Osteoarthritis: Review of Medications for Long Term Pain Control

PainRelief.com Interview with:
Dr. RovatiLucio Rovati, M.D.
Department of Medicine and Surgery
School of Medicine
Monza – Italy

PainRelief.com: What is the background for this study?  

Response: This is the first meta-analysis in osteoarthritis (OA) that takes into account only long-term (defined as at least 12-month duration) clinical trials. In addition, this is a network meta-analysis, i.e. we could take into account virtually all available medications and all experimental pharmacological treatments with published studies.

Analysis of long-term data is particularly important because OA is a chronic and progressive disease, but most medications are studied mainly for their short-term effects, i.e. mostly up to 3-6 months only. This creates troubles when physicians have to perform a chronic management of their patients.

MedicalResearch.com: What are the main findings?

Response: Although we were able to retrieve 47 trials in approximately 22,000 knee osteoarthritis patients, only a minority of the 33 interventions identified, provided repeated evidence, i.e. were studied in at least 2 randomized clinical trials. For this reason, there is large uncertainty around the estimates of effect size for change in the primary endpoint (pain) for all medications vs. placebo.

However, two medications emerged as statistically significant:

  • The NSAID celecoxib, but the effect size was small and was not significant anymore when only high-quality studies (70% of the total) were analyzed, or other analyses were performed.
  • Prescription-quality glucosamine sulfate, i.e. only the product approved as a drug in Europe and elsewhere in a specific (and patented, as far as I know) formulation, which is also available in the USA as a branded nutraceutical. It is important to note that all other dietary supplement glucosamines (consisting of glucosamine hydrochloride, with or without the addition of sodium sulfate to get a false label of glucosamine “sulfate”, i.e. all products excluding the prescription or prescription-quality formulation) were devoid of any effects, similarly to their combination with chondroitin sulfate.
  • Prescription glucosamine sulfate was also the only medication with a statistically significant association with improvement in physical function. Three medications reached a significant association with improved joint structure: again prescription glucosamine sulfate, and then chondroitin sulfate and strontium ranelate, an osteoporosis drug available only in Europe and under restricted use due to safety issues: however, none of the latter two were associated with improved symptoms.

PainRelief.com: What should readers take away from your report?

Response: Physicians should be aware that the clinical trial evidence to support long-term pharmacological management of knee osteoarthritis is scarce. None of the medications was significantly associated with long-term improvement in pain, except celecoxib and prescription-grade glucosamine sulfate. However, the effect size of celecoxib was not clinically relevant and not significant in high quality trials. In addition, safety concerns remain that discourage use of this and any other NSAID beyond short-term use. Prescription glucosamine sulfate (but not other glucosamine formulations) was significantly associated with improvement in pain (clinically significant, although not large), physical function and joint structure.
Further long-term clinical trials of medications in knee OA are needed.

PainRelief.com: What recommendations do you have for future research as a result of this work?

Response: Long-term clinical trials of old and new medications for osteoarthritis are urgently needed. Less emphasis should be put on the short-term evidence, that makes interpretation difficult when dealing with patients in the common clinical practice.

PainRelief.com: Is there anything else you would like to add? 

Response: I am professor of Clinical Pharmacology at the University of Milano – Bicocca, School of Medicine, Milano, Italy. Moreover, I am Chief Scientific Officer of Rottapharm Biotech, an Italian biotech start-up with no current revenues and devoted to the discovery of new medications in OA, other rheumatologic diseases and in other areas.

My conflicts of interest, as well as those of my co-authors are listed at the end of the article. My background is M.D. with a specialty in Clinical Pharmacology.
This was a collaboration between my clinical research team and a group of experienced statisticians from the University of Padova in Italy.


Gregori D, Giacovelli G, Minto C, et al. Association of Pharmacological Treatments With Long-term Pain Control in Patients With Knee Osteoarthritis: A Systematic Review and Meta-analysis. JAMA. 2018;320(24):2564–2579. doi:10.1001/jama.2018.19319


The information on PainRelief.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.


Last Updated on April 15, 2020 by PainRelief.com