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Nonsteroid anti-inflammatory drug choices in patients with juvenile idiopathic arthritis: A systematic review


Background: Disease-modifying anti-rheumatic drugs (DMARDs) are still a priority in treating juvenile idiopathic arthritis (JIA). The choice of drug therapy for the NSAIDs as an alternative to the therapy used in managing JIA cases due to the side effects of DMARDs. However, the former discussion of the choices therapy of NSAID therapy in JIA patients is still limited. This systematic review was conducted to present any choices of NSAIDs used for the treatment JIA and presented their effectiveness and adverse reaction compared with other NSAIDs used for treating JIA.

Methods: Comprehensive electronic searches were performed in PubMed/Medline, EMBASE, and Cochrane Library, choosing Randomized Controlled Trials of NSAIDs for treating children with JIA up to January 2009. The risk of bias was assessed using the Cochrane Risk of Bias Tools for randomized controlled trials.

Results: Eight eligible randomized controlled trials (RCT) out of 1309 studies were included, with a total of 1112 participants with JIA identified, addressing 19 kinds of interventions with nine types of medications. First RCT concluded that Celecoxib 3 mg/kg and Celecoxib 6 mg/kg were at least as effective as naproxen 7.5 mg/kg in terms of reducing clinical symptoms of arthritis and joint swelling. Second RCT concluded that Low Dose (0,3 mg/kg) and High Dose (0.6mg/kg) Rofecoxib showed a greater improvement than the Naproxen group to relieve the pain. The third RCT stated that good efficacy or satisfaction is most frequent in the participant with Meloxicam 0.125 mg/kg rather than Meloxicam 0.25 mg/kg or Naproxen 10 mg/kg. Fourth RCT concluded that Ibuprofen 30-40 mg/kg/d is an effective agent for symptomatic treatment of JIA and is well-tolerated in many children. Fifth RCT informed that Piroxicam show more effective in controlling the symptoms and improving function than Naproxen 10 mg/kg/day. Sixth RCT concluded that Acetylsalicylic acid 75 mg/kg/day has better efficacy than Naproxen 10 mg/kg/d in relieving the symptoms. The seventh study stated that both diclofenac sodium 2-3 mg/kg/day and acetylsalicylic acid 50-100 mg/kg/d at least as good as placebo. The last RCTs study stated that tolmetin 15 mg/kg/day decreased the duration of morning stiffness and reduced joint pain. Also, aspirin 50mg/kg/day resulted in ROM improvement in JIA patients.

Conclusions: We present Celecoxib, Rofecoxib, Meloxicam, Ibuprofen, Piroxicam, Acetylsalicylic Acid (ASA), Diclofenac Sodium, Tolmetin Sodium, and Naproxen as the NSAIDs choice drugs on pediatric patient diagnosed with JIA. which has each adverse event on each therapy.


  1. Solomon L, Warwick D, Nayagam S. Apley and Solomon’s Concise System of Orthopaedics and Trauma [Internet]. CRC Press; 2014. Available from:
  2. Wilson FC. Textbook of Disorders and Injuries of the Musculoskeletal System. An Introduction to Orthopaedics, Fractures and Joint Injuries, Rheumatology, Metabolic Bone Disease and Rehabilitation. Ed. 3. J Bone Jt Surgery-American Vol. 2000;82(2):297. Available from:
  3. Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004;31(2):390–2.
  4. Ringold S, Angeles-Han ST, Beukelman T, Lovell D, Cuello CA, Becker ML, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Non-Systemic Polyarthritis, Sacroiliitis, and Enthesitis. Arthritis Care Res (Hoboken). 2019/04/25. 2019;71(6):717–34. Available from:
  5. Moore RA, Derry S, Makinson GT, McQuay HJ. Tolerability and adverse events in clinical trials of celecoxib in osteoarthritis and rheumatoid arthritis: systematic review and meta-analysis of information from company clinical trial reports. Arthritis Res Ther. 2005/03/24. 2005;7(3):R644–65. Available from:
  6. Huang H, Pan J, Yang W, Chen H, Liang G, Zeng L, et al. Celecoxib vs diclofenac sodium in patients with knee osteoarthritis: A protocol for systematic review and meta analysis. Medicine (Baltimore). 2020;99(15):e19680–e19680. Available from:
  7. Wan R, Li P, Jiang H. The efficacy of celecoxib for pain management of arthroscopy: A meta-analysis of randomized controlled trials. Medicine (Baltimore). 2019;98(49):e17808–e17808. Available from:
  8. Caldwell DM, Ades AE, Higgins JPT. Simultaneous comparison of multiple treatments: combining direct and indirect evidence. BMJ. 2005;331(7521):897–900. Available from:
  9. Catalá-López F, Tobías A, Cameron C, Moher D, Hutton B. Network meta-analysis for comparing treatment effects of multiple interventions: an introduction. Rheumatol Int. 2014;34(11):1489–96. Available from:
  10. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700–b2700. Available from:
  11. Cumpston M, Li T, Page MJ, Chandler J, Welch VA, Higgins JPT, et al. Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions. Cochrane Database Syst Rev. 2019; Available from:
  12. Dechartres A, Altman DG, Trinquart L, Boutron I, Ravaud P. Association Between Analytic Strategy and Estimates of Treatment Outcomes in Meta-analyses. JAMA. 2014;312(6):623. Available from:
  13. Bhettay AJG E& T. Double-blind study of ketoprofen and indomethacin in juvenile chronic arthritis. South African Med J. 1978;54(7):276–8.
  14. Foeldvari I, Szer IS, Zemel LS, Lovell DJ, Giannini EH, Robbins JL, et al. A Prospective Study Comparing Celecoxib with Naproxen in Children with Juvenile Rheumatoid Arthritis. J Rheumatol. 2009;36(1):174–82. Available from:
  15. Reiff A, Lovell DJ, Van Adelsberg J, Kiss MHB, Goodman S, Zavaler MF, et al. Evaluation of the comparative efficacy and tolerability of rofecoxib and naproxen in children and adolescents with juvenile rheumatoid arthritis: a 12-week randomized controlled clinical trial with a 52-week open-label extension. J Rheumatol. 2006;33(5):985–95.
  16. Ruperto N, Nikishina I, Pachanov ED, Shachbazian Y, Prieur AM, Mouy R, et al. A randomized, double-blind clinical trial of two doses of meloxicam compared with naproxen in children with juvenile idiopathic arthritis: Short- and long-term efficacy and safety results. Arthritis & Rheum. 2005;52(2):563–72. Available from:
  17. Giannini EH, Brewer EJ, Miller ML, Gibbas D, Passo MH, Hoyeraal HM, et al. Ibuprofen suspension in the treatment of juvenile rheumatoid arthritis. J Pediatr. 1990;117(4):645–52. Available from:
  18. Garcia-Morteo O, Maldonado-Cocco JA, Cuttica R, Garay SM. Piroxicam in juvenile rheumatoid arthritis. Eur J Rheumatol Inflamm. 1987;8(1):49–53.
  19. Kvien TK, Høyeraal HM, Sandstad B. Naproxen and Acetylsalicylic Acid in the Treatment of Pauciarticular and Polyarticular Juvenile Rheumatoid ArthritisAssessment of Tolerance and Efficacy in a Single-centre 24-week Double-blind Parallel Study. Scand J Rheumatol. 1984;13(4):342–50. Available from:
  20. Haapasaari J, Wuolijoki E, Ylijoki H. Treatment of Juvenile Rheumatoid Arthritis with Diclofenac Sodium. Scand J Rheumatol. 1983;12(4):325–30. Available from:
  21. Levinson JE, Baum J, Brewer E, Fink C, Hanson V, Schaller J. Comparison of tolmetin sodium and aspirin in the treatment of juvenile rheumatoid arthritis. J Pediatr. 1977;91(5):799–804. Available from:
  22. Giannini EH, Ruperto N, Ravelli A, Lovell DJ, Felson DT, Martini A. Preliminary definition of improvement in juvenile arthritis. Arthritis & Rheum. 1997;40(7):1202–9. Available from:
  23. Burnett HF, Regier DA, Feldman BM, Miller FA, Ungar WJ. Parents’ preferences for drug treatments in juvenile idiopathic arthritis: A discrete choice experiment. Arthritis Care & Res. 2012;64(9):1382–91. Available from:
  24. Demirkaya E, Lanni S, Bovis F, Galasso R, Ravelli A, Palmisani E, et al. A Meta-Analysis to Estimate the Placebo Effect in Randomized Controlled Trials in Juvenile Idiopathic Arthritis. Arthritis & Rheumatol. 2016;68(6):1540–50. Available from:
  25. Song GG, Seo YH, Kim J-H, Choi SJ, Ji JD, Lee YH. Relative efficacy and tolerability of etoricoxib, celecoxib, and naproxen in the treatment of osteoarthritis. Z Rheumatol. 2016;75(5):508–16. Available from:
  26. Castellsague J, Riera-Guardia N, Calingaert B, Varas-Lorenzo C, Fourrier-Reglat A, Nicotra F, et al. Individual NSAIDs and upper gastrointestinal complications: a systematic review and meta-analysis of observational studies (the SOS project). Drug Saf. 2012;35(12):1127–46. Available from:
  27. DeWitt EM, Sherry DD, Cron RQ. Pediatric Rheumatology for the Adult Rheumatologist I. JCR J Clin Rheumatol. 2005;11(1):21–33. Available from:
  28. Keenan GF, Giannini EH, Athreya BH. Clinically significant gastropathy associated with nonsteroidal antiinflammatory drug use in children with juvenile rheumatoid arthritis. J Rheumatol. 1995;22(6):1149–51.
  29. Mulberg AE, Linz C, Bern E, Tucker L, Verhave M, Grand RJ. Identification of nonsteroidal antiinflammatory drug-induced gastroduodenal injury in children with juvenile rheumatoid arthritis. J Pediatr. 1993;122(4):647–9. Available from:
  30. Hermaszewski R, Hayllar J, Woo P. Gastro-duodenal damage due to non-steroidal anti-inflammatory drugs in children. Rheumatology. 1993;32(1):69–72. Available from:
  31. Dowd JE, Cimaz R, Fink CW. Nonsteroidal antiinflammatory drug-induced gastroduodenal injury in children. Arthritis & Rheum. 1995;38(9):1225–31. Available from:
  32. Bresalier RS, Sandler RS, Quan H, Bolognese JA, Oxenius B, Horgan K, et al. Cardiovascular Events Associated with Rofecoxib in a Colorectal Adenoma Chemoprevention Trial. N Engl J Med. 2005;352(11):1092–102. Available from:

How to Cite

Biantara, Y. P., Widhiarma, S. F. ., & Kusuma, W. T. . (2022). Nonsteroid anti-inflammatory drug choices in patients with juvenile idiopathic arthritis: A systematic review. Intisari Sains Medis, 13(2), 404–409.




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Yogi Priyatna Biantara
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Surya Fajari Widhiarma
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Widia Trilaksana Kusuma
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