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1.
Bert Vander Cruyssen Patrick Durez Rene Westhovens Filip De Keyser 《Arthritis research & therapy》2010,12(3):1-8
Introduction
This study is based on the results from a Belgian expanded access program in which patients with active refractory and erosive rheumatoid arthritis (RA) were treated with intravenous infusions of infliximab in combination with methotrexate. The objectives of this study were to evaluate the continuation rate of infliximab and its clinical effect over a 7-year period and to document the reasons for discontinuation.Methods
Between 2000 and 2001, 511 patients with severe and refractory RA were enrolled and treated with infliximab. After 7 years, apart from routine clinical follow-up, treating rheumatologists were asked to complete a questionnaire designed specifically for the present study to evaluate the current therapy with infliximab, the level of disease activity (Disease Activity Score in 28 joints [DAS28]) and the reasons for infliximab discontinuation.Results
After 7 years, 160 of 511 patients (31%) were still on infliximab treatment. The major reasons for infliximab discontinuation included lack of efficacy (104 patients), adverse events (107 patients) and elective change of therapy (70 patients). The majority of cases of treatment discontinuation for safety reasons occurred during the first 2 years. In contrast, discontinuation due to ineffectiveness showed a more constant rate over the 7-year period. Mean DAS for patients still on treatment with infliximab decreased from 5.7 (standard error [SE] 0.1) at baseline to 3.0 (SE 0.1) at year 4 and remained that low until year 7 (3.0 [SE 0.1]). Low disease activity (defined as DAS28 <3.2) was present in 60.9% of patients, and 45.5% achieved remission (DAS28 <2.6). DAS28 at the time of treatment discontinuation due to ineffectiveness decreased over the 7-year period from 5.6 (SE 0.3) in 2001 to 4.8 (SE 0.3) in 2008.Conclusions
This observational study revealed that patients who continue to receive infliximab experience sustained clinical benefit. The majority of safety issues occurred during the first 2 years of infliximab therapy. We observed that the DAS at the time of therapy discontinuation showed a trend to decrease over time. 相似文献2.
Isabelle Delabaye Filip De Keyser the REMITRACT study group 《Arthritis research & therapy》2010,12(3):R121
Introduction
The objective was to describe the prevalence, types, and predictors of adverse events (AEs) in rheumatoid arthritis (RA) patients treated with infliximab and methotrexate in a daily clinical setting. 相似文献3.
Introduction
In this study, we aimed to determine the relationship between flow-mediated endothelium-dependent vasodilatation (FMD) and carotid artery intima-media wall thickness (IMT), two surrogate markers of atherosclerosis, in a series of Spanish patients with rheumatoid arthritis (RA) without clinically evident cardiovascular (CV) disease. 相似文献4.
Bobbio-Pallavicini F Alpini C Caporali R Avalle S Bugatti S Montecucco C 《Arthritis research & therapy》2004,6(3):R264-R272
The aim of the present study was to investigate the effect of long-term infliximab treatment on various autoantibodies in
patients with rheumatoid arthritis. Serum samples from 30 consecutive patients, who were prospectively followed during infliximab
and methotrexate therapy for refractory rheumatoid arthritis, were tested at baseline and after 30, 54 and 78 weeks. At these
points, median values of the Disease Activity Score were 6.38 (interquartile range 5.30–6.75), 3.69 (2.67–4.62), 2.9 (2.39–4.65)
and 3.71 (2.62–5.06), respectively. Various autoantibodies were assessed by standard indirect immunofluorescence and/or ELISA.
Initially, 50% of patients were positive for antinuclear antibodies, and this figure increased to 80% after 78 weeks (P = 0.029). A less marked, similar increase was found for IgG and IgM anticardiolipin antibody titre, whereas the frequency
of anti-double-stranded DNA antibodies (by ELISA) exhibited a transient rise (up to 16.7%) at 54 weeks and dropped to 0% at
78 weeks. Antibodies to proteinase-3 and myeloperoxidase were not detected. The proportion of patients who were positive for
rheumatoid factor (RF) was similar at baseline and at 78 weeks (87% and 80%, respectively). However, the median RF titre exhibited
a progressive reduction from 128 IU/ml (interquartile range 47–290 IU/ml) to 53 IU/ml (18–106 IU/ml). Anti-cyclic citrullinated
peptide (CCP) antibodies were found in 83% of patients before therapy; anti-CCP antibody titre significantly decreased at
30 weeks but returned to baseline thereafter. In conclusion, the presence of anti-double-stranded DNA antibodies is a transient
phenomenon, despite a stable increase in antinuclear and anticardiolipin antibodies. Also, the evolution of RF titres and
that of anti-CCP antibody titres differed during long-term infliximab therapy. 相似文献
5.
Ravi C Dwivedi Navjot Dhindsa Oleg V Krokhin John Cortens John A Wilkins Hani S El-Gabalawy 《Arthritis research & therapy》2009,11(2):R32-11
Introduction
Although the clinical effects of infliximab therapy in rheumatoid arthritis have been documented extensively, the biological effects of this intervention continue to be defined. We sought to examine the impact of infliximab therapy on the serum proteome of rheumatoid arthritis patients by means of a mass spectrometry-based approach. 相似文献6.
Forty-one patients with rheumatoid arthritis involving the cervical spine had a posterior cervical arthrodesis. They were followed for a minimum period of seven years. The diagnoses prior to surgery included cranial settling, atlantoaxial subluxation, subaxial subluxation, and any combination of these three. All patients had posterior arthrodesis, with or without methylmethacrylate, and iliac crest autogenous bone graft. In addition, one patient had an anterior vertebrectomy, and two had transoral resection of the odontoid. Follow-up consisted of a subjective questionnaire, standard radiographs, and physical examination, including a neurologic exam. This information was compared to preoperative data available in the patient''s medical record, postoperative data, and the information obtained in a similar study undertaken in 1987. At the time of follow-up, thirteen patients were known to be dead. One patient could not be located. Of the remaining twenty-six patients, eighteen underwent the full examination, including physical exam and radiographs. The remaining nine patients were contacted and interviewed, but were unavailable for exam and radiographs. All patients considered the operation a success. Only one patient at follow-up had a non-union. This was stable over time. No patient had a deterioration in neurologic function. There was no significant degeneration or instability seen at levels adjacent to the fused segments as compared to the rest of the cervical spine. Posterior cervical spine arthrodesis for rheumatoid involvement of the neck is a safe, efficacious procedure with no significant deterioration of effects over time. 相似文献
7.
Popa C Netea MG Barrera P Radstake TR van Riel PL Kullberg BJ Van der Meer JW 《Cytokine》2005,30(2):72-77
Patients with rheumatoid arthritis (RA) treated with anti-tumor necrosis factor (TNF) strategies have an increased susceptibility to infections, especially those caused by intracellular pathogens. In this study we assessed the cytokine production capacity in patients with RA and we further investigated whether anti-TNF therapy modulates the production of pro-inflammatory cytokines involved in the resistance against infections. Whole blood cultures from 10 RA patients and 10 healthy controls were stimulated with heat-killed Candida albicans, Salmonella typhimurium, Staphyloccocus aureus, Aspergillus fumigatus or Mycobacterium tuberculosis and production of interleukin (IL)-1beta, IL-6, IL-10, interferon (IFN)-gamma and TNF-alpha was measured. Before anti-TNF therapy, whole blood cultures from RA patients released significantly less IFN-gamma than healthy controls after stimulation with all tested microorganisms. Short-term anti-TNF therapy did not have an inhibitory effect on the release of the cytokines tested. We conclude that cells of patients with RA have a strongly reduced production capacity of IFN-gamma after bacterial challenge. Although short-term therapy with anti-TNF agents did not further decrease the release of other proinflammatory cytokines, the combination of defective IFN-gamma production in basal conditions and TNF neutralization during anti-TNF therapy is likely to be responsible for the higher susceptibility to infections in patients with RA. 相似文献
8.
Takeuchi T Nakanishi T Tabushi Y Hata A Shoda T Kotani T Shimizu A Takubo T Makino S Hanafusa T 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2007,855(1):66-70
We analyzed the changes in the serum protein profile by infliximab using two-dimensional gel electrophoresis and mass spectrometry. More than 50 gel spots were seen to increase or decrease in correlation with clinical improvements of RA. The spots corresponding to CRP, C3, and Apo J showed reduced staining intensity, while the spots corresponding to Apo A-I, RBP, and transthyretin were enhanced. The protein profile of RA patients treated with infliximab was mostly similar to that of normal healthy controls except for several protein spots. This suggested that infliximab normalized the serum protein profile of RA patients, leading to modification in the serum lipid profile and antioxidant status in RA. 相似文献
9.
The Disease Activity Score using 28 joint counts (DAS28) has been developed in a cohort of patients with rheumatoid arthritis
in which only conventional anti-rheumatic treatments were used. It has extensively been validated to monitor disease activity
in daily clinical practice as well as in clinical trials. The study of Vander Cruyssen and colleagues showed that the DAS28
correlated best with the decisions of rheumatologists to increase the infliximab dose because of insufficient response. This
result once more confirms the validity of the DAS28 to monitor disease activity in patients with rheumatoid arthritis and
to titrate treatment with biologicals. 相似文献
10.
Pascale Nicaise Roland Sabine Grootenboer Mignot Alessandra Bruns Margarita Hurtado Elisabeth Palazzo Gilles Hayem Philippe Dieudé Olivier Meyer Sylvie Chollet Martin 《Arthritis research & therapy》2008,10(6):R142
Introduction
Antibodies against cyclic citrullinated peptides (CCPs) are useful for diagnosing rheumatoid arthritis (RA). Antibodies to mutated citrullinated vimentin (MCV) were described recently in RA. The aims of this study were to evaluate the usefulness of anti-MCV for diagnosing RA in anti-CCP-negative patients and to monitor anti-MCV titres during infliximab therapy for RA. 相似文献11.
M. Atteritano S. Mazzaferro S. Mantuano G. L. Bagnato G. F. Bagnato 《Cytotechnology》2016,68(2):313-318
The aim of this study was to evaluate in a 24-weeks the effect of anti-TNF-alpha, infliximab, on cytogenetic biomarkers in peripheral lymphocytes of patients with rheumatoid arthritis (RA). A total of 40 patients with RA met the criteria to be treated with methotrexate (15 mg/week) were evaluated. Twenty patients, randomly selected, were treated with infliximab in addition to methotrexate (group I), whereas the other 20 patients continued with only methotrexate treatment (group M). Twenty healthy volunteers matched for age, gender and smoking habits served as control group (group C). At baseline, sister chromatid exchange rate was 7.20 ± 2.21 in group I, 7.40 ± 1.60 in group M and 4.97 ± 1.32 in group C (P < 0.01 vs group I and M). After 24-weeks, sister chromatid exchange rate was 7.87 ± 2.54 in group I and 7.81 ± 1.95 in group M (P = ns). High frequency cells count was 4.9 % and 4.7 % in the groups I and M, respectively, at the end of the study (P = ns). The basal chromosomal aberration frequency was 4.90 % in group I and 5.20 % in groups M; after 24-weeks, this was 5.10 % in group I and 5.10 % in groups M (P = ns). Infliximab treatment, for 24 weeks, did not increase the cytogenetic biomarkers in patients with RA. Our data show that the use of infliximab has not a genotoxic effect in patients with RA. 相似文献
12.
Virginia Pascual-Ramos Irazú Contreras-Yá?ez Antonio R Villa Javier Cabiedes Marina Rull-Gabayet 《Arthritis research & therapy》2009,11(1):R26
Introduction
Aggressive treatment with disease-modifying antirheumatic drugs (DMARDs) plays a major role in improving early rheumatoid arthritis (RA) patient outcomes. Persistence and adherence with medication occurs variably (20% to 70%). The objectives of the study were to determine medication persistence (MP) in early RA patients over 13 consecutive visits each 2 months apart, to investigate the relationship between MP and disease activity, disability and structural damage, and to identify baseline prognosticators. 相似文献13.
Virginia Pascual-Ramos Irazú Contreras-Yáñez Antonio R Villa Javier Cabiedes Marina Rull-Gabayet 《Arthritis research & therapy》2009,11(1):1-11
Introduction
Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a tumour necrosis factor (TNF) family member capable of inducing apoptosis in many cell types.Methods
Using immunohistochemistry, terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling (TUNEL) and real-time PCR we investigated the expression of TRAIL, TRAIL receptors and several key molecules of the intracellular apoptotic pathway in human synovial tissues from various types of arthritis and normal controls. Synovial tissues from patients with active rheumatoid arthritis (RA), inactive RA, osteoarthritis (OA) or spondyloarthritis (SpA) and normal individuals were studied.Results
Significantly higher levels of TRAIL, TRAIL R1, TRAIL R2 and TRAIL R4 were observed in synovial tissues from patients with active RA compared with normal controls (p < 0.05). TRAIL, TRAIL R1 and TRAIL R4 were expressed by many of the cells expressing CD68 (macrophages). Lower levels of TUNEL but higher levels of cleaved caspase-3 staining were detected in tissue from active RA compared with inactive RA patients (p < 0.05). Higher levels of survivin and x-linked inhibitor of apoptosis protein (xIAP) were expressed in active RA synovial tissues compared with inactive RA observed at both the protein and mRNA levels.Conclusions
This study indicates that the induction of apoptosis in active RA synovial tissues is inhibited despite stimulation of the intracellular pathway(s) that lead to apoptosis. This inhibition of apoptosis was observed downstream of caspase-3 and may involve the caspase-3 inhibitors, survivin and xIAP. 相似文献14.
Tang TT Song Y Ding YJ Liao YH Yu X Du R Xiao H Yuan J Zhou ZH Liao MY Yao R Jevallee H Shi GP Cheng X 《Journal of lipid research》2011,52(5):1023-1032
In this study, we investigated the hypothesis that regulatory T cells (T(reg)) are involved in the immunomodulatory effects of statins on rheumatoid arthritis (RA) patients. The 12-week study cohort consisted of 55 RA patients and 42 control subjects allocated to either a group treated with atorvastatin (AT) (20 mg/day) or a non-AT group. T(reg) numbers, suppressive function, serum inflammatory markers, and disease activity were evaluated before and after the therapy. Furthermore, the effects of AT on the frequency and suppressive function of T(reg) were determined in vitro. Our data revealed that the suppressive function of T(reg) from RA patients significantly decreased compared with that of control subjects. AT significantly reduced erythrosedimentation, C-reactive protein, and disease activity. Concomitantly, T(reg) numbers and suppressive functions were significantly improved by AT. Consistent with the in vivo experiments, AT promoted the generation of T(reg) from primary T cells and enhanced preexisting T(reg) function in vitro. Moreover, we showed that PI3K-Akt-mTOR and ERK signal pathways were involved in the induction of T(reg) by AT. In conclusion, AT significantly increased T(reg) numbers and restored their suppressive function in the RA patients, and this may be relevant in the modulation of uncontrolled inflammation in this disorder. 相似文献
15.
Vander Cruyssen B Van Looy S Wyns B Westhovens R Durez P Van den Bosch F Veys EM Mielants H De Clerck L Peretz A Malaise M Verbruggen L Vastesaeger N Geldhof A Boullart L De Keyser F 《Arthritis research & therapy》2005,7(5):R1063-R1071
This study is based on an expanded access program in which 511 patients suffering from active refractory rheumatoid arthritis (RA) were treated with intravenous infusions of infliximab (3 mg/kg+methotrexate (MTX)) at weeks 0, 2, 6 and every 8 weeks thereafter. At week 22, 474 patients were still in follow-up, of whom 102 (21.5%), who were not optimally responding to treatment, received a dose increase from week 30 onward. We aimed to build a model to discriminate the decision to give a dose increase. This decision was based on the treating rheumatologist's clinical judgment and therefore can be considered as a clinical measure of insufficient response. Different single and composite measures at weeks 0, 6, 14 and 22, and their differences over time were taken into account for the model building. Ranking of the continuous variables based on areas under the curve of receiver-operating characteristic (ROC) curve analysis, displayed the momentary DAS28 (Disease Activity Score including a 28-joint count) as the most important discriminating variable. Subsequently, we proved that the response scores and the changes over time were less important than the momentary evaluations to discriminate the physician's decision. The final model we thus obtained was a model with only slightly better discriminative characteristics than the DAS28. Finally, we fitted a discriminant function using the single variables of the DAS28. This displayed similar scores and coefficients as the DAS28. In conclusion, we evaluated different variables and models to discriminate the treating rheumatologist's decision to increase the dose of infliximab (+MTX), which indicates an insufficient response to infliximab at 3 mg/kg in patients with RA. We proved that the momentary DAS28 score correlates best with this decision and demonstrated the robustness of the score and the coefficients of the DAS28 in a cohort of RA patients under infliximab therapy. 相似文献
16.
Our objective was to clarify the heterogeneity in response to infliximab treatment in rheumatoid arthritis (RA); to this end, a bioassay was designed to explore the contribution of circulating tumour necrosis factor (TNF)-alpha bioactivity and its possible link to response. The bioassay is based on the induction of IL-6 and osteoprotegerin (OPG) production by synoviocytes in response to TNF-alpha. RA synoviocytes were cultured with TNF-alpha (5 ng/ml) and 42 RA plasma samples collected just before starting therapy. Levels of IL-6 and OPG were measured in supernatants. In 20 of the patients, plasma samples collected before and 4 hours after the first and the ninth infusions were tested in the same way. Plasma concentrations of TNF-alpha and p55 and p75 soluble receptors were measured using ELISA. TNF-alpha induced IL-6 and OPG production by synoviocytes, which was further increased with patient plasma dilutions and inhibited by infliximab. With plasma samples obtained before the first infusion, the IL-6-induced production was greater in patients with a good clinical response than in the poor responders (44.4 +/- 23.3 ng/ml versus 27.4 +/- 20.9 ng/ml; P = 0.05). This high circulating TNF-alpha bioactivity was strongly inhibited with the first infliximab infusion. The difference between IL-6 levels induced with plasma samples obtained before and 4 hours after the first infusion was greater in patients with a good clinical response (40.0 +/- 23.7 ng/ml versus 3.4 +/- 10.0 ng/ml; P = 0.001). Similar findings were obtained for OPG production (7.0 +/- 6.2 ng/ml versus 0.0 +/- 3.0 ng/ml; P < 0.05). Levels of circulating TNF-alpha bioactivity were predictive of clinical response to TNF-alpha inhibition, confirming a key role for TNF-alpha in these RA patients. 相似文献
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19.
Marike van der Leeden Martijn PM Steultjens Dirkjan van Schaardenburg Joost Dekker 《Arthritis research & therapy》2010,12(1):R3
Introduction
The aim of our study was to investigate the presence of disease activity in the metatarsophalangeal (MTP) joints of the forefoot in rheumatoid arthritis (RA) patients in remission according to the Disease Activity Score based on 28 joints (DAS28) remission criterion. 相似文献20.
YK Onno Teng Gillian Wheater Vanessa E Hogan Philip Stocks EW Nivine Levarht Tom WJ Huizinga Rene EM Toes Jacob M van Laar 《Arthritis research & therapy》2012,14(2):R57