the cholinergic system in young healthy volunteers induces modifications in P300 reminiscent of the aging brain. We use this type of observation to build a model in which it can be verified whether the deterioration can be counteracted by treatment with "cognition-enhancing" drugs. If we accept the extrapolation of the pharmacological effects to symptomatology, scalp potential analysis offers an appropriate tool for the study of drug interactions in early proof-of-concept models.

scholarly journals Characterization of Bone Metabolism in Hungarian Psoriatic Arthritis Patients: A Case–Control Study.

2020 ◽  
Author(s):  
Zsofia Petho ◽  
Edit Kalina ◽  
Zoltan Pap ◽  
Katalin Hodosi ◽  
Rebeka Falcsik ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Bone Mass ◽  
Fracture Risk ◽  
Disease Activity ◽  
Bone Metabolism ◽  
Osteoporotic Fracture ◽  
Independent Predictor ◽  
Low Bone Mass ◽  
Major Osteoporotic Fracture ◽  
Volumetric Bmd

Abstract Background: Skeletal manifestations are predominant in psoriatic arthritis (PsA). The aim of this cross-sectional, case-controlled study is the complex assessment of areal and volumetric bone mineral density (BMD), fracture risk, vitamin D status and bone turnover markers, and its association with disease-related variables.Methods: Lumbar spine (L1-L4) and femur neck (FN) areal, and distal radius (DR) volumetric BMD, 10-year probability of major and hip osteoporotic fracture as assessed by the fracture risk assessment (FRAX) tool, markers of bone metabolism and disease activity were assessed.Results: Upon comparison of the disease and age- and sex-matched control groups, there was a statistically significant difference in FN areal (0.955±0.145 g/cm2 vs. 1.034±0.148 g/cm2; p=0.001) and DR total volumetric (285.7±61.8 mg/cm3 vs. 369.6±23.6 mg/cm3; p<0.001) BMD, 10 year probability for major osteoporotic (5.0% (0.7%-32%) vs. 3.5% (0%-17.5%); p=0.003) and hip (1.1% (0%-16%) vs. 0.5% (0%-6.1%); p=0.002) fracture and 25-hydroxyvitamin D status (53 (10-120) nmol/L vs. 67 (10-137; p<0.001) nmol/L). As compared to areal assessment, volumetric BMD measurements identified a significantly higher number of patients with low bone mass (T-Score £ -1.00) (34% vs. 88%, p<0.001). Upon multiple linear regression analysis, disease activity score, as determined by DAS28 assessment, was an independent predictor of 10-year probability for major osteoporotic fracture (B (95%CI) = 1.351 (0.379–2.323); p = 0.007).Conclusion: In the studied PsA cohort, disease activity was an independent predictor of 10-year probability for a major osteoporotic fracture, and complemented assessment of volumetric and areal BMD assured better efficacy at identifying those with low bone mass.

scholarly journals Novel Composite Radiographic Score for Longitudinal Observational Studies of Psoriatic Arthritis: A Proof-of-concept Study

2016 ◽  
Vol 43 (2) ◽  
pp. 367-370 ◽  
Author(s):  
William Tillett ◽  
Gavin Shaddick ◽  
Deepak Jadon ◽  
Graham Robinson ◽  
Eleanor Korendowych ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Observational Studies ◽  
Joint Space Narrowing ◽  
Joint Space ◽  
Proof Of Concept ◽  
X Ray ◽  
Radiographic Score ◽  
Hands And Feet ◽  
Longitudinal Observational Studies ◽  
Data Reductions

Objective.To devise a feasible composite radiographic score for use in observational studies of psoriatic arthritis (PsA).Methods.Radiographs from 50 patients with PsA were evaluated with the PsA-modified Sharp, Sharp/van der Heijde (SvdH), and Ratingen scores. Data reductions were made to devise a concise score.Results.The Reductive X-ray Score for Psoriatic Arthritis (ReXSPA) required the assessment of only 22 joints (234 points), including erosion, joint space narrowing, and osteoproliferation in the hands and feet. The ReXSPA accounted for 80% of change detected with the SvdH score.Conclusion.We report a proof-of-concept radiographic score for observational studies derived though data reduction.

Sign in / Sign up

Export Citation Format

Share Document