Combination Therapy for Knee Osteoarthritis Inferior to Placebo

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The primary outcome was mean change in VAS global pain score after 6 months.
The primary outcome was mean change in VAS global pain score after 6 months.

There were no significant differences in pain reduction and functional improvements for patients with knee osteoarthritis (OA) receiving combination chondroitin sulfate and glucosamine sulfate compared with a control group of knee OA patients receiving only placebo, according to recent research published in Arthritis & Rheumatology.1 

“The objective of our study was to assess the efficacy and safety of combination therapy with chondroitin sulfate and glucosamine sulfate (CS + GS) compared with placebo in patients with symptomatic knee OA,” Gabriel Herrero-Beaumont, MD, PhD, from the Rheumatology Department and Joint and Bone Research Unit at Fundación Jiménez Díaz in Madrid, Spain, told Rheumatology Advisor in an interview. “Intriguingly, CS+GS combination therapy was inferior to placebo in the reduction of joint pain.”

Dr Herrero-Beaumont and colleagues performed a randomized, double-blinded, placebo-controlled multicenter study consisting of 164 patients with knee OA and moderate to severe knee pain. Patients had Kellgren/Lawrence grade 2 or grade 3 radiographic knee OA and a mean global Visual Analog Scale (VAS) pain score of 62.1 ± 11.3 mm on a VAS 100-mm scale.

The researchers randomly assigned patients to receive daily combined CS (1200 mg) and GS (1500 mg) in an oral dose or a placebo for 6 months. The primary outcome was mean change in VAS global pain score after 6 months, with secondary outcomes including mean changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total scores, WOMAC pain and function subscale scores, use of rescue medication, investigator's global assessment of disease activity, and responder rates for the Outcome Measures in Rheumatology (OMERACT)–Osteoarthritis Research Society International (OARSI) 2004 response.

“Both placebo treatment and CS/GS combination treatment improved to a similar extent [for] the total WOMAC score as well as the pain and function WOMAC subscale scores, both in the modified intent-to-treat (mITT) population and in the per-protocol completers,” Dr Herrero-Beaumont said.

Over 6 months, the mITT group had a 19% reduction in joint pain (mean VAS global pain score = −11.8 ± 2.4 mm) compared with a 33% reduction in joint pain (mean VAS global pain score = −20.5 ± 2.4 mm) in the placebo group, according to the abstract. Dr Herrero-Beaumont and colleagues noted there was no significant difference seen in per-protocol completers, but there was a 14.2% peak-group difference in global pain score at 6 months (8.7 mm; P <.03). There were also similar total WOMAC and WOMAC pain and function subscale scores in the mITT and per-protocol completer groups.

“Neither the OMERACT–OARSI responder rate nor the frequency of rescue medication use differed between the treatment groups,” Dr Herrero-Beaumont said. “Severe adverse events were uncommon and equally distributed.”

Summary & Clinical Applicability 

“[T]he results of this trial demonstrate a lack of superiority of CS/GS combination therapy over placebo in terms of reducing joint pain and functional impairment in patients with symptomatic knee OA over 6 months,” Dr Herrero-Beaumont told Rheumatology Advisor. “Further research might fully elucidate the suitability of CS/GS combination therapy in patients with OA.”

In a related commentary, Jonathan S. Coblyn, MD, from the NEJM Journal Watch General Medicine board, said that patients continue to receive chondroitin/glucosamine treatment without studies showing the treatment provides a benefit.

“Although this result might be explained by limited statistical power or inadequate dosing of chondroitin/glucosamine, the most likely explanation is that chondroitin/glucosamine really is no better than placebo for this patient population,” Dr Coblyn said.

Study Limitations

  • The study sample was small, although adequate enough to demonstrate nonsuperiority of the active treatment arm.
  • The analgesic effect conferred by the use of a pain killer (acetaminophen) as a rescue medication – which is permitted in all OA clinical trials – could be a confounding factor.
  • A higher number of dropouts due to adverse events was detected in the CS/GS combination group, which may interfere with the patient's global pain assessment.
  • Failure to meet therapeutic goals could be attributed to the dosage regimen used in this study. In previous studies, combined CS and GS was administered twice per day, whereas the same total dose was administered only once daily in the current study.

Disclosures

The authors report that Tedec Meiji Farma (Madrid, Spain) provided the study drug but had no role in the study design or in the collection, analysis, or interpretation of the data, the writing of the manuscript, or the decision to submit the manuscript for publication. They added that publication of the study was not contingent upon approval by Tedec Meiji Farma.

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Reference

  1. Roman-Blas JA, Castañeda S, Sánchez-Pernaute O, et al. Combined treatment with chondroitin sulfate and glucosamine sulfate shows no superiority over placebo for reduction of joint pain and functional impairment in patients with knee osteoarthritis: a six-month multicenter, randomized, double-blind, placebo-controlled clinical trial. Arthritis Rheumatol. 2017;69(1):77-85. doi: 10.1002/art.39819
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