Comparing the Efficacy of Topical Ketorolac and Diclofenac in the Management of Knee Osteoarthritis: A Double-blind Randomized Clinical Trial
Farahnaz Hoseinzadeh, Farhad Mohammadi, Mehdi Rostami, Hamidreza Soltani, Hamidreza Bashiri, Mojtaba Mojtahedzadeh, Adeleh Sahebnasagh, Fatemeh SaghafiIntroduction:
Osteoarthritis (OA) is a common whole-joint disorder associated with cartilage damage, synovial inflammation, pain, and functional limitation. Although topical NSAIDs are frequently used to control knee OA symptoms because of their lower systemic exposure, direct head-to-head evidence comparing individual topical NSAID formulations remains limited. This study aimed to compare the clinical efficacy and safety of a 2% topical ketorolac formulation with standard topical diclofenac 1% cream in patients with symptomatic knee OA.
Methods:
In this double-blind randomized clinical trial, 51 patients with radiographically confirmed primary knee osteoarthritis (Kellgren-Lawrence grade 1-3) were randomly assigned to receive either topical ketorolac 2% cream or diclofenac 1% cream, applied three times daily for 14 days; 50 patients completed follow-up and were included in the final analysis. Primary outcomes included changes in pain intensity measured by the Visual Analog Scale (VAS) and functional status assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcomes included quality of life (QOL), assessed using a previously reported 5-point ordinal questionnaire (graded 0-4, with higher scores indicating greater impairment in daily activities), as well as the incidence of adverse events.
Results:
Both groups demonstrated significant within-group improvements in pain and function over time (p < 0.001). Diclofenac resulted in significantly lower VAS pain scores at day 7 and day 14 (p = 0.024 and p = 0.021, respectively). WOMAC scores improved significantly over time in both groups (p < 0.001), with a significant group × time interaction (p = 0.021), indicating different patterns of functional change over time without consistent superiority of either treatment. No significant between-group differences were observed in QOL. No serious adverse events were observed.
Discussion:
These findings suggest that topical diclofenac provides greater short-term pain relief, whereas functional outcomes showed differing patterns of change over time without a consistent advantage of either treatment. The absence of serious adverse events supports the shortterm tolerability of both topical NSAID formulations.
Conclusion:
Both topical ketorolac and diclofenac were associated with improvements in pain and functional status and were well tolerated during the 2-week treatment period. Diclofenac was associated with greater short-term pain reduction, whereas functional outcomes showed different temporal patterns without a consistent between-group advantage. Given the short treatment duration and limited sample size, these findings should be interpreted cautiously and require confirmation in larger, longer-term randomized studies.