Background Diclofenac, a traditional NSAID was developed 40 years back by Novartis for the treatment of acute and chronic pain. NSAIDs are used for pain management in osteoarthritis (OA), and have recently been under scrutiny due to possible safety risks. Both benefits and risks of different treatments should be analyzed to inform clinical decision making. In order to gain insight into data available from old studies (many unpublished) of diclofenac, comparative efficacy and safety evaluation using a novel methodology was conducted in OA.
Objectives To assess the efficacy and safety of diclofenac 100 and 150 mg/day relative to other NSAIDs for the treatment of OA.
Methods Protocol summarized the scope and PICOS (Patient, Intervention, Comparator, Outcomes, Study design) selection criteria of clinical trials included in the network meta-analysis (NMA). Clinical study reports (CSRs) from the Novartis archives were reviewed to identify randomized controlled trials (RCTs) conducted between 1982 and 1999, reporting efficacy and/or safety data of diclofenac or other active therapies or placebo, for more than 4 weeks for treatment of OA. Efficacy outcomes were pain, patient global assessment and investigator global assessment evaluated at 2, 4 and 12 weeks using a visual analogue scale (VAS). Tolerability outcomes were withdrawals due to all causes, adverse events and lack of efficacy. Safety outcomes were any serious adverse events. All trials were analyzed simultaneously using Bayesian NMA and relative treatment effects between all pairwise treatments were estimated .
Results Of the 35 retrieved CSRs, 19 RCTs were included in the NMA satisfying the selection criteria. All studies, except one (single blind), were double blind. They included 5030 patients. As measured by VAS change from baseline, diclofenac 100 mg/day was found to give a better patient global satisfaction at 4 weeks compared to ibuprofen 1200 mg/day, with an added value of 5.6 mm (95%CrI: 0.5; 10.8). It was comparable to ibuprofen 1200 and 2400 mg/day and naproxen 750 mg/day in terms of pain relief. Diclofenac 150 mg/day reduced pain compared to ibuprofen 1200 mg/day by 10 mm (95%CrI: 2; 17) at 4 weeks and by 6 mm (95%CrI: 1; 11) at 12 weeks, and was comparable to ibuprofen 2400 mg/day and naproxen 750 mg/day. Fewer withdrawals due to lack of efficacy were reported for diclofenac 100 mg/day compared to naproxen 500 mg/day and ibuprofen 2400 mg/day with rate ratios of 0.4 (95%CrI: 0.2; 0.8). Fewer withdrawals due to lack of efficacy were reported for diclofenac 150 mg/day compared to ibuprofen 2400 mg/day with a rate ratio of 0.6 (95%CrI: 0.4; 0.9). In terms of withdrawals due to all causes, diclofenac 100 and 150 mg/day were comparable to naproxen 500, 750 and 100 mg/day as well as to ibuprofen 1200 and 2400 mg/day.
Conclusions Diclofenac 100 and 150 mg/day show an efficacy and safety profile at least comparable to naproxen and ibuprofen based on a NMA using clinical trials data in osteoarthritis patients.
Dias, S., N.J. Welton, A.J. Sutton and A.E. Ades (2011). NICE DSU technical support document 2: a generalised linear modelling framework for pairwise and network meta-analysis of randomised controlled trials. Decision Support Unit.
Disclosure of Interest P. Guyot Employee of: Mapi, S. Pandhi Shareholder of: Novartis, Employee of: Novartis, R. Nixon Employee of: Novartis, A. Iqbal Employee of: Novartis, R. Chaves Employee of: Novartis, A. Karabis Employee of: Mapi, A. Moore Grant/research support from: Grünenthal, Reckitt Benckiser, Consultant for: Grünenthal, Reckitt Benckiser, Novartis, Menarini, Speakers bureau: Grünenthal, Reckitt Benckiser, Novartis, Menarini, MSD