In a recent meta-analysis, the researchers have found that celecoxib and glucosamine sulphate improve pain in knee osteoarthritis. However, the present analysis of 47 randomised controlled trials also shows uncertainty around estimates of effect size for change in pain for all comparisons with placebo. The study has been published in The Journal of the American Medical Association.
Dario Gregori, Ph.D., from the University of Padova in Italy, and colleagues reviewed and analyzed long-term (≥12 months) outcomes from randomized clinical trials (RCTs) of medications for knee osteoarthritis. Data were included from 47 RCTs with 22,037 patients.The researchers assessed 33 pharmacological interventions for knee osteoarthritis (mean age, 55-70 years; n=22,037. Of the 33 interventions, 31 were studied for pain, 13 for physical function, and 16 for joint structure, and the duration of trials ranged from 1 to 4 years.
Associations for decrease in pain were found for nonsteroidal anti-inflammatory drug (NSAID), celecoxib (standardised mean difference [SMD], −0.18; 95% credibility intervals [CrI], −0.35 to −0.01) and for a sympathetic slow-acting drug, glucosamine sulphate (SMD, −0.29; 95% CrI, −0.49 to −0.09). Both drugs were associated with large uncertainty in the estimates compared with placebo.
When the data were analysed as a mean difference on a normalised scale from 0 to 100, glucosamine sulphate continued to be associated with a decrease in pain. Additionally, when researchers excluded studies at high risk of bias, glucosamine sulphate was still associated with improvement in pain (SMD, −0.29; 95% CrI, −0.49 to −0.10; mean difference, −4.10; 95% CrI, −7.14 to −1.12). Improvement in joint space narrowing was also noted with glucosamine sulphate (SMD, −0.42; 95% CrI, −0.65 to −0.19), chondroitin sulphate (SMD, −0.20; 95% CrI, −0.31 to −0.07), and strontium ranelate (SMD, −0.20; 95% CrI, −0.36 to −0.05)
The surface under the cumulative ranking (SUCRA) curve values indicates that glucosamine sulphate had the highest probability for being the best long-term treatment compared with celecoxib (SUCRA, 0.92 vs 0.79). Similarly, glucosamine sulphate had the highest probability to be the best treatment for physical function.
The authors stated, “glucosamine sulphate was consistently associated with improvement in pain, physical function, and joint space narrowing”. Owing to the uncertainties observed in the effect sizes, they suggested for a need of larger randomised controlled trials.
Even though osteoarthritis is a chronic and progressive disease, pharmacological agents are mainly studied over short-term periods, resulting in unclear recommendations for long-term disease management.