Comments on "OARSI Guidelines for the Non-Surgical Management of Knee Osteoarthritis".

To the Editor: The 2014 OARSI Guidelines1McAlindon T. Bannuru R. Sullivan M. Arden N. Berenbaum F. Bierma-Zeinstra S. et al.OARSI guidelines for the non-surgical management of knee osteoarthritis.Osteoarthritis and Cartilage. 2014; https://doi.org/10.1016/j.joca.2014.01.003Abstract Full Text Full Text PDF PubMed Scopus (1933) Google Scholar for the management of hip and knee osteoarthritis (OA) with pharmacological therapies are indeed improved by reference to the 2008/2010 OARSI recommendations because the presence or absence of co-morbidities is taken into account. However, by defining treatment appropriateness simply as appropriate, uncertain and not appropriate, the 2013 recommendations do not specify how to treat the OA in a significant number of patients: those with moderate and high co-morbidities risks. For these patients, the appropriateness of any oral treatment is uncertain, except IACS and duloxetine. To illustrate the importance of the population with OA and co-morbidity risks, among the US population with OA, less than 65 years old, the prevalence of metabolic syndrome is 59%, hypertension 75%, abdominal obesity 63%, hyperglycemia 30%, and renal impairment 37%; indeed, aging and obesity should also be considered co-morbidities2Puenpatom R.A. Victor T.W. Increased prevalence of metabolic syndrome in individuals with osteoarthritis: an analysis of NHANES III data.Postgrad Med. 2009; 121: 9-20Crossref PubMed Scopus (221) Google Scholar. It has to be emphasized that these patients with co-morbidities are exposed to polypharmacy and therefore, at risk of drug–drug interactions and of serious adverse events. Keeping in mind that clinical practice guidelines (CPG) are not easily applicable to patients with co-morbidities, primarily in older patients3Mutasingwa D.R. Ge H. Upshur R.E. How applicable are clinical practice guidelines to elderly patients with comorbidities?.Can Fam Physician. 2011; 57: e253-e262PubMed Google Scholar, it may be important to remember before defining the treatment of patients with OA and co-morbidities the aphorism "primum non nocere". Accordingly, since in patients with co-morbidities the effect of all oral drugs has been classified as uncertain (except duloxetine), the appropriate oral drug to use should be among the drugs that produce less adverse effects and those who are less prone to produce a drug–drug interaction. Among the drugs listed in the 2013 OARSI recommendations, the safest drugs, almost devoid of drug–drug interactions, are the SYSADOAs chondroitin sulfate and glucosamine chloride/sulfate. The effect size for pain ranges from 0.18 to 0.75 for chondroitin sulfate and 0.17 to 0.47 for glucosamine chloride/sulfate. The symptomatic response may vary from one patient to another, but between half and two thirds of patients do respond rather satisfactorily to SYSADOAs. The use of SYSADOAs does not require gastroprotection, which is recommended for patients with moderate or high co-morbidity risks, even when NSAIDs are considered not appropriate. This recommendation for patients with moderate and high co-morbidity risk should be better explained and/or revised, because gastroprotection with proton-pump inhibitors increase cardiovascular risk, in presence or not of clopidogrel [hazard ratio 1.29 (CI, 1.21–1.37)] and aspirin [hazard ratio 1.46 (CI, 1.33–1.61)]4Charlot M. Grove E.L. Hansen P.R. Jørgensen C.H. Sørensen R. Abildstrøm S.Z. et al.Proton pump inhibitor use and risk of adverse cardiovascular events in aspirin treated patients with first time myocardial infarction: nationwide propensity score matched study.Br Med J. 2011; 342: d2690Crossref PubMed Scopus (175) Google Scholar. Gastroprotection in patients with co-morbidity risks administered NSAIDs may increase significantly the cardiovascular risks. In contrast to NSAIDs and acetaminophen, SYSADOAs may reduce cardiovascular mortality5Bell G.A. Kantor E.D. Lampe J.W. Shen D.D. White E. Use of glucosamine and chondroitin in relation to mortality.Eur J Epidemiol. 2012; 27: 593-603Crossref PubMed Scopus (56) Google Scholar. Due to the significant number of patients with OA and co-morbidity risks, from a clinical point of view, the 2013 OARSI recommendations should explicitly recommend the use for 3–6 months of SYSADOAs in elderly patients and patients with co-morbidities. Appropriateness of treatment should then be revised. It is striking to realize that the 2013 OARSI recommendations consider chondroitin sulfate and glucosamine chloride/sulfate as uncertain or not appropriate for disease modification, when RCTs have demonstrated that glucosamine6Bruyere O. Pavelka K. Rovati L.C. Gatterová J. Giacovelli G. Olejarová M. et al.Total joint replacement after glucosamine sulphate treatment in knee osteoarthritis: results of a mean 8-year observation of patients from two previous 3-year, randomised, placebo-controlled trials.Osteoarthritis and Cartilage. 2008; 16: 254-260Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar and chondroitin sulfate7Kahan A. Uebelhart D. De Vathaire F. Delmas P.D. Reginster J.Y. Long-term effects of chondroitins 4 and 6 sulfate on knee osteoarthritis: the study on osteoarthritis progression prevention, a two-year, randomized, double-blind, placebo-controlled trial.Arthritis Rheum. 2009; 60: 524-533Crossref PubMed Scopus (218) Google Scholar diminish the progression of the narrowing of the joint space width. Several meta-analyses have confirmed these reports8Hochberg M.C. Structure-modifying effects of chondroitin sulfate in knee osteoarthritis: an updated meta-analysis of randomized placebo-controlled trials of 2-year duration.Osteoarthritis & Cartilage. 2010; 18: S28-S31Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar. Supporting a disease modification effect, during an 8 years follow-up, glucosamine reduced total knee replacement by 57%6Bruyere O. Pavelka K. Rovati L.C. Gatterová J. Giacovelli G. Olejarová M. et al.Total joint replacement after glucosamine sulphate treatment in knee osteoarthritis: results of a mean 8-year observation of patients from two previous 3-year, randomised, placebo-controlled trials.Osteoarthritis and Cartilage. 2008; 16: 254-260Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar. There is preliminary evidence that 12 months treatment with chondroitin sulfate reduces total knee replacement by approximately 50% during 4 years follow-up. OARSI recommendations give a false impression on the effect of SYSADOAs as structure modifying. It is also striking that the Panel considered duloxetine as an appropriate therapy for patients with and without co-morbidities when this drug has a black box warning due to increased suicidality, in addition of a very long list of serious adverse effects, contraindications and cautions. Moreover the effect size is unknown. In summary, since recommendations on how to treat a disease and not a patient may have undesirable effects, the clinician has to be aware of the potential limitations of any treatment and the alternatives. In the case of knee OA, due to aging, obesity and the presence of co-morbidities, clinicians should be advised to start symptomatic treatment with the drugs presenting the smaller potential to harm the patient. No other authors. Author has been a consultant of WEX Pharmaceutical and has received payment for lectures from Bioibérica. 1. No other contributors, 2. No funding sources, 3. Publication funded with author's university funds. OARSI guidelines for the non-surgical management of knee osteoarthritisOsteoarthritis and CartilageVol. 22Issue 3PreviewTo develop concise, up-to-date, patient-focused, evidence-based, expert consensus guidelines for the management of knee osteoarthritis (OA), intended to inform patients, physicians, and allied healthcare professionals worldwide. Full-Text PDF Open Archive