Acetaminophen Not Superior to Placebo in Hip and Knee OA

A recent trial tested the efficacy of acetaminophen against placebo in patients with osteoarthritis (OA) of the hip and knee.

“Paracetamol (acetaminophen) is vastly recommended as the first‐line analgesic for osteoarthritis of the hip or knee,” the authors noted. “Nonetheless, past studies have not systematically reviewed and appraised the literature to investigate the effects of this drug on specific osteoarthritis sites, that is, hip or knee, or on the dose used.”

The researchers queried the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, AMED, CINAHL, Web of Science, LILACS, International Pharmaceutical Abstracts,, and the World Health Organization International Clinical Trials Registry Platform portal for randomized controlled trials that compared acetaminophen to placebo in adult hip or knee OA patients. The main outcomes included pain, function, quality of life, adverse events, withdrawals due to adverse events, serious adverse events, and abnormal liver function tests. Pain and physical function were measured using a 100-point scale, with 0 signifying no o pain or disability and 100 meaning the worst possible pain or disability.

A total of 10 trials including data on 3,541 patients were reviewed. Acetaminophen doses ranged from 1.95 g/day to 4 g/day. Most trials had only three-month follow-up. “Most trials did not clearly report [randomization] and concealment methods and were at unclear risk of selection bias,” the study authors also noted. “Trials were at low risk of performance, detection, and reporting bias.”

Acetaminophen Not Impactful at Short-term Follow-up

Three weeks’ and three months’ worth of follow-up found that acetaminophen was not significantly more effective than placebo. Acetaminophen and placebo patients reported a mean 26-point and 23-point pain reduction, respectively—an absolute reduction of 3% and relative reduction of 5%, based on seven trials with 2,355 patients. Improvements in physical function also did not significantly differ between the groups: placebo patients reported a 12-point improvement, and acetaminophen patients reported 2.9 points greater improvement than the placebo cohort— an absolute improvement of 3% and relative improvement of 5%, based on seven trials with 2,354 patients.

Eight trials provided high-quality evidence that adverse event rates did not largely differ between the groups: placebo group, 515/1,586 (325 per 1,000) versus acetaminophen group, 537/1,666 (328 per 1,000) (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.92 to 1.11). Evidence pertaining to the risk of serious adverse events, withdrawals due to adverse events, and the rate of abnormal liver function tests was only moderate quality. Based on the available data, incidence of serious adverse events were: placebo, 17/1,480 (11 per 1,000) versus acetaminophen, 28/1,729 (16 per 1,000) (RR 1.36, 95% CI 0.73 to 2.53; six trials). Rates of withdrawals due to adverse events were 65/1,000 for placebo patients and 77/1,000 for acetaminophen patients (RR 1.19, 95% CI 0.91 to 1.55; seven trials). Abnormal liver function incidence was higher in the acetaminophen cohort (70/1,000) than the placebo group (18/1,000) (RR 3.79, 95% CI 1.94 to 7.39), but the researchers noted the uncertainty of the clinical importance of this outcome. There were no quality of life data available.

The researchers wrote, “Current clinical guidelines consistently recommend paracetamol as the first‐line analgesic medication for hip or knee osteoarthritis, given its low absolute frequency of substantive harm. However, our results call for reconsideration of these recommendations.”