Mark T Brown

Pfizer Inc., New York City, New York, United States

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Publications (22)184.65 Total impact

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    ABSTRACT: Two studies evaluated efficacy and safety of tanezumab versus naproxen for treatment of knee or hip osteoarthritis (OA).
    The Journal of rheumatology. 10/2014;
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    ABSTRACT: To evaluate peripheral nerve safety and clinical efficacy of tanezumab in patients with painful osteoarthritis.
    Journal of the neurological sciences. 07/2014;
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    ABSTRACT: A non-controlled, randomized, multicenter study (NCT00924664) evaluated long-term safety and effectiveness of tanezumab in patients with chronic low back pain following a randomized placebo- and active-controlled parent study that evaluated analgesic efficacy. Patients were randomized to tanezumab 10 mg (n = 321) or 20 mg (n = 527) administered at 8-week intervals via 3 intravenous injections followed by 4 subcutaneous injections. Effectiveness analyses included change from parent study baseline in Brief Pain Inventory Short Form, Roland Morris Disability Questionnaire, and Patient's Global Assessment of low back pain. Safety assessments included adverse event documentation, physical/neurological examinations, and laboratory tests. Mean treatment duration during the extension study was 194 and 202 days with tanezumab 10 and 20 mg, respectively. Both tanezumab doses provided similar and sustained improvements in all effectiveness outcomes. The most frequently reported adverse events were arthralgia, paresthesia, and hypoesthesia. Adverse events initially described as osteonecrosis were reported in 6 patients (tanezumab 10 mg, n = 2; tanezumab 20 mg, n = 4); 9 additional patients (tanezumab 10 mg, n = 7; tanezumab 20 mg, n = 2) underwent total joint replacement (TJR). A blinded, independent adjudication committee reviewed all 6 patients with reported osteonecrosis and 4 of the 9 patients undergoing TJR. Adjudication outcomes were osteonecrosis (n = 0), worsening osteoarthritis (n = 5; 1 rapidly progressive), and another diagnosis or indeterminate (n = 5). Tanezumab 10 mg had better tolerability than tanezumab 20 mg, and may represent an effective long-term treatment for chronic low back pain.
    Pain 06/2014; · 5.64 Impact Factor
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    ABSTRACT: To evaluate whether subjects with knee or hip osteoarthritis (OA) pain on non-steroidal anti-inflammatory drugs (NSAIDs) received greater benefit when tanezumab monotherapy replaced or was coadministered with NSAIDs. Subjects (N=2700) received intravenous tanezumab (5 or 10 mg) or placebo every 8 weeks with or without oral naproxen 500 mg twice daily or celecoxib 100 mg twice daily. Efficacy was assessed as change from baseline to week 16 in three co-primary endpoints: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain, WOMAC Physical Function and Patient's Global Assessment (PGA) of OA. Safety assessments included adverse events, physical and neurological examinations, laboratory tests and vital signs. Although all tanezumab treatments provided significant improvements in WOMAC Pain and Physical Function over either NSAID alone, only tanezumab+NSAIDs were significant versus NSAIDs with PGA and met the prespecified definition of superiority. Combination treatment did not substantially improve pain or function over tanezumab monotherapy. Adverse event frequency was higher with tanezumab than with NSAIDs and highest with combination therapy. Higher incidence of all-cause total joint replacements occurred with tanezumab+NSAID versus tanezumab monotherapy or NSAIDs. Rapidly progressive OA incidence was significantly greater versus NSAID in all tanezumab groups except tanezumab 5 mg monotherapy. Subjects receiving partial symptomatic relief of OA pain with NSAIDs may receive greater benefit with tanezumab monotherapy. While only coadministration of tanezumab with NSAIDs met the definition of superiority, combination treatment did not provide important benefits over tanezumab monotherapy; small differences in efficacy were negated by treatment-limiting or irreversible safety outcomes. NCT00809354.
    Annals of the rheumatic diseases 03/2014; · 8.11 Impact Factor
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    ABSTRACT: Tanezumab, a monoclonal antibody, inhibits nerve growth factor and reduces chronic pain. This randomised, double-blind, controlled multicentre study was conducted to evaluate the efficacy and safety of tanezumab added to oral diclofenac sustained release (DSR) in patients with hip or knee osteoarthritis (OA) pain. Patients (N=604) with moderate to severe knee or hip OA tolerating stable DSR were randomised and treated with DSR 75 mg twice daily combined with intravenous tanezumab 10, 5 or 2.5 mg or placebo at weeks 0, 8 and 16. Co-primary efficacy endpoints (Western Ontario and McMaster Universities OA Index (WOMAC) Pain and Physical Function subscales and patient's global assessment of OA) were assessed at week 16. All co-primary endpoints were significantly improved for all tanezumab+DSR groups versus placebo+DSR (p≤0.039). The incidence of adverse events of abnormal peripheral sensation was lower than in previous tanezumab trials. No new safety signals emerged. Overall incidence of adverse events was higher with tanezumab+DSR (45.2%-49.7%) than with placebo+DSR (34.9%); serious adverse event rates were similar across treatments (5.3%-7.6%). Osteonecrosis was reported in six of 452 patients with tanezumab+DSR (1.3%), but an external adjudication committee did not confirm osteonecrosis in any patient. Addition of tanezumab to DSR resulted in significant improvements in pain, function and global assessments in patients with OA. Although no new safety signals were observed, the higher incidence of adverse events in the tanezumab+diclofenac group suggests that combination therapy is unfavourable. Further investigations of tanezumab monotherapy for OA pain treatment are required. NCT00864097.
    Annals of the rheumatic diseases 07/2013; · 8.11 Impact Factor
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    ABSTRACT: Tanezumab is a humanized monoclonal anti-nerve growth factor antibody in development for treatment of chronic pain. In a phase III, placebo- and active-controlled study, we investigated efficacy and safety of tanezumab for osteoarthritis (OA) hip or knee pain. Patients (N = 610) received up to two doses of intravenous tanezumab (5 or 10 mg in 8-week intervals), oral oxycodone controlled-release (10-40 mg every 12 hours), or placebo. The primary endpoint was mean change from baseline to Week 8 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain score for tanezumab versus placebo and oxycodone. Secondary endpoints included change from baseline in WOMAC Physical Function and Stiffness scores, Patient's Global Assessment (PGA) of OA, and patient response, defined as ⩾30%, ⩾50%, ⩾70%, and ⩾90% improvement from baseline in WOMAC Pain score. Tolerability and safety also were assessed. Both tanezumab groups demonstrated significant improvements in WOMAC Pain score versus placebo (P < 0.001) and oxycodone (P ⩽ 0.018). Tanezumab also provided significant improvements versus placebo and oxycodone for WOMAC Physical Function and Stiffness scores and PGA of OA (P ⩽ 0.002 for all) at Week 8. For all analyses, oxycodone did not differ from placebo. Adverse event frequency was higher with oxycodone (63.3%) than tanezumab (40.7-44.7%) or placebo (35.5%); serious adverse event frequency was similar among treatments. The adverse event profile for tanezumab was similar to previous tanezumab studies. Results indicate tanezumab is efficacious in the treatment of OA pain; no new safety signals were identified.
    Pain 04/2013; · 5.64 Impact Factor
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    ABSTRACT: Tanezumab is a humanized monoclonal antibody that specifically inhibits nerve growth factor as a treatment for chronic pain. This phase IIB study investigated the efficacy and safety of tanezumab for chronic low back pain vs placebo and naproxen. Patients (N=1347) received intravenous tanezumab (5, 10, or 20mg every 8weeks), naproxen (500mg twice daily), or placebo. The primary efficacy end point was mean change in daily average low back pain intensity (LBPI) from baseline to week 16. Secondary end points included mean change from baseline to week 16 in the Roland Morris Disability Questionnaire and Patient's Global Assessment (PGA) of low back pain. Tanezumab 10 and 20mg had similar efficacy profiles and significantly improved LBPI, Roland Morris Disability Questionnaire, and PGA scores vs both placebo and naproxen (P⩽.05). Tanezumab 5mg provided improvement of PGA scores vs placebo (P⩽.05), and naproxen resulted in significant improvement of LBPI vs placebo (P⩽.05). Adverse event incidence was comparable across tanezumab doses but higher than with placebo or naproxen. Arthralgia, pain in extremity, headache, and paresthesia were the most commonly reported adverse events by tanezumab-treated patients. The most frequently reported adverse events resulting in discontinuation of tanezumab treatment were arthralgia and paresthesia; the highest frequency was observed with tanezumab 20mg (both 1.4%). Serious adverse event incidence was similar across treatments. In conclusion, tanezumab provided significantly greater improvement in pain, function, and global scores vs placebo and naproxen in patients with chronic low back pain.
    Pain 03/2013; · 5.64 Impact Factor
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    ABSTRACT: The objective of this study was to compare the analgesic efficacy of tanezumab versus placebo in patients with osteoarthritis (OA) of the knee. This was a 32-week, randomized, double-blind, placebo-controlled phase III trial (NCT00733902). The patient criteria included diagnosis of OA; Western Ontario and McMaster Universities OA Index (WOMAC) Pain and Physical Function subscale scores of ≥5 and ≥4, respectively; Patient's Global Assessment of Osteoarthritis (PGA) ≥3; and failure of nonopiate pain medications or candidacy for invasive interventions. Patients received 3 intravenous doses of tanezumab (2.5, 5, or 10 mg) or placebo. The co-primary efficacy end points were changes in WOMAC subscales and PGA at week 16. Adverse events were monitored throughout. Overall, 690 patients (61% female) were randomized and treated. Those treated with tanezumab showed significant improvement in the 3 co-primary end points (P ≤ .015 for all). The incidence of adverse events was 55 to 60% for tanezumab-treated patients versus 48% for placebo-treated patients. Joint replacement was reported in 4 patients, 1 in each treatment group; a total of 5 joints were replaced (1 index knee and 4 hips). The tanezumab OA clinical program is currently on clinical hold due to potential adverse reactions leading to joint replacement. PERSPECTIVE: This is the first phase III randomized, controlled trial to demonstrate that nerve growth factor blockade by tanezumab has superior analgesic efficacy in OA of the knee compared with placebo. Tanezumab was well tolerated, and reports of worsening OA and/or joint replacement were evenly distributed across the treatment groups.
    The journal of pain: official journal of the American Pain Society 07/2012; 13(8):790-8. · 3.78 Impact Factor
  • Pain 03/2012; · 5.64 Impact Factor
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    ABSTRACT: Increased nerve growth factor levels are associated with chronic pain conditions, including chronic low back pain (LBP). This study examined safety and analgesic efficacy of tanezumab, a humanized anti-nerve growth factor antibody, in adults with chronic LBP. Patients received intravenous tanezumab 200 μg/kg plus oral placebo (n=88), intravenous placebo plus oral naproxen 500 mg twice a day (n=88), or intravenous placebo plus oral placebo (n=41). Primary outcome was average LBP intensity (aLBPI) at Week 6. Secondary outcomes were proportion of patients with ≥30% or ≥50% reduction in aLBPI, Roland-Morris Disability Questionnaire and Brief Pain Inventory-short form scores, Patients' Global Assessment of LBP, Patients' Global Evaluation of study medication, and rescue medication use. Mean aLBPI change from baseline to Week 6 was greater with tanezumab vs naproxen (P=0.004) and placebo (P<0.001). Greater proportions of patients reported ≥30% and ≥50% reduction in aLBPI with tanezumab vs naproxen (P≤0.013) and placebo (P<0.001), and greater improvements in Roland-Morris Disability Questionnaire (P<0.001) and other secondary outcomes except rescue medication use. Tanezumab was associated with adverse events (AEs) of abnormal peripheral sensation that were generally mild and resolved before study completion; however, there were no serious AEs. Nine patients (4 of whom were tanezumab-treated) discontinued due to AEs. In conclusion, tanezumab resulted in analgesic efficacy that was clinically and statistically superior to placebo and naproxen in patients with chronic LBP. Tanezumab clinical development is on regulatory hold due to AEs in osteoarthritis patients.
    Pain 06/2011; 152(10):2248-58. · 5.64 Impact Factor
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    ABSTRACT: Increased expression of nerve growth factor in injured or inflamed tissue is associated with increased pain. This proof-of-concept study was designed to investigate the safety and analgesic efficacy of tanezumab, a humanized monoclonal antibody that binds and inhibits nerve growth factor. We randomly assigned 450 patients with osteoarthritis of the knee to receive tanezumab (administered at a dose of 10, 25, 50, 100, or 200 μg per kilogram of body weight) or placebo on days 1 and 56. The primary efficacy measures were knee pain while walking and the patient's global assessment of response to therapy. We also assessed pain, stiffness, and physical function using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); the rate of response using the criteria of the Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative (OMERACT-OARSI); and safety. When averaged over weeks 1 through 16, the mean reductions from baseline in knee pain while walking ranged from 45 to 62% with various doses of tanezumab, as compared with 22% with placebo (P<0.001). Tanezumab, as compared with placebo, was also associated with significantly greater improvements in the response to therapy as assessed with the use of the patients' global assessment measure (mean increases in score of 29 to 47% with various doses of tanezumab, as compared with 19% with placebo; P≤0.001). The rate of response according to the OMERACT-OARSI criteria ranged from 74 to 93% with tanezumab treatment, as compared with 44% with placebo (P<0.001). The rates of adverse events were 68% and 55% in the tanezumab and placebo groups, respectively. The most common adverse events among tanezumab-treated patients were headache (9% of the patients), upper respiratory tract infection (7%), and paresthesia (7%). In this proof-of-concept study, treatment with tanezumab was associated with a reduction in joint pain and improvement in function, with mild and moderate adverse events, among patients with moderate-to-severe osteoarthritis of the knee. (Funded by Rinat Neuroscience; ClinicalTrials.gov number, NCT00394563.).
    New England Journal of Medicine 10/2010; 363(16):1521-31. · 54.42 Impact Factor
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    ABSTRACT: This multicenter, multiple-dose, randomized, double-blind, parallel-group study compared the analgesic efficacy and safety of two dosing regimens of parecoxib sodium (parecoxib) versus placebo after total hip arthroplasty. On study Day 1, 490 patients received a postoperative initial loading dose of IV parecoxib 40 mg, followed by a re-dose of parecoxib 20 mg in 484 of 490 patients. Subsequently, 479 randomized patients received double-blind treatment with parecoxib 20 mg bid (n = 159), parecoxib 20 mg qd (n = 159) followed by placebo, or placebo (n = 161) on Day 2. Patients treated with parecoxib 20 mg bid reported significantly lower summed pain intensity over 24 h (SPI-24) scores and improved patients' global evaluation of study medication (PGESM) ratings compared with placebo-treated patients on Days 2 to 5 (P < 0.05). For patients treated with parecoxib 20 mg qd, SPI-24 scores were significantly lower on Days 3 and 4 (P < 0.05), and PGESM ratings significantly improved on Day 5 compared with placebo. The incidence of adverse events was similar in all treatment groups with the exception of fever, vomiting and impaired concentration, which were significantly more common in the placebo group compared with one or other of the parecoxib treatment groups (P < 0.05). Multiple-day administration of parecoxib 20 mg once or twice daily is effective and generally well tolerated after total hip arthroplasty.
    Anesthesia and analgesia 08/2008; 107(2):652-60. · 3.08 Impact Factor
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    ABSTRACT: To determine the analgesic efficacy of 1-day and multiple-day dosing regimens of parecoxib sodium (parecoxib) after bunionectomy in 2 randomized placebo-controlled studies. The first double-blind study assessed the efficacy of intravenous parecoxib 40 mg followed by an additional dose of parecoxib 20 mg, parecoxib 40 mg followed by placebo, or 2 placebo doses over 1 day. In the second study, all patients received parecoxib 40 mg and a second dose of 20 mg on day 1. On days 2 and 3, patients were randomized to parecoxib 20 mg once daily and placebo once daily, parecoxib 20 mg twice daily, or placebo twice daily. Rescue medication (hydrocodone 5 mg/acetaminophen 500 mg) was available throughout both studies. In the single-day study, patients receiving parecoxib had significantly improved summed pain intensity difference through 24 hours, time-weighted sum of total pain relief through 24 hours, and Patient's Global Evaluation of Study Medication (PGESM) scores compared with those given placebo. In the multiday study, patients given parecoxib had significantly improved summed pain intensity through 24 hours and PGESM scores compared with patients receiving placebo. The incidence of adverse events was lower in the parecoxib groups than in the placebo group on days 2 and 3. Parecoxib treatment, in conjunction with supplemental analgesia given as needed, provided effective pain relief over 1 to 3 days in the bunionectomy model of postoperative analgesia. Bunionectomy is a useful model for testing multiple-day analgesic therapy.
    The Clinical journal of pain 01/2008; 24(9):784-92. · 3.01 Impact Factor
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    ABSTRACT: To assess the analgesic efficacy of a multidose, multiday regimen of intravenous (IV) parecoxib sodium (parecoxib). Multicenter, randomized, double-blind, placebo-controlled, parallel-group trial. Postoperative recovery area and inpatient care facility. 422 patients who had undergone gynecologic surgery via laparotomy participated (day 1), and 414 patients were randomized (day 2). After surgery on day 1, all patients received parecoxib 40 mg (IV), followed by 20 mg (IV) one to 12 hours later; patients were then randomized to receive parecoxib 20 mg (IV) twice daily (n = 211) or placebo (IV) twice daily (n = 203) on days 2 to 5. Patients were permitted rescue medication as needed. Primary efficacy measures were summed pain intensity through 24 hours (SPI-24) and Patient's Global Evaluation of Study Medication on days 2 and 3. In the parecoxib treatment group, 24-hour summed pain intensity scores were significantly lower than in the placebo treatment group (P < 0.001) on days 2 and 3. More patients in the parecoxib treatment group rated their treatment as "excellent" or "good" using the Patient's Global Evaluation of Study Medication (P < 0.001) on days 2 and 3. Patients treated with parecoxib had lower pain intensity and consumed less rescue medication compared with the placebo-treated patients. Multidose parecoxib was well tolerated over several days and provided improved pain control after gynecologic surgery.
    Journal of Clinical Anesthesia 09/2007; 19(6):448-55. · 1.15 Impact Factor
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    ABSTRACT: Two randomized, double-blind, placebo-controlled studies assessed the analgesic efficacy of valdecoxib in patients with moderate-to-severe pain after bunionectomy. Study 1 (N = 374) assessed the efficacy of two regimens of valdecoxib on the day after surgery (valdecoxib, 40 mg, with a 20-mg redose [n = 127]; valdecoxib, 40 mg, with a placebo redose [n = 122]; and placebo/placebo [n = 125]), and study 2 (N = 478) examined the efficacy of two different multiple-dose regimens on postoperative days 2 through 5 (valdecoxib, 20 mg, twice daily [n = 160]; valdecoxib, 20 mg, once daily [n = 159]; and placebo [n = 159]). Valdecoxib provided significant pain relief and reduced the use of opioid rescue medication. This efficacy was accompanied by improved global scores, decreased pain interference with function, and increased patient satisfaction.
    Journal of the American Podiatric Medical Association 09/2006; 96(5):393-407. · 0.77 Impact Factor
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    ABSTRACT: Valdecoxib and its intravenous prodrug parecoxib are reported to increase thromboembolic risk after coronary artery bypass grafting. The authors conducted a randomized trial to examine their safety and analgesic efficacy in patients recovering from major noncardiac surgical procedures. The trial was randomized and double-blind, with 10 days of treatment and 30 days of follow-up. Patients (n = 1,062) received either parenteral parecoxib for 3 days and oral valdecoxib for the rest of the treatment period or placebo medications throughout. The frequency of predefined adjudicated postrandomization adverse events, including cardiovascular thromboembolism, renal dysfunction, gastroduodenal ulceration, and wound-healing complications, was assessed in each group. Secondary efficacy endpoints included patients' pain ratings, opioid analgesic consumption (recorded as morphine equivalents), and reports of opioid-related adverse effects. Predefined adjudicated adverse events had similar frequencies among patients who received parecoxib and valdecoxib (2.7%) and placebo patients (3.2%) (P = 0.58), including cardiovascular thromboembolic events (1.0% in each group; P = 1.0). Placebo patients consumed more morphine equivalents (66.2 +/- 92.4 mg) than did patients receiving parecoxib and valdecoxib (43.2 +/- 65.7 mg) (P < 0.001). Placebo patients had higher mean pain ratings on each of study days 2-10 (P < 0.01) and reported more opioid-related symptom distress on days 2-6 (P < 0.01). Parecoxib and valdecoxib are useful adjuncts to opioids for the treatment of postoperative pain in noncardiac surgical patients. Further study will be required to determine the safety profile of parecoxib and valdecoxib administered to patients with known atherosclerotic disease after noncardiac surgery.
    Anesthesiology 04/2006; 104(3):518-26. · 5.16 Impact Factor
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    ABSTRACT: The primary aim of this work was to compare the efficacy of valdecoxib 10, 20, and 40 mg QD with that of placebo and naproxen 500 mg BID in patients with rheumatoid arthritis (RA). The overall safety and tolerability profiles of valdecoxib and naproxen were also compared. A 12-week, multicenter, randomized, double-blind, parallel-group, placebo- and active-controlled study was performed in patients with adult-onset RA whose disease was in a flare state after discontinuing NSAIDs or other analgesics. Patients were randomly assigned to valdecoxib 10, 20, or 40 mg QD, naproxen 500 mg BID, or placebo. The primary efficacy measures were the American College of Rheumatology (ACR) 20% responder index (ACR-20), physicians' assessments of tender/painful joint count and swollen joint count, and patients' and physicians' global assessments of disease activity. Adverse events, clinical laboratory data, and vital signs were assessed by the investigator and compared between treatment groups to evaluate overall tolerability and safety. A total of 1093 patients were randomized to receive either valdecoxib 10 mg QD (n=226), valdecoxib 20 mg QD (n=219), valdecoxib 40 mg QD (n=209), naproxen 500 mg BID (n=219), or placebo (n=220). At all time points, the proportion of ACR-20 responders was significantly higher in the valdecoxib groups than the placebo group at weeks 2 (10 mg, P<0.001; 20 mg, P=0.008; 40 mg, P= 0.004), 6 (all, P<0.001), and 12 (10 mg, P=0.006; 20 mg, P=0.004; 40 mg, P<0.001). Similarly, at all time points, the proportion of ACR-20 responders was significantly higher in the naproxen 500-mg group than the placebo group (all time points, P<0.001). In addition, mean changes in the number of tender/painful joint counts were significantly greater in the valdecoxib groups than the placebo group at weeks 2 (all, P<0.001), 6 (10 mg, P=0.002; 20 and 40 mg, P<0.001), and 12 (10 mg, P=0.004; 20 mg, P= 0.012; 40 mg, P<0.001). Naproxen treatment was also associated with greater reductions in tender/painful joint count than placebo (all, P<0.001). Mean changes in swollen joint count decreased at all time points in all groups, with significantly greater changes in the valdecoxib and naproxen treatment groups than the placebo group (valdecoxib 20 and 40 mg: week 6, P= 0.014 and P=0.003, respectively; naproxen: week 2, P=0.014; week 6, P=0.015; week 12, P=0.030). Physicians' global assessments of disease activity scores were significantly lower in the valdecoxib (10 mg: weeks 2 and 6, P<0.001; week 12, P=0.001; 20 and 40 mg: all weeks, P<0.001) and naproxen (all time points, P<0.001) treatment groups than the placebo group. Adverse events were reported by 45.5% patients in the placebo group, 51.8% in the valdecoxib 10 mg QD group, 58.0% in the valdecoxib 20 mg QD group, 56.9% in the valdecoxib 40 mg QD group, and 62.6% in the naproxen 500 mg BID treatment group. Valdecoxib 10, 20, and 40 mg QD were efficacious for treating the signs and symptoms of RA in these patients. The efficacy of valdecoxib 20 and 40 mg QD was not significantly different from that of naproxen 500 mg BID. Valdecoxib was generally well tolerated in this study.
    Clinical Therapeutics 03/2006; 28(2):204-21. · 2.23 Impact Factor
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    ABSTRACT: Background: Valdecoxib and its intravenous prodrug parecoxib are reported to increase thromboembolic risk after coronary artery bypass grafting. The authors conducted a randomized trial to examine their safety and analgesic efficacy in patients recovering from major noncardiac surgical procedures.
    Anesthesiology 02/2006; 104(3):518-526. · 5.16 Impact Factor
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    ABSTRACT: Valdecoxib and its intravenous prodrug parecoxib are used to treat postoperative pain but may involve risk after coronary-artery bypass grafting (CABG). We conducted a randomized trial to assess the safety of these drugs after CABG. In this randomized, double-blind study involving 10 days of treatment and 30 days of follow-up, 1671 patients were randomly assigned to receive intravenous parecoxib for at least 3 days, followed by oral valdecoxib through day 10; intravenous placebo followed by oral valdecoxib; or placebo for 10 days. All patients had access to standard opioid medications. The primary end point was the frequency of predefined adverse events, including cardiovascular events, renal failure or dysfunction, gastroduodenal ulceration, and wound-healing complications. As compared with the group given placebo alone, both the group given parecoxib and valdecoxib and the group given placebo and valdecoxib had a higher proportion of patients with at least one confirmed adverse event (7.4 percent in each of these two groups vs. 4.0 percent in the placebo group; risk ratio for each comparison, 1.9; 95 percent confidence interval, 1.1 to 3.2; P=0.02 for each comparison with the placebo group). In particular, cardiovascular events (including myocardial infarction, cardiac arrest, stroke, and pulmonary embolism) were more frequent among the patients given parecoxib and valdecoxib than among those given placebo (2.0 percent vs. 0.5 percent; risk ratio, 3.7; 95 percent confidence interval, 1.0 to 13.5; P=0.03). The use of parecoxib and valdecoxib after CABG was associated with an increased incidence of cardiovascular events, arousing serious concern about the use of these drugs in such circumstances.
    New England Journal of Medicine 04/2005; 352(11):1081-91. · 54.42 Impact Factor
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    ABSTRACT: An abstract is unavailable. This article is available as HTML full text and PDF.
    Obstetrics and Gynecology 03/2005; 105(4):103S. · 4.80 Impact Factor

Publication Stats

936 Citations
184.65 Total Impact Points

Institutions

  • 2012–2014
    • Pfizer Inc.
      New York City, New York, United States
  • 2013
    • Harvard Medical School
      Boston, Massachusetts, United States
    • Carol Davila University of Medicine and Pharmacy
      • Department of Internal Medicine and Rheumatology
      Bucharest, Bucuresti, Romania
    • Altoona Center for Clinical Research
      Duncansville, Pennsylvania, United States
  • 2010
    • University of California, Davis
      • School of Medicine
      Davis, CA, United States
  • 2008
    • Thomas Jefferson University
      • Department of Anesthesiology
      Philadelphia, PA, United States
    • The University of Chicago Medical Center
      • Department of Anesthesia and Critical Care
      Chicago, Illinois, United States