A prospective, randomised, placebo-controlled study to identify biomarkers associated with active treatment in psoriatic arthritis: effects of adalimumab treatment on synovial tissue

Kuijk, Arno W R van; Gerlag, Daniëlle M.; Vos, Koen; Wolbink, Gertjan; Groot, Marjan de; Rie, Menno A. de; Zwinderman, A. H.; Dijkmans, Ben A. C.; Tak, Paul P.

doi:10.1136/ard.2008.091389

Cited by 90 publications

(83 citation statements)

References 41 publications

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“…Alefacept, a fusion protein that inhibits T cell activation by blocking the interaction of lymphocyte function-associated antigen with CD2, has been shown to improve the psoriatic skin lesions and the signs and symptoms of arthritis in patients with active PsA (19)(20)(21). The beneficial effect of TNF blockade in PsA is associated with a marked decrease in synovial T cell infiltration (22). Thus, inhibition of T cell activation may lead to clinical benefits in patients with PsA.…”

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confidence: 99%

Abatacept in the treatment of patients with psoriatic arthritis: Results of a six‐month, multicenter, randomized, double‐blind, placebo‐controlled, phase II trial

Mease¹,

Genovese²,

Gladstein³

et al. 2011

Arthritis & Rheumatism

270

166

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Objective. To assess the safety and efficacy of abatacept, a selective T cell costimulation modulator, in patients with psoriatic arthritis (PsA).Methods. In this 6-month, multicenter, randomized, double-blind, placebo-controlled, phase II study, 170 PsA patients with a psoriasis target lesion (TL) >2 cm who had previously taken disease-modifying antirheumatic drugs (DMARDs), including anti-tumor necrosis factor (anti-TNF) agents, were randomized (1:1: 1:1) to receive placebo or abatacept at doses of 3 mg/kg, 10 mg/kg, or 30/10 mg/kg (2 initial doses of 30 mg/kg, followed by 10 mg/kg) on days 1, 15, and 29 and then once every 28 days thereafter. The primary end point was the American College of Rheumatology 20% criteria for improvement (ACR20 response) on day 169. Other key end points were magnetic resonance imaging (MRI) scores for joint erosion, osteitis, and synovitis, scores on the Health Assessment Questionnaire (HAQ) and the Short Form-36 (SF-36) health survey, the investigator's global assessment of psoriasis, the TL score, and the Psoriasis Area and Severity Index (PASI) score.Results. Proportions of patients achieving an ACR20 response were 19%, 33%, 48%, and 42% in the placebo, the abatacept 3 mg/kg, the abatacept 10 mg/kg, and the abatacept 30/10 mg/kg groups, respectively. Compared with placebo, improvements were significantly higher for the abatacept 10 mg/kg (P ‫؍‬ 0.006) and 30/10 mg/kg (P ‫؍‬ 0.022) groups, but not for 3 mg/kg group (P ‫؍‬ 0.121). All abatacept regimens resulted in improved MRI, HAQ, and SF-36 scores, with 10 mg/kg showing the greatest improvements. Improvements in the TL and PASI scores were observed in all abatacept arms; a response according to the investigator's global assessment was seen only with 3 mg/kg of abatacept. The safety profiles were similar among the treatment arms.Conclusion. The results of this study suggest that 10 mg/kg of abatacept, the approved dosage for rheumatoid arthritis and juvenile idiopathic arthritis, may be an effective treatment option for PsA.Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by both arthritis and psoriasis ClinicalTrials.gov identifier: NCT00534313.

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confidence: 99%

Abatacept in the treatment of patients with psoriatic arthritis: Results of a six‐month, multicenter, randomized, double‐blind, placebo‐controlled, phase II trial

Mease¹,

Genovese²,

Gladstein³

et al. 2011

Arthritis & Rheumatism

270

166

View full text Add to dashboard Cite

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“…The total integrated optical density (IOD), a parameter representing the expression levels of FABP1 and gastrin R in the testicular tissue, was determined using a Bx41 cast-grid microscope with DP10 camera (Olympus, Tokyo, Japan) together with an image-analysis program (MetaMorph offline, version 4.65; Molecular Devices, Sunnyvale, CA, USA). Under a magnification of x200, five images were examined in each immunostained section and the average IOD was calculated (15)(16)(17).…”

Section: Methodsmentioning

confidence: 99%

Changes in FABP1 and gastrin receptor expression in the testes of rats that have undergone electrical injury

Huang

Liu

2015

Experimental and Therapeutic Medicine

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Abstract. Testicular trauma may occur due to accidental electrical injury. The aim of this study was to investigate alterations in the levels of fatty acid-binding protein 1 (FABP1) and gastrin receptor (gastrin R) in the testes following electrical injury. Sprague-Dawley rats were divided into control, fatal electrocution (220 V, 50 Hz, 60 sec) and electrical injury (220 V, 50 Hz, 60 sec) groups (n=8 per group). The animals in the fatal electrocution and electrical injury groups were deeply anesthetized with sodium pentobarbital prior to each treatment, in which the current was delivered via an anode connected to the left foreleg and a cathode to the right hindleg. The rats that survived were subsequently sacrificed by cervical dislocation. Control animals received cervical dislocation alone. Immunohistochemical analysis was performed to evaluate the protein expression of FABP1 and gastrin R in the testes. Sections were evaluated by digital image analysis. The expression levels of FABP1 and gastrin R were significantly increased following electrical injury, supported by an increase in the integrated optical density (IOD) when compared with that in the control group (P<0.05). However, no significant difference was found in FABP1 and gastrin R expression levels between the fatal electrocution and control groups. In summary, the protein expression levels of FABP1 and gastrin R were found to be significantly altered by electrical injury, suggesting that these two proteins may be important in underlying mechanisms of testicular injury during electrical injury. The findings indicate that such alterations would be reflected in abnormal testicular function.

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“…Total integrated optical density (IOD), a parameter representing the expression levels of enolase and cav-1 in cardiac tissue, was determined using a cast-grid microscope (MetaMorph/DP10/Bx41, UIC/Olympus, US/JP) together with an image-analysis program (MetaMorph offline, version 4.65). Under magnification of x400, five images were captured for each immunostained section and the average IOD value was calculated as previously described (18,19).…”

Section: Methodsmentioning

confidence: 99%

“…After washing, tissue sections were incubated for 10 min in streptavidin-peroxidase and then washed three more times in PBS. Positive signals were visualized with diaminobenzidine, followed by counter-staining with methyl green as previously described (17)(18)(19). PBS was substituted for the primary antibody for the negative control.…”

Section: Methodsmentioning

confidence: 99%

Elevated enolase and caveolin-1 in the heart of rats following dexamethasone-induced toxicity

Huang

Liu

2012

Mol Med Report

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Abstract. Dexamethasone (DEX)-induced heart damage is associated with enzyme and protein alterations. The purpose of this study was to investigate DEX-induced alterations in cardiac enolase and caveolin-1 (cav-1) following DEX administration. Male Wistar rats were randomly divided into two groups: a control and a DEX. The DEX group intraperitoneally received DEX at the single dose of 10 mg/kg for 7 consecutive days, and the control was given the same amount of saline via the same route. On day 8, the rats were anesthetized, and a thoracotomy was performed in all animals. Immunohistochemical analysis was performed to evaluate protein expression of enolase and cav-1. Sections were analyzed by digital image analysis. Our results demonstrated that cardiac protein expression of enolase and cav-1 was altered following DEX-induced toxicity in the rat. The expression of enolase and cav-1 was significantly increased after DEX treatment, supported by integrated optical density compared with the control (P<0.05). In conclusion, following DEX-induced toxicity, protein expression of enolase and cav-1 was significantly elevated. The current findings indicate that such alterations would be reflected in abnormal cardiac function, and the proteins identified in this study may be useful in revealing the mechanisms underlying DEX-induced toxicity and also in providing various clues for further research.

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A prospective, randomised, placebo-controlled study to identify biomarkers associated with active treatment in psoriatic arthritis: effects of adalimumab treatment on synovial tissue

Cited by 90 publications

References 41 publications

Abatacept in the treatment of patients with psoriatic arthritis: Results of a six‐month, multicenter, randomized, double‐blind, placebo‐controlled, phase II trial

Abatacept in the treatment of patients with psoriatic arthritis: Results of a six‐month, multicenter, randomized, double‐blind, placebo‐controlled, phase II trial

Changes in FABP1 and gastrin receptor expression in the testes of rats that have undergone electrical injury

Elevated enolase and caveolin-1 in the heart of rats following dexamethasone-induced toxicity

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