Dexibuprofen in rheumatology practice: A review of clinical studies and pharmacological aspects

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the primary tool for pain control in rheumatic diseases. However, their use significantly limits the risk of developing class-specific complications affecting the gastrointestinal tract, cardiovascular system, and kidneys.

Dexibuprofen (dIBF) is a modified form of one of the most popular NSAIDs, ibuprofen. Its biologically active dextrorotatory stereoisomer ((S)-(+)), with therapeutic doses half that of the racemate, offers good therapeutic potential and is better tolerated than “regular” ibuprofen.

The aim of this study was to review clinical trials of dexibuprofen in rheumatic diseases.

Materials and methods. A search of publications in PubMed, Web of Science, Scopus, and Cochrane electronic libraries was conducted using the keywords “dexibuprofen”, “S(+)-ibuprofen”, “rheumatic disease”, “treatment”, “efficacy”, and “safety”. The review included original publications representing randomized controlled trials, open-label studies, or observational studies that examined the efficacy and safety of dexibuprofen in the treatment of rheumatic diseases.

Results. Seven publications were identified, including four double-blind, randomized controlled trials (a total of 925 patients), one open-label, controlled safety study with endoscopic monitoring, and two observational studies aimed at assessing the safety of dexibuprofen in real-world clinical practice. An analysis of these studies showed that dexibuprofen is as effective as “regular” ibuprofen (although the latter’s dose is twice as high) and diclofenac at a dose of 150 mg/day, while the incidence of gastrointestinal complications with dexibuprofen is statistically significantly lower. Observational studies of dexibuprofen in real-world practice also demonstrate good therapeutic efficacy and a favorable safety profile for this drug.

Conclusion. Dexibuprofen is an effective, well-tolerated analgesic that can be successfully used in the combination treatment of rheumatic diseases.

1. Nasonov EL, Yakhno NN, Karateev AE, Alekseeva LI, Barinov AN, Barulin AE, et al. General principles of treatment for musculoskeletal pain: Interdisciplinary consensus. Nauchno-Prakticheskaya Revmatologia = Rheumatology Science and Practice. 2016;54(3):247-265 (In Russ.). doi: 10.14412/1995-4484-2016-247-265

2. Mease PJ, Liu M, Rebello S, Kang H, Yi E, Park Y, et al. Comparative disease burden in patients with rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis: Data from two Corrona registries. Rheumatol Ther. 2019;6(4):529-542. doi: 10.1007/s40744-019-00172-9

3. Albrecht K, Marschall U, Callhoff J. Prescription of analgesics in patients with rheumatic diseases in Germany: A claims data analysis. Z Rheumatol. 2021;80(Suppl 2):68-75. doi: 10.1007/s00393-021-00971-y

4. Scott IC, Whittle R, Bailey J, Twohig H, Hider SL, Mallen CD, et al. Analgesic prescribing in patients with inflammatory arthritis in England: Observational studies in the Clinical Practice Research Datalink. Rheumatology (Oxford). 2024;63(6):1672-1681. doi: 10.1093/rheumatology/kead463

5. Hallberg S, Rolfson O, Karppinen J, Schiøttz-Christensen B, Stubhaug A, Rivano Fischer M, et al. Burden of disease and management of osteoarthritis and chronic low back pain: Healthcare utilization and sick leave in Sweden, Norway, Finland and Denmark (BISCUITS): Study design and patient characteristics of a real world data study. Scand J Pain. 2022;23(1):126-138. doi: 10.1515/sjpain-2021-0212

6. Hunter T, Nguyen C, Birt J, Smith J, Shan M, Tan H, et al. Pain medication and corticosteroid use in ankylosing spondylitis, psoriatic arthritis, and rheumatoid arthritis in the United States: A retrospective observational study. Rheumatol Ther. 2021;8(3):13711382. doi: 10.1007/s40744-021-00344-6

7. Lee ZM, Yang YH, Kuo HC, Shen YH, Yu HR, Su YJ. Comparison of glucocorticoids and painkiller prescribed days between rheumatoid arthritis patients receiving early and late treatment with a biological agent via a population-based cohort study. Medicine (Baltimore). 2022;101(47):e31986. doi: 10.1097/MD.0000000000031986

8. Wirth T, Lafforgue P, Pham T. NSAID: Current limits to prescription. Joint Bone Spine. 2024;91(4):105685. doi: 10.1016/j.jbspin.2023.105685

9. Cox N, Mallen CD, Scott IC. Pharmacological pain management in patients with rheumatoid arthritis: A narrative literature review. BMC Med. 2025;23(1):54. doi: 10.1186/s12916-025-03870-0

10. Coxib and traditional NSAID Trialists’ (CNT) Collaboration; Bhala N, Emberson J, Merhi A, Abramson S, Arber N, et al. Vascular and upper gastrointestinal effects of non-steroidal antiinflammatory drugs: Meta-analyses of individual participant data from randomised trials. Lancet. 2013;382(9894):769-779. doi: 10.1016/S0140-6736(13)60900-9

11. McGettigan P, Henry D. Cardiovascular risk with non-steroidal anti-inflammatory drugs: Systematic review of population-based controlled observational studies. PLoS Med. 2011;8(9):e1001098. doi: 10.1371/journal.pmed.1001098

12. Kaehler ST, Phleps W, Hesse E. Dexibuprofen: Pharmacology, therapeutic uses and safety. Inflammopharmacology. 2003;11(4):371-383. doi: 10.1163/156856003322699555

13. Phleps W. Overview on clinical data of dexibuprofen. Clin Rheumatol. 2001;20(Suppl 1):15-21. doi: 10.1007/BF03342663

14. Gliszczyńska A, Sánchez-López E. Dexibuprofen therapeutic advances: Prodrugs and nanotechnological formulations. Pharmaceutics. 2021;13(3):414. doi: 10.3390/pharmaceutics13030414

15. Hawel R, Klein G, Mitterhuber J, Brugger A. Doppelblinde Studie zum Vergleich der Wirksamkeit und Verträglichkeit von 900 mg Dexibuprofen und 150 mg Diclofenac-Natrium bei Patienten mit schmerzhafter Gonarthrose [Double-blind comparative study of the effectiveness and tolerance of 900 mg dexibuprofen and 150 mg diclofenac sodium in patients with painful gonarthrosis]. Wien Klin Wochenschr. 1997;109(2):53-59 (In German).

16. Singer F, Mayrhofer F, Klein G, Hawel R, Kollenz CJ. Evaluation of the efficacy and dose-response relationship of dexibuprofen (S(+)-ibuprofen) in patients with osteoarthritis of the hip and comparison with racemic ibuprofen using the WOMAC osteoarthritis index. Int J Clin Pharmacol Ther. 2000;38(1):15-24. doi: 10.5414/cpp38015

17. Hawel R, Klein G, Singer F, Mayrhofer F, Kähler ST. Comparison of the efficacy and tolerability of dexibuprofen and celecoxib in the treatment of osteoarthritis of the hip. Int J Clin Pharmacol Ther. 2003;41(4):153-164. doi: 10.5414/cpp41153

18. Zamani O, Böttcher E, Rieger JD, Mitterhuber J, Hawel R, Stallinger S, et al. Comparison of safety, efficacy and tolerability of dexibuprofen and ibuprofen in the treatment of osteoarthritis of the hip or knee. Wien Klin Wochenschr. 2014;126(11-12):368-375. doi: 10.1007/s00508-014-0544-2

19. Gómez BJ, Caunedo A, Redondo L, Esteban J, Sáenz-Dana M, Blasco M, et al. Modification of pepsinogen I levels and their correlation with gastrointestinal injury after administration of dexibuprofen, ibuprofen or diclofenac: A randomized, open-label, controlled clinical trial. Int J Clin Pharmacol Ther. 2006;44(4):154-162. doi: 10.5414/cpp44154

20. Chlud K. Evaluation of tolerance and efficacy of S(+)-ibuprofen (Seractil) in daily practice: A post-marketing-surveillance study in 1400 patients. J Clin Pharmacol. 1995;35:938.

21. Mayrhofer F. Efficacy and long-term safety of dexibuprofen [S(+)-ibuprofen]: A short-term efficacy study in patients with osteoarthritis of the hip and a 1-year tolerability study in patients with rheumatic disorders. Clin Rheumatol. 2001;20(Suppl 1):22-29. doi: 10.1007/BF03342664

22. Derry S, Best J, Moore RA. Single dose oral dexibuprofen [S(+)ibuprofen] for acute postoperative pain in adults. Cochrane Database Syst Rev. 2013;2013(10):CD007550. doi: 10.1002/14651858.CD007550.pub3

23. Kollenz C, Phleps W, Kaehler ST. ADIDAC trial: Analgesia with dexibuprofen versus ibuprofen in patients suffering from primary dysmenorrhea: A crossover trial. Gynecol Obstet Invest. 2009;67(1):25-31. doi: 10.1159/000158648

24. Masclee GMC, Straatman H, Arfè A, Castellsague J, Garbe E, Herings R, et al. Risk of acute myocardial infarction during use of individual NSAIDs: A nested case-control study from the SOS project. PLoS One. 2018;13(11):e0204746. doi: 10.1371/journal.pone.0204746

25. Leising G, Resel R, Stelzer F, Tasch S, Lanziner A, Hantich G. Physical aspects of dexibuprofen and racemic ibuprofen. J Clin Pharmacol. 1996;36(Suppl 12):3S-6S.

26. Cattaneo D, Clementi E. Clinical pharmacokinetics of ibuprofen arginine. Curr Clin Pharmacol. 2010;5(4):239-245. doi: 10.2174/157488410793352012

27. Fini A, Zecchi V, Tartarini A. Dissolution profiles of NSAID carboxylic acids and their salts with different counter ions. Pharm Acta Helv. 1985;60:58-62.

28. Dong JQ, Ni L, Scott CS, Retsch-Bogart GZ, Smith PC. Pharmacokinetics of ibuprofen enantiomers in children with cystic fibrosis. J Clin Pharmacol. 2000;40(8):861-868. doi: 10.1177/00912700022009594

29. Evans AM. Comparative pharmacology of S(+)-ibuprofen and (RS)-ibuprofen. Clin Rheumatol. 2001;20(Suppl 1):9-14. doi: 10.1007/BF03342662

30. Cajaraville JP. Ibuprofen arginate for rapid-onset pain relief in daily practice: A review of its use in different pain conditions. J Pain Res. 2021;14:117-126. doi: 10.2147/JPR.S280571

31. Dionne RA, McCullagh L. Enhanced analgesia and suppression of plasma beta-endorphin by the S(+)-isomer of ibuprofen. Clin Pharmacol Ther. 1998;63(6):694-701. doi: 10.1016/S0009-9236(98)90094-7

32. Badokin VV. The effect of nonsteroidal antiinflammatory drugs on articular cartilage metabolism. RMJ. 2013;32:1657 (In Russ.).

33. Berk B. Effects of nonsteroidal anti-inflammatory drugs on chondrogenic differentiation. J Drug Delivery Therapeut. 2024;14(9):60-65. doi: 10.22270/jddt.v14i9.6781

34. Yao Y, Wang Y. ATDC5: An excellent in vitro model cell line for skeletal development. J Cell Biochem. 2013;114(6):1223-1229. doi: 10.1002/jcb.24467

35. Neale PA, Branch A, Khan SJ, Leusch FDL. Evaluating the enantiospecific differences of non-steroidal anti-inflammatory drugs (NSAIDs) using an ecotoxicity bioassay test battery. Sci Total Environ. 2019;694:133659. doi: 10.1016/j.scitotenv.2019.133659