Synthesis on the clinical use of Chondroitin Sulfate in Europe

Symptomatic Slow-Acting Drugs for the treatment of Osteoarthritis (SYSADOA) are compounds which are mostly prescribed as drugs in european countries since many years, whereas they are sold as nutraceuticals in USA.

The registration of orally administered chondroitin 4&6 sulfate (CS) as a drug for the treatment of OA was first done in Switzerland in 1982 under the trade name of Condrosulf (R) for the following indication: “degenerative joint diseases, such as OA of the knee, hip, fingers”, followed by Italy (1990), France (1993), Austria (1994), Hungary 1995), Slovak Republik (1995), Czech Republic (1996), Portugal (2000), Spain (2002) whereas registration of the compound in other countries of the European community is pending; this registration profile might explain the special interest and knowledge of the european medical community in treating OA disease with this SYSADOA.

There are still open questions raised both on a regulatory-affairs perspective and some specialized subcommittees on osteoarthritis guidelines such as ACR to accept CS as a validated therapeutic tool in the treatment of osteoarthritis.

In Europe, the publication of the “EULAR Recommendations for the treatment of knee OA” in 2003 has listed oral CS as evidence 1A and strength of recommendation A which represents the highest level for a therapeutic strategy (Jordan KM et al., 2003). This publication has certainly brought a large support to the oral CS therapy for knee OA in Europe.

SYSADOA’s are intended to be used as ground therapy for osteoarthritis; these compounds are not rapidly acting agents such as NSAIDs and their clinical efficacy on algo-functional symptoms can only be demonstrated after a couple of weeks of regular intake. Interestingly, once the administration is stopped, they do show a carry-over effect of various duration, from about 3 months with the oral formulations to 6-9 months with intra-articular formulations. The main rationale behind the use of the SYSADOA therapeutic class is the reduction of NSAIDs in the overall drug management of OA disease and therefore consequently to limit the very significant risks of upper GI tract erosions, ulcers with bleeding and/or deleterious renal effects in elderly patients.

Two previous meta-analyses regarding both glucosamine and/or CS as treatment modalities for OA (Leeb BF et al., 2000; McAlindon TE et al., 2000) did provide some new evidences suggesting that these compounds could be of some help in the management strategy of painful OA disease. In addition, a recent meta-analysis confirmed these positive outcomes for oral CS (Richy F et al., 2003)

The evidence for clinical efficacy of oral CS as a drug able to significantly improve the algo-functional symptoms of OA disease does come from a set of clinical studies published a couple of years ago. Indeed, it was demonstrated that the drug was effective in knee (Bourgeois P et al., 1998; Bucsi L, Poor G, 1998; Uebelhart D et al., 1998) and finger osteoarthritis (Verbruggen G et al., 1998), whereas previous data suggested that hip OA patients could also benefit from it (Vignon et al., unpublished results). In addition, oral CS supported the comparison with NSAIDs such as diclofenac sodium in a medium/longterm clinical study in patients with knee OA (Morreale P. et al., 1996). A dose-finding study in patients with knee OA did provide strong data supporting the administration of 800 mg of CS orally which had nearly the same effects as 1200 mg/day (Pavelka K. et al. 1999), whereas the use of a sequential 3 months administration mode, twice a year was also shown to provide the same results as a continuous treament (Uebelhart et al, 2004).

Taken these important points into account, the author believes that we do have enough clinical available data supporting the view that oral CS is a valuable symptomatic treatment for OA disease. The symptomatic and functional benefits of the treatment do appear to be of delayed onset, but CS does have a significant carry-over effect which in clinical practice does allow 3-month duration therapy cycles. In addition, no serious adverse events has ever been linked with oral CS treatment which appears to be a safe and well tolerated compound.

The structure-modifying aspects of oral CS are not addressed in this abstract, but they do represent an important additional feature to support the clinical utilisation of oral CS.Bibliography:

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