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Effectiveness of ibuprofen plus paracetamol combination on persistence of acute musculoskeletal disorders in primary care patients

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Background General practitioners often deal with patients suffering acute musculoskeletal disorders. Paracetamol, non-steroidal anti-inflammatory drugs, and opioids are the most prescribed medications, according to pain intensity and patient’s features. Combinations of different analgesics can be adopted to enhance pain relief, but only one fixed-dose combination has been recently launched to treat acute musculoskeletal pain. Objective This study aimed to investigate the effectiveness of ibuprofen plus paracetamol (fixed-dose) combination compared to other analgesics in preventing musculoskeletal pain persistence. Setting Italian outpatients’ data extracted from a national general practice database. Method A retrospective cohort study was conducted on the Health Search Database. Patients prescribed with analgesics for acute musculoskeletal painful conditions were considered (i.e., non-chronic painful conditions, identified using a query validated by two expert General Practitioners (GPs)). For each patient, the first prescription of an analgesic was defined as index date. A new GP’s visit related to musculoskeletal disorders in the first 3 months following the index date was defined as “pain persistence”. Main outcome measure Risk of pain persistence among users of the ibuprofen plus paracetamol combination compared to other systemic analgesics. Results Overall, 102,216 patients were treated with systemic analgesics for acute musculoskeletal disorders. Most patients were middle-aged or elderly women. 939 (0.92%) patients were prescribed with the fixed-dose ibuprofen plus paracetamol combination for a mean duration of 7.23 ± 2.68 days, mainly for low back pain and cervicalgia. Musculoskeletal pain persistence was found in 22,125 (21.65%) patients. Compared to other systemic analgesics, the ibuprofen plus paracetamol combination resulted significantly more effective in preventing pain persistence (adjusted hazard ratio 0.72, 95% confidence interval 0.61–0.85). Conclusion These findings suggest that the fixed-dose ibuprofen plus paracetamol combination might be effective in controlling musculoskeletal pain persistence.

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All persons that contributed to this manuscript met the criteria for authorship and are listed as authors. Study design was contributed by Lapi and Marconi with assistance from the rest of the authors. Lapi, Bettiol and Simonetti took the lead in data analysis, assisted by the other authors, and data interpretation was performed by Lapi, Vannacci, Bettiol with assistance from the other authors. The manuscript was written primarily by Bettiol and Marconi, with assistance from the other authors, and revised by Vannacci, Lapi, Magni and Cricelli. All authors approved the final version of the manuscript.


This study was supported by Angelini SpA, which had no role in the design, analysis, and interpretation of the results.

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Correspondence to Francesco Lapi.

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Lapi and Marconi provided consultancies in protocol preparation for epidemiological studies and data analyses for IBSA, Bayer AlfaSigma and Angelini. Cricelli provided clinical consultancies for IBSA, Angelini, Grunenthal, AlfaSigma, Pfizer, Prostrakan, Molteni, Dompè and Teva. Magni provided clinical consultancies for Bayer, Angelini, Doc, and AlfaSigma. Authors Bettiol, Simonetti and Vannacci have no conflicts of interest to disclose.

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Bettiol, A., Marconi, E., Vannacci, A. et al. Effectiveness of ibuprofen plus paracetamol combination on persistence of acute musculoskeletal disorders in primary care patients. Int J Clin Pharm 43, 1045–1054 (2021).

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