Chondroitin sulfate (CS) bested placebo and proved equivalent to celecoxib for osteoarthritis (OA) of the knee in the ChONdroitin versus CElecoxib versus Placebo Trial (CONCEPT).
CONCEPT was the first trial of chondroitin to be conducted in compliance with European Medicines Agency (EMA) recommendations for investigating the efficacy of agents for symptomatic OA: a minimum 6-month duration, 2 co-primary end points evaluating pain and function, and a 3-arm design including the investigational drug, placebo, and an active control. Results were published in Annals of the Rheumatic Diseases, May 22.1
CS is classified as a SYSADOA (symptomatic slow-acting drug for Osteoarthritis). While acknowledging that some clinicians may disagree with its position, the American College of Rheumatology (ACR) conditionally recommended that patients with OA of the knee avoid CS use in their 2012 guidelines. Reasons cited by the ACR included the lack of US Food and Drug Administration (FDA)-approved prescription-quality CS formulations, several meta-analyses of studies on CS showing a high degree of heterogeneity in effect size, and results from a 2010 network analysis that failed to demonstrate a clinically relevant effect of CS, glucosamine, or a combination of the two on perceived joint pain.2
In contrast, CS is recommended for OA of the knee in guidelines from the European League Against Rheumatism (EULAR), European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO), and Osteoarthritis Research International (OARSI).3-5
In the CONCEPT study, the research team randomly assigned 604 patients older than 50 with knee OA to receive 1 tablet of CS 800 mg and 1 capsule of placebo celecoxib (CS group), 1 tablet of placebo CS and 1 capsule of celecoxib 200 mg (celecoxib group), or 1 tablet of placebo CS and 1 capsule of placebo celecoxib (placebo group). Patients took the study medications once daily for 6 months. Primary outcomes were the patient’s assessment of pain on a 100-mm Visual Analogue Scale (VAS), and scores from the Lequesne Index (LI), an index of severity for OA of the knee that integrates measures of both pain and function.
In the intention-to-treat (ITT) population, pain reduction at day 182 as indicated by reductions in VAS scores was greater in the CS and celecoxib groups (−42.6 mm and −39.55 mm, respectively) than in the placebo group (−33.3 mm) (P =.001 for CS and P =.009 for celecoxib).
The difference in VAS between CS and celecoxib was not statistically significant. A similar trend was noted with LI, in which improvements were greater in patients receiving CS or celecoxib. Patients in the CS, celecoxib, and placebo groups showed a reduction in LI of −4.7, −4.6, and −3.7, respectively (P =.023 for CS and P =.015 for celecoxib). No difference was noted between the CS and celecoxib groups.
Summary & Clinical Applicability
In an email interview, lead investigator Jean-Yves Reginster, MD, PhD, told Rheumatology Advisor that the CONCEPT study “paves the way for a new approach in the management of osteoporosis.” In contrast to usual treatments, pharmaceutical-grade SYSADOAs are almost free of adverse effects.
“Whereas paracetamol/acetaminophen is frequently recommended as a first-line treatment for osteoarthritis, several recent publications report a low effect-size, or magnitude of the effect, for this medication. Also, several investigations have raised a red flag suggesting that paracetamol/acetaminophen is associated with an increased overall mortality and with a substantial number of adverse events, at the level of the kidney, cardiovascular system, or liver.”
Dr Reginster cautioned, however, that the results should not be extrapolated to CS supplements sold over the counter. “Pharmaceutical grade chondroitin differs from other preparations by a specific pharmacokinetics/pharmacodynamics profile allowing high concentration of the active substance inside the joint,” he stated.
IBSA Institut Biochimique SA, Pambio- Noranco, Switzerland, a pharmaceutical company marketing Chondroitin Sulfate, was the sponsor of the CONCEPT study.
- Reginster J-Y, Dudler J, Blicharski T, Pavelka K. Pharmaceutical-grade chondroitin sulfate is as effective as celecoxib and superior to placebo in symptomatic knee osteoarthritis: the ChONdroitin versus CElecoxib versus Placebo Trial (CONCEPT). Ann Rheum Dis. May 2017. doi:10.1136/annrheumdis-2016-210860
- Hochberg MC, Altman RD, April KT, et al. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res. 2012;64(4):465-474. doi:10.1002/acr.21596
- Jordan KM, Arden NK, Doherty M, et al. EULAR Recommendations 2003: an evidence based approach to the management of knee osteoarthritis: Report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Ann Rheum Dis. 2003;62:1145-1155. doi:10.1136/ard.2003.011742
- Bruyère O, Cooper C, Pelletier J-P, et al. A consensus statement on the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) algorithm for the management of knee osteoarthritis–from evidence-based medicine to the real-life setting. Semin Arthritis Rheum. 2016;45(4 Suppl):S3-S11. doi:10.1016/j.semarthrit.2015.11.010
- McAlindon TE, Bannuru RR, Sullivan MC, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis Cartilage. 2014;22:363-388. doi:10.1016/j.joca.2014.01.003