Objective
Summarize the comparative effectiveness of oral non-steroidal anti-inflammatory drugs (NSAIDs) and opioids in reducing knee osteoarthritis (OA) pain.
Methods
Two reviewers independently screened reports of randomized controlled trials, published in English between 1982 and 2015, evaluating oral NSAIDs or opioids for knee OA. Included studies were at least eight weeks duration, conducted in Western Europe, the Americas, New Zealand, or Australia, and reported baseline and follow-up pain using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain subscale (0–100, 100-worst). Effectiveness was evaluated as reduction in pain, accounting for study dropout and heterogeneity.
Results
27 treatment arms (9 celecoxib, 4 non-selective NSAIDs [diclofenac, naproxen, piroxicam], 11 less potent opioids [tramadol], and 3 potent opioids [hydromorphone, oxycodone]) from 17 studies were included. NSAID and opioid studies reported similar baseline demographics and efficacy withdrawal rates; NSAID studies reported lower baseline pain and toxicity withdrawal rates. Accounting for efficacy-related withdrawals, all drug classes were associated with similar pain reductions (NSAIDs: −18; less potent opioids: −18; potent opioids: −19). Meta-regression did not reveal differential effectiveness by drug class but found that study cohorts with a higher proportion of male subjects and worse mean baseline pain had greater pain reduction. Similarly, results of the network meta-analysis did not find a significant difference in WOMAC Pain reduction for the three analgesic classes.
Conclusion
NSAIDs and opioids offer similar pain relief in OA patients. These data could help clinicians and patients discuss likely benefits of alternative analgesics.
Objective
To estimate the lifetime risk of knee osteoarthritis (OA) and total knee replacement (TKR) in persons sustaining ACL tear by age 25.
Methods
We used the Osteoarthritis Policy Model to project the cumulative incidence of symptomatic knee OA requiring TKR in persons with: 1) no prevalent or incident injury; 2) isolated ACL tear, surgically treated; 3) isolated ACL tear, non-operatively treated; or 4) prevalent history or surgically treated ACL and meniscal tear (MT). We estimated MT prevalence and incidence and increased risk of knee OA associated with ACL injury and MT from published literature. We conducted a range of sensitivity analyses to examine the impact of uncertainty in input parameters.
Results
Estimated lifetime risk of symptomatic knee OA was 34% for the cohort with ACL injury and MT, compared to 14% for the no injury cohort. ACL injury without MT was associated with a lifetime risk of knee OA between 16%–17%, depending on ACL treatment modality. Estimated lifetime risk of TKR ranged from 6% in the no injury cohort to 22% for the ACL injury and MT cohort. Subjects in the ACL injury and MT cohort developed OA ~1.5 years earlier (55.7 vs. 57.1) and underwent TKR ~2 years earlier (66 vs. 68) than the cohort without knee injuries.
Conclusions
Sustaining ACL injury early in adulthood leads to greater lifetime risk and earlier onset of knee OA and TKR; concomitant MTs compound this risk. These data provide insight into the impact of sustainable injury prevention interventions in young adults.
Objective
To evaluate long-term clinical and economic outcomes of naproxen, ibuprofen, celecoxib or tramadol for OA patients with cardiovascular disease (CVD) and diabetes.
Design
We used the Osteoarthritis Policy Model to examine treatment with these analgesics after standard of care -- acetaminophen and corticosteroid injections -- failed to control pain. NSAID regimens were evaluated with and without proton pump inhibitors (PPIs). We evaluated over-the-counter (OTC) regimens where available. Estimates of treatment efficacy (pain reduction, occurring in ~ 57% of patients on all regimens) and toxicity (major cardiac or gastrointestinal toxicity or fractures, risk ranging from 1.09% with celecoxib to 5.62% with tramadol) were derived from published literature. Annual costs came from Red Book Online®. Outcomes were discounted at 3%/year and included costs, quality-adjusted life expectancy, and incremental cost-effectiveness ratios (ICERs). Key input parameters were varied in sensitivity analyses.
Results
Adding ibuprofen to standard of care was cost saving, increasing QALYs by 0.07 while decreasing cost by $800. Incorporating OTC naproxen rather than ibuprofen added 0.01 QALYs and increased costs by $300, resulting in an ICER of $54,800/QALY. Using prescription naproxen with OTC PPIs led to an ICER of $76,700/QALY, while use of prescription naproxen with prescription PPIs resulted in an ICER of $252,300/QALY. Regimens including tramadol or celecoxib cost more but added fewer QALYs and thus were dominated by several of the naproxen-containing regimens.
Conclusions
In patients with multiple comorbidities, naproxen- and ibuprofen-containing regimens are more effective and cost-effective in managing OA pain than opioids, celecoxib or standard of care.
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