AIM: To compare the efficacy, tolerability and safety of celecoxib, naproxen and placebo in Asian patients with osteoarthritis (OA) of the knee.
METHOD: Patients of Asian descent with knee OA, aged ≥ 45 years, in a flare state with a functional capacity classification of I-III, received celecoxib 200 mg once daily, naproxen 500 mg twice daily or placebo, for 6 weeks. The change in Patient's Assessment of Arthritis Pain (week 6 vs. baseline) was the primary endpoint. Secondary endpoints, including Patient's and Physician's Global Assessments of Arthritis, Western Ontario and McMaster Universities OA Index (WOMAC), use of complementary and alternative medicines, incidence of treatment-emergent adverse events (TEAEs) and measurements of upper gastrointestinal tolerability, were also assessed.
RESULTS: Three hundred and sixty-seven patients were randomized: 145 to celecoxib, 144 to naproxen and 78 to placebo. Celecoxib was as effective as naproxen in reducing OA pain (least squares mean change from baseline in visual analogue scale score [standard error] -37.1 [2.0] for celecoxib and -37.5 [2.0] for naproxen). Patient's and Physician's Global Assessment of Arthritis, WOMAC scores, Pain Satisfaction Scale and Patient Health Questionnaire-9 showed statistically significant improvement in active treatment groups versus placebo, with the exception of naproxen WOMAC scores. Treatment-related TEAEs occurred in 19 (13%), 34 (24%) and six (8%) patients in the celecoxib, naproxen and placebo groups, respectively.
CONCLUSION: Celecoxib and naproxen were comparable in their effects to reduce the signs and symptoms of knee OA in Asian patients. Celecoxib was shown to be safe and well tolerated in this patient population.
BACKGROUND: The effectiveness of diclofenac versus paracetamol in primary care patients with pain caused by knee osteoarthritis is unclear.
AIM: To assess the effectiveness of diclofenac compared with paracetamol over a period of 2, 4, and 12 weeks in patients with knee osteoarthritis.
DESIGN AND SETTING: Randomised controlled trial in general practice.
METHOD: There were 104 patients included in the study, they were aged ≥45 years consulting their GP with knee pain caused by knee osteoarthritis. Patients were randomly allocated to diclofenac (n = 52) or paracetamol (n = 52) for at least 2 weeks. Primary outcomes were daily knee pain severity, and knee pain and function measured with the Knee Injury and Osteoarthritis Outcome Score (KOOS).
RESULTS: Over a period of 2- and 4-weeks follow-up, no significant difference in daily knee pain was found between the patient groups: estimated differences of 0.5 (95% CI = -0.2 to 1.3) and -0.2 (95% CI = -1.0 to 0.7), respectively. Over the 12-weeks follow-up, no significant differences were found between both groups for KOOS pain: estimated difference of -2.8 (95% CI = -10.7 to 5.1) and KOOS function of -2.7 (-10.6 to 5.0).
CONCLUSION: Over a period of 2- and 4-weeks follow-up no significant difference in daily measured knee pain severity was found between primary care patients with knee osteoarthritis taking paracetamol or diclofenac. Also, over a period of 12-weeks follow-up no significant differences were found regarding KOOS pain and KOOS function between both groups. Patients more frequently reported minor adverse events after taking diclofenac (64%) than paracetamol (46%).
Abstract OBJECTIVE: To compare the gastrointestinal (GI) tolerability and efficacy of aceclofenac with diclofenac in patients with knee osteoarthritis (OA). METHODS: In this randomized, double-blind, double-dummy, multicentric, comparative study, post 7 day placebo washout, patients were randomly allocated to receive either aceclofenac 100 mg b.i.d. or diclofenac 50 mg t.i.d. and were followed up for the next 6 weeks. The GI tolerability was evaluated based on the incidence and severity of predefined GI adverse events (AEs), number of gastroprotective agents (GPAs) consumed by patients, and discontinuation from the study due to GI AEs. The secondary outcome included assessment of pain intensity using a visual analogue scale (VAS), Western Ontario and McMaster Universities (WOMAC) score, pain relief score, and investigators' and patients' overall assessments of response to study drugs. RESULTS: A total of 591 (aceclofenac group: 297; diclofenac group: 294) patients were enrolled. The cumulative incidence of GI AEs for dyspepsia (28.1% versus 37.9%; p = 0.014), abdominal pain (19% versus 26.3%; p = 0.037), overall incidence of predefined GI AEs (57.3% versus 73.6%; p < 0.001) and number of patients reporting GI AEs (28.9% versus 36.5%; p = 0.053) were significantly less in the aceclofenac group compared to the diclofenac group throughout the study. All the AEs were mild to moderate in intensity. Fewer patients from the aceclofenac group required GPAs compared to the diclofenac group (28.17% versus 33.68%; p = 0.155). During first 7 days of therapy, >90% of patients from aceclofenac group did not require GPAs. There were no differences between the study groups in the various pain assessment scales when measured during the study period. CONCLUSION: Aceclofenac was better tolerated in terms of incidence and severity of GI AEs and GPA requirement and was as efficacious as diclofenac. The need for GPAs increased with the increase in duration of treatment with NSAIDs. Hence, it could be concluded that usual practice of co-prescription of GPAs with aceclofenac could be avoided to improve patient compliance and reduce cost of treatment. However, long term trials with endoscopic evaluation in the wider population are required to assess the GI tolerability of aceclofenac and diclofenac in detail.
OBJETIVO: Evaluar la eficacia y la tolerabilidad de celecoxib frente a naproxeno en pacientes con osteoartritis (OA) de rodilla.
MÉTODOS: 6 meses, aleatorizado, doble ciego, doble simulación se llevó a cabo en 47 centros en los EE.UU.. Los pacientes con artrosis de rodilla fueron asignados al azar para recibir 200 mg de celecoxib oral una vez al día o 500 mg de naproxeno por vía oral dos veces al día. La variable principal se definió como una mejora del 20% desde el inicio hasta 6 meses en Western Ontario y McMaster Universidades puntuación total (WOMAC) OA.
RESULTADOS: Un total de 586 de cada 589 pacientes asignados al azar recibieron al menos una dosis de celecoxib (n = 294) o el naproxeno (n = 292). El criterio principal de valoración (tasa de respuesta de 6 meses) se logró un 52,7% y el 49,7% de los pacientes en los grupos de tratamiento con celecoxib y naproxeno, respectivamente. Significativamente menos interrupciones debido a eventos adversos gastrointestinales ocurrieron en pacientes que recibieron celecoxib que en los que recibieron naproxeno (4,1% frente a 15,1%, respectivamente).
Conclusiones: Durante el período de estudio 6 meses, celecoxib proporcionado mejoras similares en los síntomas de OA a naproxeno. Además, celecoxib proporciona una mejor tolerabilidad gastrointestinal superior que el naproxeno.
The purpose of this study is to compare the efficacy of tramadol 37.5 mg/acetaminophen 325 mg combination tablets (tramadol/APAP) with that of nonsteroidal anti-inflammatory drugs (NSAIDs) as maintenance therapy following tramadol/APAP and NSAID combination therapy in knee osteoarthritis (OA) pain which was inadequately controlled by NSAIDs. Subjects with knee OA for over 1 year and moderate pain (numerical rating scale [NRS] ≥5) despite at least 4 weeks' NSAID therapy (meloxicam 7.5 mg or 15 mg qd or aceclofenac 100 mg bid) received tramadol/APAP add-on (combination with NSAID) for 4 weeks. Thereafter, subjects with significant pain improvement (NRS <4) were randomized to receive either tramadol/APAP or NSAID for 8 weeks. On days 29 and 57, Western Ontario and McMaster Universities (WOMAC) OA index score was measured. Secondary measures included pain intensity (NRS), pain relief score, and subjects' and investigators' overall medication assessments. Of 143 subjects enrolled, 112 completed the 4-week tramadol/APAP and NSAID combination phase and 97 (67.8%) experienced significant pain improvement. Of the 97 subjects randomized, 36 in tramadol/APAP group and 47 in NSAID group completed the 8-week comparator study. On days 29 and 57, WOMAC scores and pain intensities did not increase in both groups compared to measurements immediately after the combination therapy. At these two time points, there were no significant differences in WOMAC scores, pain intensities, and other secondary measures between the two groups. Overall adverse event rates were similar in both groups. Tramadol/APAP add-on significantly improved knee OA pain which had been inadequately controlled by NSAIDs. In those subjects who showed favorable response to tramadol/APAP and NSAID combination therapy, both tramadol/APAP and NSAIDs were effective at maintaining the pain-reduced state and there was no significant difference in efficacy between tramadol/APAP and NSAIDs.
OBJETIVO: Demostrar que una combinación de dosis fija de recubrimiento entérico naproxeno 500 mg y de liberación inmediata esomeprazol magnesio 20 mg tiene una eficacia comparable a celecoxib para la osteoartritis de rodilla.
Material y métodos: Dos estudios aleatorizados, doble ciego, de grupos paralelos,, multicéntrico de fase III controlados con placebo (PN400-307 y PN400-309) reclutaron pacientes de ≥50 años con artrosis sintomática de rodilla. A raíz de un brote de la osteoartritis, los pacientes recibieron naproxeno / esomeprazol magnesio dos veces al día, celecoxib 200 mg una vez al día, o placebo durante 12 semanas.
Registro de ensayos clínicos: NCT00664560 y NCT00665431.
Principales medidas de resultado: Tres variables de eficacia coprimarios fueron el cambio medio desde el inicio hasta la semana 12 en Western Ontario y McMaster Artrosis Index (WOMAC) de dolor y función subescalas, y evaluación global del paciente de la artrosis mediante una escala analógica visual (PGA-VAS).
RESULTADOS: En el Estudio 307, 619 pacientes fueron aleatorizados y 614 tratados. En el estudio 309, 615 pacientes fueron aleatorizados y 610 tratados. Tanto el naproxeno / esomeprazol magnesio y celecoxib se asociaron con mejoras (media de mínimos cuadrados cambio desde el inicio hasta la semana 12) en el dolor WOMAC (Estudio 307: -42,0 y -41,8, respectivamente; Estudio 309: -44,2 y -42,9, respectivamente), WOMAC función (Estudio 307: -36,4 y -36,3, respectivamente; Estudio 309: -38,9 y -36,8, respectivamente), y el PGA-VAS (Estudio 307: 21,2 y 21,6, respectivamente; Estudio 309: 29,0 y 25,6, respectivamente). Un margen de no inferioridad especificado previamente de 10 mm entre el naproxeno / esomeprazol magnesio y celecoxib estaba satisfecho por cada co-principal punto final en la semana 12 en ambos estudios. Mejoras significativas se observaron con naproxeno / esomeprazol magnesio versus placebo en ambos estudios (p <0,05). El celecoxib fue significativamente diferente del placebo en el Estudio 307 (p <0,05); Sin embargo, las mejoras no fueron significativas en el Estudio 309. El uso de paracetamol y la expectativa del paciente de recibir tratamiento activo (80% de probabilidad) pueden haber contribuido a una respuesta de alta placebo observado.
CONCLUSIONES: El naproxeno / esomeprazol de magnesio tiene una eficacia comparable a celecoxib para el tratamiento del dolor asociado con la osteoartritis de la rodilla durante 12 semanas.
OBJETIVO: Comparación de naproxcinod (375 y 750 mg), placebo (hasta 13 semanas), y naproxeno 500 mg (todo el bid) para el tratamiento de la osteoartritis (OA) los signos y síntomas.
MÉTODOS: A 53 semanas de duración, aleatorizado, doble ciego, de grupos paralelos. Mil veinte pacientes con artrosis de rodilla primaria fueron aleatorizados para naproxcinod 750 mg, 375 mg naproxcinod, naproxeno 500 mg, o placebo (todo el bid). Variables de eficacia fueron coprimarios Western Ontario y McMaster Universidades Artrosis Index (WOMAC ™) de dolor y función subescalas y calificación global del paciente de su situación sanitaria. Un análisis del modelo de covarianza probada superioridad para ambas dosis naproxcinod sobre el placebo en la semana 13, y de no inferioridad de naproxcinod 750 mg dos veces al frente naproxeno en las semanas 13 y 26.
RESULTADOS: los cambios medios mínimos cuadrados con respecto al inicio fueron mayores para ambas dosis naproxcinod en comparación con placebo en la semana 13 para el dolor WOMAC (-31,3 [error estándar 1,67], -28,1 [1,64], y -20,4 [1,62] mm con naproxcinod 750 mg oferta [P <0,0001], 375 mg dos veces [p = 0,0008], y placebo, respectivamente), la función WOMAC (-27,8 [1,60], -23,8 [1,58], y -14,9 [1,56] mm, respectivamente, P <0.0001 ), y la valoración global del paciente de la condición de la enfermedad (1,00 [0,061], 0,81 [0,060] y 0,49 [0,059], respectivamente; p <0,0001). Naproxcinod 750 mg dos veces no fue inferior al naproxeno en las semanas 13 y 26. Naproxcinod fue bien tolerado, sin diferencias notables en la respuesta de la presión arterial ortostática entre tratamientos.
CONCLUSIÓN: Naproxcinod 750 mg dos veces y 375 mg oferta demostraron una eficacia superior al placebo para el tratamiento de la OA y fueron bien toleradas más de 1 año. Naproxcinod 750 mg dos veces no fue inferior al naproxeno 500 mg dos veces.
To compare the efficacy, tolerability and safety of celecoxib, naproxen and placebo in Asian patients with osteoarthritis (OA) of the knee.
METHOD:
Patients of Asian descent with knee OA, aged ≥ 45 years, in a flare state with a functional capacity classification of I-III, received celecoxib 200 mg once daily, naproxen 500 mg twice daily or placebo, for 6 weeks. The change in Patient's Assessment of Arthritis Pain (week 6 vs. baseline) was the primary endpoint. Secondary endpoints, including Patient's and Physician's Global Assessments of Arthritis, Western Ontario and McMaster Universities OA Index (WOMAC), use of complementary and alternative medicines, incidence of treatment-emergent adverse events (TEAEs) and measurements of upper gastrointestinal tolerability, were also assessed.
RESULTS:
Three hundred and sixty-seven patients were randomized: 145 to celecoxib, 144 to naproxen and 78 to placebo. Celecoxib was as effective as naproxen in reducing OA pain (least squares mean change from baseline in visual analogue scale score [standard error] -37.1 [2.0] for celecoxib and -37.5 [2.0] for naproxen). Patient's and Physician's Global Assessment of Arthritis, WOMAC scores, Pain Satisfaction Scale and Patient Health Questionnaire-9 showed statistically significant improvement in active treatment groups versus placebo, with the exception of naproxen WOMAC scores. Treatment-related TEAEs occurred in 19 (13%), 34 (24%) and six (8%) patients in the celecoxib, naproxen and placebo groups, respectively.
CONCLUSION:
Celecoxib and naproxen were comparable in their effects to reduce the signs and symptoms of knee OA in Asian patients. Celecoxib was shown to be safe and well tolerated in this patient population.
