The Experts below are selected from a list of 4503 Experts worldwide ranked by ideXlab platform
Dorothy Mccabe - One of the best experts on this subject based on the ideXlab platform.
-
long term safety and maintenance of clinical improvement following treatment with Anakinra recombinant human interleukin 1 receptor antagonist in patients with rheumatoid arthritis extension phase of a randomized double blind placebo controlled trial
Arthritis & Rheumatism, 2002Co-Authors: Moraye B Bear, George Nuki, Barry Bresnihan, Dorothy MccabeAbstract:Objective To demonstrate the long-term efficacy of Anakinra, a human recombinant interleukin-1 receptor antagonist, in patients with rheumatoid arthritis (RA), and to assess the long-term safety of Anakinra at different daily doses. Methods The efficacy and safety of Anakinra were previously demonstrated in a double-blind, placebo-controlled, 24-week evaluation in 472 patients with active RA. Of 345 patients who completed the placebo-controlled phase of the study, 309 continued in a 52-week, multicenter, double-blind, parallel-group extension phase of the study. Patients received subcutaneous injections of Anakinra (30, 75, or 150 mg) once daily. Efficacy was assessed among the 309 patients for the first 24 weeks of the extension phase (48 weeks total therapy), using the American College of Rheumatology composite score (ACR20), its components, and radiographs of the hands and wrists. Safety was assessed in all 472 patients over the entire 52-week extension phase (76 weeks total exposure). Results A total of 218 patients completed the extension phase. Of the 91 patients who withdrew prematurely, 46 did so following adverse events, and 26 withdrew because of lack of efficacy. Among patients receiving Anakinra who entered the extension phase, the level of improvement was maintained for 48 weeks. The ACR20 response was 51% at week 24 and 46% at week 48, and this effect was consistent across all dose groups. The durability of the response to Anakinra was further demonstrated in an evaluation of the sustained ACR20 response, which was similar during the first and second 24-week periods (36% and 42%, respectively). At week 48, ACR50 and ACR70 responses were demonstrated in 18% and 3% of patients, respectively, who continued taking Anakinra (all dose groups) and in 20% and 1% of patients, respectively, who were originally receiving placebo and then were randomized to all doses of Anakinra. Anakinra was well tolerated for 76 weeks. The only side effects that appeared to be treatment-related were skin reactions at the injection site. There was no evidence of decreased tolerance, an increased number of withdrawals, or an increased incidence of clinical complications associated with extended Anakinra therapy. Conclusion The clinical benefits of treatment with daily self-administered subcutaneous injections of Anakinra in a cohort of patients with active RA were maintained for up to 48 weeks. Anakinra was well tolerated over 76 weeks. These observations support the long-term use of Anakinra for the treatment of patients with RA.
-
treatment of rheumatoid arthritis with Anakinra a recombinant human interleukin 1 receptor antagonist in combination with methotrexate results of a twenty four week multicenter randomized double blind placebo controlled trial
Arthritis & Rheumatism, 2002Co-Authors: Stanley N Cohen, Eric R Hurd, John J Cush, Michael Schiff, Michael E Weinblatt, Larry W Moreland, Joel M Kremer, Moraye B Bear, William Rich, Dorothy MccabeAbstract:Objective To evaluate the efficacy and safety of Anakinra in combination with methotrexate (MTX) in patients with active rheumatoid arthritis (RA). Methods Patients with moderate-to-severe active RA who were receiving MTX for 6 consecutive months, with stable doses for ≥3 months (those with disease duration of >6 months but <12 years) were randomized into 6 groups: placebo or 0.04, 0.1, 0.4, 1.0, or 2.0 mg/kg of Anakinra administered in a single, daily, subcutaneous injection. The primary efficacy end point was the proportion of subjects who met the American College of Rheumatology 20% improvement criteria (attained an ACR20 response) at week 12. Results A total of 419 patients were randomized in the study. Patient demographics and disease status were similar in the 6 treatment groups. The ACR20 responses at week 12 in the 5 active treatment plus MTX groups demonstrated a statistically significant (P = 0.001) dose-response relationship compared with the ACR20 response in the placebo plus MTX group. The ACR20 response rate in the Anakinra 1.0-mg/kg (46%; P = 0.001) and 2.0-mg/kg (38%; P = 0.007) dose groups was significantly greater than that in the placebo group (19%). The ACR20 responses at 24 weeks were consistent with those at 12 weeks. Similar improvements in Anakinra-treated subjects were noted in individual ACR components, erythrocyte sedimentation rate, onset of ACR20 response, sustainability of ACR20 response, and magnitude of ACR response. Anakinra was safe and well tolerated. Injection site reaction was the most frequently noted adverse event, and this led to premature study withdrawal in 7% (1.0-mg/kg group) to 10% (2.0-mg/kg group) of patients receiving higher doses. Conclusion In patients with persistently active RA, the combination of Anakinra and MTX was safe and well tolerated and provided significantly greater clinical benefit than MTX alone.
Agnes Duquesne - One of the best experts on this subject based on the ideXlab platform.
-
A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist Anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial).
Annals of the rheumatic diseases, 2011Co-Authors: Pierre Quartier, Claude Messiaen, Florence Allantaz, Jacques Bienvenu, Christophe Bardin, Pierre Pillet, Rolando Cimaz, A. Boutten, Xavier Bossuyt, Agnes DuquesneAbstract:OBJECTIVES: To assess the efficacy of the interleukin 1 receptor antagonist Anakinra in systemic-onset juvenile idiopathic arthritis (SJIA).\n\nMETHODS: A multicentre, randomised, double-blind, placebo-controlled trial was conducted. The primary objective was to compare the efficacy of a 1-month treatment with Anakinra (2 mg/kg subcutaneous daily, maximum 100 mg) with a placebo between two groups each with 12 patients with SJIA. Response was defined by a 30% improvement of the paediatric American College of Rheumatology criteria for JIA, resolution of systemic symptoms and a decrease of at least 50% of both C-reactive protein and erythrocyte sedimentation rate compared with baseline. After month 1 (M1), patients taking placebo were switched to Anakinra. Secondary objectives included tolerance and efficacy assessment for 12 months, and analyses of treatment effect on blood gene expression profiling.\n\nRESULTS: At M1, 8/12 responders were receiving Anakinra and 1 responder receiving placebo (p=0.003). Ten patients from the placebo group switched to Anakinra; nine were responders at M2. Between M1 and M12, six patients stopped treatment owing to an adverse event (n=2), lack of efficacy (n=2) or a disease flare (n=2). Blood gene expression profiling at enrollment and at 6 months' follow-up showed one set of dysregulated genes that reverted to normal values in the clinical responders and a different set, including interferon (IFN)-inducible genes, that was induced by Anakinra.\n\nCONCLUSIONS: Anakinra treatment is effective in SJIA, at least in the short term. It is associated with normalisation of blood gene expression profiles in clinical responders and induces a de novo IFN signature.\n\nTRIAL REGISTRATION NUMBER: NCT00339157.
Pierre Quartier - One of the best experts on this subject based on the ideXlab platform.
-
Efficacy of interleukin-1-targeting drugs in mevalonate kinase deficiency
Rheumatology, 2012Co-Authors: Caroline Galeotti, Pierre Quartier, Brigitte Bader-meunier, Linda Rossi-semerano, Pascal Pillet, Ulrich Meinzer, Isabelle Koné-pautAbstract:Objective. To describe the efficacy and safety of IL-1-targeting drugs, Anakinra and canakinumab, in patients with mevalonate kinase deficiency (MKD). Methods. A questionnaire was sent to French paediatric and adult rheumatologists to retrospectively collect information on disease activity before and after treatment with IL-1 antagonists from genetically confirmed MKD patients. We assessed the frequency of crises and their intensity using a 12-item clinical score built for the purpose of the study. Results. Eleven patients were included. Anti-IL-1-targeting drugs were used continuously in all but one patient who received Anakinra on demand. Daily Anakinra (nine patients) or canakinumab injections every 48 weeks (six patients, in four cases following Anakinra treatment) were associated with complete remission in four cases and partial remission in seven. The median score during MKD attacks decreased from 7/12 before treatment to 3/12 after Anakinra and 1/12 after canakinumab. The number of days with fever during attacks decreased from 5 before treatment to 3 after Anakinra and 2 after canakinumab. Marked decrease of C-reactive protein and serum amyloid A protein were recorded. Side effects were mild or moderate; they consisted of local pain and inflammation at injection site, infections and hepatic cytolysis. Conclusion. Continuous IL-1 blockade brings substantial benefit to MKD patients. Controlled trials are necessary to further assess the clinical benefit and treatment modalities in these patients.
-
A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist Anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial).
Annals of the rheumatic diseases, 2011Co-Authors: Pierre Quartier, Claude Messiaen, Florence Allantaz, Jacques Bienvenu, Christophe Bardin, Pierre Pillet, Rolando Cimaz, A. Boutten, Xavier Bossuyt, Agnes DuquesneAbstract:OBJECTIVES: To assess the efficacy of the interleukin 1 receptor antagonist Anakinra in systemic-onset juvenile idiopathic arthritis (SJIA).\n\nMETHODS: A multicentre, randomised, double-blind, placebo-controlled trial was conducted. The primary objective was to compare the efficacy of a 1-month treatment with Anakinra (2 mg/kg subcutaneous daily, maximum 100 mg) with a placebo between two groups each with 12 patients with SJIA. Response was defined by a 30% improvement of the paediatric American College of Rheumatology criteria for JIA, resolution of systemic symptoms and a decrease of at least 50% of both C-reactive protein and erythrocyte sedimentation rate compared with baseline. After month 1 (M1), patients taking placebo were switched to Anakinra. Secondary objectives included tolerance and efficacy assessment for 12 months, and analyses of treatment effect on blood gene expression profiling.\n\nRESULTS: At M1, 8/12 responders were receiving Anakinra and 1 responder receiving placebo (p=0.003). Ten patients from the placebo group switched to Anakinra; nine were responders at M2. Between M1 and M12, six patients stopped treatment owing to an adverse event (n=2), lack of efficacy (n=2) or a disease flare (n=2). Blood gene expression profiling at enrollment and at 6 months' follow-up showed one set of dysregulated genes that reverted to normal values in the clinical responders and a different set, including interferon (IFN)-inducible genes, that was induced by Anakinra.\n\nCONCLUSIONS: Anakinra treatment is effective in SJIA, at least in the short term. It is associated with normalisation of blood gene expression profiles in clinical responders and induces a de novo IFN signature.\n\nTRIAL REGISTRATION NUMBER: NCT00339157.
Antonio L'abbate - One of the best experts on this subject based on the ideXlab platform.
-
effects of interleukin 1 blockade with Anakinra on adverse cardiac remodeling and heart failure after acute myocardial infarction from the virginia commonwealth university Anakinra remodeling trial 2 vcu art2 pilot study
American Journal of Cardiology, 2013Co-Authors: Antonio L'abbate, Giuseppe Biondizoccai, Benjamin W Van Tassell, Michael C Kontos, John D Grizzard, Debra Whittaker Spillman, Claudia Oddi, Charlotte S Roberts, Ryan Melchior, George MuellerAbstract:A first pilot study of interleukin-1 blockade in ST-segment elevation acute myocardial infarction showed improved remodeling. In the present second pilot study, we enrolled 30 patients with clinically stable ST-segment elevation acute myocardial infarction randomized to Anakinra, recombinant interleukin-1 receptor antagonist, 100 mg/day for 14 days or placebo in a double-blind fashion. The primary end point was the difference in the interval change in left ventricular (LV) end-systolic volume index between the 2 groups within 10 to 14 weeks. The secondary end points included changes in the LV end-diastolic volume index, LV ejection fraction, and C-reactive protein levels. No significant changes in end-systolic volume index, LV end-diastolic volume index, or LV ejection fraction were seen in the placebo group. Compared to placebo, treatment with Anakinra led to no measurable differences in these parameters. Anakinra significantly blunted the increase in C-reactive protein between admission and 72 hours (+0.8 mg/dl, interquartile range −6.4 to +4.2, vs +21.1 mg/dl, interquartile range +8.7 to +36.6, p = 0.002), which correlated with the changes in LV end-diastolic volume index and LV end-systolic volume index at 10 to 14 weeks (R = +0.83, p = 0.002, and R = +0.55, p = 0.077, respectively). One patient in the placebo group (7%) died. One patient (7%) in the Anakinra group developed recurrent acute myocardial infarction. More patients were diagnosed with new-onset heart failure in the placebo group (4, 27%) than in the Anakinra group (1, 7%; p = 0.13). When the data were pooled with those from the first Virginia Commonwealth University-Anakinra Remodeling Trial (n = 40), this difference reached statistical significance (30% vs 5%, p = 0.035). In conclusion, interleukin-1 blockade with Anakinra blunted the acute inflammatory response associated with ST-segment elevation acute myocardial infarction. Although it failed to show a statistically significant effect on LV end-systolic volume index, LV end-diastolic volume index, or LV ejection fraction in this cohort of clinically stable patients with near-normal LV dimensions and function, Anakinra led to a numerically lower incidence of heart failure.
-
Anakinra in experimental acute myocardial infarction does dosage or duration of treatment matter
Cardiovascular Drugs and Therapy, 2009Co-Authors: Fadi N Salloum, Nicholas N Hoke, Giuseppe Biondizoccai, Vinh Q Chau, Amit Varma, Stefano Toldo, Filippo Crea, George W Vetrovec, Antonio L'abbateAbstract:Purpose Interleukin-1 (IL-1) receptor antagonist (Ra) is a naturally occurring IL-1 blocker with a cardioprotective effect during acute myocardial infarction (AMI). Anakinra, recombinant-human IL-1Ra, has been used to prevent heart failure in a mouse model of AMI. The aim of this study was to determine the optimal therapeutic regimen for Anakinra in AMI.
-
Anakinra a recombinant human interleukin 1 receptor antagonist inhibits apoptosis in experimental acute myocardial infarction
Circulation, 2008Co-Authors: Antonio L'abbate, Elena Vecile, Stefania Straino, Jonerik Houser, Ian Z Qureshi, Evan D Ownby, Nicholas N Hoke, Giuseppe Biondizoccai, Fadi N Salloum, Edoardo GustiniAbstract:Background— Experimental interleukin-1 receptor antagonist gene overexpression has shown that interleukin-1 receptor antagonist is cardioprotective during global cardiac ischemia. The aim of the present study was to test the impact of an exogenous recombinant human interleukin-1 receptor antagonist (Anakinra) in experimental acute myocardial infarction. Methods and Results— Two animal studies were conducted: one of immediate Anakinra administration during ischemia in the mouse and one of delayed Anakinra administration 24 hours after ischemia in the rat. Seventy-eight Institute of Cancer Research mice and 20 Wistar rats underwent surgical coronary artery ligation (or sham operation) and were treated with either Anakinra 1 mg/kg or NaCl 0.9% (saline). Treatment was administered during surgery and then daily for 6 doses in the mice and starting on day 2 daily for 5 doses in the rats. Twenty-eight mice underwent infarct size assessment 24 hours after surgery, 6 saline-treated mice and 22 mice treated with in...
George Nuki - One of the best experts on this subject based on the ideXlab platform.
-
long term safety and maintenance of clinical improvement following treatment with Anakinra recombinant human interleukin 1 receptor antagonist in patients with rheumatoid arthritis extension phase of a randomized double blind placebo controlled trial
Arthritis & Rheumatism, 2002Co-Authors: Moraye B Bear, George Nuki, Barry Bresnihan, Dorothy MccabeAbstract:Objective To demonstrate the long-term efficacy of Anakinra, a human recombinant interleukin-1 receptor antagonist, in patients with rheumatoid arthritis (RA), and to assess the long-term safety of Anakinra at different daily doses. Methods The efficacy and safety of Anakinra were previously demonstrated in a double-blind, placebo-controlled, 24-week evaluation in 472 patients with active RA. Of 345 patients who completed the placebo-controlled phase of the study, 309 continued in a 52-week, multicenter, double-blind, parallel-group extension phase of the study. Patients received subcutaneous injections of Anakinra (30, 75, or 150 mg) once daily. Efficacy was assessed among the 309 patients for the first 24 weeks of the extension phase (48 weeks total therapy), using the American College of Rheumatology composite score (ACR20), its components, and radiographs of the hands and wrists. Safety was assessed in all 472 patients over the entire 52-week extension phase (76 weeks total exposure). Results A total of 218 patients completed the extension phase. Of the 91 patients who withdrew prematurely, 46 did so following adverse events, and 26 withdrew because of lack of efficacy. Among patients receiving Anakinra who entered the extension phase, the level of improvement was maintained for 48 weeks. The ACR20 response was 51% at week 24 and 46% at week 48, and this effect was consistent across all dose groups. The durability of the response to Anakinra was further demonstrated in an evaluation of the sustained ACR20 response, which was similar during the first and second 24-week periods (36% and 42%, respectively). At week 48, ACR50 and ACR70 responses were demonstrated in 18% and 3% of patients, respectively, who continued taking Anakinra (all dose groups) and in 20% and 1% of patients, respectively, who were originally receiving placebo and then were randomized to all doses of Anakinra. Anakinra was well tolerated for 76 weeks. The only side effects that appeared to be treatment-related were skin reactions at the injection site. There was no evidence of decreased tolerance, an increased number of withdrawals, or an increased incidence of clinical complications associated with extended Anakinra therapy. Conclusion The clinical benefits of treatment with daily self-administered subcutaneous injections of Anakinra in a cohort of patients with active RA were maintained for up to 48 weeks. Anakinra was well tolerated over 76 weeks. These observations support the long-term use of Anakinra for the treatment of patients with RA.