Evaluation of the efficacy and safety of etoricoxib in the treatment of hemophilic arthropathy

Penn State Hershey Medical Center and Penn State College of Medicine, Hershey, Pennsylvania, United States
Blood (Impact Factor: 10.45). 03/2006; 107(5):1785-90. DOI: 10.1182/blood-2004-09-3501
Source: PubMed


This 2-part, double-blind, placebo-controlled study was conducted to determine the safety and efficacy of etoricoxib, a COX-2 selective inhibitor, for the treatment of hemophilic arthropathy. In part 1 (6 weeks), 102 patients (> or = 12 years old) with hemophilic arthropathy were randomized to receive 90 mg etoricoxib once daily or placebo (1:1 ratio). In part 2 (6 months), 51 patients taking placebo in part 1 were randomized to receive 90 mg etoricoxib or 25 mg rofecoxib once daily; patients taking etoricoxib in part 1 continued the same treatment. Efficacy end points included Patient Assessment of Arthropathy Pain, Patient Global Assessment of Arthropathy Disease Status, and Investigator Global Assessment of Arthropathy Disease Status. Safety was evaluated at each study visit. Etoricoxib provided significant improvement in all end points versus placebo (P < .001). Fewer patients taking etoricoxib discontinued due to a lack of efficacy versus placebo (P = .048). During part 2, efficacy was maintained; etoricoxib and rofecoxib demonstrated similar results. The most common adverse experiences were upper respiratory infection and headache. The incidence of joint bleeding during part 1 was similar between etoricoxib (66.7%) and placebo (72.6%) and during part 2 between etoricoxib (77.0%) and rofecoxib (78.9%). We conclude that etoricoxib provided superior efficacy versus placebo for the treatment of hemophilic arthropathy and was generally safe and well tolerated.

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    • "Two other NSAIDs have pediatric indications (indomethacin, for patent ductus arteriosus (PDA), and ketorolac administered in a single dose for pain). There are few studies of selective COX-2 NSAIDs in children, but include the treatment of acute post-surgical pain[16,17], juvenile arthritis[18,19], the arthropathy of hemophilia[20-22], and in the therapeutic regimen for fibrodysplasia ossificans progressiva[23]. Overexpression of the COX-2 enzyme has been recognized in childhood brain tumors, and may be a future target for treatment[24]. "
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    ABSTRACT: To examine the prescribing habits of NSAIDs among pediatric medical and surgical practitioners, and to examine concerns and barriers to their use. A sample of 1289 pediatricians, pediatric rheumatologists, sports medicine physicians, pediatric surgeons and pediatric orthopedic surgeons in the United States and Canada were sent an email link to a 22-question web-based survey. 338 surveys (28%) were completed, 84 were undeliverable. Of all respondents, 164 (50%) had never prescribed a selective cyclooxygenase-2 (COX-2) NSAID. The most common reasons for ever prescribing an NSAID were musculoskeletal pain, soft-tissue injury, fever, arthritis, fracture, and headache. Compared to traditional NSAIDs, selective COX-2 NSAIDs were believed to be as safe (42%) or safer (24%); have equal (52%) to greater efficacy (20%) for pain; have equal (59%) to greater efficacy (15%) for inflammation; and have equal (39%) to improved (44%) tolerability. Pediatric rheumatologists reported significantly more frequent abdominal pain (81% vs. 23%), epistaxis (13% vs. 2%), easy bruising (64% vs. 8%), headaches (21% vs. 1%) and fatigue (12% vs. 1%) for traditional NSAIDs than for selective COX-2 NSAIDs. Prescribing habits of NSAIDs have changed since the voluntary withdrawal of rofecoxib and valdecoxib; 3% of pediatric rheumatologists reported giving fewer traditional NSAID prescriptions, and while 57% reported giving fewer selective COX-2 NSAIDs, 26% reported that they no longer prescribed these medications. Traditional and selective COX-2 NSAIDs were perceived as safe by pediatric specialists. The data were compared to the published pediatric safety literature.
    Pediatric Rheumatology 02/2010; 8(1):7. DOI:10.1186/1546-0096-8-7 · 1.61 Impact Factor
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    • "Recent studies have reported on the effective use of COX-2 inhibitors, which do not interfere with platelet function, to treat patients with haemophilia (Rattray et al, 2005, 2006; Tsoukas et al, 2006). A double-blind, placebocontrolled study demonstrated superior efficacy of etoricoxib compared with placebo to treat pain in patients with haemophilic arthropathy (Tsoukas et al, 2006). However, further evaluation of the safety and efficacy of these drugs in patients with haemophilia is needed, particularly because of the concerns of increased cardiovascular events associated with some of these drugs. "
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    ABSTRACT: Currently available factor concentrates for treatment of patients with haemophilia are virally inactivated or are made by recombinant technology and their broad use in developed nations has resulted in the dramatic elimination of the treatment-related viral illnesses that decimated the haemophilia community in the late 20th century. The major morbidity experienced by patients with haemophilia today is joint disease, a result of repeated bleeding episodes into joint spaces. Although administration of factor concentrates to prevent bleeding has been demonstrated to prevent haemophilic joint disease when applied assiduously, repeated bleeding episodes induce synovitis that is irreversible and may progress despite subsequent prophylaxis. Surgical and nuclear medicine interventions are available to reduce the pain of haemophilic arthropathy and to reduce further bleeding episodes. Patients with high titre inhibitors are at great risk for the development of joint disease and present the greatest therapeutic challenges when joint surgery is needed.
    British Journal of Haematology 04/2007; 136(6):777-87. DOI:10.1111/j.1365-2141.2007.06490.x · 4.71 Impact Factor
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    ABSTRACT: Adverse effects of selective cyclooxygenase 2 (COX-2) inhibitors on renal events and arrhythmia have been controversial, with suggestions of a class effect. To quantitatively evaluate adverse risks of renal events (renal dysfunction, hypertension, and peripheral edema) and arrhythmia events and to explore drug class effects and temporal trends of apparent effects of the COX-2 inhibitors: rofecoxib, celecoxib, valdecoxib, parecoxib, etoricoxib, and lumiracoxib. A systematic search of EMBASE and MEDLINE (through June 2006), bibliographies, US Food and Drug Administration reports, and pharmaceutical industry clinical trial databases. From relevant reports, 114 randomized double-blind clinical trials were included. Information on publication year, participant characteristics, trial duration, drug, control, dose, and events were extracted using a standardized protocol. Results were pooled via random-effects models and meta-regressions. Of 116 094 participants from 114 trial reports including 127 trial populations (40 rofecoxib, 37 celecoxib, 29 valdecoxib + parecoxib, 15 etoricoxib, and 6 lumiracoxib), there were a total of 6394 composite renal events (2670 peripheral edema, 3489 hypertension, 235 renal dysfunction) and 286 arrhythmia events. Results indicated significant heterogeneity of renal effects across agents (P for interaction = .02), indicating no class effect. Compared with controls, rofecoxib was associated with increased risk of arrhythmia (relative risk [RR], 2.90; 95% confidence interval [CI], 1.07-7.88) and composite renal events (RR, 1.53; 95% CI, 1.33-1.76); adverse renal effects increased with greater dose and duration (both P< or =.05). For all individual renal end points, rofecoxib was associated with increased risk of peripheral edema (RR, 1.43; 95% CI, 1.23-1.66), hypertension (RR, 1.55; 95% CI, 1.29-1.85), and renal dysfunction (RR, 2.31; 95% CI, 1.05-5.07). In contrast, celecoxib was associated with lower risk of both renal dysfunction (RR, 0.61; 95% CI, 0.40-0.94) and hypertension (RR, 0.83; 95% CI, 0.71-0.97) compared with controls. Other agents were not significantly associated with risk. Time-cumulative analyses indicated that for rofecoxib the adverse risks for peripheral edema and hypertension were evident by the end of year 2000 and for risk of arrhythmia by 2004. In this comprehensive analysis of 114 randomized trials with 116,094 participants, rofecoxib was associated with increased renal and arrhythmia risks. A COX-2 inhibitor class effect was not evident. Future safety monitoring is warranted and may benefit from an active and continuous cumulative surveillance system.
    JAMA The Journal of the American Medical Association 10/2006; 296(13):1619-32. DOI:10.1001/jama.296.13.jrv60015 · 35.29 Impact Factor
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