Trajectories and risk profiles of pain in persons with radiographic, symptomatic knee osteoarthritis: data from the osteoarthritis initiative.

BACKGROUND: Little is known about the temporal evolution of pain severity in persons with knee osteoarthritis (OA). We sought to describe the pain trajectory over 6 years in a cohort of subjects with radiographic, symptomatic knee OA. METHODS: We used data from the Osteoarthritis Initiative (OAI), a multi-center, longitudinal study of subjects with diagnosed radiographic evidence of knee OA. Pain was assessed at baseline and annually for 6 years. Our analysis cohort included subjects with symptomatic knee OA at baseline, defined as baseline Kellgren-Lawrence (KL) score ≥2 with Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score >0. We used group-based trajectory modeling to identify distinct patterns of pain progression over a 6-year follow-up. Factors examined included sex, race, education, comorbidities, age, body mass index (BMI), alignment, KL grade, and depression. RESULTS: We used data from 1753 OAI participants with symptomatic knee OA. Mean baseline WOMAC pain score was 26.5 (0-100, 100=worst) with standard deviation (SD) 19. Group-based trajectory modeling identified five distinct pain trajectories; baseline pain scores for each ranged from 15 to 62. None of the trajectories exhibited substantial worsening. One fifth of subjects in the two trajectories with the greatest pain underwent total knee replacement (TKR) over follow-up. Higher KL grade, obesity, depression, medical comorbidities, female sex, non-white race, lower education, and younger age were associated with trajectories characterized by greater pain. CONCLUSION: We found that knee pain changes little, on average, over 6 years in most subjects. These observations suggest knee OA is characterized by persistent rather than inexorably worsening symptoms.

Pharmacologic regimens for knee osteoarthritis prevention: can they be cost-effective?

OBJECTIVE: We sought to determine the target populations and drug efficacy, toxicity, cost, and initiation age thresholds under which a pharmacologic regimen for knee osteoarthritis (OA) prevention could be cost-effective. DESIGN: We used the Osteoarthritis Policy (OAPol) Model, a validated state-transition simulation model of knee OA, to evaluate the cost-effectiveness of using disease-modifying OA drugs (DMOADs) as prophylaxis for the disease. We assessed four cohorts at varying risk for developing OA: (1) no risk factors, (2) obese, (3) history of knee injury, and (4) high-risk (obese with history of knee injury). The base case DMOAD was initiated at age 50 with 40% efficacy in the first year, 5% failure per subsequent year, 0.22% major toxicity, and annual cost of $1,000. Outcomes included costs, quality-adjusted life expectancy (QALE), and incremental cost-effectiveness ratios (ICERs). Key parameters were varied in sensitivity analyses. RESULTS: For the high-risk cohort, base case prophylaxis increased quality-adjusted life-years (QALYs) by 0.04 and lifetime costs by $4,600, and produced an ICER of $118,000 per QALY gained. ICERs >$150,000/QALY were observed when comparing the base case DMOAD to the standard of care in the knee injury only cohort; for the obese only and no risk factors cohorts, the base case DMOAD was less cost-effective than the standard of care. Regimens priced at $3,000 per year and higher demonstrated ICERs above cost-effectiveness thresholds consistent with current US standards. CONCLUSIONS: The cost-effectiveness of DMOADs for OA prevention for persons at high risk for incident OA may be comparable to other accepted preventive therapies.

Studies of pain management in osteoarthritis: bedside to policy.

OBJECTIVE: Osteoarthritis (OA) is a debilitating chronic condition requiring long-term treatment of pain and functional impairment. Our objective was to characterize studies addressing management of OA-related pain with respect to the breadth of interventions, trial duration and size, outcome measures, and funding sources. DESIGN: We identified studies focused on 'pain' and 'osteoarthritis' from ClinicalTrals.gov and abstracted data on study status, sample size, design, funding source, duration, outcomes measured, and interventions evaluated. We examined associations among intervention type, funding source, sample size, duration, and outcomes measured. RESULTS: We identified 287 registered studies, of which 69% investigated pharmacologic interventions, 11% behavioral interventions, and 5% surgical procedures or devices, while the remainder examined other types of interventions. Eighty-seven percent evaluated knee OA. The average sample size was 290 subjects and average study duration was 7.4 months, with 52% using durations ≤3 months and 21% ≥12 months. Industry funded 64% of studies, either fully or partially. Of 180 completed studies, 139 were pharmacologic studies. Of these, 34 (24%) posted results to the registry. Among the studies funded by industry, 60% had durations ≤3 months as compared with 36% among non-industry funded studies (P < 0.0001). Behavioral intervention trials tended to be of longer duration than pharmacologic trials and were less likely to be funded by industry. CONCLUSION: Over half of OA pain studies and >80% of those funded by industry used trial durations of less than 6 months. Future studies should take into consideration the need for long-term pain management for OA when designing trial protocols.