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Published in: Drugs & Aging 2/2016

Open Access 01-02-2016 | Current Opinion

Diacerein: Benefits, Risks and Place in the Management of Osteoarthritis. An Opinion-Based Report from the ESCEO

Authors: Karel Pavelka, Olivier Bruyère, Cyrus Cooper, John A. Kanis, Burkhard F. Leeb, Emmanuel Maheu, Johanne Martel-Pelletier, Jordi Monfort, Jean-Pierre Pelletier, René Rizzoli, Jean-Yves Reginster

Published in: Drugs & Aging | Issue 2/2016

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Abstract

Diacerein is a symptomatic slow-acting drug in osteoarthritis (SYSADOA) with anti-inflammatory, anti-catabolic and pro-anabolic properties on cartilage and synovial membrane. It has also recently been shown to have protective effects against subchondral bone remodelling. Following the end of the revision procedure by the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency, the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) constituted a panel of 11 experts to better define the real place of diacerein in the armamentarium for treating OA. Based on a literature review of clinical trials and meta-analyses, the ESCEO confirms that the efficacy of diacerein is similar to that of non-steroidal anti-inflammatory drugs (NSAIDs) after the first month of treatment, and superior to that of paracetamol. Additionally, diacerein has shown a prolonged effect on symptoms of several months once treatment was stopped. The use of diacerein is associated with common gastrointestinal disorders such as soft stools and diarrhoea, common mild skin reactions, and, uncommonly, hepatobiliary disorders. However, NSAIDs and paracetamol are known to cause potentially severe hepatic, gastrointestinal, renal, cutaneous and cardiovascular reactions. Therefore, the ESCEO concludes that the benefit–risk balance of diacerein remains positive in the symptomatic treatment of hip and knee osteoarthritis. Furthermore, similarly to other SYSADOAs, the ESCEO positions diacerein as a first-line pharmacological background treatment of osteoarthritis, particularly for patients in whom NSAIDs or paracetamol are contraindicated.
Literature
1.
go back to reference Hunter DJ, Schofield D, Callander E. The individual and socioeconomic impact of osteoarthritis. Nat Rev Rheumatol. 2014;10(7):437–41.PubMed Hunter DJ, Schofield D, Callander E. The individual and socioeconomic impact of osteoarthritis. Nat Rev Rheumatol. 2014;10(7):437–41.PubMed
2.
go back to reference Jordan KM, Arden NK, Doherty M, Bannwarth B, Bijlsma JW, Dieppe P, 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). Ann Rheum Dis. 2003;62(12):1145–55.CrossRefPubMedPubMedCentral Jordan KM, Arden NK, Doherty M, Bannwarth B, Bijlsma JW, Dieppe P, 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). Ann Rheum Dis. 2003;62(12):1145–55.CrossRefPubMedPubMedCentral
4.
go back to reference Pelletier JP, Martel-Pelletier J. Therapeutic targets in osteoarthritis: from today to tomorrow with new imaging technology. Ann Rheum Dis. 2003;62 (Suppl 2):ii79–ii82. Pelletier JP, Martel-Pelletier J. Therapeutic targets in osteoarthritis: from today to tomorrow with new imaging technology. Ann Rheum Dis. 2003;62 (Suppl 2):ii79–ii82.
5.
go back to reference McAlindon TE, Bannuru RR, Sullivan MC, Arden NK, Berenbaum F, Bierma-Zeinstra SM, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthr Cartil. 2014;22:363–88 (Comment in: Osteoarthr Cartil. 2014;22(6):888–9; author’s reply 890–1; Corrigendum in: Osteoarthr Cartil. 2015;23(6):1026–34). McAlindon TE, Bannuru RR, Sullivan MC, Arden NK, Berenbaum F, Bierma-Zeinstra SM, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthr Cartil. 2014;22:363–88 (Comment in: Osteoarthr Cartil. 2014;22(6):888–9; author’s reply 890–1; Corrigendum in: Osteoarthr Cartil. 2015;23(6):1026–34).
6.
go back to reference Zhang W, Nuki G, Moskowitz RW, Abramson S, Altman RD, Arden NK, et al. OARSI recommendations for the management of hip and knee osteoarthritis: part III: changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthr Cartil. 2010;18(4):476–99.CrossRefPubMed Zhang W, Nuki G, Moskowitz RW, Abramson S, Altman RD, Arden NK, et al. OARSI recommendations for the management of hip and knee osteoarthritis: part III: changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthr Cartil. 2010;18(4):476–99.CrossRefPubMed
7.
go back to reference National Institute for Health and Clinical Excellence (NHS). Osteoarthritis: the care and management of osteoarthritis in adults. In: NICE clinical guideline 59. 2008. http://www.nice.org.uk/CG059. Accessed 1 Feb 2013. National Institute for Health and Clinical Excellence (NHS). Osteoarthritis: the care and management of osteoarthritis in adults. In: NICE clinical guideline 59. 2008. http://​www.​nice.​org.​uk/​CG059. Accessed 1 Feb 2013.
8.
go back to reference Bruyere O, Cooper C, Pelletier JP, Branco J, Luisa Brandi M, Guillemin F, et al. An algorithm recommendation for the management of knee osteoarthritis in Europe and internationally: a report from a task force of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). Semin Arthritis Rheum. 2014;44(3):253–63.CrossRefPubMed Bruyere O, Cooper C, Pelletier JP, Branco J, Luisa Brandi M, Guillemin F, et al. An algorithm recommendation for the management of knee osteoarthritis in Europe and internationally: a report from a task force of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). Semin Arthritis Rheum. 2014;44(3):253–63.CrossRefPubMed
9.
go back to reference Martel-Pelletier J, Pelletier JP. Effects of diacerein at the molecular level in the osteoarthritis disease process. Ther Adv Musculoskelet Dis. 2010;2(2):95–104.CrossRefPubMedPubMedCentral Martel-Pelletier J, Pelletier JP. Effects of diacerein at the molecular level in the osteoarthritis disease process. Ther Adv Musculoskelet Dis. 2010;2(2):95–104.CrossRefPubMedPubMedCentral
10.
go back to reference Moldovan F, Pelletier JP, Jolicoeur FC, Cloutier JM, Martel-Pelletier J. Diacerhein and rhein reduce the ICE-induced IL-1 beta and IL-18 activation in human osteoarthritic cartilage. Osteoarthr Cartil. 2000;8:186–96.CrossRefPubMed Moldovan F, Pelletier JP, Jolicoeur FC, Cloutier JM, Martel-Pelletier J. Diacerhein and rhein reduce the ICE-induced IL-1 beta and IL-18 activation in human osteoarthritic cartilage. Osteoarthr Cartil. 2000;8:186–96.CrossRefPubMed
11.
go back to reference Martel-Pelletier J, Mineau F, Jolicoeur FC, Cloutier JM, Pelletier JP. In vitro effects of diacerhein and rhein on interleukin 1 and tumor necrosis factor-alpha systems in human osteoarthritic synovium and chondrocytes. J Rheumatol. 1998;25(4):753–62.PubMed Martel-Pelletier J, Mineau F, Jolicoeur FC, Cloutier JM, Pelletier JP. In vitro effects of diacerhein and rhein on interleukin 1 and tumor necrosis factor-alpha systems in human osteoarthritic synovium and chondrocytes. J Rheumatol. 1998;25(4):753–62.PubMed
12.
go back to reference Pelletier JP, Mineau F, Ranger P, Tardif G, Martel-Pelletier J. The increased synthesis of inducible nitric oxide inhibits IL-1ra synthesis by human articular chondrocytes: possible role in osteoarthritic cartilage degradation. Osteoarthr Cartil. 1996;4(1):77–84.CrossRefPubMed Pelletier JP, Mineau F, Ranger P, Tardif G, Martel-Pelletier J. The increased synthesis of inducible nitric oxide inhibits IL-1ra synthesis by human articular chondrocytes: possible role in osteoarthritic cartilage degradation. Osteoarthr Cartil. 1996;4(1):77–84.CrossRefPubMed
13.
go back to reference Yaron M, Shirazi I, Yaron I. Anti-interleukin-1 effects of diacerein and rhein in human osteoarthritic synovial tissue and cartilage cultures. Osteoarthr Cartil. 1999;7(3):272–80.CrossRefPubMed Yaron M, Shirazi I, Yaron I. Anti-interleukin-1 effects of diacerein and rhein in human osteoarthritic synovial tissue and cartilage cultures. Osteoarthr Cartil. 1999;7(3):272–80.CrossRefPubMed
14.
go back to reference Barnes PJ, Karin M. Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med. 1997;336(15):1066–71.CrossRefPubMed Barnes PJ, Karin M. Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med. 1997;336(15):1066–71.CrossRefPubMed
15.
go back to reference Martin G, Bogdanowicz P, Domagala F, Ficheux H, Pujol JP. Rhein inhibits interleukin-1beta-induced activation of MEK/ERK pathway and DNA binding of NF-kappaB and AP-1 in chondrocytes cultured in hypoxia: a potential mechanism for its disease-modifying effect in osteoarthritis. Inflammation. 2003;27(4):233–46.CrossRefPubMed Martin G, Bogdanowicz P, Domagala F, Ficheux H, Pujol JP. Rhein inhibits interleukin-1beta-induced activation of MEK/ERK pathway and DNA binding of NF-kappaB and AP-1 in chondrocytes cultured in hypoxia: a potential mechanism for its disease-modifying effect in osteoarthritis. Inflammation. 2003;27(4):233–46.CrossRefPubMed
16.
go back to reference Ferreira Mendes A, Caramona MM, de Carvalho AP, Lopes MC. Diacerhein and rhein prevent interleukin-1 beta-induced nuclear factor-kappa B activation by inhibiting the degradation of inhibitor kappa B-alpha. Pharmacol Toxicol. 2002;91(1):22–8. Ferreira Mendes A, Caramona MM, de Carvalho AP, Lopes MC. Diacerhein and rhein prevent interleukin-1 beta-induced nuclear factor-kappa B activation by inhibiting the degradation of inhibitor kappa B-alpha. Pharmacol Toxicol. 2002;91(1):22–8.
17.
go back to reference Mathieu P. L’interleukine 1: son role, son dosage, ses difficultés d’approche dans l’arthrose. Résultats d’une étude ‘pilote ‘ avec la diacerhéine (ART 50) dans la gonarthrose [Interleukin 1 its role, quantitative determination and the difficulties in studying its role in osteoarthritis. Results of a ‘pilot’ study with diacerein (ART 50) in knee osteoarthritis]. Rev Prat. 1999;49(Suppl 13):S15–8. French. Mathieu P. L’interleukine 1: son role, son dosage, ses difficultés d’approche dans l’arthrose. Résultats d’une étude ‘pilote ‘ avec la diacerhéine (ART 50) dans la gonarthrose [Interleukin 1 its role, quantitative determination and the difficulties in studying its role in osteoarthritis. Results of a ‘pilot’ study with diacerein (ART 50) in knee osteoarthritis]. Rev Prat. 1999;49(Suppl 13):S15–8. French.
18.
go back to reference Felisaz N, Boumediene K, Ghayor C, Herrouin JF, Bogdanowicz P, Galerra P, et al. Stimulating effect of diacerein on TGF beta 1 and beta 2 expression in articular chondrocytes cultured with and without interleukin-1. Osteoarthr Cartil. 1999;7(3):255–64.CrossRefPubMed Felisaz N, Boumediene K, Ghayor C, Herrouin JF, Bogdanowicz P, Galerra P, et al. Stimulating effect of diacerein on TGF beta 1 and beta 2 expression in articular chondrocytes cultured with and without interleukin-1. Osteoarthr Cartil. 1999;7(3):255–64.CrossRefPubMed
19.
go back to reference Sanchez C, Mathy-Hartert M, Deberg MA, Ficheux H, Reginster JY, Henrotin YE. Effects of rhein on human articular chondrocytes in alginate beads. Biochem Pharmacol. 2003;65(3):377–88.CrossRefPubMed Sanchez C, Mathy-Hartert M, Deberg MA, Ficheux H, Reginster JY, Henrotin YE. Effects of rhein on human articular chondrocytes in alginate beads. Biochem Pharmacol. 2003;65(3):377–88.CrossRefPubMed
20.
go back to reference Schöngen RN, Giannetti BM, Van de Leur E, Reinards R, Greiling H. Effect of diacetylrhein on the phagocytosis of polymorphonuclear leucocytes and its influence on the biosynthesis of hyaluronate in synovial cells. Arzneimittelforschung. 1988;38(I)(5):744–8. Schöngen RN, Giannetti BM, Van de Leur E, Reinards R, Greiling H. Effect of diacetylrhein on the phagocytosis of polymorphonuclear leucocytes and its influence on the biosynthesis of hyaluronate in synovial cells. Arzneimittelforschung. 1988;38(I)(5):744–8.
21.
go back to reference Pelletier JP, Lajeunesse D, Reboul P, Mineau F, Fernandes JC, Sabouret P, et al. Diacerein reduces the excess synthesis of bone remodeling factors by human osteoblast cells from osteoarthritic subchondral bone. J Rheumatol. 2001;28(4):814–24.PubMed Pelletier JP, Lajeunesse D, Reboul P, Mineau F, Fernandes JC, Sabouret P, et al. Diacerein reduces the excess synthesis of bone remodeling factors by human osteoblast cells from osteoarthritic subchondral bone. J Rheumatol. 2001;28(4):814–24.PubMed
22.
go back to reference Legendre F, Bogdanowicz P, Martin G, Domagala F, Leclercq S, Pujol JP, et al. Rhein, a diacerhein-derived metabolite, modulates the expression of matrix degrading enzymes and the cell proliferation of articular chondrocytes by inhibiting ERK and JNK-AP-1 dependent pathways. Clin Exp Rheumatol. 2007;25(4):546–55.PubMed Legendre F, Bogdanowicz P, Martin G, Domagala F, Leclercq S, Pujol JP, et al. Rhein, a diacerhein-derived metabolite, modulates the expression of matrix degrading enzymes and the cell proliferation of articular chondrocytes by inhibiting ERK and JNK-AP-1 dependent pathways. Clin Exp Rheumatol. 2007;25(4):546–55.PubMed
23.
go back to reference Pelletier JP, Mineau F, Fernandes JC, Duval N, Martel-Pelletier J. Diacerhein and rhein reduce the interleukin 1 beta stimulated inducible nitric oxide synthesis level and activity while stimulating cyclooxygenase-2 synthesis in human osteoarthritic chondrocytes. J Rheumatol. 1998;25(12):2417–24.PubMed Pelletier JP, Mineau F, Fernandes JC, Duval N, Martel-Pelletier J. Diacerhein and rhein reduce the interleukin 1 beta stimulated inducible nitric oxide synthesis level and activity while stimulating cyclooxygenase-2 synthesis in human osteoarthritic chondrocytes. J Rheumatol. 1998;25(12):2417–24.PubMed
24.
go back to reference Martel-Pelletier J, Mineau F, Caron J, Pelletier JP. Effect of diacerein/rhein on the Wnt system in human osteoarthritic subchondral bone [abstract]. Ann Rheum Dis. 2011;70(Suppl 3):354 (Abstract no. FRI0025). Martel-Pelletier J, Mineau F, Caron J, Pelletier JP. Effect of diacerein/rhein on the Wnt system in human osteoarthritic subchondral bone [abstract]. Ann Rheum Dis. 2011;70(Suppl 3):354 (Abstract no. FRI0025).
25.
go back to reference Boileau C, Tat SK, Pelletier JP, Cheng S, Martel-Pelletier J. Diacerein inhibits the synthesis of resorptive enzymes and reduces osteoclastic differentiation/survival in osteoarthritic subchondral bone: a possible mechanism for a protective effect against subchondral bone remodelling. Arthritis Res Ther. 2008;10(3):R71.CrossRefPubMedPubMedCentral Boileau C, Tat SK, Pelletier JP, Cheng S, Martel-Pelletier J. Diacerein inhibits the synthesis of resorptive enzymes and reduces osteoclastic differentiation/survival in osteoarthritic subchondral bone: a possible mechanism for a protective effect against subchondral bone remodelling. Arthritis Res Ther. 2008;10(3):R71.CrossRefPubMedPubMedCentral
26.
go back to reference Brandt KD, Smith G, Kang SY, Myers S, O’Connor B, Albrecht M. Effects of diacerhein in an accelerated canine model of osteoarthritis. Osteoarthr Cartil. 1997;5:438–49.CrossRefPubMed Brandt KD, Smith G, Kang SY, Myers S, O’Connor B, Albrecht M. Effects of diacerhein in an accelerated canine model of osteoarthritis. Osteoarthr Cartil. 1997;5:438–49.CrossRefPubMed
27.
go back to reference Smith GN Jr, Myers SL, Brandt KD, Mickler EA, Albrecht ME. Diacerhein treatment reduces the severity of osteoarthritis in the canine cruciate-deficiency model of osteoarthritis. Arthritis Rheum. 1999;42(3):545–54.CrossRefPubMed Smith GN Jr, Myers SL, Brandt KD, Mickler EA, Albrecht ME. Diacerhein treatment reduces the severity of osteoarthritis in the canine cruciate-deficiency model of osteoarthritis. Arthritis Rheum. 1999;42(3):545–54.CrossRefPubMed
28.
go back to reference Ghosh P, Xu A, Hwa SY, Burkhardt D, Little C. Evaluation des effets de la diacerhéine dans un modele ovin d’arthrose [Evaluation of the effects of diacerhein in an ovine model of osteoarthritis]. Rev Prat. 1998;48(Suppl 17):S24–30. French. Ghosh P, Xu A, Hwa SY, Burkhardt D, Little C. Evaluation des effets de la diacerhéine dans un modele ovin d’arthrose [Evaluation of the effects of diacerhein in an ovine model of osteoarthritis]. Rev Prat. 1998;48(Suppl 17):S24–30. French.
29.
go back to reference Bendele AM, Bendele RA, Hulman JF, Swann BP. Effets bénéfiques d’un traitement par la diacerhéine chez des cobayes atteints d’arthrose [The beneficial effects of diacerein treatment in a guinea pig model of osteoarthritis]. Rev Prat. 1996;46:S35–9. French.PubMed Bendele AM, Bendele RA, Hulman JF, Swann BP. Effets bénéfiques d’un traitement par la diacerhéine chez des cobayes atteints d’arthrose [The beneficial effects of diacerein treatment in a guinea pig model of osteoarthritis]. Rev Prat. 1996;46:S35–9. French.PubMed
30.
go back to reference Mazieres B, Berda L. Effect of diacerheine (ART 50) on an experimental post-contusive model of OA. Osteoarthr Cartil. 1993;1(1):47. Mazieres B, Berda L. Effect of diacerheine (ART 50) on an experimental post-contusive model of OA. Osteoarthr Cartil. 1993;1(1):47.
31.
go back to reference Kitadai HK, Takahashi HK, Straus AH, Ibanez JF, Lucas R, Kitadai FT, et al. Effect of oral diacerein (DAR) in an experimental hip chondrolysis model. J Orthop Res. 2006;24(6):1240–8.CrossRefPubMed Kitadai HK, Takahashi HK, Straus AH, Ibanez JF, Lucas R, Kitadai FT, et al. Effect of oral diacerein (DAR) in an experimental hip chondrolysis model. J Orthop Res. 2006;24(6):1240–8.CrossRefPubMed
32.
go back to reference de Rezende MU, de Campos Gurgel HM, Vilaca Junior PR, Kuroba RK, Lopes AS, Phillipi RZ, et al. Diacerhein versus glucosamine in a rat model of osteoarthritis. Clinics. 2006;61(5):461–6.CrossRefPubMed de Rezende MU, de Campos Gurgel HM, Vilaca Junior PR, Kuroba RK, Lopes AS, Phillipi RZ, et al. Diacerhein versus glucosamine in a rat model of osteoarthritis. Clinics. 2006;61(5):461–6.CrossRefPubMed
33.
go back to reference Marcolongo R, Fioravanti A, Adami S, Tozzi E, Mian M, Zampieri A. Efficacy and tolerability of Diacerhein in the treatment of osteoarthrosis. Curr Ther Res. 1988;43(5):878–87. Marcolongo R, Fioravanti A, Adami S, Tozzi E, Mian M, Zampieri A. Efficacy and tolerability of Diacerhein in the treatment of osteoarthrosis. Curr Ther Res. 1988;43(5):878–87.
34.
go back to reference Nguyen M, Dougados M, Berdah L, Amor B. Diacerhein in the treatment of osteoarthritis of the hip. Arthritis Rheum. 1994;37(4):529–36.CrossRefPubMed Nguyen M, Dougados M, Berdah L, Amor B. Diacerhein in the treatment of osteoarthritis of the hip. Arthritis Rheum. 1994;37(4):529–36.CrossRefPubMed
35.
go back to reference Delcambre B, Taccoen A. Etude d’ART 50 en pratique rhumatologique quotidienne [Study of ART 50 in daily rheumatological practice]. Rev Prat. 1996;46(6 Spec No):S49–S52. French. Delcambre B, Taccoen A. Etude d’ART 50 en pratique rhumatologique quotidienne [Study of ART 50 in daily rheumatological practice]. Rev Prat. 1996;46(6 Spec No):S49–S52. French.
36.
go back to reference Fagnani F, Bouvenot G, Valat JP, Bardin T, Berdah L, Lafuma A, et al. Medico-economic analysis of diacerein with or without standard therapy in the treatment of osteoarthritis. Pharmacoeconomics. 1998;13(1 Pt 2):135–46.CrossRefPubMed Fagnani F, Bouvenot G, Valat JP, Bardin T, Berdah L, Lafuma A, et al. Medico-economic analysis of diacerein with or without standard therapy in the treatment of osteoarthritis. Pharmacoeconomics. 1998;13(1 Pt 2):135–46.CrossRefPubMed
37.
go back to reference Lequesne M, Berdah L, Gérentes I. Efficacité et tolérance de la diacerhéine dans le traitement de la gonarthrose et de la coxarthrose [Efficacy and tolerance of diacerhein in the treatment of gonarthrosis and coxarthrosis]. Rev Prat. 1998;48(Suppl 17):S31–5. French. Lequesne M, Berdah L, Gérentes I. Efficacité et tolérance de la diacerhéine dans le traitement de la gonarthrose et de la coxarthrose [Efficacy and tolerance of diacerhein in the treatment of gonarthrosis and coxarthrosis]. Rev Prat. 1998;48(Suppl 17):S31–5. French.
38.
go back to reference Chantre P, Cappelaere A, Leblan D, Guedon D, Vandermander J, Fournie B. Efficacy and tolerance of Harpagophytum procumbens versus diacerhein in treatment of osteoarthritis. Phytomedicine. 2000;7(3):177–83.CrossRefPubMed Chantre P, Cappelaere A, Leblan D, Guedon D, Vandermander J, Fournie B. Efficacy and tolerance of Harpagophytum procumbens versus diacerhein in treatment of osteoarthritis. Phytomedicine. 2000;7(3):177–83.CrossRefPubMed
39.
go back to reference Pelletier JP, Yaron M, Haraoui B, Cohen P, Nahir MA, Choquette D, et al. Efficacy and safety of diacerein in osteoarthritis of the knee: a double-blind, placebo-controlled trial. The Diacerein Study Group. Arthritis Rheum. 2000;43(10):2339–48.CrossRefPubMed Pelletier JP, Yaron M, Haraoui B, Cohen P, Nahir MA, Choquette D, et al. Efficacy and safety of diacerein in osteoarthritis of the knee: a double-blind, placebo-controlled trial. The Diacerein Study Group. Arthritis Rheum. 2000;43(10):2339–48.CrossRefPubMed
40.
go back to reference Dougados M, Nguyen M, Berdah L, Mazieres B, Vignon E, Lequesne M. Evaluation of the structure-modifying effects of diacerein in hip osteoarthritis: ECHODIAH, a three-year, placebo-controlled trial. Arthritis Rheum. 2001;44(11):2539–47.CrossRefPubMed Dougados M, Nguyen M, Berdah L, Mazieres B, Vignon E, Lequesne M. Evaluation of the structure-modifying effects of diacerein in hip osteoarthritis: ECHODIAH, a three-year, placebo-controlled trial. Arthritis Rheum. 2001;44(11):2539–47.CrossRefPubMed
41.
go back to reference Pham T, Le Henanff A, Ravaud P, Dieppe P, Paolozzi L, Dougados M. Evaluation of the symptomatic and structural efficacy of a new hyaluronic acid compound, NRD101, in comparison with diacerein and placebo in a 1 year randomised controlled study in symptomatic knee osteoarthritis. Ann Rheum Dis. 2004;63(12):1611–7.CrossRefPubMedPubMedCentral Pham T, Le Henanff A, Ravaud P, Dieppe P, Paolozzi L, Dougados M. Evaluation of the symptomatic and structural efficacy of a new hyaluronic acid compound, NRD101, in comparison with diacerein and placebo in a 1 year randomised controlled study in symptomatic knee osteoarthritis. Ann Rheum Dis. 2004;63(12):1611–7.CrossRefPubMedPubMedCentral
42.
go back to reference Jayaram S, Shetty N, Krishnamurthy V, Sharma VD, Naik MN, Apsangikar PD. Clinical study of the efficacy and tolerability of diacerein in the treatment of mild to moderate osteoarthritis: a randomized, multicentre, comparative study. Indian Pract. 2005;58(11):683–91. Jayaram S, Shetty N, Krishnamurthy V, Sharma VD, Naik MN, Apsangikar PD. Clinical study of the efficacy and tolerability of diacerein in the treatment of mild to moderate osteoarthritis: a randomized, multicentre, comparative study. Indian Pract. 2005;58(11):683–91.
43.
go back to reference Zheng WJ, Tang FL, Li J, Zhang FC, Li ZG, Su Y, et al. Efficacy and safety of diacerein in osteoarthritis of the knee: a randomized, multicenter, double-dummy, diclofenac-controlled trial in China. APLAR J Rheumatol. 2006;9(1):64–9.CrossRef Zheng WJ, Tang FL, Li J, Zhang FC, Li ZG, Su Y, et al. Efficacy and safety of diacerein in osteoarthritis of the knee: a randomized, multicenter, double-dummy, diclofenac-controlled trial in China. APLAR J Rheumatol. 2006;9(1):64–9.CrossRef
44.
go back to reference Pavelka K, Trc T, Karpas K, Vitek P, Sedlackova M, Vlasakova V, et al. The efficacy and safety of diacerein in the treatment of painful osteoarthritis of the knee: a randomized, multicenter, double-blind, placebo-controlled study with primary end points at two months after the end of a three-month treatment period. Arthritis Rheum. 2007;56(12):4055–64.CrossRefPubMed Pavelka K, Trc T, Karpas K, Vitek P, Sedlackova M, Vlasakova V, et al. The efficacy and safety of diacerein in the treatment of painful osteoarthritis of the knee: a randomized, multicenter, double-blind, placebo-controlled study with primary end points at two months after the end of a three-month treatment period. Arthritis Rheum. 2007;56(12):4055–64.CrossRefPubMed
45.
go back to reference Louthrenoo W, Nilganuwong S, Aksaranugraha S, Asavatanabodee P, Saengnipanthkul S, The Thai Study Group. The efficacy, safety and carry-over effect of diacerein in the treatment of painful knee osteoarthritis: a randomised, double-blind, NSAID-controlled study. Osteoarthr Cartil. 2007;15(6):605–14.CrossRefPubMed Louthrenoo W, Nilganuwong S, Aksaranugraha S, Asavatanabodee P, Saengnipanthkul S, The Thai Study Group. The efficacy, safety and carry-over effect of diacerein in the treatment of painful knee osteoarthritis: a randomised, double-blind, NSAID-controlled study. Osteoarthr Cartil. 2007;15(6):605–14.CrossRefPubMed
46.
go back to reference Sharma A, Rathod R, Baliga VP. An open prospective study on postmarketing evaluation of the efficacy and tolerability of diacerein in osteo-arthritis of the knee (DOK). J Indian Med Assoc. 2008;106(1):54–6, 58. Sharma A, Rathod R, Baliga VP. An open prospective study on postmarketing evaluation of the efficacy and tolerability of diacerein in osteo-arthritis of the knee (DOK). J Indian Med Assoc. 2008;106(1):54–6, 58.
47.
go back to reference Brahmachari B, Chatterjee S, Ghosh A. Efficacy and safety of diacerein in early knee osteoarthritis: a randomized placebo-controlled trial. Clin Rheumatol. 2009;28(10):1193–8.CrossRefPubMed Brahmachari B, Chatterjee S, Ghosh A. Efficacy and safety of diacerein in early knee osteoarthritis: a randomized placebo-controlled trial. Clin Rheumatol. 2009;28(10):1193–8.CrossRefPubMed
48.
go back to reference Singh K, Sharma R, Rai J. Diacerein as adjuvant to diclofenac sodium in osteoarthritis knee. Int J Rheum Dis. 2012;15(1):69–77.CrossRefPubMed Singh K, Sharma R, Rai J. Diacerein as adjuvant to diclofenac sodium in osteoarthritis knee. Int J Rheum Dis. 2012;15(1):69–77.CrossRefPubMed
49.
go back to reference Rintelen B, Neumann K, Leeb BF. A meta-analysis of controlled clinical studies with diacerein in the treatment of osteoarthritis. Arch Intern Med. 2006;166(17):1899–906 (Erratum in: Arch Intern Med. 2007;167(5):444). Rintelen B, Neumann K, Leeb BF. A meta-analysis of controlled clinical studies with diacerein in the treatment of osteoarthritis. Arch Intern Med. 2006;166(17):1899–906 (Erratum in: Arch Intern Med. 2007;167(5):444).
50.
go back to reference Fidelix TS, Soares B, Fernandes Moca Trevisani V. Diacerein for osteoarthritis. Cochrane Database Syst Rev. 2006;1:CD005117. Fidelix TS, Soares B, Fernandes Moca Trevisani V. Diacerein for osteoarthritis. Cochrane Database Syst Rev. 2006;1:CD005117.
51.
go back to reference Fidelix TS, Macedo CR, Maxwell LJ, Fernandes Moca Trevisani V. Diacerein for osteoarthritis. Cochrane Database Syst Rev. 2014;2:CD005117. Fidelix TS, Macedo CR, Maxwell LJ, Fernandes Moca Trevisani V. Diacerein for osteoarthritis. Cochrane Database Syst Rev. 2014;2:CD005117.
52.
go back to reference Bartels EM, Bliddal H, Schondorff PK, Altman RD, Zhang W, Christensen R. Symptomatic efficacy and safety of diacerein in the treatment of osteoarthritis: a meta-analysis of randomized placebo-controlled trials. Osteoarthr Cartil. 2010;18(3):289–96.CrossRefPubMed Bartels EM, Bliddal H, Schondorff PK, Altman RD, Zhang W, Christensen R. Symptomatic efficacy and safety of diacerein in the treatment of osteoarthritis: a meta-analysis of randomized placebo-controlled trials. Osteoarthr Cartil. 2010;18(3):289–96.CrossRefPubMed
53.
go back to reference Mattara L. DAR: indagini “controllate” nel trattamento della osteoartosi [DAR “Controlled” studies in treatment of osteoarthrosis]. Paper presented at: Simposio Proter sulla diacereina. 86th Congresso Nazionale della Societa Italiana di Medicina Interna, 1985 Sep 24–27; Sorrento, Italy. Italian. Mattara L. DAR: indagini “controllate” nel trattamento della osteoartosi [DAR “Controlled” studies in treatment of osteoarthrosis]. Paper presented at: Simposio Proter sulla diacereina. 86th Congresso Nazionale della Societa Italiana di Medicina Interna, 1985 Sep 24–27; Sorrento, Italy. Italian.
54.
go back to reference Pietrogrande V, Leonardi M, Pacchioni C. Risultati della sperimentazione clinica in pazienti artrosici di un nuovo farmaco: la diacereina [Results of a clinical study with a new drug (Diacerein) in osteoarthritis patients]. Paper presented at: Simposio Proter sulla diacereina. 86th Congresso Nazionale della Societa Italiana di Medicina Interna, 1985 Sep 24–27; Sorrento, Italy. Italian. Pietrogrande V, Leonardi M, Pacchioni C. Risultati della sperimentazione clinica in pazienti artrosici di un nuovo farmaco: la diacereina [Results of a clinical study with a new drug (Diacerein) in osteoarthritis patients]. Paper presented at: Simposio Proter sulla diacereina. 86th Congresso Nazionale della Societa Italiana di Medicina Interna, 1985 Sep 24–27; Sorrento, Italy. Italian.
55.
go back to reference Fioravanti A, Marcolongo R. Efficacia terapeutica della Diacereina (DAR) nell’artrosi del ginocchio e dell’ anca [Therapeutic effectiveness of Diacerhein (DAR) in arthrosis of knee and hip]. Paper presented at: Toscana Medicina Symposium on Diacereina, Pisa, Italy. 1985 Oct 1. Italian. Fioravanti A, Marcolongo R. Efficacia terapeutica della Diacereina (DAR) nell’artrosi del ginocchio e dell’ anca [Therapeutic effectiveness of Diacerhein (DAR) in arthrosis of knee and hip]. Paper presented at: Toscana Medicina Symposium on Diacereina, Pisa, Italy. 1985 Oct 1. Italian.
56.
go back to reference Mordini M, Nencioni C, Lavagni A, Camarri E. Diacereina VS naproxene nella coxo-gonoartrosi: studio randomizzato in doppio ciego [Diacerhein versus naproxen in coxo-gonarthrosis: double-blind randomized study]. Paper presented at: 27th Congresso Nazionale della Societa Italiana di Reumatologia, 1986 Oct 30–Nov 2; Montecatini, Italy. Italian. Mordini M, Nencioni C, Lavagni A, Camarri E. Diacereina VS naproxene nella coxo-gonoartrosi: studio randomizzato in doppio ciego [Diacerhein versus naproxen in coxo-gonarthrosis: double-blind randomized study]. Paper presented at: 27th Congresso Nazionale della Societa Italiana di Reumatologia, 1986 Oct 30–Nov 2; Montecatini, Italy. Italian.
57.
go back to reference Mantia S. A controlled study of the efficacy and tolerability of Diacetylrhein in the functional manifestations of osteoarthritis of the hip and the knee. A double-blind study versus diclofenac [study report]. Palermo (Italy): Hospital of Palermo; 1987. Mantia S. A controlled study of the efficacy and tolerability of Diacetylrhein in the functional manifestations of osteoarthritis of the hip and the knee. A double-blind study versus diclofenac [study report]. Palermo (Italy): Hospital of Palermo; 1987.
58.
go back to reference Portioli I. A naproxen-controlled study on the efficacy and tolerability of diacetylrhein in the functional manifestations of osteoarthritis of the knee and hip. A double-blind study versus naproxen [study report]. Reggio Emilia (Italy): Hospital Santa Maria Nuova; 1987. Portioli I. A naproxen-controlled study on the efficacy and tolerability of diacetylrhein in the functional manifestations of osteoarthritis of the knee and hip. A double-blind study versus naproxen [study report]. Reggio Emilia (Italy): Hospital Santa Maria Nuova; 1987.
59.
go back to reference Tang FL, Wu DH, Lu ZG, Huang F, Zhou YX. The efficacy and safety of diacerein in the treatment of painful knee osteoarthritis. Paper presented at: 11th Asia Pacific League of Associations for Rheumatology (APLAR) Congress, International Convention Center (ICC), 2004 Sep 11–15; Jeju, Korea. Tang FL, Wu DH, Lu ZG, Huang F, Zhou YX. The efficacy and safety of diacerein in the treatment of painful knee osteoarthritis. Paper presented at: 11th Asia Pacific League of Associations for Rheumatology (APLAR) Congress, International Convention Center (ICC), 2004 Sep 11–15; Jeju, Korea.
60.
go back to reference Ascherl R. Longterm treatment of osteoarthritis of the knee: a six months placebo-controlled clinical trial with diacerhein. Paper presented at: 2nd OARSI International Congress Symposium: Diacerhein and Interleukin 1 inhibition: a new therapeutical approach in osteoarthritis, 1995 Feb 4–5; Nice, France. Ascherl R. Longterm treatment of osteoarthritis of the knee: a six months placebo-controlled clinical trial with diacerhein. Paper presented at: 2nd OARSI International Congress Symposium: Diacerhein and Interleukin 1 inhibition: a new therapeutical approach in osteoarthritis, 1995 Feb 4–5; Nice, France.
61.
go back to reference Schulitz KP. Clinical investigation of the efficacy and tolerance of Diacetylrhein (DAR) in the treatment of osteoarthritis of the knee [study report]. Cologne (Germany): Madaus AG; 1994 Oct 27. 468 p. Report No. R-DA139. Schulitz KP. Clinical investigation of the efficacy and tolerance of Diacetylrhein (DAR) in the treatment of osteoarthritis of the knee [study report]. Cologne (Germany): Madaus AG; 1994 Oct 27. 468 p. Report No. R-DA139.
62.
go back to reference Combe B, Dougados M, Goupille P, Cantagrel A, Eliaou JF, Sibilia J, et al. Prognostic factors for radiographic damage in early rheumatoid arthritis: a multiparameter prospective study. Arthritis Rheum. 2001;44(8):1736–43.CrossRefPubMed Combe B, Dougados M, Goupille P, Cantagrel A, Eliaou JF, Sibilia J, et al. Prognostic factors for radiographic damage in early rheumatoid arthritis: a multiparameter prospective study. Arthritis Rheum. 2001;44(8):1736–43.CrossRefPubMed
64.
go back to reference Renan X, Lepage M, Connan D, Carlhant D, Riche C, Verger P, et al. Cas clinique d’une hépatite fatale a la diacerhéine [Case report of fatal hepatitis from diacerein]. Thérapie. 2001;56(2):190–1. French (Comment in: Thérapie. 2001;56:637–638). Renan X, Lepage M, Connan D, Carlhant D, Riche C, Verger P, et al. Cas clinique d’une hépatite fatale a la diacerhéine [Case report of fatal hepatitis from diacerein]. Thérapie. 2001;56(2):190–1. French (Comment in: Thérapie. 2001;56:637–638).
65.
go back to reference Mattei E, Marzoli GA, Oberto G, Brunetti MM. Diacerein effects on the cardiovascular function of the conscious dog following repeated oral administration [study report]. Rome (Italy): RTC Research Toxicology Centre; 2009. 81 p. RTC Study No. 70600. Mattei E, Marzoli GA, Oberto G, Brunetti MM. Diacerein effects on the cardiovascular function of the conscious dog following repeated oral administration [study report]. Rome (Italy): RTC Research Toxicology Centre; 2009. 81 p. RTC Study No. 70600.
66.
go back to reference Middel B, van Sonderen E. Statistical significant change versus relevant or important change in (quasi) experimental design: some conceptual and methodological problems in estimating magnitude of intervention-related change in health services research. Int J Integr Care. 2002;2:e15.CrossRefPubMedPubMedCentral Middel B, van Sonderen E. Statistical significant change versus relevant or important change in (quasi) experimental design: some conceptual and methodological problems in estimating magnitude of intervention-related change in health services research. Int J Integr Care. 2002;2:e15.CrossRefPubMedPubMedCentral
67.
go back to reference Zhang W, Robertson J, Jones AC, Dieppe PA, Doherty M. The placebo effect and its determinants in osteoarthritis: meta-analysis of randomised controlled trials. Ann Rheum Dis. 2008;67(12):1716–23 (Comment in: Minerva. 2009;8(9):117). Zhang W, Robertson J, Jones AC, Dieppe PA, Doherty M. The placebo effect and its determinants in osteoarthritis: meta-analysis of randomised controlled trials. Ann Rheum Dis. 2008;67(12):1716–23 (Comment in: Minerva. 2009;8(9):117).
68.
go back to reference Ratnaike RN, Jones TE. Mechanisms of drug-induced diarrhoea in the elderly. Drugs Aging. 1998;13(3):245–53.CrossRefPubMed Ratnaike RN, Jones TE. Mechanisms of drug-induced diarrhoea in the elderly. Drugs Aging. 1998;13(3):245–53.CrossRefPubMed
69.
go back to reference Larson AM, Polson J, Fontana RJ, Davern TJ, Lalani E, Hynan LS, et al. Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology. 2005;42(6):1364–72.CrossRefPubMed Larson AM, Polson J, Fontana RJ, Davern TJ, Lalani E, Hynan LS, et al. Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology. 2005;42(6):1364–72.CrossRefPubMed
71.
go back to reference Gulmez SE, Larrey D, Pageaux GP, Lignot S, Lassalle R, Jove J, et al. Transplantation for acute liver failure in patients exposed to NSAIDs or paracetamol (acetaminophen): the multinational case-population SALT study. Drug Saf. 2013;36(2):135–44.CrossRefPubMedPubMedCentral Gulmez SE, Larrey D, Pageaux GP, Lignot S, Lassalle R, Jove J, et al. Transplantation for acute liver failure in patients exposed to NSAIDs or paracetamol (acetaminophen): the multinational case-population SALT study. Drug Saf. 2013;36(2):135–44.CrossRefPubMedPubMedCentral
72.
go back to reference Rahme E, Barkun A, Nedjar H, Gaugris S, Watson D. Hospitalizations for upper and lower GI events associated with traditional NSAIDs and acetaminophen among the elderly in Quebec, Canada. Am J Gastroenterol. 2008;103(4):872–82.CrossRefPubMed Rahme E, Barkun A, Nedjar H, Gaugris S, Watson D. Hospitalizations for upper and lower GI events associated with traditional NSAIDs and acetaminophen among the elderly in Quebec, Canada. Am J Gastroenterol. 2008;103(4):872–82.CrossRefPubMed
73.
go back to reference 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 anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013;382(9894):769–79 (Comment in: Lancet. 2013; 382(9894): 746–748). 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 anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013;382(9894):769–79 (Comment in: Lancet. 2013; 382(9894): 746–748).
74.
go back to reference Whelton A. Nephrotoxicity of nonsteroidal anti-inflammatory drugs: physiologic foundations and clinical implications. Am J Med. 1999;106(5B):13S–24S.CrossRefPubMed Whelton A. Nephrotoxicity of nonsteroidal anti-inflammatory drugs: physiologic foundations and clinical implications. Am J Med. 1999;106(5B):13S–24S.CrossRefPubMed
75.
go back to reference Schneider V, Levesque LE, Zhang B, Hutchinson T, Brophy JM. Association of selective and conventional nonsteroidal antiinflammatory drugs with acute renal failure: A population-based, nested case-control analysis. Am J Epidemiol. 2006;164(9):881–9.CrossRefPubMed Schneider V, Levesque LE, Zhang B, Hutchinson T, Brophy JM. Association of selective and conventional nonsteroidal antiinflammatory drugs with acute renal failure: A population-based, nested case-control analysis. Am J Epidemiol. 2006;164(9):881–9.CrossRefPubMed
76.
77.
go back to reference Roberts E, Delgado Nunes V, Buckner S, Latchem S, Constanti M, Miller P, et al. Paracetamol: not as safe as we thought? A systematic literature review of observational studies. Ann Rheum Dis. 2015. Roberts E, Delgado Nunes V, Buckner S, Latchem S, Constanti M, Miller P, et al. Paracetamol: not as safe as we thought? A systematic literature review of observational studies. Ann Rheum Dis. 2015.
78.
go back to reference Svensson CK, Cowen EW, Gaspari AA. Cutaneous drug reactions. Pharmacol Rev. 2000;53:357–79. Svensson CK, Cowen EW, Gaspari AA. Cutaneous drug reactions. Pharmacol Rev. 2000;53:357–79.
80.
go back to reference Jüni P, Nartey L, Reichenbach S, Sterchi R, Dieppe PA, Egger M. Risk of cardiovascular events and rofecoxib: cumulative meta-analysis. Lancet. 2004;364(9450):2021–9.CrossRefPubMed Jüni P, Nartey L, Reichenbach S, Sterchi R, Dieppe PA, Egger M. Risk of cardiovascular events and rofecoxib: cumulative meta-analysis. Lancet. 2004;364(9450):2021–9.CrossRefPubMed
81.
go back to reference Chan AT, Manson JE, Albert CM, Chae CU, Rexrode KM, Curhan GC, et al. Nonsteroidal antiinflammatory drugs, acetaminophen, and the risk of cardiovascular events. Circulation. 2006;113(12):1578–87.CrossRefPubMed Chan AT, Manson JE, Albert CM, Chae CU, Rexrode KM, Curhan GC, et al. Nonsteroidal antiinflammatory drugs, acetaminophen, and the risk of cardiovascular events. Circulation. 2006;113(12):1578–87.CrossRefPubMed
82.
go back to reference 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):1–18.CrossRef 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):1–18.CrossRef
83.
go back to reference Walker AM. Quantitative studies of the risk of serious hepatic injury in persons using nonsteroidal antiinflammatory drugs. Arthritis Rheum. 1997;40(2):201–8.CrossRefPubMed Walker AM. Quantitative studies of the risk of serious hepatic injury in persons using nonsteroidal antiinflammatory drugs. Arthritis Rheum. 1997;40(2):201–8.CrossRefPubMed
84.
go back to reference Kowalski ML, Makowska JS, Blanca M, Bavbek S, Bochenek G, Bousquet J, et al. Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs)—classification, diagnosis and management: review of the EAACI/ENDA and GA2LEN/HANNA. Allergy. 2011;66(7):818–29.CrossRefPubMed Kowalski ML, Makowska JS, Blanca M, Bavbek S, Bochenek G, Bousquet J, et al. Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs)—classification, diagnosis and management: review of the EAACI/ENDA and GA2LEN/HANNA. Allergy. 2011;66(7):818–29.CrossRefPubMed
85.
go back to reference Sanmarkan AD, Sori T, Thappa DM, Jaisankar TJ. Retrospective analysis of Stevens–Johnson syndrome and toxic epidermal necrolysis over a period of 10 years. Indian J Dermatol. 2011;56(1):25–9.CrossRefPubMedPubMedCentral Sanmarkan AD, Sori T, Thappa DM, Jaisankar TJ. Retrospective analysis of Stevens–Johnson syndrome and toxic epidermal necrolysis over a period of 10 years. Indian J Dermatol. 2011;56(1):25–9.CrossRefPubMedPubMedCentral
86.
go back to reference Page J, Henry D. Consumption of NSAIDs and the development of congestive heart failure in elderly patients: an underrecognized public health problem. Arch Intern Med. 2000;160(6):777–84.CrossRefPubMed Page J, Henry D. Consumption of NSAIDs and the development of congestive heart failure in elderly patients: an underrecognized public health problem. Arch Intern Med. 2000;160(6):777–84.CrossRefPubMed
87.
go back to reference Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ. 2006;332(7553):1302–8.CrossRefPubMedPubMedCentral Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ. 2006;332(7553):1302–8.CrossRefPubMedPubMedCentral
88.
go back to reference Panova E, Jones G. Benefit-risk assessment of diacerein in the treatment of osteoarthritis. Drug Saf. 2015;38:245–52.CrossRefPubMed Panova E, Jones G. Benefit-risk assessment of diacerein in the treatment of osteoarthritis. Drug Saf. 2015;38:245–52.CrossRefPubMed
89.
go back to reference Bruyere O, Cooper C, Arden N, Branco J, Brandi ML, Herrero-Beaumont G, et al. Can we identify patients with high risk of osteoarthritis progression who will respond to treatment? A focus on epidemiology and phenotype of osteoarthritis. Drugs Aging. 2015;32(3):179–87.CrossRefPubMedPubMedCentral Bruyere O, Cooper C, Arden N, Branco J, Brandi ML, Herrero-Beaumont G, et al. Can we identify patients with high risk of osteoarthritis progression who will respond to treatment? A focus on epidemiology and phenotype of osteoarthritis. Drugs Aging. 2015;32(3):179–87.CrossRefPubMedPubMedCentral
Metadata
Title
Diacerein: Benefits, Risks and Place in the Management of Osteoarthritis. An Opinion-Based Report from the ESCEO
Authors
Karel Pavelka
Olivier Bruyère
Cyrus Cooper
John A. Kanis
Burkhard F. Leeb
Emmanuel Maheu
Johanne Martel-Pelletier
Jordi Monfort
Jean-Pierre Pelletier
René Rizzoli
Jean-Yves Reginster
Publication date
01-02-2016
Publisher
Springer International Publishing
Published in
Drugs & Aging / Issue 2/2016
Print ISSN: 1170-229X
Electronic ISSN: 1179-1969
DOI
https://doi.org/10.1007/s40266-016-0347-4

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