Responder Profile to Pharmaceutical-Grade Chondroitin Sulfate: An Analysis of the CONCEPT Trial

Olivier Bruyère, Nadia Dardenne, Anne-Françoise Donneau, Jean-Yves Reginster, Olivier Bruyère, Nadia Dardenne, Anne-Françoise Donneau, Jean-Yves Reginster

Abstract

Introduction: The recent CONCEPT study showed that 800 mg/day of pharmaceutical-grade chondroitin sulfate (CS) was superior to placebo and similar to celecoxib in reducing pain and improving function over 6 months in patients with symptomatic knee osteoarthritis (OA). We investigate, in the present study, whether a responder profile to CS could be defined (i.e., to determine a patient's profile with the best response to treatment).

Methods: Subjects from the CS group of the CONCEPT study were included in the present analysis. Within the CS group, various subgroups were created on the basis of different categories of age, sex, body mass index, Kellgren and Lawrence grade, age since the beginning of OA, and baseline level of pain (i.e., VAS) or function (i.e., Lequesne index). The nonparametric Kruskal-Wallis (KW) test was applied to compare the VAS pain/Lequesne index evolutions between the subgroups, and the Dwass, Steel, Critchlow, Fligner (DSCF) procedure was used to compute multiple comparisons. The impact of various covariates on the VAS pain/Lequesne index evolution was assessed by means of multiple regression.

Results: Across all analyses, the probability of response to CS treatment was significantly associated with the duration between the date of diagnosis and the initiation of treatment. In other words, the shorter the interval between the diagnosis and the beginning of the treatment, the higher the response for both pain and function, particularly for patients with a duration of less than 5 years compared to patients with a duration of 10 years or more. No other criteria were found to be consistently associated with the response to CS treatment.

Conclusion: The treatment of OA with CS has the highest chance of success if administered in the early stage of the disease. Further research with other clinical outcomes should be carried out prior to widespread application of these findings.

Trial registration: ClinicalTrials.gov identifier, NCT03200288.

Keywords: Chondroitin sulfate; Osteoarthritis; Pain; Responders; Treatment.

Figures

Fig. 1
Fig. 1
Changes in the 100-mm visual analogue scale (VAS) after 6 months of chondroitin sulfate treatment according to the time from the diagnosis of knee osteoarthritis

References

    1. Martel-Pelletier J, Maheu E, Pelletier JP, Alekseeva L, et al. A new decision tree for diagnosis of osteoarthritis in primary care: international consensus of experts. Aging Clin Exp Res. 2019;31(1):19–30. doi: 10.1007/s40520-018-1077-8.
    1. Jordan KM, Arden NK, Doherty M. 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(12):1145–1155. doi: 10.1136/ard.2003.011742.
    1. 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.
    1. NICE . Osteoarthritis care and management in adults: methods, evidence and recommendations. National Clinical Guideline Centre. Clinical Guidance. London: National Institute for Health and Care Excellence; 2014.
    1. Bannuru RR, Osani MC, Vaysbrot EE, et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage. 2019 doi: 10.1016/j.joca.2019.06.011.
    1. Bruyere O, Honvo G, Veronese N, et al. An updated algorithm recommendation for the management of knee osteoarthritis from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) Semin Arthritis Rheum. 2019 doi: 10.1016/j.semarthrit.2019.04.008.
    1. Bruyere O, Cooper C, Al-Daghri NM, Dennison EM, Rizzoli R, Reginster JY. Inappropriate claims from non-equivalent medications in osteoarthritis: a position paper endorsed by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) Aging Clin Exp Res. 2018;30(2):111–117. doi: 10.1007/s40520-017-0861-1.
    1. Restaino OF, Finamore R, Stellavato A, et al. European chondroitin sulfate and glucosamine food supplements: a systematic quality and quantity assessment compared to pharmaceuticals. Carbohydr Polym. 2019;222:114984. doi: 10.1016/j.carbpol.2019.114984.
    1. Honvo G, Bruyere O, Geerinck A, Veronese N, Reginster JY. Efficacy of chondroitin Sulfate in patients with knee osteoarthritis: a comprehensive meta-analysis exploring inconsistencies in randomized. Placebo-Controlled Trials Adv Ther. 2019;36(5):1085–1099. doi: 10.1007/s12325-019-00921-w.
    1. Reginster JY, 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. 2017;76(9):1537–1543. doi: 10.1136/annrheumdis-2016-210860.
    1. Pham T, van der Heijde D, Altman RD, et al. OMERACT-OARSI initiative: Osteoarthritis Research Society International set of responder criteria for osteoarthritis clinical trials revisited. Osteoarthritis Cartilage. 2004;12(5):389–399. doi: 10.1016/j.joca.2004.02.001.
    1. Tubach F, Ravaud P, Baron G, et al. Evaluation of clinically relevant changes in patient reported outcomes in knee and hip osteoarthritis: the minimal clinically important improvement. Ann Rheum Dis. 2005;64(1):29–33. doi: 10.1136/ard.2004.022905.
    1. Tubach F, Ravaud P, Baron G, et al. Evaluation of clinically relevant states in patient reported outcomes in knee and hip osteoarthritis: the patient acceptable symptom state. Ann Rheum Dis. 2005;64(1):34–37. doi: 10.1136/ard.2004.023028.
    1. Bruyere O, Honore A, Ethgen O, et al. Correlation between radiographic severity of knee osteoarthritis and future disease progression. Results from a 3-year prospective, placebo-controlled study evaluating the effect of glucosamine sulfate. Osteoarthritis Cartilage. 2003;11(1):1–5. doi: 10.1053/joca.2002.0848.
    1. Collantes-Estevez E, Fernandez-Perez C. Improved control of osteoarthritis pain and self-reported health status in non-responders to celecoxib switched to rofecoxib: results of PAVIA, an open-label post-marketing survey in Spain. Curr Med Res Opin. 2003;19(5):402–410. doi: 10.1185/030079903125001938.
    1. Weigl M, Angst F, Aeschlimann A, Lehmann S, Stucki G. Predictors for response to rehabilitation in patients with hip or knee osteoarthritis: a comparison of logistic regression models with three different definitions of responder. Osteoarthritis Cartilage. 2006;14(7):641–651. doi: 10.1016/j.joca.2006.01.001.
    1. Cooper C, Adachi JD, Bardin T, et al. How to define responders in osteoarthritis. Curr Med Res Opin. 2013;29(6):719–729. doi: 10.1185/03007995.2013.792793.
    1. Honvo G, Reginster JY, Rabenda V, et al. Safety of symptomatic slow-acting drugs for osteoarthritis: outcomes of a systematic review and meta-analysis. Drugs Aging. 2019;36(Suppl 1):65–99. doi: 10.1007/s40266-019-00662-z.
    1. Fu Y, Persson MS, Bhattacharya A, et al. Identifying placebo responders and predictors of response in osteoarthritis: a protocol for individual patient data meta-analysis. Syst Rev. 2016;5(1):183. doi: 10.1186/s13643-016-0362-x.
    1. Zhang W, Robertson J, Jones AC, Dieppe PA, Doherty M. The placebo effect and its determinants in osteoarthritis: meta-analysis of randomised controlled trials. Ann Rheum Dis. 2008;67(12):1716–1723. doi: 10.1136/ard.2008.092015.
    1. Honvo G, Bruyère O, Reginster J-Y. Update on the role of pharmaceutical-grade chondroitin sulfate in the symptomatic management of knee osteoarthritis. Aging Clin Exp Res. 2019;31(8):1163–1167. doi: 10.1007/s40520-019-01253-z.

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit