LAUSR

Osteoarthritis (OA) is a progressive joint disease, that occurs frequently in the aging population and is a major cause of disability worldwide. Both glucosamine and chondroitin are biologically active molecules that are substrates for proteoglycan an essential component of the cartilage matrix. Evidence supports the use of prescription glucosamine sulfate and chondroitin as symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) with impact on OA symptoms and diseasemodifying effects in the long term. In a recent publication, ESCEO has noted that, while many studies are published on the use of SYSADOAs, the efficacy of this class, and notably of glucosamine and chondroitin, has been called into question largely due to inherent differences in the formulations employed in trials. It would appear that careless, uninformed and scientifically inaccurate analysis of the evidence base may still occur in the OA community, and a more considered approach to addressing the complexities of selected biologically active agents is required. Among glucosamine preparations, only the prescription pCGS formulation is proven to be efficacious for the treatment of OA symptoms of pain and functional impairment, and may even offer protection from disease progression in the long term. For all other glucosamine preparations, the evidence repeatedly demonstrates an effect close to zero. For chondroitin sulfate, the available evidence points towards a similar. Conclusion: Only the pharmaceutical-grade CS should be used for treatment of knee OA. Thus, it is ESCEO opinion that from careful consideration of the evidence base, judicious choice of glucosamine and chondroitin formulation is essential to maximise treatment benefit. In particular, in consideration of future research, ESCEO recommends that complex molecules with biological activity such as pCGS may be treated as “biosimilars” akin to EMA guidance for biological medicinal products, for which any other preparations must demonstrate comparability with the reference product in terms of physico-chemical, in vitro, non-clinical and clinical studies, in order to be considered suitable for substitution. In accordance with the 2010 European regulatory guideline on clinical investigation of medicinal products for OA, future clinical trials of SYSADOAs should measure the effect on symptom outcomes, pain and function, for a minimal duration of 6 months, and may determine structural changes over 2 years with JSN measurement. A placebo arm, and/or an active comparator arm must be included, as appropriate. In addition, we recommend the effect of SYSADOAs on symptom outcomes should be measured at multiple time points over 6 to 12 months to reflect a sustained clinical benefit. In the meantime, for current clinical practice we recommend using only SYSADOA formulations with proven efficacy and safety data.