Investigating the use of oral paracetamol and topical non-steroidal anti-inflammatory drug (NSAID) - diclofenac as a combination therapy for mild to moderate osteoarthritis (OA) pain: an evidence-based assessment using data mining and the application of machine learning (ML)

Investigating the use of oral paracetamol and topical non-steroidal anti-inflammatory drug (NSAID) - diclofenac as a combination therapy for mild to moderate osteoarthritis (OA) pain: an evidence-based assessment using data mining and the application of machine learning (ML)

Osteoarthritis (OA) is a major cause of chronic pain and disability in older adults and currently affects more than 500 million people worldwide. However, pain management in OA continues to remain suboptimal. The use of combination therapy of oral acetaminophen (APAP) and topical diclofenac (DIC), exhibiting complementary mechanisms of action, is an attractive strategy to achieve effective pain relief. However, there is limited information on the use of this combination for OA pain management. This study uses modified Delphi methodology to gather the perspectives of expert healthcare professionals (HCPs) towards the use of APAP either as monotherapy or in combination with topical NSAIDs in three different geographies, including Australia, Malaysia, and Sweden. The research shows that while oral APAP remains the gold standard treatment for the HCPs, there is limited prescription uptake for its combination with topical NSAIDs due to a lack of strong scientific evidence on their efficacy. In the absence of evidence on the combination in OA pain, the study uses a model-based meta-analysis (MBMA), a robust statistical technique, to extrapolate the combination effect from published studies conducted in acute pain setting. The MBMA indicates greater pain reduction and opioid sparing effect for the combination versus APAP monotherapy. Given the overlap in the pathophysiology of acute and chronic pain, similar beneficial effects from the use of combination can be expected on extrapolation to OA pain. Additionally, while topical DIC is considered well-tolerated due to its low systemic exposure, concerns of liver toxicity with APAP at standardised doses remain. Therefore, a separate MBMA is implemented to investigate the association between APAP and risk of hepatotoxicity. The MBMA demonstrates short-term (8-16 weeks) APAP use at standard analgesic doses (≤4000 mg/day) to be associated with a very low risk of clinically meaningful liver injury when compared with placebo. The findings in the study contribute to bridging the evidence gap in the literature on the efficacy and tolerability of combination of oral APAP and topical DIC in the management of mild to moderate OA pain.

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