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Problema de Salud AUGE N°41

Tratamiento médico en personas de 55 años y más con artrosis de cadera y/o rodilla, leve o moderado

ETD-8-2018

En personas mayores de 55 años con diagnóstico clínico de artrosis de cadera o rodilla leve o moderada en los que se plantea el uso de antinflamatorios por un periodo limitado, el Ministerio de Salud SUGIERE usar AINEs (Antiinflamatorios No Esteroideos) COX-2 específicos (coxibs) o no específicos, de acuerdo a las condiciones clínicas de cada paciente.
Comentarios del Panel de Expertos:
► Los antinflamatorios COX-2 específicos podrían ser de mayor utilidad en personas con riesgo hemorragia gastrointestinal.

El panel de expertos analizó y debatió cada uno de las preguntas de la “Tabla de la evidencia a la decisión”, considerando tanto la evidencia de investigación, experiencia clínica, conocimiento de gestión o experiencia de los pacientes. Una vez consensuada la postura del panel respecto a las preguntas, emitieron un juicio seleccionando la opción de respuesta que mejor representaba la opinión del conjunto (destacada con color). Finalmente, cuando el panel emitió su juicio sobre todas las preguntas, se formuló la recomendación.

A continuación, se presenta la “Tabla de la evidencia a la decisión” con el resumen de los juicios, la evidencia de investigación evaluada, consideraciones adicionales y comentarios planteados por el panel.

 1.- ¿El problema es una prioridad?
No Probablemente no Probablemente sí Varía No lo sé

El problema ha sido definido como prioritario en el marco de las Garantías Explícitas en Salud (GES), régimen integral de salud que prioriza un grupo de patologías o problemas de salud, garantizando el acceso a tratamiento oportuno y de calidad.

 2.- ¿Qué tan significativos son los efectos deseables anticipados?
Triviales Pequeños Moderados Grandes Varía No lo sé

Pequeños: El panel de expertos de la Guía estimó que los efectos deseables de «usar AINEs (Antiinflamatorios No Esteroideos) COX-2 específicos (coxibs) o no específico» en comparación a «no usar» son pequeños, considerando la evidencia y experiencia clínica.

Evidencia de investigación

COX-2 comparado con AINE para artrosis

Pacientes

Personas mayores de 55 años con diagnóstico clínico de artrosis de cadera y/o rodilla, leve o moderada.

Intervención

Inhibidores COX-2.

Comparación

AINES (Antinflamatorios No Esteroideos) no COX-2.

Desenlaces

Efecto relativo

(IC 95%)

Estudios/

pacientes

Efecto absoluto estimado*

Certeza de la evidencia

(GRADE)

Mensajes clave en términos sencillos

CON
 AINES no 

CON

COX-2

Diferencia

(IC 95%)

Dolor

Evaluado con VAS (0-100)*

2 ensayos/
 1180 pacientes [104,194]

41 puntos

36,5 puntos

DM: 4,5 puntos mejor

(-10,65 a 1,61)

⊕⊕⊕1

Moderada

El uso de COX-2, en comparación con AINES, probablemente tiene poca o nula diferencia dolor.

Funcionalidad

Evaluado con WOMAC (0-100)***

1 ensayo/

264 pacientes

[194]

37 puntos

31 puntos

DM: 6 puntos mejor

(-0,6 a 11)

⊕⊕⊕1

Moderada

El uso de COX-2, en comparación con AINES, probablemente tiene poca o nula diferencia funcionalidad.

Efectos adversos serios****

OR 0,92
 (0,66 a 1,28)

2404 pacientes / 5 ensayos [39,104,158,163]

68

por 1000

63

por 1000

Diferencia: 5 menos

(22 menos a 17 más)

◯◯◯2,3

Muy baja

El uso de COX-2, en comparación con AINES podría disminuir los efectos adversos. Sin embargo, existe considerable incertidumbre dado que la certeza de la evidencia es muy baja.

IC 95%: Intervalo de confianza del 95%.
RR: Riesgo relativo.
DM: Diferencia de media.
GRADE: Grados de evidencia Grading of Recommendations Assessment, Development and Evaluation.
* El riesgo CON AINES está basado en el riesgo del grupo control en los estudios. El riesgo CON COX-2 (y su intervalo de confianza) está calculado a partir del efecto relativo (y su intervalo de confianza).
**Escala VAS de 0 a 100 puntos, más puntaje es más dolor. La diferencia clínica mínimamente importante utilizada fue 9 puntos [12].
***La subescala de funcionalidad de WOMAC va de 0 a 100 puntos, más puntaje es peor funcionalidad.
**** requieren de intervención médica o amenazan la vida.
1 Se disminuyó la certeza de la evidencia por de sesgo de publicación, tal como fue constatado en la revisión Cochrane [12]
2 Se disminuyó la certeza de la evidencia en un nivel por ser indirecta, ya que los estudios miden el desenlace de manera muy variable.
3 Se disminuyó la certeza de la evidencia en dos niveles por imprecisión, debido al amplio intervalo de confianza y al bajo número de eventos.
Fecha de elaboración de la tabla: Noviembre, 2018

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202. Hochberg MC, Fort JG, Svensson O, Hwang C, Sostek M. Fixed-dose combination of enteric-coated naproxen and immediate-release esomeprazole has comparable efficacy to celecoxib for knee osteoarthritis: two randomized trials. Current medical research and opinion. 2011;27(6):1243-53.
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207. Yocum DE, Hall DB, Roszko PJ.. Efficacy and safety of meloxicam in the treatment of osteoarthritis (OA): results of a phase III double-blind, placebo controlled trial. Arthritis Rheumatism. 1999;42 suppl:S147.
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210. Lund B, Distel M, Bluhmki E. A double-blind, randomized, placebo-controlled study of efficacy and tolerance of meloxicam treatment in patients with osteoarthritis of the knee. Scandinavian journal of rheumatology. 1998;27(1):32-7.
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218. Pfizer.. Celecoxib Study 002. 2004;
219. Moskowitz RW, Jones RB, Cawkwell G. Valdecoxib 10mg demonstrates a rapid onset of action following a single dose in patients with OA of the knee in a flare state. EULAR. 2003;
220. Weaver AL, Polis AB, Petruschke RA, et al.. Onset of efficacy of rofecoxib compared to nabumetone and placebo in patients with osteoarthritis. EULAR. 2003;
221. Pfizer. Valdecoxib Study 143. 2004;
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Búsqueda y Síntesis de Evidencia

 3.- ¿Qué tan significativos son los efectos indeseables anticipados?
Grandes Moderados Pequeños Triviales Varía No lo sé

Varía: El panel de expertos de la Guía consideró que existen componentes que pueden afectar de distinta manera los efectos indeseables de «usar AINEs (Antiinflamatorios No Esteroideos) COX-2 específicos (coxibs) o no específico» en comparación a «no usar». El panel señala que los efectos indeseables depende de cada paciente según su comorbilidad. En el caso de los antiinflamatorios COX2 serían efectos cardiovasculares, y en el caso de los AINES, gastrointestinales

Evidencia de investigación

COX-2 comparado con AINE para artrosis

Pacientes

Personas mayores de 55 años con diagnóstico clínico de artrosis de cadera y/o rodilla, leve o moderada.

Intervención

Inhibidores COX-2.

Comparación

AINES (Antinflamatorios No Esteroideos) no COX-2.

Desenlaces

Efecto relativo

(IC 95%)

Estudios/

pacientes

Efecto absoluto estimado*

Certeza de la evidencia

(GRADE)

Mensajes clave en términos sencillos

CON
 AINES no 

CON

COX-2

Diferencia

(IC 95%)

Dolor

Evaluado con VAS (0-100)*

2 ensayos/
 1180 pacientes [104,194]

41 puntos

36,5 puntos

DM: 4,5 puntos mejor

(-10,65 a 1,61)

⊕⊕⊕1

Moderada

El uso de COX-2, en comparación con AINES, probablemente tiene poca o nula diferencia dolor.

Funcionalidad

Evaluado con WOMAC (0-100)***

1 ensayo/

264 pacientes

[194]

37 puntos

31 puntos

DM: 6 puntos mejor

(-0,6 a 11)

⊕⊕⊕1

Moderada

El uso de COX-2, en comparación con AINES, probablemente tiene poca o nula diferencia funcionalidad.

Efectos adversos serios****

OR 0,92
 (0,66 a 1,28)

2404 pacientes / 5 ensayos [39,104,158,163]

68

por 1000

63

por 1000

Diferencia: 5 menos

(22 menos a 17 más)

◯◯◯2,3

Muy baja

El uso de COX-2, en comparación con AINES podría disminuir los efectos adversos. Sin embargo, existe considerable incertidumbre dado que la certeza de la evidencia es muy baja.

IC 95%: Intervalo de confianza del 95%.
RR: Riesgo relativo.
DM: Diferencia de media.
GRADE: Grados de evidencia Grading of Recommendations Assessment, Development and Evaluation.
* El riesgo CON AINES está basado en el riesgo del grupo control en los estudios. El riesgo CON COX-2 (y su intervalo de confianza) está calculado a partir del efecto relativo (y su intervalo de confianza).
**Escala VAS de 0 a 100 puntos, más puntaje es más dolor. La diferencia clínica mínimamente importante utilizada fue 9 puntos [12].
***La subescala de funcionalidad de WOMAC va de 0 a 100 puntos, más puntaje es peor funcionalidad.
**** requieren de intervención médica o amenazan la vida.
1 Se disminuyó la certeza de la evidencia por de sesgo de publicación, tal como fue constatado en la revisión Cochrane [12]
2 Se disminuyó la certeza de la evidencia en un nivel por ser indirecta, ya que los estudios miden el desenlace de manera muy variable.
3 Se disminuyó la certeza de la evidencia en dos niveles por imprecisión, debido al amplio intervalo de confianza y al bajo número de eventos.
Fecha de elaboración de la tabla: Noviembre, 2018

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192. Perpignano G, Bogliolo A, Puccetti L. Double-blind comparison of the efficacy and safety of etodolac SR 600 mg u.i.d. and of tenoxicam 20 mg u.i.d. in elderly patients with osteoarthritis of the hip and of the knee. International journal of clinical pharmacology research. 1994;14(5-6):203-16.
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194. Sowers JR, White WB, Pitt B, Whelton A, Simon LS, Winer N, Kivitz A, van Ingen H, Brabant T, Fort JG, Celecoxib Rofecoxib Efficacy and Safety in Comorbidities Evaluation Trial (CRESCENT) Investigators. The Effects of cyclooxygenase-2 inhibitors and nonsteroidal anti-inflammatory therapy on 24-hour blood pressure in patients with hypertension, osteoarthritis, and type 2 diabetes mellitus. Archives of internal medicine. 2005;165(2):161-8.
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196. Williams GW, Hubbard RC, Yu SS, Zhao W, Geis GS. Comparison of once-daily and twice-daily administration of celecoxib for the treatment of osteoarthritis of the knee. Clinical therapeutics. 2001;23(2):213-27.
197. Whelton A, Fort J, Puma J, Normandin D, Bello AE, Verburg KM.. Cyclooxygenase‐2 specific inhibitors and cardiorenal function: a randomised controlled trial of celecoxib and rofecoxib in older hypertensive osteoarthritis patients [poster]. EULAR. 2000;
198. Laurenzi M, Vandormael K, Malice MP, Jasan J, Vala M, Justice S, Bozalis D.. Comparison of the tolerability profile of rofecoxib and Arthrotec(TM) in patients with osteoarthritis [poster]. EULAR.. 2000;
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203. Hawel R, Klein G, Singer F, Mayrhofer F, Kähler ST. Comparison of the efficacy and tolerability of dexibuprofen and celecoxib in the treatment of osteoarthritis of the hip. International journal of clinical pharmacology and therapeutics. 2003;41(4):153-64.
204. Schnitzer TJ, Tesser JR, Cooper KM, Altman RD. A 4-week randomized study of acetaminophen extended-release vs rofecoxib in knee osteoarthritis. Osteoarthritis and cartilage. 2009;17(1):1-7.
205. Combe B, Swergold G, McLay J, McCarthy T, Zerbini C, Emery P, Connors L, Kaur A, Curtis S, Laine L, Cannon CP. Cardiovascular safety and gastrointestinal tolerability of etoricoxib vs diclofenac in a randomized controlled clinical trial (The MEDAL study). Rheumatology (Oxford, England). 2009;48(4):425-32.
206. Schnitzer TJ, Weaver AL, Polis AB, Petruschke RA, Geba GP. Efficacy of rofecoxib, celecoxib, and acetaminophen in patients with osteoarthritis of the knee. A combined analysis of the VACT studies. The Journal of rheumatology. 2005;32(6):1093-105.
207. Yocum DE, Hall DB, Roszko PJ.. Efficacy and safety of meloxicam in the treatment of osteoarthritis (OA): results of a phase III double-blind, placebo controlled trial. Arthritis Rheumatism. 1999;42 suppl:S147.
208. Pfizer.. Celecoxib Study 107. 2004;
209. Laine L, Harper S, Simon T, Bath R, Johanson J, Schwartz H, Stern S, Quan H, Bolognese J. A randomized trial comparing the effect of rofecoxib, a cyclooxygenase 2-specific inhibitor, with that of ibuprofen on the gastroduodenal mucosa of patients with osteoarthritis. Rofecoxib Osteoarthritis Endoscopy Study Group. Gastroenterology. 1999;117(4):776-83.
210. Lund B, Distel M, Bluhmki E. A double-blind, randomized, placebo-controlled study of efficacy and tolerance of meloxicam treatment in patients with osteoarthritis of the knee. Scandinavian journal of rheumatology. 1998;27(1):32-7.
211. Schnitzer TJ, Gitton X, Jayawardene S, Sloan VS. Lumiracoxib in the treatment of osteoarthritis, rheumatoid arthritis and acute postoperative dental pain: results of three dose-response studies. Current medical research and opinion. 2005;21(1):151-61.
212. Novartis.. Lumiracoxib Study 2307. 2004;
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214. Hawkey C, PUCCINI Group.. Reduced cumulative incidence of gastroduodenal ulcers with two doses of a new coxib, COX189, compared with standard therapeutic doses of ibuprofen in osteoarthritis patients. Digestive Disease Week (DDW). 2002;
215. Hosie J, Distel M, Bluhmki E.. Efficacy and tolerability of meloxicam versus piroxicam in patients with osteoarthritis of the hip or knee. A six-month double-blind study. Clin Drug Invest. 1997;13:175-84.
216. Hunt RH, Harper S, Callegari P, Yu C, Quan H, Evans J, James C, Bowen B, Rashid F. Complementary studies of the gastrointestinal safety of the cyclo-oxygenase-2-selective inhibitor etoricoxib. Alimentary pharmacology & therapeutics. 2003;17(2):201-10.
217. Integrated clinical and statistical report for a multicenter, double blind, parallel group study comparing the incidence of gastroduodenal ulcer associated with SC-58635 200 mg with that of naproxen 500 mg BID taken for 12 weeks in patients with osteoarthritis or rheumatoid arthritis. Pharmacia. 1997;
218. Pfizer.. Celecoxib Study 002. 2004;
219. Moskowitz RW, Jones RB, Cawkwell G. Valdecoxib 10mg demonstrates a rapid onset of action following a single dose in patients with OA of the knee in a flare state. EULAR. 2003;
220. Weaver AL, Polis AB, Petruschke RA, et al.. Onset of efficacy of rofecoxib compared to nabumetone and placebo in patients with osteoarthritis. EULAR. 2003;
221. Pfizer. Valdecoxib Study 143. 2004;
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Búsqueda y Síntesis de Evidencia

 4.- ¿Cuál es la certeza general de la evidencia sobre efectos?
Muy baja Baja Moderada Alta Ningún estudio incluido

Muy Baja: Existe considerable incertidumbre respecto del efecto de «usar AINEs (Antiinflamatorios No Esteroideos) COX-2 específicos (coxibs) o no específico» en comparación a «no usar». La certeza de la evidencia general se basó en desenlaces de salud establecidos como críticos para los pacientes y con menor nivel de certeza de la evidencia, en este: efectos adversos serios.

Evidencia de investigación

Desenlaces

Importancia

Certeza en la evidencia

(GRADE)

Dolor

CRÍTICO

⊕⊕⊕1

Moderada

Funcionalidad

IMPORTANTE

⊕⊕⊕1

Moderada

Efectos adversos serios

CRÍTICO

◯◯◯2,3

Muy baja

1 Se disminuyó la certeza de la evidencia por de sesgo de publicación, tal como fue constatado en la revisión Cochrane.
2 Se disminuyó la certeza de la evidencia en un nivel por ser indirecta, ya que los estudios miden el desenlace de manera muy variable.
3 Se disminuyó la certeza de la evidencia en dos niveles por imprecisión, debido al amplio intervalo de confianza y al bajo número de eventos.

 5.- ¿Hay incertidumbre importante o variabilidad sobre qué tanto valora la gente los desenlaces principales?
Incertidumbre o variabilidad importantes Posiblemente hay incertidumbre o variabilidad importantes Probablemente no hay incertidumbre ni variabilidad importantes No hay variabilidad o incertidumbre importante

Posiblemente hay incertidumbre o variabilidad importantes: En función de la evidencia de investigación, experiencia clínica, conocimiento de gestión o experiencia de las personas con la condición o problema de salud, el panel de expertos de la Guía consideró que posiblemente existe incertidumbre o variabilidad importante respecto a lo que escogería una persona informada de los efectos deseables e indeseables de «usar AINEs (Antiinflamatorios No Esteroideos) COX-2 específicos (coxibs) o no específico» y «no usar». A criterio del panel, la variabilidad está condicionada por los distintos escenarios clínicos que podrían enfrentar los pacientes, en esta situación en particular, los pacientes no tendrían muchas opciones para la elección de su tratamiento.

Evidencia de investigación

Se identificó un estudio descriptivo que evaluaba la adherencia a los medicamentos para la artrosis, para ello se caracterizaron 4 tratamientos habituales para la artrosis en función a 7 características: Eficacia del dolor, modo de acción (inmediata/lento), frecuencia de dosis (libre demanda u horarios fijos), programa de tratamiento, costos, prescripciones y efectos secundarios. De éstos, cuatro factores tuvieron un efecto significativo en la elección de continuar con un medicamento: costos de bolsillo, efectos secundarios, modo de acción y programa de tratamiento (1).
Tras explicar las características de los tratamientos a 188 participantes, se les solicitó indicaran su disposición a continuar el tratamiento. Se observó que la probabilidad relativa de continuar con un AINE no selectivo, tomada regularmente, era negativa (probabilidad inferior a 1: ni negativo, ni positivo) =0,42. Por otro lado, la probabilidad relativa de continuar un tratamiento con AINE no selectivo fue mucho menos probable (probabilidad superior a 1= 0,04) (1).
Los factores más relevantes para la toma de decisión de los pacientes fueron: evitar efectos secundarios, disminuir los costos de bolsillo, modo de acción lento, horario de tratamiento diario. Los efectos secundarios de presión arterial alta, problemas del corazón / hígado / riñón fue considerados como los más importantes por los participantes, mientras somnolencia y el estreñimiento fueron identificados como los menos importantes (1).

Referencias

1. Laba T-L, Brien J, Fransen M, Jan S. Patient preferences for adherence to treatment for osteoarthritis: the MEdication Decisions in Osteoarthritis Study (MEDOS). BMC Musculoskelet Disord [Internet]. 2013 May 6 [cited 2018 Oct 24];14:160. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23647688

Búsqueda y Síntesis de Evidencia

 6.- El balance entre efectos deseables e indeseables favorece la intervención o la comparación?
Favorece la comparación Probablemente favorece la comparación No favorece la intervención ni la comparación Probablemente favorece la intervención Favorece la intervención Varía No lo sé

Varía: El panel de expertos de la Guía consideró que existen componentes que pueden afectar de distinta manera el balance entre efectos deseables e indeseables, en base a que los efectos deseables son pequeños, los indeseables varían, que la certeza de la evidencia es muy baja y que posiblemente hay incertidumbre o variabilidad importante en lo que escogerían las personas.

 7.- ¿Qué tan grandes son los recursos necesarios (costos)?
Costos extensos Costos moderados Costos y ahorros despreciables Ahorros moderados Ahorros extensos Varía No lo sé

Costos y ahorros despreciables: El panel de expertos de la Guía consideró que los costos y ahorros de «usar AINEs (Antiinflamatorios No Esteroideos) COX-2 específicos (coxibs) o no específico» son despreciables si se compara con «no usar», en función de los antecedentes, experiencia clínica, conocimiento de gestión o experiencia de los pacientes. Hay que considerar que la indicacion de AINES como tratamiento crónico se debe adicionar el uso de inhibidores de la bomba de protones.

Evidencia de investigación

A continuación, se muestran los costos referenciales, es preciso considerar que estos costos fueron recogidos con el único objetivo de constituir un antecedente aproximado.

El porcentaje de cobertura del seguro de salud sobre el precio de las prestaciones sanitarias, dependerá del tipo de seguro de cada paciente.

ítem

Intervención: usar inhibidores COX-2

Comparación: usar AINES (Antinflamatorios No Esteroideos) no coxibs

Costo mensual del tratamiento por medicamento

Posología

Inhibidor selectivo de la ciclooxigenasa -2: etoricoxib 60 MG 1

$ 518

$ 15.530

60 mg/día

Inhibidor selectivo de la ciclooxigenasa -2: celecoxib 200 MG 1

$ 61

$ 1.839

200 mg/día

Ibuprofeno 400 MG 1

$ 14

$ 1.285

1.200 mg/día

Diclofenaco 50 MG 1

$ 7

$ 643

150 mg/día

Naproxeno 550 MG 1

$ 70

$ 6.319

1650 mg/día

Ketoprofeno 50 MG 1

$ 30

$ 1.806

100 mg/día

Clonixinato de lisina 125 MG 1

$ 36

$ 1.071

125 mg/día

Ketorolaco 10 MG 1

$ 35

$ 1.042

20 mg/día

Total tratamiento mensual

Rango: $2.106 a $15.530

Rango: $643 a $3.319

Referencias

1. Precio de compra por Establecimientos de Salud Públicos a través de plataforma Mercado Público, al 2018. Precio incluye IVA.

Búsqueda y Síntesis de Evidencia

 8.- ¿La costo-efectividad de la intervención beneficia la intervención o la comparación?
Favorece la comparación Probablemente favorece la comparación No favorece la intervención ni la comparación Probablemente favorece la intervención Favorece la intervención Varía Ningún estudio incluido

Varía: El panel de expertos de la Guía considera que existen componentes que pueden afectar de distinta manera la costo-efectividad. Depende del tipo de pacientes y de sus comorbilidades.

No se realizó la búsqueda de evidencia que abordaran la costo-efectividad ya que las intervenciones evaluadas no es consideraron de alto costo, según el Decreto 80 «Determinar umbral nacional de costo anual al que se refiere el artículo 6° de la Ley 20.850».

 9.- ¿Cuál sería el impacto en equidad en salud?
Reducido Probablemente reducido Probablemente ningún impacto Probablemente aumentado Aumentado Varía No lo sé

Probablemente reducida: El panel de expertos de la Guía consideró que la equidad en salud se probablemente se reduciría si se recomendase «usar AINEs (Antiinflamatorios No Esteroideos) COX-2 específicos (coxibs) o no específico», dado la garantía GES que cubre este tratamiento está determinada por un tiempo definido y no considera el grupo de pacientes que se beneficiarían con el uso de los COX2.

 10.- ¿La intervención es aceptable para las partes interesadas?
No Probablemente no Probablemente sí Varía No lo sé

Sí: El panel de expertos de la Guía consideró que «usar AINEs (Antiinflamatorios No Esteroideos) COX-2 específicos (coxibs) o no específico» SÍ es aceptable para las partes interesadas (profesionales de la salud, gestores de centros de salud, directivos de centros de salud, pacientes, cuidadores, seguros de salud, otros).

 11.- ¿Es factible implementar la intervención?
No Probablemente no Probablemente sí Varía No lo sé

Sí: El panel de expertos de la Guía consideró que «usar AINEs (Antiinflamatorios No Esteroideos) COX-2 específicos (coxibs) o no específico» SÍ es factible implementar, contemplando la capacidad de la red asistencial, los recursos humanos disponibles a nivel país, recursos financieros, etc.