title: A 6-week, multicentre, randomised, double-blind, double-dummy, active-controlled, clinical safety study of lumiracoxib and rofecoxib in osteoarthritis patients.
abstract: BACKGROUND
  Lumiracoxib is a selective cyclooxygenase-2 inhibitor effective in the treatment of osteoarthritis (OA) with a superior gastrointestinal (GI) safety profile as compared to traditional non-steroidal anti-inflammatory drugs (NSAIDs, ibuprofen and naproxen). This safety study compared the GI tolerability, the blood pressure (BP) profile and the incidence of oedema with lumiracoxib and rofecoxib in the treatment of OA. Rofecoxib was withdrawn worldwide due to an associated increased risk of CV events and lumiracoxib has been withdrawn from Australia, Canada, Europe and a few other countries following reports of suspected adverse liver reactions.
  
  
  METHODS
  This randomised, double-blind study enrolled 309 patients (aged greater than or equal to 50 years) with primary OA across 51 centres in Europe. Patients were randomly allocated to receive either lumiracoxib 400 mg od (four times the recommended dose in OA) (n = 154) or rofecoxib 25 mg od (n = 155). The study was conducted for 6 weeks and assessments were performed at Weeks 3 and 6. The primary safety measures were the incidence of predefined GI adverse events (AEs) and peripheral oedema. The secondary safety measures included effect of treatment on the mean sitting systolic and diastolic blood pressure (msSBP and msDBP). Tolerability of lumiracoxib 400 mg was assessed by the incidence of AEs.
  
  
  RESULTS
  Lumiracoxib and rofecoxib displayed similar GI safety profiles with no statistically significant difference in predefined GI AEs between the two groups (43.5% vs. 37.4%, respectively). The incidence and severity of individual predefined GI AEs was comparable between the two groups. The incidence of peripheral oedema was low and identical in both the groups (n = 9, 5.8%). Only one patient in the lumiracoxib group and three patients in the rofecoxib group had a moderate or severe event. At Week 6 there was a significantly lower msSBP and msDBP in the lumiracoxib group compared to the rofecoxib group (p < 0.05). A similar percentage of patients in both groups showed an improvement in target joint pain and disease activity. The tolerability profile was similar in both the treatment groups.
  
  
  CONCLUSIONS
  Lumiracoxib 400 mg od (four times the recommended dose in OA) provided a comparable GI safety profile to rofecoxib 25 mg od (therapeutic dose). However, lumiracoxib was associated with a significantly better BP profile as compared to rofecoxib.
  
  
  BACKGROUND
  NCT00637949.
authors.affiliation: Novartis Pharma AG Postfach, CH-4002, Basel, Switzerland. kirstin.stricker@novartis.com
authors.forename: Kirstin
authors.initials: K
authors.lastname: Stricker
authors.forename: Sue
authors.initials: S
authors.lastname: Yu
authors.forename: Gerhard
authors.initials: G
authors.lastname: Krammer
mesh_terms: D000368:Aged; D018771:Arthralgia / Q000209:etiology / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D004008:Diclofenac / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004487:Edema / Q000139:chemically induced / Q000453:epidemiology; D005060:Europe; D005260:Female; D041981:Gastrointestinal Tract / Q000187:drug effects; D006801:Humans; D015994:Incidence; D007668:Kidney / Q000187:drug effects; D007783:Lactones / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D013450:Sulfones / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D004008:Diclofenac; C473384:lumiracoxib
references.citation: BMJ. 2006 Jun 3;332(7553):1302-8
references.pmid: 16740558
references.citation: Arch Intern Med. 1996 Jul 22;156(14):1530-6
references.pmid: 8687261
references.citation: Acta Anaesthesiol Scand. 2005 Nov;49(10):1491-500
references.pmid: 16223396
references.citation: Lancet. 2004 Aug 21-27;364(9435):665-74
references.pmid: 15325831
references.citation: BMC Musculoskelet Disord. 2008 Mar 07;9:32
references.pmid: 18328090
references.citation: J Rheumatol. 2003 Apr;30(4):714-9
references.pmid: 12672188
references.citation: Dig Dis Sci. 1995 Jun;40(6):1345-50
references.pmid: 7781458
references.citation: Bull World Health Organ. 2003;81(9):646-56
references.pmid: 14710506
references.citation: Hypertension. 2005 Jan;45(1):92-7
references.pmid: 15545508
references.citation: Hosp Pract (1995). 1996 Dec 15;31(12):37-44, 47-8
references.pmid: 8969678
references.citation: Lancet. 2006 Nov 18;368(9549):1771-81
references.pmid: 17113426
references.citation: BMJ. 2003 Jul 5;327(7405):18-22
references.pmid: 12842950
references.citation: Rheumatology (Oxford). 2007 Jul;46(7):1126-32
references.pmid: 17478464
references.citation: Lancet. 2002 Dec 14;360(9349):1903-13
references.pmid: 12493255
references.citation: J Rheumatol Suppl. 1999 Apr;56:18-24
references.pmid: 10225536
references.citation: Arch Intern Med. 2005 Mar 14;165(5):490-6
references.pmid: 15710786
references.citation: Ann Intern Med. 1994 Aug 15;121(4):289-300
references.pmid: 8037411
references.citation: Semin Arthritis Rheum. 2002 Dec;32(3 Suppl 1):25-32
references.pmid: 12528071
references.citation: Arthritis Rheum. 2000 Sep;43(9):1905-15
references.pmid: 11014340
references.citation: JAMA. 1999 Nov 24;282(20):1929-33
references.pmid: 10580458
references.citation: Lancet. 2004 Aug 21-27;364(9435):675-84
references.pmid: 15325832
references.citation: Aliment Pharmacol Ther. 2008 May;27(9):838-45
references.pmid: 18221410
references.citation: Arthritis Res Ther. 2006;8(5):R153
references.pmid: 16995929
references.citation: Am J Gastroenterol. 2001 Apr;96(4):1019-27
references.pmid: 11316141
references.citation: Int J Clin Pract. 2004 Mar;58(3):251-6
references.pmid: 15117091
references.citation: Gastroenterology. 2001 Feb;120(3):594-606
references.pmid: 11179238