Figure 1. Treatment Sequences for OA Management.

The figure depicts the treatment sequences through which subjects can progress. Each year while on a regimen, subjects are evaluated for sufficient pain relief, discontinuation, or major toxicity. If the regimen fails to provide pain relief or the subject experiences a major toxicity or discontinuation, the subject is removed from the regimen and progresses to the next regimen in the sequence. Conservative therapy includes non-steroidal anti-inflammatory drugs, physical therapy, and corticosteroid injections. Following conservative therapy, subjects on the opioid-sparing strategy may either undergo TKA immediately or enter a waiting period (not depicted), taking acetaminophen as needed for pain relief, until deemed eligible and accept surgical intervention. Subjects on opioid-based strategies progress to tramadol following conservative therapy; those on the tramadol + oxycodone sequence may advance to oxycodone if tramadol fails to provide sufficient pain relief in the first or any subsequent year of tramadol treatment. Following treatment with opioids, subjects on opioid-based strategies may progress to total knee arthroplasty or take acetaminophen as needed (not depicted) until eligible and willing to undergo surgical intervention. Death may occur at any stage throughout the treatment sequence. Abbreviations: NSAIDs, non-steroidal anti-inflammatory drugs; PT, physical therapy; TKA, total knee arthroplasty; PRN, as needed.