VISCOSUPPLEMENTATION ET OSTEOARTHRITE QUESTION : Chez les patients avec arthrose du genou qui désirent une amélioration de leur qualité de vie, est-ce que la viscosupplémentation est plus efficace que l infiltration avec des corticosteroides pour améliorer la qualité de vie? AUTEUR : Marie-Isabelle Desrosiers (OCTOBRE 2007) P : patient avec OA genou I : viscosupplémentation C : infiltration aux corticostéroïdes O : amélioration qualité de vie (réduction douleur, durée d'efficacité et amélioration mobilité) CONTEXTE: Une de mes patientes âgées avec une arthose au genou et calcifications méniscales n'obtient pas de soulagement adéquat avec Pennsaid et acétaminophène. Elle ne désire pas de chirurgie et me demande d'augmenter sa qualité de vie. Toutefois, je ne connaissais pas les résultats potentiels de la viscosupplémentation versus l'infiltration pour l aider à faire un choix éclairé. Je n'avais que des données anectodales de médecins. RECHERCHE: Bandolier : Oestoarthritis and injection* : 4 revues intéressantes : Intra-articular hyaluronic acid for knee osteoarthritis; Hyaluronic acid injections for OA knee; Hylan G-F20 for arthritis and Steroid injections for OA knee Clinical evidence: 1 revue: OA of the knee Up to Date: information simiuilaire donc non discutée ici RÉSULTATS: 1) BANDOLIER. Intra-articular hyaluronic acid for knee osteoarthritis J Arrich et al. Intra-articular hyaluronic acid for the treatment of osteoarthritis of the knee: systematic review and meta-analysis. Canadian Medical Association Journal, 2005 Apr 12;172(8):1039-43 Revue systématique des revues publiées jusqu en avril 2004. Ils ont examiné des issues cliniques prédéfinies comme la douleur au repos, la douleur au mouvement, etc. Selon le site Bandolier, c est la meilleure revue sur le sujet et la seule à émettre des commentaires sur la méthodologie des études évoquées.
Leur conclusion : No trial that was randomised, double blind, and with an intention to treat analysis could demonstrate any benefit. Benefit was shown in trials that were open, or which were of per-protocol analysis. It may not be beyond the bounds of belief that a small number of patients could benefit with long term use of injections of hyaluronic acid into their knee joints. As things stand, this does not look like a reasonable therapy. Other systematic reviews of the same topic: M Pagnano, G Westrich. Successful nonoperative management of chronic osteoarthritis of the knee: safety and efficacy of retreatment with intraarticular hyaluronate. Osteoarthritis and cartilage 2005 13: 751-761. The review of Pagnano & Westrich examines the evidence from studies of continued long term use, and concludes that there is benefit. However, of the six studies, only one is randomised. Studies are small, some with just a few patients. CT Wang et al. Therapeutic effects of hyaluronic acid on osteoarthritis of the knee. A meta-analysis of randomized controlled trials. Journal of Bone and Joint Surgery 2004; 86-A (3): 538-545. The review examines the evidence from 20 trials (for a total of 1647 randomly assigned knees (818 knees treated with hyaluronic acid injection and 829 treated with placebo injection). Only singleblind or double-blind randomized controlled trials that compared the therapeutic effect of intra-articular injection of hyaluronic acid with that of intra-articular injection of a placebo to treat osteoarthritis of the knee were included in this meta-analysis. Subgroup analysis and meta-regression analysis showed that lower methodological quality such as a single-blind or single-center design resulted in higher estimates of hyaluronic acid efficacy, that introduction of acetaminophen as an escape analgesic in the trial resulted in lower estimates of hyaluronic acid efficacy, and that patients older than sixty-five years of age and those with the most advanced radiographic stage of osteoarthritis (complete loss of the joint space) were less likely to benefit from intra-articular injection of hyaluronic acid. 2) BANDOLIER. Hyaluronic acid injections for OA knee Deux revues systématiques : a) GH Lo et al. Intra-articular hyaluronic acid in treatment of knee osteoarthritis: a meta-analysis. JAMA 2003 290: 3115-3121. This review included 22 trials, 19 published in full, with 2949 patients. Trial size was 24 to 408 participants. Effect size was calculated for each study, and pooled. Of the 22 trials, only three individually had a statistically significant effect size. Overall the effect size was 0.3 (95% CI 0.2 to 0.5), indicating a small effect. Omitting three trials with the largest molecular weight (6,000 kd), the effect size was even smaller at 0.2 (0.1 to 0.3).
Three trials (268 patients) used 6,000 kd hyaluronic acid, one of which was very small, with just 30 patients. The two larger studies differed in their conclusion, one with a very large effect size, and one no different from placebo. b) A Aggarwal, IP Sempowski. Hyaluronic acid injections for knee osteoarthritis. Systematic review of the literature. Canadian Family Physician 2004 50: 249-256. The second review included 13 randomised trials and five case series. The randomised trials were included in the first review. Three of the five case series were prospective, were small, and lasted six months to two years. Three used 6,000 kd hyaluronic acid, but only one was prospective. All reported some degree of pain relief in some patients. N.B. Adverse events reported included injection site pain and swelling in 2% to 23% of injections. Gastrointestinal adverse events and back pain were also reported. Leur conclusion : Bandolier looks for outcomes that are more meaningful, like patients improved, or changes in a scale, or, better still, some clinically useful but simply described outcome that we can understand. Then we have the chance of comparing interventions, and can check whether the patients in different trials are the same. Here we failed. 3) BANDOLIER. Hylan G-F20 for arthritis M Espallargues, JM Pons. Efficacy and safety of viscosupplementation with Hylan G-F 20 for the treatment of knee osteoarthritis. International Journal of Technology Assessment in Health Care 2003 19: 41-56. Hylan G-F 20 in limited studies appears to be more effective than placebo, and perhaps as effective as NSAIDs for reducing pain in knee osteoarthritis. There were fourteen identified studies, seven of which were randomised trials, and of which four were full publications and three abstracts. Four of the other seven reports were abstracts. Four of the randomised studies compared Hylan G-F 20 with placebo. All were described as double blind. Three were of at least 12 weeks duration, and mean VAS pain scores at the end of treatment. Two studies apparently also reported the number of patients with pain scores of 20 mm or below at the end of treatment, with NNTs in individual studies of 1.3 (90% of patients with Hylan G-F 20 with low pain scores) and 3.8 (39% with low pain scores). Two randomised trials comparing Hylan G-F 20 with oral NSAIDs showed little difference, but with a tendency for lower scores at the end of treatment with Hylan G-F 20 than with NSAID.
Leur conclusion: This is a comprehensive review, though with information on only 190 patients in longer term comparisons with placebo in randomised trials. Of course, placebo in this context is not necessarily doing nothing, as arthrocentesis itself may involve removing the joint effusion, and both sham injections and saline injections were used as placebo. The reality, though, is that there is insufficient high-quality research upon which to build definite conclusions. 4) BANDOLIER. Steroid injections for OA knee 2 revues systématiques : M Godwin, M Dawes. Intra-articular steroid injections for painful knees: systematic review with meta-analysis. Canadian Family Physician 2004 50: 241-248. Révision de la littérature jusqu à décembre 2002. RCT avec injection intra-articulaire de corticostéroides de longue action comparativement au placebo : 5 études. B Arroll, F Goodyear-Smith. Corticosteroid injections for osteoarthritis of the knee: meta-analysis. British Medical Journal 2004 328: 869-870. Révision de la littérature jusqu à 2003. RCT avec n importe quel stéroïde comparé à un placebo :10 études (placebo= injection de salin dans toutes les études sauf une; pour cette dernière «sham injection»). La majorité des RCT était réalisés avec une dose de stéroides qui équivalait de 25 à 50 mg de prednisone (bien que l écart fut de 6 à 80 mg). There were six studies with outcomes of improvement up to two weeks. This was not a clearly defined term in many of the studies. In these six studies with 317 patients, five used long acting corticosteroids. Improvement up to two weeks occurred in 74% of patients with a steroid injection and 45% given placebo. The relative benefit was 1.7 (95% CI 1.4 to 2.0), and the number needed to treat for one patient to have improvement was 3.4 (2.5 to 5.1). The weighted mean reduction in visual analogue pain scores was 17 mm on a 100 mm scale. There were three studies with 192 patients had results at 16-24 weeks after the injection. Two used long acting corticosteroid, and the other used hydrocortisone (and was an older study with a low quality score). Overall, 33% of steroid treated patients had improvement at 16-24 weeks compared, and 16% of those given placebo. The relative benefit was 2.1 (1.2 to 3.5), and the NNT 5.8 (3.4 to 19). Adverse consequences of the intra-articular injections were not reported. Leur conclusion: What we have here is some very limited data with implications for clinical practice. It is likely that intra-articular corticosteroids produce some pain relief, perhaps for some weeks. There are many problems, though:
-The outcome of improvement or decreased pain is not robust. It may well be that a more rigorous examination of this literature could eliminate some or all of the studies because of the lack of definition of outcomes or their measurement. The studies might not be valid. -The trials may not mirror clinical practice, especially with regard to use of local anaesthetic, with the practice of joint lavage, and with regard to choice of corticosteroid or dose used. The studies may not be relevant. -The studies were small individually, and in total. The results could be overturned by a large, well-conducted, negative study being published, or by uncovering negative unpublished studies. Clinical practice and experience suggests that intra-articular steroid injections are helpful for painful knees in osteoarthritis. The trouble is that half of the patients improved with saline alone, and the additional benefits of adding steroid were moderate. Some will say that this is the power of psychiatry with needles, but it is equally possible that the improvement would have come about anyway, because of the ups and downs of symptoms. In many ways the situation resembles that of many alternative therapies, though those usually have less evidence to support them. 5) CLINICAL EVIDENCE : Osteoarthritis of the knee Ils ont fait une revue systématique en 2006 des traitements chirurgicaux et nonchirurgicaux pour l osteoarthrie du genou (Révision en de bases de données diverses de 1966 à octobre 2006). Ils classifient les corticostéroides intraarticulaires et l hyaluronan intra-articulaire de «likely to be beneficial» pour diminuer la douleur mais spécifient que les études sont de pauvre qualité. a) Corticostéroides intra-articulaire : Comparé avec placebo : diminue la douleur à 1-3 sem, mais pas long terme (évidence de basse qualité). Comparé avec hyaluronan : pourrait être moins efficace à diminuer la douleur, cependant pourrait être autant efficace dans le court terme (évidence de très basse qualité). Bénéfices : Corticostéroides intra-articulaire vs placebo 1 revue systématique qui démontre une diminution de la douleur à une semaine si on compare avec un placebo (8 RCT; WMD -21.9, 95% CI -29.9 to -13.9). Il y avait aussi un bénéfice à 2 semaines (RR 1.81, 95% CI 1.09-3.00) et à 3 semaines (RR 3.11, 95% CI 1.61 6.01). Toutefois, il manque d évidences après 4 semaines.
Corticostéroides intra-articulaire vs hyaluronan 1 revue systématique sans différence significative de la douleur à 1-4 semaines (3RCT, 85 personnes, WMD -4.90; 95% CI -9.9 à 0.01 P=0.05). L hyaluronan et ses dérivés sont significativement plus efficaces que les corticostéroides pour réduire la douleur à 5-13 semaines (2 RCT, WMD -7.73, 95%, CI -12.81 to -2,64 P = 0.0003). Effets néfastes : Les complications répertoriées sont rares : augmentation des symptômes, atrophie des tissus, nécrose graisseuse, calcification, athropathie secondaire aux corticostéroides et nécrose vasculaire. Il y a un risque théorique d infection, mais aucune évidence à cet effet. b) Hyaluronan intra-articulaire : Comparé avec placebo : possible amélioration de la douleur et de la fonction jusqu à 13 semaines, mais pas de bénéfices à long-terme (évidence de basse qualité). Comparé avec corticostéroides intra-articulaire : pourrait être plus efficace à diminuer la douleur à 5-13 sem, cependant les 2 pourraient être aussi efficaces un que l autre dans le court terme (évidence de très basse qualité). Bénéfices : Hyaluronan vs placebo 2 revues systématiques et 2 RCT. Amélioration de la mise en charge entre 1-26 semaines (1-4 sem (22 RCT : WMD -7.7, 95% CI -11.3 to -4.1, P < 0.0001) 5-13 sem (17 RCT : wmd -13.0, CI -17.8-8.2 p < 0.00001) 14-26 sem (9 RCT : CI -14.8 to -3.2 p=0.002). Pas d amélioration entre 45-52 sem. Diminution de la douleur (2 e revue, 11 RCT, 1443 personnes) : efficace modérément entre 5-7 sem, 8-10 sem, mais pas entre 15-22 sem (visual analogue scale 4.4 à 1 sem, 95% CI 1.1 to 7.2 VS 17.7 at 5 to 7 wks, 95% CI 7.5 to 28.0 VS 18.1 at 12-15 wks, 95% CI 6.3 to 29.9; p value not reported). Donc évidence qui suggère une diminution des symptômes jusqu à 6 mois. Effets néfastes : Les complications sont rares et sont principalement des effets locaux et des plaintes gastro-intestinales.
CONCLUSION : Il n'existe donc pas beaucoup de preuves que l un ou l autre des traitements proposés (stéroides intra-articulaires ou acide hyaluronique intra-articulaire) soit très efficace. Lorsque l on compare les corticostéroides et l injection de hyaluronan avec le placebo, on dénote dans beaucoup d études une diminution de la douleur à court terme, mais pas à long terme sauf dans une revue où le bénéfice de l hyaluronan s était prolongé jusqu à 6 mois. Dans la seule revue systématique comparant les steroides intra-articulaires à l hyaluronan, ce dernier semble mieux contrôler la douleur à moyen terme (5-13 semaines). Ces deux modalités de traitement demeurent donc des choix qui pourraient s avérer bénéfiques pour la clientèle dont les douleurs ne répondent pas bien aux exercices et/ou aux anti-inflammatoires. Toutefois, il est important de bien informer le patient sur la variabilité des réponses cliniques à la douleur. Il y a aussi le coût de l hyaluronan, qui est un facteur pouvant influencer la décision.