22 results on '"Majin, Castillo"'
Search Results
2. Evaluation of the Relationship Between Serum Urate Levels, Clinical Manifestations of Gout, and Death From Cardiovascular Causes in Patients Receiving Febuxostat or Allopurinol in an Outcomes Trial
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Kenneth G, Saag, Michael A, Becker, William B, White, Andrew, Whelton, Jeffrey S, Borer, Philip B, Gorelick, Barbara, Hunt, Majin, Castillo, Lhanoo, Gunawardhana, and Danielle, Johnson
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Thiazoles ,Febuxostat ,Treatment Outcome ,Gout ,Allopurinol ,Humans ,Hyperuricemia ,Gout Suppressants ,Uric Acid - Abstract
To investigate whether serum urate levels, number of gout flares, and tophi burden are related to death from cardiovascular (CV) causes after treatment with febuxostat or allopurinol in patients with gout from the Cardiovascular Safety of Febuxostat or Allopurinol in Patients With Gout and Cardiovascular Comorbidities (CARES) trial.Patients were randomly assigned to receive febuxostat (40 mg or 80 mg once daily, according to serum urate levels at week 2) or allopurinol titrated in 100-mg increments from 200-400 mg or 300-600 mg (with dose determined according to kidney function). Changes from baseline in serum urate level, gout flares, and tophus resolution were key exploratory efficacy parameters in the overall population and in subgroups of patients who died and those who did not die from a CV-related cause. The latter subgroup included patients who died due to non-CV causes and those who did not die due to any cause.Patients received treatment with febuxostat (n = 3,098) or allopurinol (n = 3,092) for a median follow-up period of 32 months (for a maximum of 85 months). In the overall population, mean serum urate levels were lower in those receiving febuxostat compared with those receiving allopurinol at most study visits. There were no associations between serum urate levels and death from CV causes with febuxostat. The number of gout flares requiring treatment was higher within 1 year of treatment with febuxostat compared with allopurinol (mean incidence of gout flares per patient-years of exposure 1.33 versus 1.20), but was comparable thereafter and decreased overall throughout the study period (mean incidence of gout flares per patient-years of exposure 0.35 versus 0.34 after 1 year of treatment; overall mean incidence 0.68 versus 0.63) irrespective of whether the patient died from a CV-related cause. Overall, 20.8% of patients had ≥1 tophus at baseline; tophus resolution rates were similar between treatment groups, with cumulative resolution rates of50%.In the CARES trial, febuxostat and allopurinol (≤600 mg doses) had comparable efficacy in patients with gout and CV disease, and there was no evidence of a relationship between death from CV causes and serum urate levels, number of gout flares, or tophus resolution among the patients receiving febuxostat.
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- 2022
3. Efficacy and Safety of Febuxostat Extended and Immediate Release in Patients With Gout and Renal Impairment: A Phase <scp>III</scp> Placebo‐Controlled Study
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Barbara Hunt, Kenneth G. Saag, Michael Becker, Lhanoo Gunawardhana, Majin Castillo, Andrew Whelton, and K Kisfalvi
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Male ,Gout ,Placebo-controlled study ,Severity of Illness Index ,law.invention ,Naproxen ,0302 clinical medicine ,Randomized controlled trial ,law ,Immunology and Allergy ,030212 general & internal medicine ,Respiratory Tract Infections ,Headache ,Alanine Transaminase ,gamma-Glutamyltransferase ,Middle Aged ,Treatment Outcome ,Creatinine ,Hypertension ,Original Article ,Drug Therapy, Combination ,Female ,Febuxostat ,Glomerular Filtration Rate ,medicine.drug ,Adult ,Diarrhea ,medicine.medical_specialty ,Immunology ,Urology ,Renal function ,Placebo ,Gout Suppressants ,03 medical and health sciences ,Double-Blind Method ,Rheumatology ,Severity of illness ,medicine ,Humans ,Aspartate Aminotransferases ,Renal Insufficiency, Chronic ,Adverse effect ,Aged ,030203 arthritis & rheumatology ,business.industry ,medicine.disease ,Uric Acid ,Cough ,Nasopharyngitis ,Delayed-Action Preparations ,Colchicine ,business - Abstract
Objective To assess the efficacy and safety of febuxostat extended release (XR) and immediate release (IR) in patients with gout and normal or impaired renal function. Methods This was a 3‐month, phase III, multicenter, double‐blind, placebo‐controlled study. Patients (n = 1,790) with a history of gout and normal or impaired (mild‐to‐severe) renal function were randomized to receive placebo, febuxostat IR 40 or 80 mg, or febuxostat XR 40 or 80 mg once daily (1:1:1:1:1 ratio). End points included proportions of patients with a serum urate (UA) level of
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- 2018
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4. Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout
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William B, White, Kenneth G, Saag, Michael A, Becker, Jeffrey S, Borer, Philip B, Gorelick, Andrew, Whelton, Barbara, Hunt, Majin, Castillo, Lhanoo, Gunawardhana, and Esha, Desai
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musculoskeletal diseases ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Gout ,medicine.drug_class ,Allopurinol ,030204 cardiovascular system & hematology ,law.invention ,Gout Suppressants ,03 medical and health sciences ,0302 clinical medicine ,Febuxostat ,Randomized controlled trial ,Double-Blind Method ,law ,Internal medicine ,Cause of Death ,medicine ,Clinical endpoint ,Humans ,Xanthine oxidase inhibitor ,Cause of death ,Aged ,030203 arthritis & rheumatology ,Unstable angina ,business.industry ,nutritional and metabolic diseases ,General Medicine ,Middle Aged ,medicine.disease ,Cardiovascular Diseases ,Female ,business ,medicine.drug - Abstract
Cardiovascular risk is increased in patients with gout. We compared cardiovascular outcomes associated with febuxostat, a nonpurine xanthine oxidase inhibitor, with those associated with allopurinol, a purine base analogue xanthine oxidase inhibitor, in patients with gout and cardiovascular disease.We conducted a multicenter, double-blind, noninferiority trial involving patients with gout and cardiovascular disease; patients were randomly assigned to receive febuxostat or allopurinol and were stratified according to kidney function. The trial had a prespecified noninferiority margin of 1.3 for the hazard ratio for the primary end point (a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or unstable angina with urgent revascularization).In total, 6190 patients underwent randomization, received febuxostat or allopurinol, and were followed for a median of 32 months (maximum, 85 months). The trial regimen was discontinued in 56.6% of patients, and 45.0% discontinued follow-up. In the modified intention-to-treat analysis, a primary end-point event occurred in 335 patients (10.8%) in the febuxostat group and in 321 patients (10.4%) in the allopurinol group (hazard ratio, 1.03; upper limit of the one-sided 98.5% confidence interval [CI], 1.23; P=0.002 for noninferiority). All-cause and cardiovascular mortality were higher in the febuxostat group than in the allopurinol group (hazard ratio for death from any cause, 1.22 [95% CI, 1.01 to 1.47]; hazard ratio for cardiovascular death, 1.34 [95% CI, 1.03 to 1.73]). The results with regard to the primary end point and all-cause and cardiovascular mortality in the analysis of events that occurred while patients were being treated were similar to the results in the modified intention-to-treat analysis.In patients with gout and major cardiovascular coexisting conditions, febuxostat was noninferior to allopurinol with respect to rates of adverse cardiovascular events. All-cause mortality and cardiovascular mortality were higher with febuxostat than with allopurinol. (Funded by Takeda Development Center Americas; CARES ClinicalTrials.gov number, NCT01101035 .).
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- 2018
5. Additional file 1: of Efficacy and safety of febuxostat extended release and immediate release in patients with gout and moderate renal impairment: phase II placebo-controlled study
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Lhanoo Gunawardhana, Becker, Michael, Whelton, Andrew, Hunt, Barbara, Majin Castillo, and Saag, Kenneth
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food and beverages - Abstract
Table S1. Summary of medical histories of patients with nonfatal serious TEAEs. (DOCX 21Â kb)
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- 2018
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6. Efficacy and safety of febuxostat extended release and immediate release in patients with gout and moderate renal impairment: phase II placebo-controlled study
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Lhanoo Gunawardhana, Majin Castillo, Michael Becker, Kenneth G. Saag, Andrew Whelton, and Barbara Hunt
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Male ,medicine.medical_specialty ,lcsh:Diseases of the musculoskeletal system ,Gout ,medicine.drug_class ,Gastrointestinal Diseases ,030232 urology & nephrology ,Placebo-controlled study ,Hyperuricemia ,Placebo ,Gastroenterology ,Gout Suppressants ,03 medical and health sciences ,0302 clinical medicine ,Febuxostat ,Serum uric acid ,Double-Blind Method ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Adverse effect ,Renal impairment ,Xanthine oxidase inhibitor ,Aged ,030203 arthritis & rheumatology ,business.industry ,Middle Aged ,medicine.disease ,Extended release ,Treatment Outcome ,Cardiovascular Diseases ,Delayed-Action Preparations ,Female ,Kidney Diseases ,lcsh:RC925-935 ,business ,medicine.drug ,Glomerular Filtration Rate ,Research Article - Abstract
Background Febuxostat immediate release (IR), a xanthine oxidase inhibitor, is indicated for the management of hyperuricemia in patients with gout by lowering urate levels. An extended release (XR) formulation of febuxostat was developed to provide equal or superior efficacy on urate lowering compared with the IR formulation and potentially lower the risk of treatment-initiated gout flares due to an altered pattern of drug exposure. The present study evaluated the efficacy and safety of febuxostat XR and IR formulations in patients with gout and moderate renal impairment (estimated glomerular filtrate rate ≥ 30 and
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- 2017
7. Exploring the use of adalimumab for patients with moderate Crohn's disease: Subanalyses from induction and maintenance trials
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Mei Yang, William J. Sandborn, Qian Zhou, Roopal Thakkar, Julián Panés, Anne M. Robinson, Majin Castillo, and Jean-Frederic Colombel
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Adult ,Male ,medicine.medical_specialty ,Anti-Inflammatory Agents ,Disease ,Antibodies, Monoclonal, Humanized ,Placebo ,Severity of Illness Index ,Gastroenterology ,Inflammatory bowel disease ,Maintenance Chemotherapy ,Young Adult ,Crohn Disease ,Predictive Value of Tests ,Internal medicine ,Severity of illness ,Adalimumab ,medicine ,Humans ,Crohn's disease ,biology ,business.industry ,Remission Induction ,C-reactive protein ,General Medicine ,Middle Aged ,medicine.disease ,Crohn's Disease Activity Index ,C-Reactive Protein ,biology.protein ,Female ,business ,medicine.drug - Abstract
Anti-TNF agents are often reserved for patients with severe Crohn's disease (CD).We explored the predictive value of baseline disease activity and C-reactive protein (CRP) for disease course, adalimumab efficacy for remission (induction and maintenance) in patients with moderate and severe CD, and adalimumab efficacy in moderate CD by CRP category.Post hoc analyses of remission data were performed for all randomized patients from induction (CLASSIC I) and maintenance (CHARM, EXTEND) adalimumab trials in patients with moderate (CDAI≤300) or severe (CDAI300) CD, and in high (≥10 mg/L) or low (10 mg/L) CRP moderate CD subgroups. Placebo-treated CHARM patients were evaluated for disease activity over time and time to CD-related hospitalization, by baseline disease severity and CRP.Moderate CD patients had the highest clinical remission rate and largest treatment effect size compared with placebo at week 4 after 160/80 mg induction (46.3% adalimumab, 17.4% placebo; versus 22.9%, 3.6% for severe patients). Moderate-CD/high-CRP patients had the most pronounced efficacy (57.1% adalimumab, 6.7% placebo; versus 40.7%, 20.0% for lower CRP group). Adalimumab maintenance treatment (40 mg every-other-week) achieved superior remission versus placebo at one year in moderate (32.9% versus 13.7%) and severe (27.2% versus 7.5%) cohorts. Among moderate patients, efficacy was similar by CRP category. Moderate-CD/high-CRP placebo-treated patients experienced disease activity and hospitalization rates at week 56 of CHARM approaching those of severe CD patients.This analysis suggests that moderate CD patients can be treated effectively with adalimumab, and supports using CRP to identify moderate CD patients at greatest risk of disease progression.
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- 2013
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8. Association of baseline C-reactive protein and prior anti-tumor necrosis factor therapy with need for weekly dosing during maintenance therapy with adalimumab in patients with moderate to severe Crohn's disease
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Jean-Frederic Colombel, Roopal Thakkar, Scott E. Plevy, William J. Sandborn, Paul F. Pollack, Julián Panés, G. D'Haens, Anne M. Robinson, Majin Castillo, Qian Zhou, Amsterdam Gastroenterology Endocrinology Metabolism, and Gastroenterology and Hepatology
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Adult ,Male ,medicine.medical_specialty ,Time Factors ,Anti-Inflammatory Agents ,Antibodies, Monoclonal, Humanized ,Placebo ,Severity of Illness Index ,Gastroenterology ,Crohn Disease ,Double-Blind Method ,Maintenance therapy ,Internal medicine ,Post-hoc analysis ,medicine ,Adalimumab ,Humans ,Dosing ,Crohn's disease ,biology ,Tumor Necrosis Factor-alpha ,business.industry ,C-reactive protein ,General Medicine ,Middle Aged ,medicine.disease ,Surgery ,Anti-Tumor Necrosis Factor Therapy ,C-Reactive Protein ,biology.protein ,Female ,business ,medicine.drug - Abstract
A post hoc analysis of data from the adalimumab Crohn's disease (CD) maintenance trial (CHARM, NCT00077779), examining the relationship between adalimumab dosing and maintenance of remission and response in subgroups stratified by previous anti-TNF use and baseline CRP. All patients received open-label induction (adalimumab: 80 mg, week [wk] 0; 40 mg, wk 2). At wk 4, all patients were randomized to double-blind maintenance adalimumab (40 mg weekly or every other week [eow]) or placebo for 52 weeks. In this analysis, clinical remission (CDAI
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- 2013
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9. Long-term Effectiveness of Adalimumab in Crohnʼs Disease: Observational Data from the PYRAMID Registry
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Jingdong Chao, Samantha Eichner, Geert DʼHaens, Edward V. Loftus, Remo Panaccione, Roopal Thakkar, Parvez Mulani, Jack Satsangi, Majin Castillo, Martha Skup, Walter Reinisch, and Natalia Kan-Dobrosky
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Pediatrics ,medicine.medical_specialty ,Hepatology ,business.industry ,Pyramid ,Gastroenterology ,Adalimumab ,medicine ,Observational study ,Disease ,business ,medicine.drug ,Term (time) - Published
- 2013
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10. PTU-111 Baseline C reactive protein is associated with disease progression in patients with Crohn's disease: Abstract PTU-111 Table 1
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W J Sandborn, Majin Castillo, Bidan Huang, Roopal Thakkar, J-F Colombel, and Qian Zhou
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medicine.medical_specialty ,Crohn's disease ,business.operation ,biology ,Abbott Laboratories ,business.industry ,C-reactive protein ,Disease progression ,Gastroenterology ,Schering-Plough ,medicine.disease ,Internal medicine ,Post-hoc analysis ,medicine ,biology.protein ,Adalimumab ,In patient ,business ,medicine.drug - Abstract
Introduction Elevated C reactive protein (CRP), a marker of inflammation, is known to correlate with Crohn9s disease (CD) activity 1 2 and to be a predictor of disease relapse in CD. 3 4 However, in patients with moderate or severe CD it is not known whether CRP is associated with disease progression. Methods This post hoc analysis evaluated the association of baseline (BL) CRP and change in CDAI over time in patients with moderate (CDAI >220 to ≤300) to severe (CDAI >300) CD who were randomised to the placebo group in the CHARM trial 5 (N=238). Patients received open-label adalimumab (ADA) induction (week 0: 80 mg; week 2: 40 mg) followed by blinded weekly placebo treatment from weeks 4–56, with switch to open-label ADA allowed after week 12 for disease flare. This analysis grouped patients by CD severity and BL CRP (severe, high: CDAI >300, CRP≥10 mg/l; severe, low: CDAI >300, CRP Results CDAI decreased from BL in all subgroups after ADA induction (Week 4, Abstract PTU-111 table 1). By week 56, the mean CDAI in all subgroups had increased compared with week 4, and was greater in patients who had higher CRP vs lower CRP at BL (244 vs 223, 306 vs 260, for moderate and severe groups, respectively). In patients with moderate CD and high CRP, week 12 and week 56 CDAI approached that of patients with severe CD and low CRP, despite BL differences in CDAI of over 90 points (week 12: 235 vs 243; week 56: 244 vs 260). Conclusion This post hoc analysis of disease activity and CRP demonstrates that an elevated BL CRP in patients with moderate or severe CD is associated with higher disease scores after 1 year. Disease activity over time in patients with moderate CD and higher CRP behaved similarly to that of patients with severe CD and lower CRP. Competing interests J-F Colombel Shareholder with: Intestinal Biotech Development, Grant/Research Support from: Astra-Zeneca, Danisco, Danone, Dysphar, Ferring, Giuliani, Lesaffre, Mapi Naxis, Ocerra Therapeutics, Roquette, Schering-Plough, and UCB, Consultant for: Abbott Laboratories, ActoGeniX NV, Albireo Pharma, Astra Zeneca, Bayer Schering Pharma, Biogen Idec, Boehringer-Ingelheim, Bristol-Myers Squibb, Cellerix, Centocor, Chemocentryx, Cosmo Technologies, Danone France, Elan, Genentech, Giuliani, Given Imaging, GlaxoSmithKline, Merck, Millennium, NeoVacs, Ocerra, Otsuka American, PDL Biopharma, Pfizer, Ribo Vacs Biotech, Schering-Plough, Shire, Synta, Teva and Petah Tikva, Therakos, UCB, and Wyeth, Speaker bureau with: Abbott Laboratories, Astra Zeneca, Centocor, Elan, Falk, Ferring, Given Imaging, Otsuka American, PDL, Schering-Plough, Shire and UCB, W Sandborn Grant/Research Support from: Centocor Ortho Biotech, Abbott Laboratories, and UCB Pharma, Consultant for: Centocor Ortho Biotech, Abbott Laboratories, UCB Pharma, and Merck (previously Schering Plough), M Castillo Shareholder with: Abbott, Employee of: Abbott, B Huang Shareholder with: Abbott, Employee of: Abbott, Q Zhou Shareholder with: Abbott, Employee of: Abbott, R Thakkar Shareholder with: Abbott, Employee of: Abbott. References 1. Solem C . Inflamm Bowel Dis 2005; 11 :707. 2. Henriksen M . Gut 2008; 57 :1518. 3. Bitton A . Gut 2008; 57 :1386. 4. Consigny Y . Inflamm Bowel Dis 2006; 12 :551. 5. Colombel JF . Gastroenterology 2007; 132 :52.
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- 2012
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11. Efficacy and Safety of Adalimumab in Moderate Compared with Severe Crohnʼs Disease: Pooled Data from the CHARM and EXTEND Trials
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Jean-Frederic Colombel, Majin Castillo, William J. Sandborn, Roopal Thakkar, and Qian Zhou
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medicine.medical_specialty ,Hepatology ,business.industry ,Internal medicine ,Gastroenterology ,Adalimumab ,medicine ,Pooled data ,Disease ,Charm (quantum number) ,business ,medicine.drug - Published
- 2011
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12. Mo1219 Adalimumab Achieves Efficacy in Mucosal Healing Regardless of Baseline Disease Severity in Patients With Crohn's Disease: Data From EXTEND
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Julián Panés, Majin Castillo, Qian Zhou, William J. Sandborn, Douglas C. Wolf, Annalisa Iezzi, Anne M. Robinson, Roopal Thakkar, Jean-Frederic Colombel, and Samantha Eichner
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medicine.medical_specialty ,Crohn's disease ,Pathology ,Hepatology ,Exacerbation ,business.industry ,Gastroenterology ,medicine.disease ,Discontinuation ,Disease severity ,Internal medicine ,Mucosal healing ,Plasma concentration ,medicine ,Adalimumab ,In patient ,business ,medicine.drug - Abstract
68% had inflammatory (B1) disease behavior; 30% had prior resections. Over 7 years, 117 pts completed, while 478 discontinued (36% due to AEs; 28% due to pt decision; 17% due to no improvement/disease deterioration). Discontinuation rates were 29.2%, 13.6%, 16.1%, 7.9%, 5.0%, 4.5% and 3.9% during years 1 7, respectively. Over 71% of pts were exposed to CZP for >1 year; the average number of CZP injections was 41. No new safety signals were identified during this study. The most common AE was CD exacerbation (30%); most common OI was herpes simplex (3.4%). The observed annual remission rates ranged from 68% 76% (Year 1 to 7, table). The remission rates analyzed by LOCF and NRI methods were 58% and 45% at year 1, 56% and 26% at year 3 and 55% and 13% at year 7, respectively. FC levels had no trends toward change; CRP levels were relatively stable. The geometric mean CZP plasma concentrations ranged from 6 10 ug/mL up to year 6; CZP concentrations were typically lower in pts who were anti-CZP antibody positive vs. negative throughout the study (e.g. 3μg/ml vs. 9μg/ml at Wk 54, 3μg/ml vs. 10μg/ml at Wk 210, respectively). Conclusions: The P3 study demonstrates that the long-term safety of CZP is consistent with short-term studies.[1, 2] Additionally, the observed rates of clinical remission were sustainable for 7 years. PRECiSE3 Remission Rates Over 7 Years, observed cases
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- 2014
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13. P-139 PYRAMID Registry
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Edward V. Loftus, Natalia Kan-Dobrosky, Roopal Thakkar, Samantha Eichner, Walter Reinisch, Remo Panaccione, Geert DʼHaens, Jack Satsangi, and Majin Castillo
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Pediatrics ,medicine.medical_specialty ,business.industry ,Pyramid ,Gastroenterology ,Adalimumab ,medicine ,Immunology and Allergy ,Observational study ,Disease ,business ,medicine.drug - Published
- 2013
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14. Pyramid Registry: An Observational Study of Adalimumab in Crohnʼs Disease: Results at Year Five
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Walter Reinisch, Geert DʼHaens, Remo Panaccione, Majin Castillo, Edward V. Loftus, Jack Satsangi, Roopal Thakkar, Samantha Eichner, and Natalia Kan-Dobrosky
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Pediatrics ,medicine.medical_specialty ,Hepatology ,business.industry ,Pyramid ,Gastroenterology ,Adalimumab ,medicine ,Observational study ,Disease ,business ,medicine.drug - Published
- 2013
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15. Risk of Malignancy, Infection, Serious Infection, and Acute Health Care Use in Patients With Crohnʼs Disease Treated With Adalimumab vs. Immunosuppressants
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Jingdong Chao, Parvez Mulani, Roopal Thakkar, Martha Skup, Anne M. Robinson, Majin Castillo, Jean-Frederic Colombel, Elyse Swallow, Rachael Sorg, and Mei Yang
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medicine.medical_specialty ,Hepatology ,business.industry ,Risk of malignancy ,Gastroenterology ,Disease ,Serious infection ,Internal medicine ,Health care ,medicine ,Adalimumab ,In patient ,business ,medicine.drug - Published
- 2012
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16. PTU-110 Elevated C reactive protein in anti-TNF-naïve patients is associated with higher remission rates: Abstract PTU-110 Table 1
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J-F Colombel, Roopal Thakkar, Qian Zhou, W J Sandborn, and Majin Castillo
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medicine.medical_specialty ,biology ,business.operation ,business.industry ,Abbott Laboratories ,C-reactive protein ,Gastroenterology ,Schering-Plough ,Placebo ,Maintenance therapy ,Internal medicine ,Post-hoc analysis ,Adalimumab ,medicine ,biology.protein ,Population study ,business ,medicine.drug - Abstract
Introduction The CHARM trial 1 demonstrated that adalimumab (ADA) was effective for the maintenance of remission in patients with moderate to severe Crohn9s disease (CD), and that remission rates are influenced by a patient9s baseline C reactive protein (CRP) concentration and prior anti-TNF experience. 1 Patients who were either anti-TNF-naive or had an elevated baseline CRP achieved higher rates of remission than the general study population. In this post hoc analysis we examined whether patients who were anti-TNF-naive and had an elevated CRP at baseline could achieve higher remission rates than those previously reported. Methods Data from CHARM, a 56-week, randomised, placebo-controlled trial of ADA maintenance therapy, were analysed. All patients received open-label ADA during a 4-week induction period, and were then randomised to ADA (40 mg weekly or every other week [eow]) or placebo for a 52-week double-blind period. In this analysis, clinical remission at week 56 was determined for randomised responders (patients who had a decrease in CDAI ≥70 at week 4 compared with baseline) who were naive to prior anti-TNF treatment, by baseline CRP subgroups (high: ≥10 mg/l, vs low: Results ADA treatment (weekly or eow) resulted in statistically significantly greater rates of clinical remission at week 56 compared with placebo treatment in each CRP subgroup of anti-TNF-naive patients (Abstract PTU-110 table 1). The percentage of patients in clinical remission was greater in the high CRP subgroup for both weekly and eow ADA treatment. Conclusion In the CHARM trial, anti-TNF-naive patients with baseline CRP≥10 mg/l experienced greater rates of clinical remission, regardless of ADA dose frequency, compared with patients with baseline CRP Competing interests W Sandborn Grant/Research Support from: Centocor Ortho Biotech, Abbott Laboratories, and UCB Pharma, Consultant for: Centocor Ortho Biotech, Abbott Laboratories, UCB Pharma, and Merck (previously Schering Plough), J-F Colombel Shareholder with: Intestinal Biotech Development, Grant/Research Support from: Astra-Zeneca, Danisco, Danone, Dysphar, Ferring, Giuliani, Lesaffre, Mapi Naxis, Ocerra Therapeutics, Roquette, Schering-Plough, and UCB, Consultant for: Abbott Laboratories, ActoGeniX NV, Albireo Pharma, Astra Zeneca, Bayer Schering Pharma, Biogen Idec, Boehringer-Ingelheim, Bristol-Myers Squibb, Cellerix, Centocor, Chemocentryx, Cosmo Technologies, Danone France, Elan, Genentech, Giuliani, Given Imaging, GlaxoSmithKline, Merck, Millennium, NeoVacs, Ocerra, Otsuka American, PDL Biopharma, Pfizer, Ribo Vacs Biotech, Schering-Plough, Shire, Synta, Teva and Petah Tikva, Therakos, UCB, and Wyeth, Speaker bureau with: Abbott Laboratories, Astra Zeneca, Centocor, Elan, Falk, Ferring, Given Imaging, Otsuka American, PDL, Schering-Plough, Shire and UCB, M Castillo Shareholder with: Abbott, Employee of: Abbott, Q Zhou Employee of: Abbott, R Thakkar Shareholder with: Abbott, Employee of: Abbott. Reference 1. Colombel JF . Gastroenterology 2007; 132 :52.
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- 2012
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17. PWE-260 Optimal C reactive protein cut-off point for predicting hospitalisation in patients with moderately active Crohn's disease
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W J Sandborn, T Finney-Hayward, Roopal Thakkar, Mei Yang, Parvez Mulani, Edouard Louis, Jingdong Chao, J-F Colombel, Remo Panaccione, and Majin Castillo
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medicine.medical_specialty ,education.field_of_study ,Receiver operating characteristic ,biology ,Proportional hazards model ,business.industry ,Population ,C-reactive protein ,Gastroenterology ,Area under the curve ,urologic and male genital diseases ,Placebo ,Surgery ,Internal medicine ,medicine ,Adalimumab ,biology.protein ,education ,business ,Body mass index ,medicine.drug - Abstract
Introduction To identify high risk patients among patients with moderate Crohn9s disease (CD), we explored the association between C reactive protein (CRP) concentration and hospitalisation risk for patients with moderately active CD and identified the optimal CRP cut-off point as a marker to predict CD-related hospitalisation. CRP is a well-studied and commonly used laboratory marker of inflammation in CD. 1 The relationship between CRP and hospitalisation risk given the same Crohn9s Disease Activity Impairment (CDAI) score in patients with moderate CD has not been studied. Methods Data from CHARM, a 56-week (wk), randomised, placebo-controlled trial of adalimumab maintenance therapy, were analysed. All patients received adalimumab during a 4-wk, open-label induction period; patients were then randomised to adalimumab or placebo for a 52-wk double-blind period. For this analysis, only patients who were randomised to placebo at Wk 4 and had moderate CD, defined as CDAI ≤300 at Wk 4, were analysed. A Cox model was applied to analyse the association between Wk-4 CRP concentration and the probability of having a CD-related hospitalisation during the 52-wk double-blind period. Wk-4 CDAI score, Wk-4 steroid use, age, sex, weight, body mass index, and prior anti–tumour necrosis factor use were also adjusted in the model. Patients were censored if they switched to open-label adalimumab or dropped out. A receiver operating characteristic (ROC) curve was used to identify the optimal CRP cut-off point to best predict the 52-wk CD-related hospitalisation rate. Results The analysis population included 214 patients randomised to placebo with Wk-4 CDAI ≤300. An elevated Wk-4 CRP concentration was associated with a greater chance of CD-related hospitalisation (HR=1.24; p=0.002). The ROC curve identified a CRP concentration =1.41 mg/dl as the dichotomising point (area under the curve=0.68; sensitivity=0.58; specificity=0.80). Risk of CD-related hospitalisation during the double-blind period was 3.4 times greater for patients with CRP concentrations ≥1.41 mg/dl at Wk 4 vs patients with CRP concentrations Conclusion Early CRP concentration represents a moderate to good marker to predict CD-related hospitalisation for patients with moderately active CD given the same CDAI score. CRP concentration of 1.41 mg/dl was the optimal cut-off point for predicting long-term CD-related hospitalisation. Competing interests J-F Colombel Consultant for: Abbott, Speaker bureau with: Abbott, W Sandborn Grant/Research Support from: Abbott, Consultant for: Abbott, E Louis Speaker bureau with: Abbott, Conflict with: Abbott, R Panaccione Grant/Research Support from: Abbott, Consultant for: Abbott, Speaker bureau with: Abbott, Conflict with: Abbott, R Thakkar Shareholder with: Abbott, Employee of: Abbott, M Castillo Shareholder with: Abbott, Employee of: Abbott, M Yang Shareholder with: Abbott, Employee of: Abbott, T Finney-Hayward Shareholder with: Abbott, Employee of: Abbott, J Chao Shareholder with: Abbott, Employee of: Abbott, P Mulani Shareholder with: Abbott, Employee of: Abbott. Reference 1. Henriksen M , et al . Gut 2008; 57 :1518–23.
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- 2012
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18. PTU-109 Efficacy and safety of adalimumab in moderate compared with severe Crohn's disease: pooled data from the charm and extend trials: Abstract PTU-109 Table 1
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Roopal Thakkar, J-F Colombel, Majin Castillo, Qian Zhou, and W J Sandborn
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medicine.medical_specialty ,Crohn's disease ,business.operation ,business.industry ,Abbott Laboratories ,Gastroenterology ,Schering-Plough ,medicine.disease ,Placebo ,Pooled analysis ,Internal medicine ,medicine ,Adalimumab ,In patient ,Pooled data ,business ,medicine.drug - Abstract
Introduction The efficacy of adalimumab (ADA) in Crohn9s disease (CD) by disease duration has been explored, 1 but efficacy and safety of ADA by disease severity have not been investigated. The CHARM 2 and EXTEND 3 trials assessed ADA treatment for the maintenance of remission in patients with moderate to severe CD. Results from CHARM and EXTEND in patients with moderate vs severe CD were pooled to assess efficacy and safety by disease severity. Methods This analysis of pooled data were performed to assess clinical response and clinical remission at week 56 (CHARM) or 52 (EXTEND) in patients with moderate (CDAI ≤300) or severe (CDAI >300) CD, treated with blinded ADA every other week (eow) or placebo. In both trials, patients received open-label ADA induction (CHARM: 80 mg at week 0, 40 mg at week 2; EXTEND: 160 mg at week 0, 80 mg at week 2), followed by blinded treatment (ADA 40 mg eow or weekly, or placebo in CHARM, 40 mg eow or placebo in EXTEND) from weeks 4 to the end of the trial (week 56 in CHARM, week 52 in EXTEND). Data from the ADA 40 mg eow arm of CHARM was pooled with data from EXTEND; safety and efficacy (proportion of patients in clinical remission, defined as CDAI Results A total of 438 patients were included in the pooled analysis: 187 with moderate CD (placebo: 92; ADA: 95) and 251 with severe CD (placebo: 126; ADA: 125). For both moderate and severe CD groups, a statistically significantly greater proportion of patients treated with ADA 40 mg eow achieved clinical response and clinical remission at week 56/52 compared with placebo treated patients (Abstract PTU-109 table 1). The safety profiles in the moderate and severe CD subgroups were similar. Conclusion The analysis of the pooled data from CHARM and EXTEND suggests that ADA 40 mg eow is safe and effective for the treatment of either moderate or severe CD. Competing interests J-F Colombel Shareholder with: Intestinal Biotech Development, Grant/Research Support from: Astra-Zeneca, Danisco, Danone, Dysphar, Ferring, Giuliani, Lesaffre, Mapi Naxis, Ocerra Therapeutics, Roquette, Schering-Plough, and UCB, Consultant for: Abbott Laboratories, ActoGeniX NV, Albireo Pharma, Astra Zeneca, Bayer Schering Pharma, Biogen Idec, Boehringer-Ingelheim, Bristol-Myers Squibb, Cellerix, Centocor, Chemocentryx, Cosmo Technologies, Danone France, Elan, Genentech, Giuliani, Given Imaging, GlaxoSmithKline, Merck, Millennium, NeoVacs, Ocerra, Otsuka American, PDL Biopharma, Pfizer, Ribo Vacs Biotech, Schering-Plough, Shire, Synta, Teva and Petah Tikva, Therakos, UCB, and Wyeth, Speaker bureau with: Abbott Laboratories, Astra Zeneca, Centocor, Elan, Falk, Ferring, Given Imaging, Otsuka American, PDL, Schering-Plough, Shire and UCB, W Sandborn Grant/Research Support from: Centocor Ortho Biotech, Abbott Laboratories, and UCB Pharma, Consultant for: Centocor Ortho Biotech, Abbott Laboratories, UCB Pharma, and Merck (previously Schering Plough), M Castillo Shareholder with: Abbott, Employee of: Abbott, Q Zhou Employee of: Abbott, R Thakkar Shareholder with: Abbott, Employee of: Abbott. References 1. Schreiber S . Gastroenterology 2007; 132 :A-147. 2. Colombel JF . Gastroenterology 2007; 132 :52. 3. Rutgeerts P . Gastroenterology 2009; 136 :A-116.
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- 2012
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19. Baseline C-reactive protein is associated with disease progression in patients with Crohnʼs disease
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Jean-Frederic Colombel, Roopal Thakkar, Majin Castillo, Bidan Huang, William J. Sandborn, and Qian Zhou
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medicine.medical_specialty ,biology ,business.industry ,Disease progression ,C-reactive protein ,Gastroenterology ,Disease ,Internal medicine ,medicine ,biology.protein ,Immunology and Allergy ,In patient ,Baseline (configuration management) ,business - Published
- 2011
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20. Baseline C-Reactive Protein is Associated With Disease Progression in Patients with Crohnʼs Disease
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Majin Castillo, Jean-Frederic Colombel, Roopal Thakkar, Bidan Huang, Qian Zhou, and William J. Sandborn
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medicine.medical_specialty ,Hepatology ,biology ,business.industry ,C-reactive protein ,Disease progression ,Gastroenterology ,Disease ,Internal medicine ,biology.protein ,medicine ,In patient ,business ,Baseline (configuration management) - Published
- 2011
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21. Elevated C-reactive Protein in Anti-TNF-Naïve Patients is Associated with Higher Remission Rates
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Roopal Thakkar, William J. Sandborn, Jean-Frederic Colombel, Qian Zhou, and Majin Castillo
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Therapy naive ,Hepatology ,business.industry ,Immunology ,Gastroenterology ,Medicine ,Tumor necrosis factor alpha ,business ,Elevated C-reactive protein - Published
- 2011
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22. Optimal C-Reactive Protein Cutoff Point for Predicting Hospitalization in Patients With Moderately Active Crohn's Disease
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Roopal Thakkar, Edouard Louis, Parvez Mulani, Jean-Frederic Colombel, William J. Sandborn, Mei Yang, Remo Panaccione, Jingdong Chao, and Majin Castillo
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medicine.medical_specialty ,Crohn's disease ,Hepatology ,biology ,business.industry ,C-reactive protein ,Gastroenterology ,medicine.disease ,Internal medicine ,medicine ,biology.protein ,In patient ,Cutoff point ,business - Published
- 2011
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