RESUMEN

The aim of this 13-week, multicenter, randomized, double-blind, double-dummy, placebo- and positive-internal (celecoxib)-controlled, parallel-group study was to demonstrate the efficacy, safety, and tolerability of lumiracoxib in primary hip osteoarthritis (OA) patients. Eligible patients (n = 1,262; ACR criteria) were randomized (1:1:1) to receive lumiracoxib 100 mg once daily (o.d.) (n = 427), celecoxib 200 mg o.d. (n = 419), or matching placebo o.d. (n = 416) administered orally. The primary objective was to compare lumiracoxib 100 mg o.d. and placebo with respect to three co-primary efficacy variables: the pain subscale of the Western Ontario and McMaster Universities Osteoarthritis Index Likert version 3.1 (WOMAC™ LK 3.1) questionnaire, the function subscale of the WOMAC™ LK 3.1 questionnaire, and patient's global assessment of disease activity (100-mm visual analog scale (VAS)) after 13 weeks of treatment. Of the 1,262 randomized patients, 951 completed the study. All randomized patients were included in the intention-to-treat and safety populations. Lumiracoxib was superior to the placebo (p < 0.001) after 13 weeks for all three co-primary endpoints. By week 13, the patient's global assessment of disease activity (100-mm VAS) improved by 23.3 mm (±SD, 27.83 mm) with lumiracoxib and 13.3 mm (±26.71 mm) with placebo. The WOMAC™ function score decreased by 10.4 (±13.56) with lumiracoxib and 6.8 (±12.55) with placebo. The WOMAC™ pain scores decreased by 3.4 (±4.16) with lumiracoxib and 2.2 (±3.94) with placebo at week 13. Similar results were observed for secondary endpoints: OA pain intensity and WOMAC™ total score. Lumiracoxib was similar to celecoxib for all three co-primary endpoints. All treatments were well tolerated. In conclusion, lumiracoxib is effective in reducing pain and improving function in hip OA patients.

Asunto(s)

Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Diclofenaco/análogos & derivados , Osteoartritis de la Cadera/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Inhibidores de la Ciclooxigenasa 2/efectos adversos , Diclofenaco/efectos adversos , Diclofenaco/uso terapéutico , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dolor/tratamiento farmacológico , Dimensión del Dolor , Resultado del Tratamiento

RESUMEN

OBJECTIVES: Nonsteroidal anti-inflammatory drugs vary in their impact on blood pressure and the effect of lumiracoxib 100 mg once daily has not been studied previously. To examine whether lumiracoxib 100 mg once daily would result in lower 24-h mean systolic ambulatory blood pressure than ibuprofen 600 mg three times daily in osteoarthritis patients with controlled hypertension, a 4-week, randomized, double-blind, parallel-group study was conducted in 79 centres in nine countries. METHODS: Hypertensive osteoarthritis patients of 50 years at least whose office blood pressure was less than 140/90 mmHg on stable antihypertensive treatment were randomized to lumiracoxib (n = 394) 100 mg once daily or ibuprofen 600 mg three times daily (n = 393) and 24-h ambulatory blood pressure monitoring was performed at baseline and end of study. The primary outcome measure was a comparison of the change in 24-h mean systolic ambulatory blood pressure from baseline to week 4. Secondary analyses included other blood pressure-related endpoints and efficacy (pain) measurements. RESULTS: Compared with baseline, the 24-h mean systolic ambulatory blood pressure (least square mean) decreased in lumiracoxib-treated patients (-2.7 mmHg) and increased in ibuprofen-treated patients (+2.2 mmHg) at 4 weeks, estimated difference -5.0 mmHg (95% confidence interval -6.1 to -3.8) in favour of lumiracoxib. The 24-h mean diastolic ambulatory blood pressure changes were -1.5 mmHg (lumiracoxib), +0.5 mmHg (ibuprofen), difference -2.0 mmHg (95% confidence interval -2.7 to -1.3). Efficacy results were comparable. CONCLUSIONS: Treatment with lumiracoxib 100 mg once daily resulted in clinically significant lower blood pressure compared with ibuprofen 600 mg three times daily in osteoarthritis patients with well controlled hypertension.

Asunto(s)

Antiinflamatorios no Esteroideos/administración & dosificación , Inhibidores de la Ciclooxigenasa 2/administración & dosificación , Diclofenaco/análogos & derivados , Hipertensión/tratamiento farmacológico , Ibuprofeno/administración & dosificación , Osteoartritis/tratamiento farmacológico , Anciano , Antiinflamatorios no Esteroideos/efectos adversos , Presión Sanguínea/efectos de los fármacos , Monitoreo Ambulatorio de la Presión Arterial , Inhibidores de la Ciclooxigenasa 2/efectos adversos , Diclofenaco/administración & dosificación , Diclofenaco/efectos adversos , Humanos , Hipertensión/complicaciones , Ibuprofeno/efectos adversos , Persona de Mediana Edad , Osteoartritis/complicaciones , Resultado del Tratamiento

RESUMEN

BACKGROUND & AIMS: The selective cyclooxygenase-2 inhibitor lumiracoxib has been shown to reduce endoscopically detected ulcers and ulcer complications in the upper gastrointestinal tract compared with nonselective nonsteroidal anti-inflammatory drugs. We investigated whether lumiracoxib would reduce small-bowel injury compared with naproxen plus omeprazole. METHODS: Healthy volunteers were randomized to receive lumiracoxib 100 mg once daily, naproxen 500 mg twice daily plus omeprazole 20 mg once daily, or placebo in a 16-day double-blind, parallel-group study. Small-bowel mucosal injury and inflammation were assessed by video capsule endoscopy, the lactulose:L-rhamnose permeability assessment, and the fecal calprotectin test. RESULTS: Of 152 randomized subjects, 139 completed the study with valid video capsule endoscopies (lumiracoxib, n = 47; naproxen plus omeprazole, n = 45; placebo, n = 47). Compared with placebo, an increased number of subjects on naproxen plus omeprazole had small-bowel mucosal breaks (77.8% vs 40.4%, P < .001), with increased permeability (P = .023) and increased fecal calprotectin (increase, 96.8 vs 14.5 mg/kg for placebo; P < .001). With lumiracoxib, 27.7% of subjects had small-bowel mucosal breaks (P = .196 vs placebo; P < .001 vs naproxen), there was no increase in permeability (P = .157 vs placebo; P = .364 vs naproxen), and no increase in fecal calprotectin (-5.7 mg/kg; P = .377 vs placebo; P < .001 vs naproxen). CONCLUSIONS: As assessed by 3 different measures, acute small-bowel injury on lumiracoxib treatment is less frequent than with naproxen plus omeprazole and similar to placebo.

Asunto(s)

Inhibidores de la Ciclooxigenasa/efectos adversos , Diclofenaco/análogos & derivados , Intestino Delgado/efectos de los fármacos , Naproxeno/efectos adversos , Omeprazol/efectos adversos , Úlcera/inducido químicamente , Administración Oral , Adulto , Anciano , Endoscopios en Cápsulas , Estudios Cruzados , Inhibidores de la Ciclooxigenasa/administración & dosificación , Diclofenaco/administración & dosificación , Diclofenaco/efectos adversos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Quimioterapia Combinada , Endoscopía Gastrointestinal/métodos , Femenino , Humanos , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Intestino Delgado/patología , Masculino , Persona de Mediana Edad , Naproxeno/administración & dosificación , Omeprazol/administración & dosificación , Probabilidad , Valores de Referencia , Medición de Riesgo , Úlcera/patología

RESUMEN

We compared the efficacy and safety of preemptive vs postoperative dosing of lumiracoxib 400 mg in patients undergoing minor ambulatory arthroscopic knee surgery. Eligible patients were randomized to preemptive lumiracoxib, postoperative lumiracoxib, and placebo. The main efficacy parameter was pain intensity (PI) (0-100 mm visual analog scale) in the target knee upon movement, 2 hours after surgery. Other efficacy variables included PI in the target knee at rest and upon movement at 1, 3, 4, and 24 hours, time to first rescue medication intake. In the lumiracoxib preemptive and postoperative groups, the estimated treatment difference compared to placebo for primary endpoint was -4.0 (95% CI: -9, -1; p = 0.007) and -3.5 (95% CI: -8.5, 0; p = 0.052), respectively. There was no statistical significant difference between two active treatment groups (p = 0.602). Both preemptive and postoperative lumiracoxib resulted in significantly lower PI scores at rest and after movement at all time-points and no statistically significant difference was observed between the active treatments. Time to rescue medication intake was comparable for both active treatments. The proportion of adverse events was similar among all groups. We conclude that the efficacy of lumiracoxib 400 mg is not affected by the timing of administration (preemptive or postoperative).