Naproxen- and ibuprofen-containing regimens are more effective, and also cost-effective, than tramadol and celecoxib for patients with knee osteoarthritis who also have cardiovascular disease and diabetes, a new model of benefits and costs has concluded.

Writing in Osteoarthritis and Cartilage, a team based at the Brigham and Women’s Hospital at Harvard Medical School, analysed the analgesic efficacy, risk of side effects and the associated costs for 14 different regimens.

The ‘standard of care’ included physical therapy, paracetamol and corticosteroid injections, while the other regimens included combinations of naproxen, ibuprofen, proton pump inhibitors (PPIs), celecoxib and tramadol.

Naproxen, for example, was estimated to cause major GI toxicity in 1.59% of this patient group in the first year of treatment and associated mortality of 11.60%, but the addition of PPIs reduced the risk of major GI events to 0.56%.

The modelling calculated that adding ibuprofen to standard care was cost saving, adding a fraction of a quality-adjusted life year while saving $800.

Use of naproxen was also cost-effective, with less toxicity.

“Regimens including tramadol or celecoxib cost more but added fewer QALYs,” the researchers said.

“Pain management in knee OA patients with multiple comorbidities is costly and requires a

delicate balance of pain relief and toxicity.

“Tramadol’s higher rates of toxicity and discontinuation led to smaller gains in QALYs than

NSAID regimens while celecoxib’s higher cardiac toxicity led to smaller gains than most naproxen regimens.”

Celecoxib regimens were most costly.

Despite the fact that comorbidities affect up to 40% of knee OA patients, existing treatment guidelines are inconsistent and the role of opioids is especially unclear.

“We urgently need studies on the long-term efficacy, toxicity and costs of analgesics,” the researchers said.

“From a clinical perspective, our findings challenge the reluctance of physicians to use non-selective NSAIDs in patients with multiple comorbidities.

They also indicated that: “No treatment, tramadol and celecoxib are poor choices in this setting, whereas naproxen (prescription or OTC) with PPI OTC or prescription naproxen alone can be recommended as cost-effective regimens in older patients with knee OA and cardiovascular disease and diabetes” they concluded.