Licofelone in osteoarthritis: is this the awaited drug? a systematic review
DOI:
https://doi.org/10.18203/2319-2003.ijbcp20211654Keywords:
Osteoarthritis, NSAIDs, COX/5-LOX dual inhibitors, LicofeloneAbstract
Osteoarthritis is a progressive joint disease associated with aging in elderly is, characterized by pain, inflammation, and difficulty in movement. The pathways involved in the progression of this disease remain unclear. The mediators, eicosanoids and leukotrienes are produced by COX-1/COX-2 or 5-LOX. Physicians have always used nonsteroidal anti-inflammatory drugs to treat the pain associated with osteoarthritis. A competitive inhibitor of LOX-5 and COX-2 that has both analgesic and anti-inflammatory activity is licofelone; one of the most promising candidates for the treatment of osteoarthritis is under clinical trial in treatment. A significant reduction in cartilage volume was displayed. A significant improvement over baseline on the WOMAC index and GI tolerance was also observed. Improving the symptoms related pain sensation with a happier life. With new strategies in OA, new methods to target pain, inflammation and movement restrictions would be the ultimate goal in patient satisfaction for the future. Licofelone was found to be effective compared to NSAIDs or coxibs in the treatment of OA. Does this mean this could be the answer?
Metrics
References
Molloy ES, McCarthy GM. Eicosanoids, osteoarthritis, and crystal deposition diseases. Curr Opin Rheumatol. 2005;17(3):346-50.
Franceschi C, Bonafè M, Valensin S, Olivieri F, De Luca M, Ottaviani E, et al. Inflammaging: an evolutionary perspective on immunosenescence. Ann NY Acad Sci. 2000;908(1):244-54.
López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013; 153(6):1194-217.
Brune K. Safety of anti-inflammatory treatment new ways of thinking. Rheumatol. 2004; 43(1):i16-20.
Raisz LG. Prostaglandins and bone: physiology and pathophysiology. Osteoarthr Cartil. 1999;7(4):419-21.
Martel-Pelletier J, Mineau F, Fahmi H, Laufer S, Reboul P, Boileau C, et al. Regulation of the expression of 5-lipoxygenase–activating protein/5-lipoxygenase and the synthesis of leukotriene B4 in osteoarthritic chondrocytes: Role of transforming growth factor β and eicosanoids. Arthritis Rheum. 2004;50(12):3925-33.
Khanapure SP, Garvey DS, Janero DR, Gordon Letts L. Eicosanoids in inflammation: biosynthesis, pharmacology, and therapeutic frontiers. Curr Top Med Chem. 2007;7(3):311-40.
Piomelli D. Arachidonic acid in cell signaling. Curr Opin Cell Biol. 1993;5(2):274-80.
Capdevila JH, Falck JR, Estabrook RW. Cytochrome P450 and the arachidonate cascade 1. FASEB J. 1992;6(2):731-6.
Tager AM, Luster AD. BLT1 and BLT2: the leukotriene B4 receptors. Prostaglan Leukot Essent Fatty Acids. 2003;69(2-3):123-34.
Janusz JM, Young PA, Scherz MW, Enzweiler K, Wu LI, Gan L, et al. New cyclooxygenase-2/5-lipoxygenase inhibitors. 2. 7-tert-butyl-2, 3-dihydro-3, 3-dimethylbenzofuran derivatives as gastro-intestinal safe antiinflammatory and analgesic agents: variations of the dihydrobenzofuran ring. J Med Chem. 1998;41(7):1124-37.
Prete PE, Gurakar-Osborne A. The contribution of synovial fluid lipoproteins to the chronic synovitis of rheumatoid arthritis. Prostaglandins. 1997;54(4):689-98.
Martel-Pelletier J, Lajeunesse D, Reboul P, Pelletier JP. Therapeutic role of dual inhibitors of 5-LOX and COX, selective and non-selective non-steroidal anti-inflammatory drugs. Ann Rheum Dis. 2003;62(6):501-9.
Martel-Pelletier J, Lajeunesse D, Pelletier JP. Etiopathogenesis of osteoarthritis. Arthritis and Allied Conditions. Ann Rheum Dis. 2005;15:2199-226.
Warner TD, Mitchell JA. Cyclooxygenases: new forms, new inhibitors, and lessons from the clinic. FASEB J. 2004;18(7):790-804.
Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. N Engl J Med. 2000;343(21):1520-8.
Benito MJ, Veale DJ, FitzGerald O, van den Berg WB, Bresnihan B. Synovial tissue inflammation in early and late osteoarthritis. Ann Rheum Dis. 2005;64(9):1263-7.
Bertolini A, Ottani A, Sandrini M. Selective COX-2 inhibitors and dual acting anti-inflammatory drugs: critical remarks. Curr Med Chem. 2002;9(10):1033-43.
Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature New Biol. 1971;231(25):232-5.
Rotondo S, Krauze-Brzósko K, Manarini S, Evangelista V, Cerletti C. Licofelone, an inhibitor of cyclooxygenase and 5-lipoxygenase, specifically inhibits cyclooxygenase-1-dependent platelet activation. Eur J Pharmacol. 2004;488(1-3):79-83.
Wallace JL, Chin BC. Inflammatory mediators in gastrointestinal defense and injury. Proc Soc Exp Biol Med. 1997;214(3):192-203.
Scheiman JM. Gastroduodenal safety of cyclooxygenase-2 inhibitors. Curr Pharm Des. 2003;9(27):2197-206.
Silverman ES, Drazen JM. The biology of 5-lipoxygenase: function, structure, and regulatory mechanisms. Proc Assoc Am Physicians. 1999;111(6):525-36.
Ding C, Cicuttini F. Licofelone (Merckle). I Drugs. 2003;6(8):802-8.
Simon LS, Lanza FL, Lipsky PE, Hubbard RC, Talwalker S, Schwartz BD, et al. Preliminary study of the safety and efficacy of SC-58635, a novel cyclooxygenase 2 inhibitor: efficacy and safety in two placebo controlled trials in osteoarthritis and rheumatoid arthritis, and studies of gastrointestinal and platelet effects. Arthritis Rheumat. 1998;41(9):1591-602.
Cicero AF, Laghi L. Activity and potential role of licofelone in the management of osteoarthritis. Clin Interv Aging. 2007;2(1):73.
Parente L. Pros and cons of selective inhibition of cyclooxygenase-2 versus dual lipoxygenase/ cyclooxygenase inhibition: is two better than one?. J Rheumatol. 2001;28(11):2375-82.
Leval XD, Julémont F, Delarge J, Pirotte B, Dogné JM. New trends in dual 5-LOX/COX inhibition. Curr Med Chem. 2002;9(9):941-62.
Tries S, Neupert W, Laufer S. The mechanism of action of the new antiinflammatory compound ML3000: inhibition of 5-LOX and COX-1/2. Inflamm Res. 2002;51(3):135-43.
Jia QI. Generating and screening a natural product library for cyclooxygenase and lipoxygenase dual inhibitors. Stud Nat Prod Chem. 2003;29:643-718.
Alvaro-Gracia JM. Licofelone-clinical update on a novel LOX/COX inhibitor for the treatment of osteoarthritis. Rheumatology. 2004;43(1):i21-5.
Cicero AF, Derosa G, Gaddi A. Combined lipoxygenase/cyclo-oxygenase inhibition in the elderly. Drugs Aging. 2005;22(5):393-403.
Dyer RD, Connor DT. Dual inhibitors of prostaglandin and leukotriene biosynthesis. Curr Pharm Des. 1997;3:463-72.
Bellamy NI, Kirwan J, Boers M, Brooks P, Strand VI, Tugwell P, et al. Recommendations for a core set of outcome measures for future phase III clinical trials in knee, hip, and hand osteoarthritis. Consensus development at OMERACT III. J Rheumatol. 1997;24(4):799-802.
Henriksen M, Hansen JB, Klokker L, Bliddal H, Christensen R. Comparable effects of exercise and analgesics for pain secondary to knee osteoarthritis: a meta-analysis of trials included in Cochrane systematic reviews. J Comp Eff Res. 2016;5(4):417-31.
Juhl C, Lund H, Roos EM, Zhang W, Christensen R. A hierarchy of patient-reported outcomes for meta-analysis of knee osteoarthritis trials: empirical evidence from a survey of high impact journals. Arthritis. 2012.
Lee KP, Schotland M, Bacchetti P, Bero LA. Association of journal quality indicators with methodological quality of clinical research articles. JAMA. 2002;287(21):2805-8.
Raynauld JP, Martel-Pelletier J, Bias P, Laufer S, Haraoui B, Choquette D, et al. Protective effects of licofelone, a 5-lipoxygenase and cyclo-oxygenase inhibitor, versus naproxen on cartilage loss in knee osteoarthritis: a first multicentre clinical trial using quantitative MRI. Ann Rheum Dis. 2009;68(6):938-47.
Sprangers MA, de Regt EB, Andries F, van Agt HM, Bijl RV, de Boer JB, Foets M, Hoeymans N, Jacobs AE, Kempen GI, Miedema HS. Which chronic conditions are associated with better or poorer quality of life?. J Clin Epidemiol. 2000;53(9):895-907.
Reginster JY. The prevalence and burden of arthritis. Rheumatology. 2002;41(1):3-6.
Davis MA. Epidemiology of osteoarthritis. Clin Geriatr Med. 1988;4(2):241-55.
Hilal G, Martel-Pelletier J, Pelletier JP, Ranger P, Lajeunesse D. Osteoblast like cells from human subchondral osteoarthritic bone demonstrate an altered phenotype in vitro: Possible role in subchondral bone sclerosis. Arthritis Rheum. 1998;41(5):891-9.
Smith WL, Garavito RM, DeWitt DL. Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and-2. J Biol Chem. 1996;271(52):33157-60.
Huskisson EC, Berry H, Gishen P, Jubb RW, Whitehead J. Effects of antiinflammatory drugs on the progression of osteoarthritis of the knee. LINK Study Group. Longitudinal Investigation of Nonsteroidal Antiinflammatory Drugs in Knee Osteoarthritis. J Rheumatol. 1995;22(10):1941-6.
Martel-Pelletier J, Lajeunesse D, Pelletier JP. Etiopathogenesis of osteoarthritis. Arthritis and Allied Conditions. J Rheumatol. 2005;15:2199-226.
Yang K, Ma W, Liang H, Ouyang Q, Tang C, Lai L. Dynamic simulations on the arachidonic acid metabolic network. PLoS Comput Biol. 2007;3(3):e55.
He W, Pelletier JP, Martel-Pelletier J, Laufer S, Di Battista JA. Synthesis of interleukin 1beta, tumor necrosis factor-alpha, and interstitial collagenase (MMP-1) is eicosanoid dependent in human osteoarthritis synovial membrane explants: interactions with antiinflammatory cytokines. J Rheumatol. 2002;29(3):546-53.
Cheng S, Afif H, Martel-Pelletier J, Pelletier JP, Li X, Farrajota K, et al. Activation of peroxisome proliferator-activated receptor γ inhibits interleukin-1β-induced membrane-associated prostaglandin E2 synthase-1 expression in human synovial fibroblasts by interfering with Egr-1. J Biol Chem. 2004; 279(21):22057-65.
Martel-Pelletier J, Mineau F, Fahmi H, Laufer S, Reboul P, Boileau C, et al. Regulation of the expression of 5-lipoxygenase–activating protein/5-lipoxygenase and the synthesis of leukotriene B4 in osteoarthritic chondrocytes: Role of transforming growth factor β and eicosanoids. Arthritis Rheum. 2004;50(12):3925-33.
Marcouiller P, Pelletier JP, Guévremont M, Martel-Pelletier J, Ranger P, Laufer S, et al. Leukotriene and prostaglandin synthesis pathways in osteoarthritic synovial membranes: regulating factors for interleukin 1beta synthesis. J Rheumatol. 2005;32(4): 704-12.
Paredes Y, Massicotte F, Pelletier JP, Martel-Pelletier J, Laufer S, Lajeunesse D. Study of the role of leukotriene B4 in abnormal function of human subchondral osteoarthritis osteoblasts: Effects of cyclooxygenase and/or 5-lipoxygenase inhibition. Arthritis Rheum. 2002;46(7):1804-12.
Laufer S. Discovery and development of ML3000. Inflammopharmacol. 2001;9(1):101-12.
Pelletier JP, Martel-Pelletier J, Abramson SB. Osteoarthritis, an inflammatory disease: potential implication for the selection of new therapeutic targets. Arthritis Rheum. 2001;44(6):1237-47.
Reginster JY. The prevalence and burden of arthritis. Rheumatology. 2002; 41(1):3-6.
Blanco FJ, Buchner A, Bias P, Lammerich A, Schulz U. Licofelone, an inhibitor of COX-1, COX-2 and 5-LOX, is as effective as naproxen and shows improved safety during 12 months of treatment in patients with osteoarthritis of the knee. Ann Rheum Dis. 2003;62:262-5.
Raynauld JP, Martel-Pelletier J, Bias P, Laufer S, Haraoui B, Choquette D, et al. Protective effects of licofelone, a 5-lipoxygenase and cyclo-oxygenase inhibitor, versus naproxen on cartilage loss in knee osteoarthritis: a first multicentre clinical trial using quantitative MRI. Ann Rheum Dis. 2009;68(6):938-47.
Aigner T, Hemmel M, Neureiter D, Gebhard PM, Zeiler G, Kirchner T, et al. Apoptotic cell death is not a widespread phenomenon in normal aging and osteoarthritic human articular knee cartilage: a study of proliferation, programmed cell death (apoptosis), and viability of chondrocytes in normal and osteoarthritic human knee cartilage. Arthritis Rheum. 2001;44(6):1304-12.
Burr DB, Schaffler MB. The involvement of subchondral mineralized tissues in osteoarthrosis: quantitative microscopic evidence. Microsc Res Tech. 1997;37(4):343-57.
Rodier F, Campisi J. Four faces of cellular senescenceFour faces of senescence. J Cell Biol. 2011;192(4):547-56.
Brophy RH, Rai MF, Zhang Z, Torgomyan A, Sandell LJ. Molecular analysis of age and sex-related gene expression in meniscal tears with and without a concomitant anterior cruciate ligament tear. The J Bone Joint Surg. 2012;94(5):385.
Greene MA, Loeser RF. Aging-related inflammation in osteoarthritis. Osteoarthr Cartil. 2015;23(11): 1966-71.
Raynauld JP, Martel-Pelletier J, Bias P, Laufer S, Haraoui B, Choquette D, et al. Protective effects of licofelone, a 5-lipoxygenase and cyclo-oxygenase inhibitor, versus naproxen on cartilage loss in knee osteoarthritis: a first multicentre clinical trial using quantitative MRI. Ann Rheum Dis. 2009;68(6):938-47.
Parente L. Pros and cons of selective inhibition of cyclooxygenase-2 versus dual lipoxygenase/cyclooxygenase inhibition: is two better than one?. J Rheumatol. 2001;28(11):2375-82.
Freund A, Orjalo AV, Desprez PY, Campisi J. Inflammatory networks during cellular senescence: causes and consequences. Trends Mol Med. 2010; 16(5):238-46.
Sohn DH, Sokolove J, Sharpe O, Erhart JC, Chandra PE, Lahey LJ, et al. Plasma proteins present in osteoarthritic synovial fluid can stimulate cytokine production via Toll-like receptor 4. Arthritis Res Ther. 2012;14(1):1-3.
Alaaeddine N, Olee T, Hashimoto S, Creighton-Achermann L, Lotz M. Production of the chemokine RANTES by articular chondrocytes and role in cartilage degradation. Arthritis Rheum. 2001;44(7): 1633-43.
Li WQ, Dehnade F, Zafarullah M. Oncostatin M-induced matrix metalloproteinase and tissue inhibitor of metalloproteinase-3 genes expression in chondrocytes requires Janus kinase/STAT signaling pathway. J Immun. 2001;166(5):3491-8.
Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum. 2012;64(6):1697.
Freund A, Patil CK, Campisi J. p38MAPK is a novel DNA damage response independent regulator of the senescence associated secretory phenotype. EMBO J. 2011;30(8):1536-48.
Reijman M, Bierma-Zeinstra SM, Pols HA, Koes BW, Stricker BH, Hazes JM. Is there an association between the use of different types of nonsteroidal antiinflammatory drugs and radiologic progression of osteoarthritis? The rotterdam study. Arthritis Rheum. 2005;52(10):3137-42.
Downloads
Published
How to Cite
Issue
Section
