Joint counts in routine practice.
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Arthritis, Rheumatoid↗
Biomedical subjects
C Antoni
Publications and source records attributed to C Antoni.
[Treatment of psoriatic arthritis with TNF alpha-antagonists].
The proinflammatory cytokine TNF alpha is in the pathogenesis of PsA as important as in RA. TNF-alpha is increased in the psoriatic skin lesion and in the synovium of the inflamed joint. The TNF alpha blockage has been tested in double blind trials with etanercept and infliximab. All studies proved a significant and durable response in the reduction of synovitis in a comparable extend in both drugs. Etanercept showed after 12 weeks an ACR20 response in 59% of the patients versus 15% in the placebo arm. Infliximab had after 14 weeks a 69% ACR20 response versus 8% placebo response. The psoriatic skin lesion improved with both drugs. The PASI was reduced by 47% with etanercept and by 81% with infliximab. The safety-profile was similar to the RA-trials. For etanercept the one year data have shown a reduction in x-ray progression. Etanercept has been approved in the USA and in Europe.
Antibodies, Monoclonal↗
Treatment of psoriatic arthritis with antitumour necrosis factor-alpha antibody clears skin lesions of psoriasis resistant to treatment with methotrexate.
BACKGROUND: In inflamed skin, keratinocytes and inflammatory cells both produce large amounts of tumour necrosis factor (TNF) -alpha, a cytokine with broad effects that are relevant to inflammation. Blockade of this proinflammatory cytokine by a monoclonal anti-TNF-alpha antibody might be effectively used in the treatment of inflammatory skin diseases. OBJECTIVES: To gather information about the efficacy of an anti-TNF-alpha antibody (infliximab) in the treatment of skin lesions of psoriatic arthritis. METHODS: Six patients with progressive joint disease and psoriatic skin lesions unresponsive to methotrexate therapy were treated with anti-TNF-alpha antibody. The Psoriasis Area and Severity Index was determined before and 10 weeks after initiation of therapy. RESULTS: Improvement of psoriatic skin lesions was observed in all patients. In addition, a marked improvement of the joint disease was noted. CONCLUSIONS: Therapy with anti-TNF-alpha antibody may be an effective treatment regimen for both psoriatic arthritis and psoriatic skin lesions.
Antibodies, Monoclonal↗
Successful treatment of a small cohort of patients with adult onset of Still's disease with infliximab: first experiences.
OBJECTIVE: To test the efficacy of infliximab in the treatment of patients with severe and active adult onset Still's syndrome (AOSD) despite conventional immunosuppressive therapy. PATIENTS AND METHODS: Six patients with the diagnosis of AOSD according to the Yamagushi criteria of 1992 were treated with infliximab. All patients had severe disease with high clinical and serological activity. Patients were treated initially with high dose steroids or more intensive immunosuppressive therapy. Two patients had a history of multiple disease modifying antirheumatic drug (DMARD) treatments. One patient had a history of three years of AOSD with fever, chills, pleural and pericardial effusions, and hepatosplenomegaly. Despite these treatments, he developed increasing serological signs of inflammation and arthritis of both hips and peripheral joints. Another patient had a history of five years of AOSD with oligoarthritis, myalgias, and recurrent fever despite multiple DMARD treatment, including cyclophosphamide pulse therapy. Our patients with AOSD presented with massive polyarthralgias, polyarthritis, splenomegaly or hepatomegaly, the typical rash, sore throat, weight loss, serositis, continuing fever, leucocytosis, and raised C reactive protein (CRP), erythrocyte sedimentation rate (ESR), and ferritin levels. Four patients with early onset of the disease, fulfilling the diagnostic criteria for AOSD and a clinical and serological high disease activity, were included in our pilot study without any further DMARD treatment apart from the initial steroid treatment. Reduction of established treatment, mainly with steroids, caused a relapse of the disease in all our patients. Patients then received 3-5 mg/kg infliximab on weeks 0, 2, and 6, continuing with intervals of 6-8 weeks depending on the patient's individual disease activity. RESULTS: In all patients, fever, arthralgias, myalgias, hepatosplenomegaly, and the rash resolved after the first courses of treatment with infliximab. All serological variables (CRP, ESR, hyperferritinaemia) returned to normal. After three courses of infliximab infusions, splenomegaly could not be detected in any of our patients. One caused by hip postarthritic osteoarthrosis, requiring hip replacement. After three courses of treatment with infliximab, splenomegaly could not be detected in any of our patients. Up to now, our patients have received infliximab infusion treatment for between five and 28 months. Throughout this period all patients have continued to benefit from this treatment, with improvement in their clinical symptoms, joint counts, and serological disease activity. One of our patients had a moderate infusion reaction during the second treatment. The infusion was discontinued for one hour and then was resumed with no further problems. CONCLUSION: The disease improved remarkably in all six patients with AOSD after treatment with infliximab, also in the early stage of AOSD. These preliminary data suggest the potential therapeutic benefit of anti-tumour necrosis factor alpha treatment in AOSD.
Acute Disease↗
In vivo blockade of tumor necrosis factor-alpha in patients with rheumatoid arthritis: longterm effects after repeated infusion of chimeric monoclonal antibody cA2.
OBJECTIVE: To investigate the longterm consequences of tumor necrosis factor-alpha (TNF-alpha) blockade in patients with rheumatoid arthritis (RA), to compare changes after repeated infusion of cA2 monoclonal antibody with those occurring after the initial treatment, and to investigate significant correlations of cellular or serological changes to the duration of clinical benefit for each patient. METHODS: A clinical trial testing TNF-alpha monoclonal antibody cA2 in treatment of RA showed this therapeutic agent is highly effective. A dosage of 1 mg/kg or 10 mg/kg cA2, given in a single infusion, was compared to placebo. After clinical relapse all patients were (re)treated with 3 or 10 mg/kg cA2. In parallel to this clinical study, we investigated cellular and molecular changes induced by in vivo blockade of TNF-alpha. RESULTS: After an initial transient increase, T lymphocyte counts were not significantly different from starting values throughout the observation period. Monocyte counts as well as serum interleukin 6 (IL-6) and soluble intercellular adhesion molecule 1 (sICAM-1) concentrations remained decreased for several weeks after infusion. After a repeated infusion, increases in numbers of T cells and decreases in monocytes and IL-6 and sICAM-1 concentrations were evident again. Changes in cell counts, however, were smaller, especially in the group initially treated with the low dose (1 mg/kg), despite a higher retreatment dosage of 3 or 10 mg/kg cA2. Similarly, in this group decrease of IL-6 and sICAM-1 concentrations was less pronounced, was delayed to Day 7 after infusion, and lasted for a shorter period than seen after initial treatment. CONCLUSION: We conclude that in vivo TNF-alpha blockade leads to prolonged cellular and serological changes. This effect appears to be less pronounced after repeated infusion of cA2 compared to the initial treatment, mainly in the low dose group.
Adult↗
Regulation of cytokines, cytokine inhibitors, and acute-phase proteins following anti-TNF-alpha therapy in rheumatoid arthritis.
Treatment with a chimeric mAb to TNF-alpha has been shown to suppress inflammation and improve patient well-being in rheumatoid arthritis (RA), but the mechanisms of action of such treatment have not been fully explored. Here we show that in vivo administration of anti-TNF-alpha Ab, using a longitudinal analysis, results in the rapid down-regulation of a spectrum of cytokines, cytokine inhibitors, and acute-phase proteins. Marked diurnal variation in the serum levels of some of these were detected. These results were consistent with the concept of a cytokine-dependent cytokine cascade, and the degree of clinical benefit noted after anti-TNF-alpha therapy is probably due to the reduction in many proinflammatory mediators apart from TNF-alpha, such as IL-6, which reached normal levels within 24 h. Serum levels of cytokine inhibitors such as soluble p75 and p55 TNFR were reduced as was IL-1 receptor antagonist. Reductions in acute-phase proteins occurred after serum IL-6 fell and included serum amyloid A, haptoglobin, and fibrinogen. The latter reduction could be of importance, as it is a risk factor for atherosclerosis, which is augmented in RA patients.
Acute-Phase Proteins↗
Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis.
OBJECTIVE: To evaluate the efficacy, pharmacokinetics, immunogenicity, and safety of multiple infusions of a chimeric monoclonal anti-tumor necrosis factor alpha antibody (cA2) (infliximab; Remicade, Centocor, Malvern, PA) given alone or in combination with low-dose methotrexate (MTX) in rheumatoid arthritis (RA) patients. METHODS: In a 26-week, double-blind, placebo-controlled, multicenter trial, 101 patients with active RA exhibiting an incomplete response or flare of disease activity while receiving low-dose MTX were randomized to 1 of 7 groups of 14-15 patients each. The patients received either intravenous cA2 at 1, 3, or 10 mg/kg, with or without MTX 7.5 mg/week, or intravenous placebo plus MTX 7.5 mg/week at weeks 0, 2, 6, 10, and 14 and were followed up through week 26. RESULTS: Approximately 60% of patients receiving cA2 at 3 or 10 mg/kg with or without MTX achieved the 20% Paulus criteria for response to treatment, for a median duration of 10.4 to >18.1 weeks (P < 0.001 versus placebo). Patients receiving cA2 at 1 mg/kg without MTX became unresponsive to repeated infusions of cA2 (median duration 2.6 weeks; P=0.126 versus placebo). However, coadministration of cA2 at 1 mg/kg with MTX appeared to be synergistic, prolonging the duration of the 20% response in >60% of patients to a median of 16.5 weeks (P < 0.001 versus placebo; P=0.006 versus no MTX) and the 50% response to 12.2 weeks (P < 0.001 versus placebo; P=0.002 versus no MTX). Patients receiving placebo infusions plus suboptimal low-dose MTX continued to have active disease, with a Paulus response lasting a median of 0 weeks. A 70-90% reduction in the swollen joint count, tender joint count, and C-reactive protein level was maintained for the entire 26 weeks in patients receiving 10 mg/kg of cA2 with MTX. In general, treatment was well tolerated and stable blood levels of cA2 were achieved in all groups, except for the group receiving 1 mg/kg of cA2 alone, at which dosage antibodies to cA2 were observed in approximately 50% of the patients. CONCLUSION: Multiple infusions of cA2 were effective and well tolerated, with the best results occurring at 3 and 10 mg/kg either alone or in combination with MTX in approximately 60% of patients with active RA despite therapy with low-dose MTX. When cA2 at 1 mg/kg was given with low-dose MTX, synergy was observed. The results of the trial provide a strategy for further evaluation of the efficacy and safety of longer-term treatment with cA2.
Adult↗
Graft-versus-host-like mucocutaneous eruptions with serological features of paraneoplastic pemphigus and systemic lupus erythematosus in a patient with non-Hodgkin's lymphoma.
A 63-year-old male patient spontaneously developed severe erosive orogenital mucositis, palmoplantar and gluteal inflammatory lesions resistant to therapy. The skin lesions clinically and histologically resembled lichen-planus-like graft-versus-host disease. Investigation for an underlying autoimmune or malignant disorder revealed a centrocytic-centroblastic low-grade non-Hodgkin's lymphoma (according to the Kiel classification) in the bone marrow, mesenterial and iliacal lymphoma. Serological titers were intermittently positive for ANA, anti-Sm/U1RNP, anti-Ro and anti-dsDNA. Immunoprecipitation of lysates from radiolabeled human keratinocytes with the patient's serum revealed circulating antibodies against 210-kD (desmoplakin II), 190- and 170-kD antigens but none against the 230-kD antigen or 250-kD desmoplakin I. Under cytostatic chemotherapy the lymphomas showed complete and long-lasting remission, whereas the mucocutaneous lesions persisted. Six years after diagnosis, the mucocutaneous lesions are sufficiently controlled by immunosuppressive therapy. In the presented case, several features of lymphoma-associated dysimmunoreactivity are assumed that bring about the intrinsic production of various autoantibodies typical of paraneoplastic pemphigus and systemic lupus erythematosus.
Diagnosis, Differential↗
NMR monitoring of rheumatoid arthritis patients receiving anti-TNF-alpha monoclonal antibody therapy.
The aim of this study was to investigate if dynamic gadolinium-DTPA-supported magnetic resonance (MR) imaging can monitor the therapeutic effect of a fast-acting immuno-modulating drug like anti-tumour necrosis factor alpha (anti-TNF-alpha) monoclonal antibody (moab) in patients with rheumatoid arthritis (RA). Dynamic MR imaging was performed on 64 joints in a total of 18 patients before and after infusion with either a placebo or 1 or 10 mg/kg of anti-TNF-alpha moab. Additionally, treating the placebo group and reinfusing the verum group with either 3 or 10 mg/kg was monitored by quantitative nuclear magnetic resonance (NMR). Time-dependent signal intensity changes were then correlated with a total of five Paulus criteria and with ESR and C-reactive protein (CRP). No changes in either the gadolinium uptake or clinical parameters were seen after the infusion of a placebo. Therapy with 1 mg/kg anti-TNF-alpha moab resulted in a significant decrease in clinical disease activity, as well as in gadolinium-DTPA uptake in dynamic NMR studies. However, correlations between singal intensity changes and Paulus criteria were only demonstrated for the variable "doctor's evaluation of disease activity". Patients given 10 mg/kg moab demonstrated a very significant improvement in all clinical manifestations of their disease, as well as a high significant reduction in gadolinium uptake (P = 0.004). In addition, the latter group showed significant correlations between time-dependent signal intensity changes and five Paulus criteria: "number of swollen joints", "number of painful joints", "duration of morning stiffness", "doctor's evaluation of disease activity" and "patient's evaluation of disease activity". No differences and correlations were seen for ESR and CRP. We concluded that dynamic NMR studies are suitable to monitor inflammatory activity in RA patients under therapy with biological response modifiers such as anti-TNF-alpha moab.
Adult↗
In vivo blockade of TNF-alpha by intravenous infusion of a chimeric monoclonal TNF-alpha antibody in patients with rheumatoid arthritis. Short term cellular and molecular effects.
Due to the unknown etiology of RA, specific treatment is not available. Recently, in a double-blinded, placebo-controlled clinical trial, in vivo blockade of TNF-alpha by a single infusion of a chimeric TNF-alpha-blocking mAb, cA2, has proven to be highly effective in the treatment of RA. In parallel to this trial, we tested the consequences of cA2 infusion in ex vivo and in vitro experiments. In this paper, we describe an increase in CD4+ and CD8+ T lymphocyte counts on day 1 and a marked decrease in monocyte counts preferentially on day 7 after cA2 treatment, without major changes in B lymphocyte or NK cell counts. In addition, we found an increased responsiveness of PBMC to CD28 mAb/PMA, but not to CD3 mAb, superantigen staphylococcus enterotoxin B, or PHA on day 1 after infusion. The increase in DNA synthesis of PBMC was paralleled by increased IL-2 mRNA and IL-4 mRNA expression and IL-2 protein secretion in culture supernatants after in vitro stimulation of PBMC with CD28 mAb/PMA. In PBMC, we did not find any significant changes in mRNA or protein expression of CD28 Ag or CD28 ligands, B7-1 and B7-2. Serum concentrations of IL-1 beta, IL-6, and soluble CD14 were significantly diminished after in vivo TNF-alpha blockade. We did not see relevant changes in granulocyte function in vitro after cA2 infusion. Finally, we observed a statistically significant decrease in slCAM-1 molecules in the serum of patients treated with verum compared with that in the serum of subjects given placebo. This change in slCAM-1 concentration was evident on days 1 and 7 after the infusion of 10 mg/kg cA2, whereas it occurred only on day 7 in the serum of patients treated with the low dose (1 mg/kg) of cA2.
Adult↗
One hundred anti-Ro (SS-A) antibody positive patients: a 10-year follow-up.
To explore further the varied clinical expression of anti-Ro(SS-A) antibody positive patients and to determine the outcomes of these patients, we followed 100 anti-Ro(SS-A) antibody positive patients, originally seen at the Johns Hopkins Medical Institutions in 1982 and 1983, over a 10-year period. The results of this study indicate that anti-Ro(SS-A) antibody positive patients have a diverse clinical presentation and that the anti-Ro(SS-A) antibody response generally persists for years. Some of these patients appear to have a static disease process for years. However, 65% (51, including 13 deaths, of 78 patients) of the patients for whom we had follow-up data had a chronic (10 years or greater) progressive disease process. Black patients, in general, have an earlier onset of disease and may have a more severe disease than white patients. At least 25% of our anti-Ro(SS-A) antibody positive patients demonstrated a dynamic change in clinical presentation with the development of Sjögren syndrome and/or a progressive "rheumatoid-like" arthritis. Interstitial pulmonary disease, central nervous system disease, and vasculitic insults occur frequently in these patients. Renal disease occurred in 19 anti-Ro(SS-A) positive patients, and in 47% of these renal disease patients, no anti-DNA antibodies (dsDNA or ssDNA) were detected. Cutaneous manifestations are prominent in anti-Ro(SS-A) antibody positive patients with lupus. Photosensitivity and a malar dermatitis were the most common features. Twenty percent of lupus patients had discoid lesions, and 20% had SCLE lesions. Based on this study, we believe that anti-Ro(SS-A) antibody positive patients should be routinely evaluated for the emergence of systemic features. Since these systemic features are at least in part, if not solely, the result of inflammation, early treatment with steroids and/or immunosuppressive agents may minimize the damage and influence in a positive manner the significant morbidity and mortality observed in some anti-Ro(SS-A) antibody positive patients.
Adolescent↗
Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis.
Tumour necrosis factor alpha (TNF alpha) is a critical inflammatory mediator in rheumatoid arthritis, and may therefore be a useful target for specific immunotherapy. In support of this hypothesis, we previously observed beneficial responses in patients with active rheumatoid arthritis after open-label administration of a chimeric monoclonal antibody to TNF alpha (cA2). We now report the results of a four-centre, randomised double-blind trial of a single infusion of 1 or 10 mg/kg cA2 compared with placebo in 73 patients with active rheumatoid arthritis. The primary endpoint of the study was the achievement at week 4 of a Paulus 20% response, an amalgam of six clinical, observational, and laboratory variables. Intention-to-treat analysis of data from individual patients showed only 2 of 24 placebo recipients responding at this time, compared with 11 of 25 patients treated with low-dose cA2 (p = 0.0083) and 19 of 24 patients treated with high-dose cA2 (p < 0.0001). Over half of the high-dose cA2 patients responded by the more stringent 50% Paulus criteria at this time (p = 0.0005). The magnitude of these responses was impressive, with maximum mean improvements in individual disease-activity assessments, such as tender or swollen-joint counts and in serum C-reactive protein, exceeding 60% for patients on high-dose treatment. There were two severe adverse events. 1 patient on 1 mg/kg cA2 developed pneumonia ("possibly" treatment-related) and 1 on 10 mg/kg had a fracture ("probably not" treatment-related). The results provide the first good evidence that specific cytokine blockade can be effective in human inflammatory disease and define a new direction for the treatment of rheumatoid arthritis.
Adolescent↗
A soluble form of the human transferrin receptor is released by activated lymphocytes in vitro.
Soluble transferrin receptors (sTfR) were detected in culture supernatants of activated human peripheral blood mononuclear cells (PBMC) using a sandwich ELISA technique with two non-cross-reacting TfR MoAbs. Mitogenic stimulation of lymphoid cells induced both up-regulation of TfR surface density and release of sTfR to the medium. Peak levels of sTfR in culture supernatants occurred at day 4 after activation, 1 day later than maximum expression of TfR in the plasma membrane. Production of sTfR was independent of proliferation, as demonstrated by measuring sTfR release by PBMC, which had been irradiated with a dose of 20 Gy before activation. In addition to these in vitro experiments, we tested the sera of 85 patients with systemic lupus erythematosus (SLE), an autoimmune disease accompanied by in vivo activation of lymphocytes, for their sTfR levels. No correlation of these data was detectable to serum concentrations of the soluble alpha-chain of the IL-2 receptor, an unequivocal marker of lymphocyte activation. However, they correlated negatively to the haemoglobin content of the patients' erythrocytes, indicating that erythroid progenitors are the predominant source of sTfR in SLE patients' sera.
Antibodies, Monoclonal↗
Do you have an addicted nurse on your unit?
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Humans↗
[Luxations and luxation fractures in tarsal region and the results of their treatment].
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Adolescent↗
Combination therapy of the chimeric monoclonal anti-tumor necrosis factor alpha antibody (infliximab) with methotrexate in patients with rheumatoid arthritis.
Infliximab, a chimeric anti-TNF alpha antibody, showed in two double-blind placebo-controlled trials efficacy in combination with methotrexate (MTX) in patients with severe rheumatoid arthritis (RA). Whereas in the first trial low-dose MTX or placebo was compared to infliximab alone and in combination, the second trial compared infliximab to placebo in patients with active RA despite maximal tolerated MTX treatment. Infliximab showed synergistic effects in combination with MTX. The immunogenicity of infliximab was reduced by the combination. Infliximab in combination with high-dose MTX is effective and safe in long-term treatment up to 54 weeks.
Animals↗
Enumeration of total viable microorganisms in an antibiotic raw material using ChemScan solid phase cytometer.
A preliminary study was performed for the enumeration of microorganism contamination of the macrolide antibiotic, Spiramycin, using epifluorescence with the ChemScan solid phase cytometer. The artificial spiking of Spiramycin powder antibiotic with pure culture of four microorganisms led to complete recovery of the tested organisms, whatever their sensitivity to the bacteriostatic activity of the drug. With the conventional plate method run in parallel, complete recovery was only obtained for Spiramycin resistant organisms. The spiked microorganisms that were sensitive to the antibiotic remained inhibited or stressed by the action of the Spiramycin and did not grow on the plate.
Anti-Bacterial Agents↗