Acta Scientific Orthopaedics (ISSN: 2581-8635)

Review Article Volume 3 Issue 12

Aceclofenac in Osteoarthritis - NSAID with Novel Mechanism of Action

Dilip Shah1, Ananda K Pal2, Gurinder Bedi3, Anu Grover4*, Amarjit Singh4, Indranil Purkait4, Apurva Jawdekar4 and Anil Pareek4

1Consultant Orthopedic Surgeon, Saifee Hospital, Mumbai, India
2Professor, Department of Orthopaedics and Traumatology, IPGMER, SSK Medical College, Kolkata, West Bengal, India
3Director Orthopedics, Fortis Hospital, New Delhi, India
4Medical Affairs Department, Ipca Laboratories, Mumbai, India

*Corresponding Author: Anu Grover, Medical Affairs Department, Ipca Laboratories, Mumbai, India.

Received: October 06, 2020; Published: November 05, 2020

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Abstract

  Osteoarthritis (OA) is the most common form of arthritis, affecting millions of people worldwide. It is an inflammatory, degenerative and progressive disease which worsens over time, resulting in joint pain, swelling and stiffness. As the disease progresses, pain and stiffness become severe making daily tasks difficult, thereby affecting the quality of life. The treatment of osteoarthritis mainly focuses on management of inflammation to control the symptoms as complete reversal of the disease is not practical. Non-steroidal anti-inflammatory drugs (NSAIDs) are most commonly used and are mainstay drugs in the symptomatic treatment of osteoarthritis. Various NSAIDs are currently available in the market and looking into the co-morbidities associated with OA, there is a need for well tolerated NSAID with proven efficacy and safety. Aceclofenac, although was a late entry in crowded NSAID market, but, now is a well established drug in management of OA pain. It predominantly inhibits the inflammatory COX-2 enzyme, and due to less inhibitory action on gastroprotective COX-1 enzyme, it can be categorized as a preferential COX-2 inhibitor. Besides prostaglandin synthesis, it also inhibits synthesis of other inflammatory mediators like interleukins, tumour necrosis factor, nitric oxide and matrix metalloproteinases. This makes its efficacy similar or superior to other NSAIDs. Its efficacy has been evaluated in international studies as well as in Indian patient setting, where it has shown significant decrease in pain and severity of symptoms and improvement of functional capacity in osteoarthritis patients. Additionally, aceclofenac has a unique chondroprotective action and hence exerts a stimulatory effect on cartilage matrix synthesis. Due to preferential COX-2 inhibition, it is well-tolerated amongst the available NSAIDs, with a lower incidence of gastrointestinal and other NSAID related side effects. Good tolerability profile of aceclofenac results in decreased withdrawal rate and greater compliance of the treatment. Aceclofenac is the preferred drug for chronic therapy of osteoarthritis as long term studies highlighting the efficacy and tolerability of the drug are available. This review mainly focuses on the efficacy of aceclofenac, and also briefly mentions its safety in osteoarthritis management

Keywords: Osteoarthritis; NSAIDs; Aceclofenac; Pain; Inflammation COX Inhibitor

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References

  1. Chen Di., et al. “Osteoarthritis: toward a comprehensive understanding of pathological mechanism”. Bone Research 5 (2017): 16044.
  2. Rainbow Roshni., et al. “Inflammation and Joint Tissue Interactions in OA: Implications for Potential Therapeutic Approaches”. Arthritis 2012 (2012): 741582.
  3. Abramson S B., et al. “Nitric oxide and inflammatory mediators in the perpetuation of osteoarthritis”. Current Rheumatology Reports6 (2001): 535-541.
  4. Kadam U T., et al. “Clinical comorbidity in patients with osteoarthritis: a case-control study of general practice consulters in England and Wales”. Annals of the Rheumatic Diseases4 (2004): 408-414.
  5. https://www.who.int/medicines/areas/priority_medicines/BP6_12Osteo.pdf
  6. Pal Chandra Prakash., et al. “Epidemiology of knee osteoarthritis in India and related factors”. Indian Journal of Orthopaedics5 (2016): 518-522.
  7. Kaur Rajvir., et al. "Prevalence of knee osteoarthritis and its determinants in 30-60 years old women of Gurdaspur, Punjab”. International Journal of Medical Science and Public Health 10 (2018): 825-830.
  8. Das AK., et al. “Prevalence and Risk Factors of Knee Osteoarthritis in a Rural Community of Odisha: A Snap Shot Study”. JMSCR 5 (2018): 15-21.
  9. Venkatachalam Jayaseelan., et al. “Prevalence of osteoarthritis of knee joint among adult population in a rural area of Kanchipuram District, Tamil Nadu”. Indian Journal of Public Health2 (2018): 117-122.
  10. Srinivasan S., et al. “Govindarajan PK. Prevalence of osteoarthritis of the knee joint among elderly population in a rural area”. IJBPR11 (2015): 849-851.
  11. Ong Kwok Leung., et al. “Arthritis: its prevalence, risk factors, and association with cardiovascular diseases in the United States, 1999 to 2008”. Annals of Epidemiology2 (2013): 80-86.
  12. Tuominen Ulla., et al. “The effect of co-morbidities on health-related quality of life in patients placed on the waiting list for total joint replacement”. Health and Quality of Life Outcomes16 (2007).
  13. Sancheti Parag., et al. “India-Based Knee Osteoarthritis Evaluation (iKare): A Multi-Centre Cross-Sectional Study on the Management of Knee Pain and Early Osteoarthritis in India”. Clinics in Orthopedic Surgery3 (2017): 286-294.
  14. Firdose S., et al. “Cost of Illness Analysis of Knee Osteoarthritis in a Tertiary Care Hospital”. Journal of Young Pharmacists 3 (2018): 322-325.
  15. Castellsague Jordi., et al. “Individual NSAIDs and upper gastrointestinal complications: a systematic review and meta-analysis of observational studies (the SOS project)”. Drug Safety 35,12 (2012): 1127-1146.
  16. Pelletier Jean-Pierre., et al. “Efficacy and safety of oral NSAIDs and analgesics in the management of osteoarthritis: Evidence from real-life setting trials and surveys”. Seminars in Arthritis and Rheumatism4 (2016): S22-27.
  17. Raber Anna., et al. “Incidence of spontaneous notifications of adverse reactions with aceclofenac, meloxicam, and rofecoxib during the first year after marketing in the United Kingdom”. Therapeutics and Clinical Risk Management2 (2007): 225-230.
  18. Pareek A., et al. “Efficacy and safety of aceclofenac in the treatment of osteoarthritis: a randomized double-blind comparative clinical trial versus diclofenac - an Indian experience”. Current Medical Research and Opinion5 (2006): 977-988.
  19. Dingle J T. “The effect of nonsteroidal antiinflammatory drugs on human articular cartilage glycosaminoglycan synthesis”. Osteoarthritis and Cartilage3 (1999): 313-314.
  20. Dingle J T. “The effects of NSAID on the matrix of human articular cartilages”. Zeitschrift fur Rheumatologie3 (1999): 125-129.
  21. Dingle JT and Parker M. “NSAID Stimulation of Human Cartilage Matrix Synthesis. A Study of the Mechanism of Action of Aceclofenac”. Clinical Drug Investigation5 (1997): 353-362.
  22. Cutolo Maurizio., et al. “Commentary on recent therapeutic guidelines for osteoarthritis”. Seminars in Arthritis and Rheumatism6 (2015): 611-617.
  23. Stanos Steven. “Osteoarthritis guidelines: a progressive role for topical NSAIDs”. The Journal of the American Osteopathic Association2 (2013): 123-127.
  24. Bruyère Olivier., et al. “A consensus statement on the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) algorithm for the management of knee osteoarthritis-From evidence-based medicine to the real-life setting”. Seminars in Arthritis and Rheumatism4 (2016): S3-11.
  25. McAlindon T E., et al. “OARSI guidelines for the non-surgical management of knee osteoarthritis”. Osteoarthritis and Cartilage3 (2014): 363-388.
  26. NICE: National Institute for Health and Care Excellence. "Osteoarthritis: care and management in adults”. NICE Guidelines (2014).
  27. Hochberg Marc C., et al. “American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee”. Arthritis Care and Research4 (2012): 465-474.
  28. The Royal Australian College of General Practitioners. Guideline for the management of knee and hip osteoarthritis. 2nd ed. East Melbourne, Vic: RACGP (2018).
  29. Jordan K M., et al. “EULAR Recommendations 2003: an evidence based approach to the management of knee osteoarthritis: Report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT)”. Annals of the Rheumatic Diseases12 (2003): 1145-1155.
  30. European Medicines Agency. “Guideline on clinical investigation of medicinal products used in the treatment of osteoarthritis” (2010).
  31. Dammann H G. “Die bevorzugte COX-2-Hemmung: ihre klinische Relevanz für die gastrointestinale NSAR-Toxizität” [Preferential COX-2 inhibition: its clinical relevance for gastrointestinal non-steroidal anti-inflammatory rheumatic drug toxicity]. Zeitschrift fur Gastroenterologie1 (1999): 45-58.
  32. Topol Eric J. “Failing the public health--rofecoxib, Merck, and the FDA”. The New England Journal of Medicine17 (2004): 1707-1709.
  33. Chou R., et al. "Analgesics for osteoarthritis: an update of the 2006 comparative effectiveness review”. (2011).
  34. Haveles, Elena Bablenis. Applied Pharmacology for the Dental Hygienist-E-Book. Elsevier Health Sciences, (2014).
  35. Grosser T. “Non-steroidal anti-inflammatory drugs and coxibs”. In: Burton ME, ed. Applied pharmacokinetics and pharmacodynamics: principles of therapeutic drug monitoring. 4th ed. Lippincott Williams and Wilkins (2006): 752-780.
  36. Lemmel Ernst-Martin., et al. “Patient and physician satisfaction with aceclofenac: results of the European Observational Cohort Study (experience with aceclofenac for inflammatory pain in daily practice). Aceclofenac is the treatment of choice for patients and physicians in the management of inflammatory pain”. Current Medical Research and Opinion3 (2002): 146-153.
  37. Ward D E., et al. “Comparison of aceclofenac with diclofenac in the treatment of osteoarthritis”. Clinical Rheumatology6 (1995): 656-662.
  38. Peréz Busquier M., et al. “Comparison of aceclofenac with piroxicam in the treatment of osteoarthritis”. Clinical Rheumatology2 (1997): 154-159.
  39. Torri G., et al. "Aceclofenac versus piroxicam in the management of osteoarthritis of the knee: a double-blind controlled study”. Current Therapeutic Research5 (1994): 576-583.
  40. Kornasoff D., et al. “Aceclofenac is a well-tolerated alternative to naproxen in the treatment of osteoarthritis”. Clinical Rheumatology1 (1997): 32-38.
  41. Pareek Anil., et al. “A randomized, multicentric, comparative evaluation of aceclofenac-paracetamol combination with aceclofenac alone in Indian patients with osteoarthritis flare-up”. Expert Opinion on Pharmacotherapy 10,5 (2009): 727-735.
  42. Waraich Harsimrat S., et al. "A comparative study to assess the safety and efficacy of etoricoxib versus aceclofenac in osteoarthritis”. International Journal of Basic and Clinical Pharmacology10 (2018): 2010.
  43. Klair Jagpal Singh. "A Comparative Study of Efficacy and Tolerability of Ibuprofen vs. Aceclofenac in Osteoarthritis of Knee Joint”. Annals of Medicine and Healthcare Research (2009): 236-280.
  44. Arfè Andrea., et al. “Non-steroidal anti-inflammatory drugs and risk of heart failure in four European countries: nested case-control study”. BMJ (Clinical research ed.) (2016): 354 i4857.
  45. Huskisson E C., et al. "A large prospective open-label, multicentre SAMM study, comparing the safety of aceclofenac with diclofenac in patients with rheumatic disease”. European Journal of Rheumatology and Inflammation 1 (2000): 1-7.
  46. Brogden R N and L R Wiseman. “Aceclofenac. A review of its pharmacodynamic properties and therapeutic potential in the treatment of rheumatic disorders and in pain management”. Drugs1 (1996): 113-124.
  47. Arslan S., et al. "A nonsteroidal antiinflammatory drug: aceclofenac”. FABA Journal of Pharmaceutical Sciences 2 (2010): 105-118.
  48. Hinz Burkhard., et al. “Aceclofenac spares cyclooxygenase 1 as a result of limited but sustained biotransformation to diclofenac”. Clinical Pharmacology and Therapeutics3 (2003): 222-235.
  49. Dooley M., et al. “Aceclofenac: a reappraisal of its use in the management of pain and rheumatic disease”. Drugs9 (2001): 1351-1378.
  50. Hinz Burkhard., et al. “Aceclofenac spares cyclooxygenase 1 as a result of limited but sustained biotransformation to diclofenac”. Clinical Pharmacology and Therapeutics3 (2003): 222-235.
  51. Alvarez-Soria M A., et al. “Long-term NSAID treatment directly decreases COX-2 and mPGES-1 production in the articular cartilage of patients with osteoarthritis”. Osteoarthritis and Cartilage 16,12 (2008): 1484-1493.
  52. Henrotin Y., et al. “In vitro effects of aceclofenac and its metabolites on the production by chondrocytes of inflammatory mediators”. Inflammation Research: Official Journal of the European Histamine Research Society 8 (2001): 391-399.
  53. Martel-Pelletier., et al. "Effects of aceclofenac and diclofenac on synovial inflammatory factors in human osteoarthritis”. Clinical Drug Investigation3 (1997): 226-232.
  54. Maneiro E., et al. “Aceclofenac increases the synthesis of interleukin 1 receptor antagonist and decreases the production of nitric oxide in human articular chondrocytes”. The Journal of Rheumatology12 (2001): 2692-2699.
  55. Yamazaki R., et al. “A major metabolite of aceclofenac, 4'-hydroxy aceclofenac, suppresses the production of interstitial pro-collagenase/proMMP-1 and pro-stromelysin-1/proMMP-3 by human rheumatoid synovial cells”. Inflammation Research: Official Journal of the European Histamine Research Society3 (2000): 133-138.
  56. Cecchettin M., et al. "Therapeutic efficacy of aceclofenac and diclofenac in acute knee arthroses-a study of e2-prostaglandin levels in synovial-fluid and in serum”. Clinical Trials Journal2 (1988): 144-151.
  57. González-Alvaro I., et al. “Aceclofenac, a new nonsteroidal antiinflammatory drug, decreases the expression and function of some adhesion molecules on human neutrophils”. The Journal of Rheumatology4 (1996): 723-729.
  58. Pelletier J P. “The influence of tissue cross-talking on OA progression: role of nonsteroidal antiinflammatory drugs”. Osteoarthritis and Cartilage4 (1999): 374-376.
  59. Blot L., et al. “Effects of diclofenac, aceclofenac and meloxicam on the metabolism of proteoglycans and hyaluronan in osteoarthritic human cartilage”. British Journal of Pharmacology7 (2000): 1413-1421.
  60. Patil Pramod Reddy., et al. "A comparative study of efficacy and safety of diclofenac and aceclofenac in the treatment of osteoarthritis patients”. Journal of Drug Delivery and Therapeutics4 (2012).
  61. Ali Shaik Mohammad., et al. "Comparative study of safety efficacy and tolerability of aceclofenac verses diclofenac in osteoarthritis patients attending a secondary care hospital in anantapuramu”. Indo American Journal of Pharmaceutical Sciences5 (2017): 1260-1277.
  62. Pareek Anil., et al. “Efficacy and safety of aceclofenac-cr and aceclofenac in the treatment of knee osteoarthritis: a 6-week, comparative, randomized, multicentric, double-blind study”. The Journal of Pain: Official Journal of the American Pain Society5 (2011): 546-553.
  63. Legrand Erik. “Aceclofenac in the management of inflammatory pain”. Expert Opinion on Pharmacotherapy6 (2004): 1347-1357.
  64. Patel Parvati B and Tejas K Patel. “Efficacy and safety of aceclofenac in osteoarthritis: A meta-analysis of randomized controlled trials”. European Journal of Rheumatology1 (2017): 11-18.
  65. Pareek Anil and Nitin Chandurkar. “Comparison of gastrointestinal safety and tolerability of aceclofenac with diclofenac: a multicenter, randomized, double-blind study in patients with knee osteoarthritis”. Current Medical Research and Opinion7 (2013): 849-859.
  66. Ibáñez Luisa., et al. “Proton pump inhibitors and risk of upper gastrointestinal bleeding in NSAID users”. The American Journal of Gastroenterology10 (2008): 2658-2659.
  67. Yanagawa Akira., et al. "Endoscopic evaluation of aceclofenac-induced gastroduodenal mucosal damage: a double-blind comparison with sodium diclofenac and placebo”. Japanese Journal of Rheumatology3 (1998): 249-259.
  68. Grau M., et al. “Pharmacology of the potent new non-steroidal anti-inflammatory agent aceclofenac”. Arzneimittel-Forschung12 (1991): 1265-1276.
  69. Agúndez José Ag., et al. “Assessment of nonsteroidal anti-inflammatory drug-induced hepatotoxicity”. Expert Opinion on Drug Metabolism and Toxicology7 (2011): 817-828.
  70. Jung Sun-Young., et al. “Comparative effectiveness of oral pharmacologic interventions for knee osteoarthritis: A network meta-analysis”. Modern Rheumatology6 (2018): 1021-1028.
  71. Peris F., et al. "Treatment compliance and safety of aceclofenac versus standard NSAIDs in patients with common arthritic disorders: a meta-analysis”. European Journal of Rheumatology and Inflammation (English edition) 16.1 (1996): 37-45.
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Citation

Citation: Anu Grover., et al. “Aceclofenac in Osteoarthritis - NSAID with Novel Mechanism of Action".Acta Scientific Orthopaedics 3.12 (2020): 02-13.




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