The Lancet on May 21, 2016, has published an appreciation and critique by Nicholas Moore and his team at the University of Bordeaux in France on the new research conducted by Bruno da Costa on how NSAIDs and paracetamol (acetaminophen) are being used to treat osteoarthritis.
Nicholas Moore called the research ‘excellent’ but wondered on why some of the non-steroidal anti-inflammatory drugs (NSAIDs) were analyzed while some were left out. He hypothesized that the reason could be that no recent research on those drugs has been conducted and the ones that did were probably too small to add in the analysis. He added that these ‘omissions were unfortunate’ as those drugs could be much cheaper and more effective than the ones analyzed.
On comparison of effectiveness of the drugs celecoxib and diclofenac, he added that celecoxib given at 200 mg/day becomes dose equipotent to diclofenac (150mg/day) at 300 mg/day so no wonder it is not as effective.
He also took note that the results may not be representative of a general practice setting as the NSAIDs were given to participants of the studies for 6-12 weeks daily whereas they are not needed on long term daily basis. NSAIDs are only needed for ‘acute flares or to surmount the usual pain’ osteoarthritis.
Moore, head of Pharmacology Department at the University of Bordeaux and an advisor for EMEA project, suggested that the researchers should now consider using need based approach of administration rather daily doses while conducting research into effectively and efficacy of the NSAIDs.
Moore also commented that the finding that paracetamol does not help in osteoarthritis pain management at any dose was not shocking and reiterated that scientists need to focus their energies to conduct research into new painkillers, perceived benefits of paracetamol and risks of NSAIDs to provide better treatment options for osteoarthritis.
The Study: Pain In Osteoarthritis
The original research meta-analysis by Bruno da Costa and colleagues was published on May 17, 2016, in journal the Lancet.
The study concluded that paracetamol did not meet the minimum standard of clinical effectiveness for reducing pain in patients with knee and hip osteoarthritis (irrespective of the dose) and among NSAIDs the most effective drug for this function was diclofenac at 150mg/day and etoricoxib at 30-60 mg/day, with 95-100% chance of improving pain.
The review showed that the highest ranking effective dose of paracetamol was 3g/day and was linked to only 21% chance of pain improvement. Doses less than 2g had only 4% chance to help with the pain.
The researchers wrote, “We see no role for single-agent paracetamol for the treatment of patients with osteoarthritis irrespective of dose.”
National Health Service (NHS) commented that though indirect comparison is often less accurate and reliable than direct comparison, lack of such comparisons leave us with indirect ones which are ‘the best we have to go on for now’.
The research was designed as a meta-analysis of data taken from 74 randomized control trial (RCTs) which compared the drugs under study with placebos to see effects in patients’ pain and degree of improvement in joint movement. Drugs like paracetamol, ibuprofen, diclofenac, naproxen, and both celecoxib and etoricoxib (commonly called COX 2 inhibitors) were analyzed.
The data was taken from 58,556 people with average follow-up of 12 weeks. A statistical technique called network meta-analysis was used which allows indirect and direct comparison of the drugs. The drugs in this study were analyzed by indirect method.
Funded by the Swiss National Science Foundation and Arco Foundation, the research was conducted by the scientists from Switzerland and Canada.
An older contradictory study published on the same subject however concluded that the pain relief and satisfaction of patients treated with paracetamol may be as great as the ones treated with NSAIDs. However, a study published in the British Medical Journal arrived at the same conclusion in 2015 and found that paracetamol ‘provides minimal short term benefit for people with osteoarthritis’.
In United States acetaminophen or paracetamol is used as first line drug for the pain management in patients with osteoarthritis. The drug is commonly referred to as Tylenol in America. Arthritis Research UK, along with NICE, also currently recommends the use of paracetamol for treatment of osteoarthritis.
However in 2014, NICE warned against routine use of the drug when new research linked the higher doses of the drug with gastrointestinal, cardiovascular and renal adverse events. NICE added at the time, ‘Be aware of the potential side effects and limited benefit’.
Osteoarthritis (OA) is the most common joint disease. Knee OA is the major cause of disability in people aged more than 65 years. The pain in osteoarthritis may be due to synovial inflammation and may also arise from subchondral bone, the joint capsule ligaments, tendons, entheses and periarticular muscle spasm.