Calle Antonio Acuña, Madrid Tfno:

Transcripción

1 Calle Antonio Acuña, Madrid Tfno: ipalacios@institutopalacios.com

2 ÚLTIMAS RECOMENDACIONES INTERNACIONALES EN ARTROSIS Y NUEVAS EVIDENCIAS PARA SU TRATAMIENTO. Ingrid Möller Instituto Poal de Reumatología Universidad de Barcelona

3 24 MOnth study on Structural changes in knee osteoarthritis Assessed by MRI with Chondroitin sulfate

4

5 DISEÑO Ensayo clínico multicéntrico, aleatorizado, a doble-ciego, controlado, comparativo entre CS y celecoxib Nº pacientes: 194 pacientes

6 TRATAMIENTO 1200 mg de condroitín sulfato/día (Condrosan, Bioiberica) o 200 mg de celecoxib/día (Celebrex, Pfizer). Paracetamol max. 3 g/ día permitido como medicación de rescate (interrumpido 48 h antes de cada visita)

7 OBJETIVO PRINCIPAL Explorar el efecto DMOAD de CS vs celecoxib sobre la pérdida de volumen de cartílago en artrosis de rodilla tras 24 meses mediante Resonancia Magnética cuantitativa (qmri).

8 PARÁMETROS DE EVALUACIÓN ESTRUCTURALES Pérdida de volumen de cartílago de la rodilla. Compartimentos: lateral medial Volumen de líquido sinovial Seguimiento necesidad de prótesis a largo plazo (tras 2 y 4 años) (en curso)

9 PARÁMETROS DE EVALUACIÓN Dolor de rodilla (EAV) Puntuación escala WOMAC y en las subescalas de dolor, función y rigidez Calidad de vida mediante SF-36 Consumo de paracetamol Tolerabilidad de los tratamientos SINTOMÁTICOS

10 DISTRIBUCIÓN DE PACIENTES

11 RESULTADOS RMN

12 PÉRDIDA DE VOLUMEN DE CARTÍLAGO Compartimento medial

13 RESULTADOS SINTOMÁTICOS

14 Relative Change from baseline WOMAC Total score (%) ESCALA WOMAC GLOBAL Visit 2 (Baseline) Visit 3 (Day 91) Visit 4 (Day 182) Visit 6 (Day 364) Visit 8 (Day 546) Visit 9 (Day 728) , , ,5-40,6-38, % -45, (p=0.104) -52,1 (p=0.100) Chondroitin Sulphate (N=97) -51,8 (p=0.725) -58,8 (p=0.154) -45,1 (p=0.942) 45.1 % Celecoxib (N=97)

15 Relative Change from baseline WOMAC Pain score (%) WOMAC DOLOR Visit 2 (Baseline) Visit 3 (Day 91) Visit 4 (Day 182) Visit 6 (Day 364) Visit 8 (Day 546) Visit 9 (Day 728) , ,92-35,79-36,75-40,15-39, % -50 (p=0.185) -40,39-46,42-53, (p=0.923) (p=0.979) -53,10 (p=0.079) 53.1 % (p=0.415) -80 Chondroitin Sulphate (N=97) Celecoxib (N=97)

16 Relative Change from baseline WOMAC Physical Function score (%) WOMAC FUNCIÓN Visit 2 (Baseline) Visit 3 (Day 91) Visit 4 (Day 182) Visit 6 (Day 364) Visit 8 (Day 546) Visit 9 (Day 728) , ,0-30,9-40,5-38, % -44, (p=0.122) -42,3 (p=0.075) Chondroitin Sulphate (N=97) -42,3 (p=0.803) -47,9 (p=0.219) (p=0.828) -42, % -80 Celecoxib (N=97)

17 Relative Change from baseline WOMAC Stiffness score (%) WOMAC RIGIDEZ Visit 2 (Baseline) Visit 3 (Day 91) Visit 4 (Day 182) Visit 6 (Day 364) Visit 8 (Day 546) Visit 9 (Day 728) ,45 (p=0.075) -35,28 12,15-34,67-30,43-38,90-40,89-41,16 (p=0.166) (p=0.428) (p=0.220) (p=0.395) 38.5 % -38,51-46, % -100 Chondroitin Sulphate (N=97) Celecoxib (N=97)

18 Relative Change from baseline Pain VAS (%) DOLOR EAV Visit 2 (Baseline) Visit 3 (Day 91) Visit 4 (Day 182) Visit 6 (Day 364) Visit 8 (Day 546) Visit 9 (Day 728) , ,5-35,12-42,06-41, % -49, ,52-46, ,71-55, % -70 (p=0.167) (p=0.078) (p=0.659) (p=0.127) (p=0.439) -80 Chondroitin Sulphate (N=97) Celecoxib (N=97)

19 CONSUMO PARACETAMOL Media (DE) consumo de paracetamol (mg/día) y número de comprimidos / día CS (N=97) Celecoxib (N=97) Valor p Consumo de n paracetamol Sí 90 (93.8%) 82 (86.3%) No 6 (6.3%) 13 (13.7%) Nº comprimidos /día n Media (DE) 1.17 ± ± Consumo diario (mg/día) n Media (DE) ± ±

20 CONCLUSIONES CS reduce significativamente la pérdida de volumen de cartílago frente a celecoxib. CS reduce el dolor, mejora la capacidad funcional y los síntomas clínicos de forma clínicamente relevante. A nivel sintomático, CS es igual de efectivo que celecoxib a lo largo de todo el estudio. CS es significativamente superior a celecoxib en la reducción de la pérdida de cartílago con igual eficacia en la reducción de los síntomas de la enfermedad en pacientes con artrosis de rodilla.

21 ESTUDIO CONCEPT

22 DISEÑO DEL ESTUDIO GRUPO 1 Condroitín sulfato 800mg GRUPO 2 Celecoxib 200mg GRUPO 3 Placebo

23 DISEÑO DEL ESTUDIO (2) 604 pacientes aleatorizados 199 Condroitín 205 Placebo 200 Celecoxib 39 abandonos 33 abandonos 27 abandonos 160 finales 172 finales 173 finales

24 % (Mean ± std Error) VARIABLE PRINCIPAL: EAV DOLOR ANCOVA 6 months Condrosulf vs Placebo p<0.05 Celebrex vs Placebo p<0.05 Condrosulf vs Celebrex p = ns -48% PLACEBO -52% CELECOXIB -52% CONDROITIN Months

25 % (Mean ± std Error) VARIABLE PRINCIPAL: INDICE LEQUESNE ANCOVA 6 months Condrosulf vs Placebo p<0.05 Celebrex vs Placebo p<0.05 Condrosulf vs Celebrex p = ns -28% PLACEBO -36% CELECOXIB -37% CONDROITIN Months

26 CONCLUSIONES CS Y CELECOXIB PRESENTAN LA MISMA EFICACIA EN ARTROSIS DE RODILLA, A NIVEL SINTOMÁTICO: CS y Celecoxib redujeron el dolor en un 52% y fueron estadísticamente superiores a Placebo. CS y Celecoxib mejoraron la función en un 37% y un 36% respectivamente, siendo estadísticamente superiores a Placebo.

27 J Clin Rheumatol ;22(7): PANLAR Consensus Recommendations for the Management in Osteoarthritis of Hand, Hip, and Knee. Rillo O, Möller I, Caballero CV, Quintero M.

28 Consenso sobre tratamiento de la OA entre 18 países pertenecientes a PANLAR que deriva de un estudio demográfico previo incluyendo 3040 pacientes con artrosis.

29 Revisión de la literatura entre según los niveles de evidencia de la The American Heart Association

30 MÉTODOS Revisión de 806 artículos incluyéndose 108

31 Participan 48 expertos en el area de OA, 18 países americanos y se consensuan tratamientos no farmacológicos, farmacológicos y quirúrgicos de acuerdo a los niveles de evidencia

32 TABLE 1. Level of Evidence Level A B C Strength of Recommendation Level I II IIa IIb III Meaning Information from various randomized clinical trials or metaanalyses. Information from a randomized clinical trial or non-randomized studies. Experts consensus, case studies or care standards. Meaning There is evidence and/or general agreement that a procedure or treatment is beneficial, useful or effective. Conflicting evidence and/or differing opinions about the efficacy of a procedure or treatment. Evidence and/or agreement favor usefulness or efficacy. Usefulness or efficacy is not established by evidence or opinion. Conditions for which there is evidence, general agreement, or both that the procedure treatment is not useful/ effective and in some cases may be harmful.

33 RECOMENDACIONES EN ARTROSIS DE MANOS

34 TABLE 2. Recommendations and Level of Evidence Relating to Hand OA Proposition Level of Evidence Non-pharmacological treatment modalities 1. Education with regard to joint protection together with an exercise regimen including muscle strengthening and range of motion exercises (IC) 1. The combination of an orthosis (splint) with an exercise regimen to improve pain and functionality in the short- and long-term. 7,14,16-26 (IIaB)

35 Pharmacological treatment modalities Topical NSAIDs are indicated as being effective and safe for mild to moderate pain in patients with few affected joints as well as in elderly patients with mild to moderate persistent pain. 13,30-34 Acetaminophen/paracetamol (up to 3 g/day) is the preferred oral analgesic for the long-term treatment particularly in elderly patients due to its relative safety in comparison with NSAIDs. 31,32 Oral NSAIDs are recommended at the lowest effective dose and for the shortest time possible if patients present inadequate response to acetaminophen/paracetamol. 13,31,35-37,42 The high risk associated with gastrointestinal and cardiovascular events should be considered. The use of chondroitin sulfate for pain relief and function is recommended as it has a good safety profile Glucosamine and chondroitin sulfate is supported in the treatment of hand and knee OA. 39 (IA) (IB) (IA) (IA) (IB)

36 RECOMENDACIONES EN ARTROSIS DE RODILLA

37 TABLE 4. Recommendations and Level of Evidence Relating to Knee OA Proposition Non-pharmacological treatment modalities Information and education regarding treatment goals and the importance of lifestyle changes to reduce the degenerative damage of the knee joint should be provided. 61,79 Hydrotherapy in a therapeutic tank may be indicated in mild knee pain without swelling or stiffness, it is especially beneficial for elderly patients. 68 A program of exercises for flexibility, mobilization and stretching can be included. 79 Mechanotherapy, including flexibility programs and mobilization and stretching exercises, can reduce pain and improve the range of motion of the knee. 79 Thermotherapy (heat and cold) may help to improve the symptoms of knee OA. 79 The use heat to reduce pain and stiffness before performing flexion exercises in moderate and persistent pain is recommended. 81 A program of flexibility, stretching and strengthening exercises for symptomatic knee OA is recommended as this reduces pain during walking and climbing stairs and improves the strength of the quadriceps femoris. 83 Level of Evidence (IA) (IIaA) (IIbA) (IIaA) (IB) (IA)

38 TABLE 4. Recommendations and Level of Evidence Relating to Knee OA Proposition Pharmacological treatment Level of Evidence Acetaminophen/paracetamol is recommended at a dose of up to 3 g/day for the treatment of mild pain resulting from knee OA. Moderate gastrolesive effects may occur and patients should be monitored for possible hepatic complications. 63,88 (IB) NSAIDs such as diclofenac, ibuprofen, naproxen and selective NSAIDs including celecoxib, and etoricoxib are indicated in moderate pain. 89,90 In all cases gastric protection, such as a proton-pump inhibitor, is required 91 and naproxen is recommended in patients with cardiovascular risk. 92 (IA) Topical NSAIDs may be indicated in patients with gastrointestinal risk, even though the analgesic response decreases after one year of use (IA)

39 TABLE 4. Recommendations and Level of Evidence Relating to Knee OA Proposition Pharmacological treatment Level of Evidence The use of tramadol in the case of severe pain in its various administration forms is recommended. 115 (IA) Capsaicin gel was shown to be an effective treatment for knee OA accompanied by mild to moderate pain. 96 (IIB) Intra-articular corticosteroid injection (ultrasound-guided) may be beneficial to provide fast pain relief. 69,70 (IIaB) Chondroitin sulfate has shown to have a beneficial effect on symptoms in patients with knee OA and a high safety profile. It has been proven that its effect persists for 3 months after stopping the treatment (carryover effect). Recent studies have provided evidence that chondroitin sulfate use may delay OA progression. 39,83-87 (IA)

40 TABLE 4. Recommendations and Level of Evidence Relating to Knee OA Proposition Level of Evidence The combination of glucosamine and chondroitin sulfate is indicated in patients with knee OA and moderate to severe pain (IA) Glucosamine may be beneficial for pain relief and for improving joint function in patients. 103 (IA) Avocado soybean unsaponifiable may help to slow the progression of joint damage associated with knee OA. (IIbA) The administration of intra-articular steroids may be reasonable for knee OA accompanied by inflammation. (IIbB) Intra-articular injection of hyaluronic acid of different molecular weights has proven to be beneficial in the treatment of knee OA. (IIaB) Oral administration of hyaluronic acid may have a beneficial therapeutic effect in patients with symptomatic knee OA and may possibly have an even greater effect (IIbC) in relatively young patients.

41 El tratamiento farmacológico de la OA se ha centrado tradicionalmente en analgésicos y AINES con sus toxicidades asociadas. Estos tratamientos son útiles en períodos breves de tiempo en los que exista excerbación del dolor.

42 Alternativas seguras que hayan demostrado eficacia y tengan evidencia demostrable son: CONDROITIN SULFATO CONDROITIN SULFATO+GLUCOSAMINA