mrjСовременная ревматологияModern Rheumatology Journal1996-70122310-158XIMA-PRESS, LLC10.14412/1996-7012-2019-2-90-95mrj-916Research ArticleОБЗОРЫREVIEWSПрименение базисных противовоспалительных препаратов в терапии остеоартритаUse of disease-modifying anti-rheumatic drugs in the therapy of osteoarthritisАникинС. Г.AnikinS. G.

115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

artos2000@yandex.ruАлексееваЛ. И.AlekseevaL. I.

115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

ЛилаА. М.LilaA. M.

115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»РоссияV.A. Nasonova Research Institute of RheumatologyRussian Federation2019200520191329095Copyright © Аникин С.Г., Алексеева Л.И., Лила А.М., 20192019Аникин С.Г., Алексеева Л.И., Лила А.М.Anikin S.G., Alekseeva L.I., Lila A.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://mrj.ima-press.net/mrj/article/view/916

Остеоартрит (ОА) является гетерогенным заболеванием с различной степенью выраженности воспалительных реакций, структурных изменений, функциональной недостаточности и прогрессирования в целом. Некоторые фенотипы ОА характеризуются высокой локальной воспалительной реакцией, постоянной болью, упорным синовитом и значительным ограничением функциональной активности. Как правило, применение у таких пациентов традиционной терапии нестероидными противовоспалительными препаратами и введение глюкокортикоидов в сустав не оказывают существенного эффекта. Учитывая важную роль воспаления и вовлечение иммунных реакций в патогенез ОА, существование его эрозивных форм, применение некоторых базисных противовоспалительных препаратов могло бы быть рациональным решением проблемы терапии этого заболевания.

Представлен обзор данных, касающихся эффективности и безопасности использования метотрексата и гидроксихлорохина при ОА. 

Osteoarthritis (OA) is a heterogeneous disease with varying degrees of inflammatory responses, structural changes, functional insufficiency, and disease progression as a whole. Some OA phenotypes are characterized by a high local inflammatory response, persistent pain, persistent synovitis, and severe functional limitation. As a rule, the use of traditional nonsteroidal anti-inflammatory drugs in these patients and the injection of glucocorticoids into the joint show no substantial effect. Taking into account the important role of inflammation and the involvement of immune responses in the pathogenesis of OA, the existence of its erosive forms, the use of some disease-modifying anti-rheumatic drugs could be a rational solution of the problem in the therapy of this disease.

The paper reviews data on the efficiency and safety of using methotrexate and hydroxychloroquine in OA. 

остеоартритметотрексатгидроксихлорохинosteoarthritismethotrexatehydroxychloroquineReferencesLane NE, Brandt K, Hawker G, et al. OARSI-FDA initiative: defining the disease state of osteoarthritis. Osteoarthritis Cartilage. 2011 May;19(5):478-82. doi: 10.1016/j.joca.2010.09.013. Epub 2011 Mar 23.Lane NE, Brandt K, Hawker G, et al. OARSI-FDA initiative: defining the disease state of osteoarthritis. Osteoarthritis Cartilage. 2011 May;19(5):478-82. doi: 10.1016/j.joca.2010.09.013. Epub 2011 Mar 23.Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum. 2012 Jun; 64(6):1697-707. doi: 10.1002/art.34453. Epub 2012 Mar 5.Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum. 2012 Jun; 64(6):1697-707. doi: 10.1002/art.34453. Epub 2012 Mar 5.Goldring MB, Otero M. Inflammation in osteoarthritis. Curr Opin Rheumatol. 2011 Sep; 23(5):471-8. doi: 10.1097/BOR.0b013e 328349c2b1.Goldring MB, Otero M. Inflammation in osteoarthritis. Curr Opin Rheumatol. 2011 Sep; 23(5):471-8. doi: 10.1097/BOR.0b013e 328349c2b1.Carla R. Scanzello. Role of low-grade inflammation in osteoarthritis. Curr Opin Rheumatol. 2017 Jan;29(1):79-85.Carla R. Scanzello. Role of low-grade inflammation in osteoarthritis. Curr Opin Rheumatol. 2017 Jan;29(1):79-85.Roemer FW, Kassim JM, Guermazi A, et al. Anatomical distribution of synovitis in knee osteoarthritis and its association withjoint effusion assessed on non-enhanced and contrastenhanced MRI. Osteoarthritis Cartilage. 2010 Oct;18(10):1269-74. doi: 10.1016/j.joca.2010.07.008. Epub 2010 Aug 5.Roemer FW, Kassim JM, Guermazi A, et al. Anatomical distribution of synovitis in knee osteoarthritis and its association withjoint effusion assessed on non-enhanced and contrastenhanced MRI. Osteoarthritis Cartilage. 2010 Oct;18(10):1269-74. doi: 10.1016/j.joca.2010.07.008. Epub 2010 Aug 5.Altobelli E, Angeletti PM, Piccolo D, de Angelis R. Synovial fluid and serum concentrationsof inflammatory markers in rheumatoid arthritis, psoriatic arthritis and osteoarthitis: A Systematic Review. Curr Rheumatol Rev. 2017;13(3):170-179. doi: 10.2174/1573397113666170427125918.Altobelli E, Angeletti PM, Piccolo D, de Angelis R. Synovial fluid and serum concentrationsof inflammatory markers in rheumatoid arthritis, psoriatic arthritis and osteoarthitis: A Systematic Review. Curr Rheumatol Rev. 2017;13(3):170-179. doi: 10.2174/1573397113666170427125918.Gazeley DJ, Yeturi S, Patel PJ, Rosenthal AK. Erosive osteoarthritis: A systematic analysis of definitions used in the literature. Semin Arthritis Rheum. 2017 Feb;46(4): 395-403. doi: 10.1016/j.semarthrit.2016.08. 013. Epub 2016 Aug 24.Gazeley DJ, Yeturi S, Patel PJ, Rosenthal AK. Erosive osteoarthritis: A systematic analysis of definitions used in the literature. Semin Arthritis Rheum. 2017 Feb;46(4): 395-403. doi: 10.1016/j.semarthrit.2016.08. 013. Epub 2016 Aug 24.Goldring MB. Anticytokine therapy for osteoarthritis. Expert Opin Biol Ther. 2001 Sep;1(5):817-29.Goldring MB. Anticytokine therapy for osteoarthritis. Expert Opin Biol Ther. 2001 Sep;1(5):817-29.Smith MD, Triantafillou S, Parker A, et al. Synovial membrane inflammation and cytokine production in patients with early osteoarthritis. J Rheumatol. 1997 Feb; 24(2):365-71.Smith MD, Triantafillou S, Parker A, et al. Synovial membrane inflammation and cytokine production in patients with early osteoarthritis. J Rheumatol. 1997 Feb; 24(2):365-71.Myers SL, Brandt KD, Ehlich JW, et al. Synovial inflammation in patients with early osteoarthritis of the knee. J Rheumatol. 1990 Dec;17(12):1662-9.Myers SL, Brandt KD, Ehlich JW, et al. Synovial inflammation in patients with early osteoarthritis of the knee. J Rheumatol. 1990 Dec;17(12):1662-9.Goldenberg DL, Egan MS, Cohen AS. Inflammatory synovitis in degenerative joint disease. J Rheumatol. 1982 Mar-Apr; 9(2):204-9.Goldenberg DL, Egan MS, Cohen AS. Inflammatory synovitis in degenerative joint disease. J Rheumatol. 1982 Mar-Apr; 9(2):204-9.Lindblad S, Hedfors E. Arthroscopic and immunohistologic characterization of knee joint synovitis in osteoarthritis. Arthritis Rheum. 1987 Oct;30(10):1081-8.Lindblad S, Hedfors E. Arthroscopic and immunohistologic characterization of knee joint synovitis in osteoarthritis. Arthritis Rheum. 1987 Oct;30(10):1081-8.Revell PA, Mayston V, Lalor P, Mapp P. The synovial membrane in osteoarthritis: ahistological study including the characterisation of the cellular infiltrate present in inflammatory osteoarthritis using monoclonal antibodies. Ann Rheum Dis. 1988 Apr;47(4):300-7.Revell PA, Mayston V, Lalor P, Mapp P. The synovial membrane in osteoarthritis: ahistological study including the characterisation of the cellular infiltrate present in inflammatory osteoarthritis using monoclonal antibodies. Ann Rheum Dis. 1988 Apr;47(4):300-7.Hasko G, Cronstein BN. Adenosine: an endogenous regulator of innate immunity. Trends Immunol. 2004 Jan;25(1):33-9.Hasko G, Cronstein BN. Adenosine: an endogenous regulator of innate immunity. Trends Immunol. 2004 Jan;25(1):33-9.Cronstein BN. Low-dose methotrexate: a mainstay in the treatment of rheumatoid arthritis. Pharmacol Rev. 2005 Jun;57(2):163-72.Cronstein BN. Low-dose methotrexate: a mainstay in the treatment of rheumatoid arthritis. Pharmacol Rev. 2005 Jun;57(2):163-72.Miranda-Carus ME, Balsa A, BenitoMiguel M, et al. IL-15 and the initiation of cell contact-dependent synovial fibroblast-T lymphocyte cross-talk in rheumatoid arthritis: effect of methotrexate. J Immunol. 2004 Jul 15; 173(2):1463-76.Miranda-Carus ME, Balsa A, BenitoMiguel M, et al. IL-15 and the initiation of cell contact-dependent synovial fibroblast-T lymphocyte cross-talk in rheumatoid arthritis: effect of methotrexate. J Immunol. 2004 Jul 15; 173(2):1463-76.Barrera P, Boerbooms AM, Demacker PN, et al. Circulating concentrations and production of cytokines and soluble receptors in rheumatoid arthritis patients: effects of a single dose methotrexate. Br J Rheumatol. 1994 Nov;33(11):1017-24.Barrera P, Boerbooms AM, Demacker PN, et al. Circulating concentrations and production of cytokines and soluble receptors in rheumatoid arthritis patients: effects of a single dose methotrexate. Br J Rheumatol. 1994 Nov;33(11):1017-24.Barrera P, Haagsma CJ, Boerbooms AM, et al. Effect of methotrexate alone or in combination with sulphasalazine on the production and circulating concentrations of cytokines and their antagonists. Longitudinal evaluation in patients with rheumatoid arthritis. Br J Rheumatol. 1995 Aug;34(8):747-55.Barrera P, Haagsma CJ, Boerbooms AM, et al. Effect of methotrexate alone or in combination with sulphasalazine on the production and circulating concentrations of cytokines and their antagonists. Longitudinal evaluation in patients with rheumatoid arthritis. Br J Rheumatol. 1995 Aug;34(8):747-55.Gerards AH, de Lathouder S, de Groot ER, et al. Inhibitionof cytokine production by methotrexate. Studies in healthy volunteers and patients withrheumatoid arthritis. Rheumatology (Oxford). 2003 Oct;42(10):1189-96. Epub 2003 May 30.Gerards AH, de Lathouder S, de Groot ER, et al. Inhibitionof cytokine production by methotrexate. Studies in healthy volunteers and patients withrheumatoid arthritis. Rheumatology (Oxford). 2003 Oct;42(10):1189-96. Epub 2003 May 30.Mello SB, Barros DM, Silva AS, et al. Methotrexate as apreferential cyclooxygenase 2 inhibitor in whole blood of patients with rheumatoid arthritis. Rheumatology (Oxford). 2000 May;39(5):533-6.Mello SB, Barros DM, Silva AS, et al. Methotrexate as apreferential cyclooxygenase 2 inhibitor in whole blood of patients with rheumatoid arthritis. Rheumatology (Oxford). 2000 May;39(5):533-6.Vergne P, Liagre B, Bertin P, et al. Methotrexate and cyclooxygenase metabolism incultured human rheumatoid synoviocytes. J Rheumatol. 1998 Mar;25(3):433-40.Vergne P, Liagre B, Bertin P, et al. Methotrexate and cyclooxygenase metabolism incultured human rheumatoid synoviocytes. J Rheumatol. 1998 Mar;25(3):433-40.Majumdar S, Aggarwal BB. Methotrexate suppresses NF-κB activation through inhibition of IκBα phosphorylation and degradation. J Immunol. 2001 Sep 1;167(5):2911-20.Majumdar S, Aggarwal BB. Methotrexate suppresses NF-κB activation through inhibition of IκBα phosphorylation and degradation. J Immunol. 2001 Sep 1;167(5):2911-20.Fiedorczyk M, Klimiuk PA, Sierakowski S, et al. Serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in patients with early rheumatoid arthritis. J Rheumatol. 2006 Aug;33(8):1523-9.Fiedorczyk M, Klimiuk PA, Sierakowski S, et al. Serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in patients with early rheumatoid arthritis. J Rheumatol. 2006 Aug;33(8):1523-9.Seitz M, Dayer JM. Enhanced production of tissue inhibitor of metalloproteinases by peripheral blood mononuclear cells of rheumatoid arthritis patients responding to methotrexate reatment. Rheumatology (Oxford). 2000 Jun;39(6):637-45.Seitz M, Dayer JM. Enhanced production of tissue inhibitor of metalloproteinases by peripheral blood mononuclear cells of rheumatoid arthritis patients responding to methotrexate reatment. Rheumatology (Oxford). 2000 Jun;39(6):637-45.Tchetverikov I, Kraan MC, van El B, et al. Leflunomide and methotrexate reduce levels of activated matrix metalloproteinases in complexes with alpha2 macroglobulin in serum of rheumatoid arthritis patients. Ann Rheum Dis. 2008 Jan;67(1):128-30. Epub 2007 Sep 17.Tchetverikov I, Kraan MC, van El B, et al. Leflunomide and methotrexate reduce levels of activated matrix metalloproteinases in complexes with alpha2 macroglobulin in serum of rheumatoid arthritis patients. Ann Rheum Dis. 2008 Jan;67(1):128-30. Epub 2007 Sep 17.Кашеварова НГ, Таскина ЕА, Кудинский ДМ, Алексеева ЛИ. Опыт назначения метотрексата при эрозивной форме остеоартрита суставов кистей. В кн.: Всероссийский конгресс с международным участием «Дни ревматологии в Санкт-Петербурге». Сборник тезисов. Санкт-Петербург: Человек и его здоровье; 2018. С. 96-7.Kashevarova NG, Taskina EA, Kudinskii DM, Alekseeva LI. Experience in the use of methotrexate in the erosive form of osteoarthritis of the joints of hands. In: Vserossiiskii kongress s mezhdunarodnym uchastiem «Dni revmatologii v SanktPeterburge». Sbornik tezisov [All-Russian Congress with international participation «days of rheumatology in St. Petersburg». Book of abstracts]. Saint-Petersburg: Chelovek i ego zdorov'e; 2018. P. 96-7.Wenham CY, Grainger AJ, Hensor EM, et al. Methotrexatefor pain relief in knee osteoarthritis: an open-label study. Rheumatology (Oxford). 2013 May;52(5): 888-92. doi: 10.1093/rheumatology/kes386. Epub 2013 Jan 7.Wenham CY, Grainger AJ, Hensor EM, et al. Methotrexatefor pain relief in knee osteoarthritis: an open-label study. Rheumatology (Oxford). 2013 May;52(5): 888-92. doi: 10.1093/rheumatology/kes386. Epub 2013 Jan 7.De Holanda HT, Pollak DF, Pucinelli ML. Low-dose methotrexate compared to placebo in the treatment of knee osteoarthritis. Rev Bras Reumatol. 2007;47(5):334-40.De Holanda HT, Pollak DF, Pucinelli ML. Low-dose methotrexate compared to placebo in the treatment of knee osteoarthritis. Rev Bras Reumatol. 2007;47(5):334-40.Abou-Raya A, Abou-Raya S, Khadrawe T. Retracted: Methotrexate in the treatmentof symptomatic knee osteoarthritis: randomised placebo-controlled trial. Ann Rheum Dis. 2018 Jul;77(7):e46. doi: 10.1136/annrheumdis2013-204856. Epub 2014 Mar 27.Abou-Raya A, Abou-Raya S, Khadrawe T. Retracted: Methotrexate in the treatmentof symptomatic knee osteoarthritis: randomised placebo-controlled trial. Ann Rheum Dis. 2018 Jul;77(7):e46. doi: 10.1136/annrheumdis2013-204856. Epub 2014 Mar 27.Kingsbury SR, Tharmanathan P, Arden NK, et al. Pain reduction with oral methotrexate in knee osteoarthritis, a pragmatic phase iii trial of treatment effectiveness (PROMOTE): study protocol for a randomized controlled trial. Trials. 2015 Mar 4;16:77. doi: 10.1186/s13063-015-0602-8.Kingsbury SR, Tharmanathan P, Arden NK, et al. Pain reduction with oral methotrexate in knee osteoarthritis, a pragmatic phase iii trial of treatment effectiveness (PROMOTE): study protocol for a randomized controlled trial. Trials. 2015 Mar 4;16:77. doi: 10.1186/s13063-015-0602-8.Pavelka K, Olejarova M, Pavelkova A. Methotrexate in the treatment of erosive OA of the hands. Ann Rheum Dis. 2006;65 (Suppl II):402.Pavelka K, Olejarova M, Pavelkova A. Methotrexate in the treatment of erosive OA of the hands. Ann Rheum Dis. 2006;65 (Suppl II):402.Rainsford KD, Parke AL, CliffordRashotte M, Kean WF. Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases. Inflammopharmacology. 2015 Oct;23(5):231-69. doi: 10.1007/s10787- 015-0239-y. Epub 2015 Aug 6.Rainsford KD, Parke AL, CliffordRashotte M, Kean WF. Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases. Inflammopharmacology. 2015 Oct;23(5):231-69. doi: 10.1007/s10787- 015-0239-y. Epub 2015 Aug 6.Silva JC, Mariz HA, Rocha LF Jr, et al. Hydroxychloroquine decreases Th17-related cytokines in systemic lupus erythematosus and rheumatoid arthritis patients. Clinics (Sao Paulo). 2013 Jun;68(6):766-71. doi: 10.6061/clinics/2013(06)07.Silva JC, Mariz HA, Rocha LF Jr, et al. Hydroxychloroquine decreases Th17-related cytokines in systemic lupus erythematosus and rheumatoid arthritis patients. Clinics (Sao Paulo). 2013 Jun;68(6):766-71. doi: 10.6061/clinics/2013(06)07.Willis R, Seif AM, McGwin G Jr, et al. Effect of hydroxychloroquine treatment on pro-inflammatory cytokines and disease activity in SLE patients: data from LUMINA (LXXV), a multiethnic US cohort. Lupus. 2012 Jul;21(8):830-5. doi: 10.1177/0961203 312437270. Epub 2012 Feb 17.Willis R, Seif AM, McGwin G Jr, et al. Effect of hydroxychloroquine treatment on pro-inflammatory cytokines and disease activity in SLE patients: data from LUMINA (LXXV), a multiethnic US cohort. Lupus. 2012 Jul;21(8):830-5. doi: 10.1177/0961203 312437270. Epub 2012 Feb 17.Wozniacka A, Lesiak A, Narbutt J, et al. Chloroquine treatment influences proinflammatory cytokine levels in systemic lupus erythematosus patients. Lupus. 2006; 15(5):268-75.Wozniacka A, Lesiak A, Narbutt J, et al. Chloroquine treatment influences proinflammatory cytokine levels in systemic lupus erythematosus patients. Lupus. 2006; 15(5):268-75.Karres I, Kremer JP, Dietl I, et al. Chloroquine inhibits proinflammatory cytokine release into human whole blood. Am J Physiol. 1998;274:1058-1064.Karres I, Kremer JP, Dietl I, et al. Chloroquine inhibits proinflammatory cytokine release into human whole blood. Am J Physiol. 1998;274:1058-1064.Ackerman NR, Jubb S, Marlowe SL. Effects of various antiinflammatory and antirheumatic agents on the synthesis, secretion and activity of a cartilage proteoglycandegrading enzyme and other macrophage enzymes. Biochem Pharmacol. 1981 Aug 1; 30(15):2147-55.Ackerman NR, Jubb S, Marlowe SL. Effects of various antiinflammatory and antirheumatic agents on the synthesis, secretion and activity of a cartilage proteoglycandegrading enzyme and other macrophage enzymes. Biochem Pharmacol. 1981 Aug 1; 30(15):2147-55.Kamel M, Bassiouni M. Chloroquine inhibits elastase enzyme activity in vitro. Clin Exp Rheumatol. 1992 Jan-Feb;10(1):99-100.Kamel M, Bassiouni M. Chloroquine inhibits elastase enzyme activity in vitro. Clin Exp Rheumatol. 1992 Jan-Feb;10(1):99-100.Lullmann-Rauch R, Pods R, von Witzendorff B. The antimalarialsquinacrine and chloroquine induce weak lysosomal storage of sulphatedglycosaminoglycans in cell culture and in vivo. Toxicology. 1996 Jun 17;110(1-3):27-37.Lullmann-Rauch R, Pods R, von Witzendorff B. The antimalarialsquinacrine and chloroquine induce weak lysosomal storage of sulphatedglycosaminoglycans in cell culture and in vivo. Toxicology. 1996 Jun 17;110(1-3):27-37.Cowey FK, Whitehouse MW. Biochemical properties of antiinflammatory drugs. VII. Inhibition of proteolytic enzymes in connective tissue by chloroquine (resorchin) and related antimalarialantirheumatic drugs. Biochem Pharmacol. 1966 Aug; 15(8):1071-84.Cowey FK, Whitehouse MW. Biochemical properties of antiinflammatory drugs. VII. Inhibition of proteolytic enzymes in connective tissue by chloroquine (resorchin) and related antimalarialantirheumatic drugs. Biochem Pharmacol. 1966 Aug; 15(8):1071-84.Punzi L, Frigato M, Frallonardo P, Ramonda R. Inflammatory osteoarthritis of the hand. Best Pract Res Clin Rheumatol. 2010 Jun;24(3):301-12. doi: 10.1016/j.berh. 2009.12.007.Punzi L, Frigato M, Frallonardo P, Ramonda R. Inflammatory osteoarthritis of the hand. Best Pract Res Clin Rheumatol. 2010 Jun;24(3):301-12. doi: 10.1016/j.berh. 2009.12.007.Ehrlick GE. Erosive inflammatory and primary generalized osteoarthritis. In: Osteoarthritis. 3rd ed. Philadelphia: W.B. Saunders; 2001.Ehrlick GE. Erosive inflammatory and primary generalized osteoarthritis. In: Osteoarthritis. 3rd ed. Philadelphia: W.B. Saunders; 2001.Robertson CR, Rice JR, Allen NB. Treatment of erosive osteoarthritis with hydroxychloroquine. Arthritis Rheum. 1993,36(Suppl):S167.Robertson CR, Rice JR, Allen NB. Treatment of erosive osteoarthritis with hydroxychloroquine. Arthritis Rheum. 1993,36(Suppl):S167.Bryant LR, des Rosier KF, Carpenter MT. Hydroxychloroquine in the treatment of erosive osteoarthritis. J Rheumatol. 1995 Aug; 22(8):1527-31.Bryant LR, des Rosier KF, Carpenter MT. Hydroxychloroquine in the treatment of erosive osteoarthritis. J Rheumatol. 1995 Aug; 22(8):1527-31.Sibtain SK, Kallankara S, Gillott TJ, et al. Role of hydroxychloroquinein management of osteoarthritis. Rheumatology (Oxford) 2007;46:161-161.Sibtain SK, Kallankara S, Gillott TJ, et al. Role of hydroxychloroquinein management of osteoarthritis. Rheumatology (Oxford) 2007;46:161-161.Punzi L, Bertazzolo N, Pianon M, et al. Soluble interleukin 2 receptors and treatment with hydroxychloroquine in erosive osteoarthritis. J Rheumatol. 1996 Aug;23(8):1477-8.Punzi L, Bertazzolo N, Pianon M, et al. Soluble interleukin 2 receptors and treatment with hydroxychloroquine in erosive osteoarthritis. J Rheumatol. 1996 Aug;23(8):1477-8.McKendry R, Thome C, Weisman M, et al. Hydroxychloroquine (HCQ) versus Acetaminophen (ACM) versus placebo (PL) in the treatment of nodal osteoarthritis (NOA) of the hands. Rheumatology (Oxford) 2001; 28:1421.McKendry R, Thome C, Weisman M, et al. Hydroxychloroquine (HCQ) versus Acetaminophen (ACM) versus placebo (PL) in the treatment of nodal osteoarthritis (NOA) of the hands. Rheumatology (Oxford) 2001; 28:1421.Jokar M, Mirfeizi Z, Keyvanpajouh K. The effect of hydroxychloroquine on symptoms of Knee osteoarthritis: a double-blind randomized controlled clinical trial. Iran J Med Sci. 2013 Sep;38(3):221-6.Jokar M, Mirfeizi Z, Keyvanpajouh K. The effect of hydroxychloroquine on symptoms of Knee osteoarthritis: a double-blind randomized controlled clinical trial. Iran J Med Sci. 2013 Sep;38(3):221-6.Abou-Raya S, Abou-Raya A, Khadrawe T. Efficacy of hydroxychloroquine in the treatment of symptomatic knee osteoarthritis in older adults: a randomized placebo-controlled trial. Ann Rheum Dis. 2014;73 (Suppl 2):756-7.Abou-Raya S, Abou-Raya A, Khadrawe T. Efficacy of hydroxychloroquine in the treatment of symptomatic knee osteoarthritis in older adults: a randomized placebo-controlled trial. Ann Rheum Dis. 2014;73 (Suppl 2):756-7.Lee W, Ruijgrok L, Boxma-de Klerk B, et al. Efficacy of Hydroxychloroquine in Hand Osteoarthritis: A Randomized,DoubleBlind, Placebo-Controlled Trial. Arthritis Care Res (Hoboken). 2018 Sep;70(9):1320-1325. doi: 10.1002/acr.23471. Epub 2018 Aug 12.Lee W, Ruijgrok L, Boxma-de Klerk B, et al. Efficacy of Hydroxychloroquine in Hand Osteoarthritis: A Randomized,DoubleBlind, Placebo-Controlled Trial. Arthritis Care Res (Hoboken). 2018 Sep;70(9):1320-1325. doi: 10.1002/acr.23471. Epub 2018 Aug 12.Kingsbury SR, Tharmanathan P, Keding A, et al. Hydroxychloroquine Effectiveness in Reducing Symptoms of Hand Osteoarthritis: A Randomized Trial. Ann Intern Med. 2018 Mar 20;168(6):385-395. doi: 10.7326/M17- 1430. Epub 2018 Feb 20.Kingsbury SR, Tharmanathan P, Keding A, et al. Hydroxychloroquine Effectiveness in Reducing Symptoms of Hand Osteoarthritis: A Randomized Trial. Ann Intern Med. 2018 Mar 20;168(6):385-395. doi: 10.7326/M17- 1430. Epub 2018 Feb 20.Detert J, Klaus P, Listing J, et al. Hydroxychloroquine in patients with inflammatory and Erosive osteoarthritis of the hands (OA TREAT): study protocol for a randomized controlled trial. Trials. 2014 Oct 27; 15:412. doi: 10.1186/1745-6215-15-412.Detert J, Klaus P, Listing J, et al. Hydroxychloroquine in patients with inflammatory and Erosive osteoarthritis of the hands (OA TREAT): study protocol for a randomized controlled trial. Trials. 2014 Oct 27; 15:412. doi: 10.1186/1745-6215-15-412.

The authors declare that there are no conflicts of interest present.