05.05.2016
by Wayne Kuznar
Contributing Writer

Incorporating opioids into the treatment of knee osteoarthritis (OA) was not cost-effective as the drugs had a negative impact on the long-term outcome in patients destined for total knee arthroplasty (TKA), researchers reported.

Tramadol with or without oxycodone increased cost and decreased quality-adjusted life-years (QALYs) compared with an opioid-sparing strategy in knee OA patients with persistent pain despite conservative treatment, according to Elena Losina, PhD, of Brigham and Women’s Hospital and Harvard University in Boston.

They conducted a cost-effectiveness analysis using a validated computer micro-simulation known as Osteoarthritis Policy Model, which models the natural history and management of OA.

The incremental cost-effectiveness ratio (ICER) of tramadol in the model was sensitive to its effect on TKA outcomes, they reported in Arthritis Care & Research.

Diminished TKA efficacy following the use of opioids has been reported previously, they noted.

“Under the base case assumptions, we found that neither tramadol nor tramadol followed by oxycodone is cost-effective in these patients,” the authors wrote. “These results are highly dependent on the effect of opioid use on TKA outcomes; when we assumed opioid use prior to TKA had no effect on early revision rates or pain outcomes, tramadol emerged as cost-effective, with ICERs below $50,000/QALY.

“We further found that incorporating tramadol, but not tramadol followed by oxycodone, into knee OA management may be a cost-effective option in patients unwilling or unable to undergo surgical interventions,” they added.

Three treatment strategies were evaluated in the model in patients with knee OA, and no comorbid conditions, whose pain persisted after conservative treatment with nonsteroidal anti-inflammatory drugs, physical therapy, and corticosteroid injections. These were an opioid-sparing strategy, tramadol alone, and tramadol followed by oxycodone in those in whom tramadol provided insufficient pain relief.

First-year costs for tramadol and oxycodone used in the model were $600 and $2,300, respectively. Annual costs included the cost of the analgesic, physician visits, and, for oxycodone, diversion of prescribed medication to illicit use. Two annual office visits for patients on tramadol and six for oxycodone were incorporated into the costs. An initial cost of $20,500 for TKA was applied.

In the base case, tramadol-treated patients remained on tramadol for an average of 2.4 years and oxycodone-treated patients for an average of 2.9 years.

Compared with the opioid-sparing strategy, the tramadol and tramadol plus oxycodone strategies delayed TKA by 7 and 9 years, respectively, reducing primary TKA utilization by 4% and 10% and revision TKA use by 23% and 39%.

The opioid-sparing strategy led to a discounted quality-adjusted life expectancy (QALE) of 11.49 QALYs and lifetime cost of $130,300. Incorporating tramadol into the treatment decreased QALE by 0.01 QALYs compared with the opioid-sparing strategy while increasing the cost to $131,000.

The tramadol plus oxycodone strategy was associated with a discounted QALE of 11.49 and cost of $134,900. Because the tramadol and tramadol plus oxycodone strategies reduced QALE while increasing cost compared with the opioid-sparing strategy, they were dominant in the model, the authors reported.

They also reported that when TKA was not a treatment option, the opioid-sparing strategy was associated with a QALE of 11.11 QALYs and cost of $118,000.

Incorporating tramadol resulted in an ICER of $39,600/QALY compared with the opioid-sparing strategy, and adding oxycodone lead to an ICER of $116,800/QALY compared with tramadol alone.

Also, the tramadol plus oxycodone strategy had ICERs above $150,000/QALY under all variations in toxicity, late pain failure, and effect on TKA outcomes.

Increasing the duration of tramadol effectiveness by 50% led to an ICER of $85,300/QALY, they noted.

When opioid use prior to TKA was assumed to have no influence on TKA outcomes, tramadol maintained ICERs below $50,000/QALY under all scenarios evaluated.

Finally, at a willingness-to-pay threshold of $100,000/QALY, tramadol had a 32% likelihood of being cost-effective when the age of opioid initiation was 60 years; the probability decreased to 9% when the age of treatment initiation increased to 70 years.

“This analysis shows for the first time that the longterm clinical benefit of opioids is highly dependent on their effects on TKA outcomes,” the authors wrote. “This finding underscores the need for research on the influence of opioids on TKA outcomes.”

From a financial perspective, “both opioid-based strategies led to higher costs without providing additional benefits, unless patients were unwilling or unable to undergo TKA later.” They added that diversion of opioids is another risk of their use.

Study limitations include estimates of longterm efficacy and toxicity informed by expert clinician opinion and inclusion into the model of only patients without comorbid conditions.

“Pharmacologic analgesics are generally more toxic in individuals of poorer health; thus, our results should not be generalized to the entire OA population,” Losina and colleagues wrote.

• Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

LAST UPDATED 05.06.2016