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Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases

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Abstract

Objectives

This review examines the pharmacokinetics, modes of action and therapeutic properties of the anti-malarial drugs, hydroxychloroquine (HCQ) and chloroquine (CQ), in the treatment of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and related conditions, as well as osteoarthritis (OA).

Key findings

Both HCQ and CQ have historically been employed successfully for the treatment of SLE and RA for over 70 years. HCQ has been used extensively for SLE where it has a good reputation for controlling the dermatological complications in SLE. It has also been reported to effectively control the symptoms of Sjøgren’s syndrome, as well as preventing thrombosis in phospholipid antibody (aPL) syndrome. In RA and SLE, HCQ is preferred because of the lower incidence of gastrointestinal adverse reactions compared with CQ and it might have a lower risk of ocular adverse reactions. There is increasing evidence that HCQ may reduce atherosclerosis and risks of cardiovascular disease in rheumatic patients. Both HCQ and CQ have been shown to improve glycaemia and reduce the risks of type II diabetes mellitus. Although both HCQ and CQ are effective in low-moderate RA, HCQ is now preferred as part of combination therapy for more severe disease. The advantages of combination therapy are that the doses of the individual drugs may be lowered so reducing adverse reactions. Both HCQ and CQ are diastereoisomers, have basic properties and are given as the sulphate and phosphate salts. While being relatively well absorbed orally and with good bioavailability, they have long and variable plasma terminal elimination half-lives (approximately 40–60 days). This reflects their high volume of distribution, V D (HCQ 44,000L; CQ 65,000L) which extends into aqueous compartments, long mean residence time (HCQ 1300 h; CQ 900 h) and with about half the drugs (metabolites) undergoing renal clearance. The strong binding to melanin reflects the ocular injury and dermatological properties of these drugs. The consensus is that the occurrence of ocular adverse reactions can be minimised by close attention to the dose (which should be set on a body weight basis) with regular (e.g. quarterly) retinal examination. Although HCQ and CQ can pass through the placenta, the use of these drugs during pregnancy does not appear to risk harm to the baby and might be beneficial to the mother with SLE and her child by controlling the SLE disease activity, which is known to be an important factor affecting pregnancy outcome. The modes of action of HCQ and CQ in these arthritides represent somewhat of an enigma. Undoubtedly, these drugs have multiple actions related, in part, their ability to accumulate in lysosomes and autophagosomes of phagocytic cells as well as affecting MHC Class II expression and antigen presentation; actions of the production of pro-inflammatory cytokines [e.g. interleukin-1 (IL-1) tumour necrosis factor-α (TNFα)]; control of toll-like receptor-9 activation; and leucocyte generation of reactive oxygen species (ROS); i.e. antioxidant activity. The actions of these drugs on T and B cells are less clear but may depend on these leucocyte-mediated actions. Anti-malarials also protect against cytokine-mediated cartilage resorption. This and other actions may underlie the potential benefits in treating OA. The exact relationships of these various actions, mostly determined in vitro, have not been specifically defined in vivo or ex vivo in relation to clinical efficacy.

Outcomes

HCQ and CQ have a good reputation for being effective and relatively safe treatments in SLE, mild-moderate RA and Sjøgren’s syndrome. There is need for (a) more information on their mode of action in relation to the control of these diseases, (b) scope for developing formulations that have improved pharmacokinetic and therapeutic properties and safety, and (c) further exploring their use in drug combinations not only with other disease-modifying agents but also with biologics.

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References

  • Abdel-Hamid H, Oddis CV, Lacomis D (2008) Severe hydroxychloroquine myopathy. Muscle Nerve 38:1206–1210

    Article  PubMed  Google Scholar 

  • Abou-Raya S et al. (2014) Efficacy of hydroxychloroquine in the treatment of symptomatic knee osteoarthritis in older adults: a randomized placebo-controlled trial. Ann Rheum Dis 73:756–757

    Google Scholar 

  • Acha-Orbea H, Groscurth P, Lang R, Stitz J, Hengartner H (1983) Characterization of cloned cytotoxic lymphocytes with NK-like activity. J Immunol 130:2952–2959

    CAS  PubMed  Google Scholar 

  • Achuthan S, Ahluwalia J, Shafig N, Pareek A, Chandurkar N, Malhotra S (2015) Hydroxychloroquine’s efficacy as an antiplatelet agent study in healthy volunteers: a proof of concept study. J Cardiovasc Pharmacol Ther 20:174–180

    Article  CAS  PubMed  Google Scholar 

  • Ackerman NR, Jubb S, Marlowe SL (1981) Effects of various anti-inflammatory and anti-rheumatic agents on the synthesis, secretion and activity of a cartilage proteoglycan-degrading enzyme and other macrophage enzymes. Biochem Pharmacol 30:2147–2155

    Article  CAS  PubMed  Google Scholar 

  • Adams EM, Yocum DE, Bell CL (1983) Hydroxychloroquine in the treatment of rheumatoid arthritis. Am J Med 75:321–326

    Article  CAS  PubMed  Google Scholar 

  • Adedoyin A, Frye RF, Mauro K, Branch RA (1998) Chloroquine modulation of specific metabolizing enzymes activities: investigation with selective five drug cocktail. Br J Clin Pharmacol 46:215–219

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Aderounmu AF, Fleckstein L (1983) Pharmacokinetics of chloroquine diphosphate in the dog. J Pharmacol Exp Ther 1983(223):633–639

    Google Scholar 

  • Adeyemi EO, Chadwick VS, Hodgson HJ (1990) The effect of some anti-inflammatory agents on elastase release from neutrophils in vitro. J Pharm Pharmacol 42:487–490

    Article  CAS  PubMed  Google Scholar 

  • Adjepon-Yamoah KK, Woolhouse NM, Prescott LF (1986) The effect of chloroquine on paracetamol disposition and kinetics. Br J Clin Pharmacol 21:322–324

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Akintonwa A, Gbajumo SA, Mabadeje AF (1988) Placental and milk transfer of chloroquine in humans. Ther Drug Monit 10:147–149

    Article  CAS  PubMed  Google Scholar 

  • Ali HM (1985) Reduced ampicillin bioavailability following oral coadministration with chloroquine. J Antimicrob Chemother 15:781–784

    Article  CAS  PubMed  Google Scholar 

  • Alisky JM, Chertkova EL, Iczkowski KA (2006) Drug interactions and pharmacogenetic reactions are the basis for chloroquine and mefloquine-induced psychosis. Med Hypotheses 67:1090–1094

    Article  CAS  PubMed  Google Scholar 

  • Andreas K, Haupl T, Lubke C, Ringe J, Morawietz L, Wachtel A, Sittinger M, Kaps C (2009) Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration. Arthritis Res Ther 11:R15

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Antoine JC, Goud B, Jouanne C, Maurice M, Feldmann G (1985) Ammonium chloride, methylamine and chloroquine reversibly inhibit antibody secretion by plasma cells. Cell Biol 55:41–54

    Article  CAS  Google Scholar 

  • Arner EC, Darnell LR, Pratta MA, Newton RC, Ackerman NR, Galbraith W (1987) Effect of antiinflammatory drugs on human interleukin-1-induced cartilage degradation. Agents Actions 21:334–336

    Article  CAS  PubMed  Google Scholar 

  • Ashraf T, Jiang W, Hogue MT, Henderson J, Wu C, Bendayan R (2014) Role of anti-inflammatory compounds in human immunodeficiency virus-1 glycoprotein120-mediated brain inflammation. J Neuroinflamm 11:11. doi:10.1186/1742-2094-11

    Article  CAS  Google Scholar 

  • Ausiello CM, Barbieri P, Spagnoli GC, Ciompi ML, Casciani CU (1986) In vivo effects of chloroquine treatment on spontaneous and interferon-induced natural killer activities in rheumatoid arthritis patients. Clin Exp Rheumatol 4:255–259

    CAS  PubMed  Google Scholar 

  • Authi KS, Traynor JR (1982) Stimulation of polymorphonuclear leucocyte phospholipase A2 activity by chloroquine and mepacrine. J Pharm Pharmacol 34:736–738

    Article  CAS  PubMed  Google Scholar 

  • Avina-Zubieta JA, Galindo-Rodriguez G, Newman S, Suarez-Almazor ME, Russell AS (1998) Long-term effectiveness of antimalarial drugs in rheumatic diseases. Ann Rheum Dis 57:582–587

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bannwarth B, Pehourcq F, Schaeverbeke T, Dehais J (1996) Clinical pharmacokinetics of low-dose pulse methotrexate in rheumatoid arthritis. Clin Pharmacokinet 30:194–210

    Article  CAS  PubMed  Google Scholar 

  • Barbieri P, Ausiello C, Spagnoli GC, Qintieri F, Ciompi ML (1985) Chloroquine treatment induces decrease of spontaneous and interferon enhanced NK activity in rheumatoid arthritis. Int J Immunother 1:211–214

    Google Scholar 

  • Bartholomew JS, Lowther DA (1987) Receptor-mediated binding of leukocyte elastase by chondrocytes. Arthritis Rheum 30:431–438

    Article  CAS  PubMed  Google Scholar 

  • Baum J (1983) Treatment of juvenile arthritis. Am Fam Physician 27:133–139

    CAS  PubMed  Google Scholar 

  • Bellamy N, Brooks PM (1986) Current practice in antimalarial drug prescribing in rheumatoid arthritis. J Rheumatol 13:551–555

    CAS  PubMed  Google Scholar 

  • Ben-Chetrit E, Fischel R, Hinz B, Levy M (2005) The effects of cochicine and hydroxychloroquine on the cyclo-oxygenases COX-1 and COX-1. Rheumatol Int 25:332–335

    Article  CAS  PubMed  Google Scholar 

  • Ben-Zvi I, Kivity S, Langevitz P, Shoenfeld Y (2012) Hydroxychloroquine: from malaria to autoimmunity. Clin Rev Allergy Immunol 42:145–153

    Article  CAS  PubMed  Google Scholar 

  • Bergqvist Y, Hed C, Funding L, Suther A (1985) Determination of chloroquine and its metabolites in urine: a field method based on ion-pair extraction. Bull WHO 63:893–898

    PubMed Central  CAS  PubMed  Google Scholar 

  • Biasi D, Caramaschi P, Carletto A, Pacor ML, Bambara LM (2000) Combination therapy with hydroxychloroquine, gold sodium thiomalate and methotrexate in early rheumatoid arthritis. An open 3-year study. Clin Rheumatol 19:505–507

    Article  CAS  PubMed  Google Scholar 

  • Blackham A, Radziwonik H, Shaw IH (1975) The Arthus reaction in guinea-pig knee joints. A test for anti-inflammatory drugs. Agents Actions 5:519–527

    Article  CAS  PubMed  Google Scholar 

  • Boelaert JR, Piette J, Sperber K (2001a) The potential place of chloroquine in the treatment of HIV-1-infected patients. J Clin Virol 20:137–140

    Article  CAS  PubMed  Google Scholar 

  • Boelaert JR, Yaro S, Augustijns P, Meda N, Schneider YJ, Schols D, Mols R, De Laere EA, Van de Perre P (2001b) Chloroquine accumulates in breast-milk cells: potential impact in the prophylaxis of postnatal mother-to-child transmission of HIV-1. AIDS 15:2205–2207

    Article  CAS  PubMed  Google Scholar 

  • Bonfante H et al. (2008) Assessment of the use of hydroxychloroquine on knees’ osteoarthritis treatment. Rev Bras Rheumatol 48:208–212

    Google Scholar 

  • Borden MB, Parke AL (2001) Antimalarial drugs in systemic lupus erythematosus: use in pregnancy. Drug Saf 24:1055–1063

    Article  CAS  PubMed  Google Scholar 

  • Boström H, Moretti A, Whitehouse M (1963) Studies of the biochemistry of heart valves. On the biosynthesis of mucopolysaccharides in bovine heart valves. Biochem Biophys Acta 74:213–221

    Article  PubMed  Google Scholar 

  • Boström H, Bernsten K, Whitehouse MW (1964) Biochemical properties of anti-inflammatory drugs-II. Some effects on sulphate-35S metabolism in vivo. Biochem Pharmacol 13:413–420

    Article  Google Scholar 

  • Brandriss MW, Schlesinger JJ (1984) Antibody-mediated infection of P388D1 cells with 17D yellow fever virus: effects of chloroquine and cytochalasin B. J Gen Virol 65:791–794

    Article  PubMed  Google Scholar 

  • Brennan FR, Negroiu G, Buzás EI, Fülöp C, Holló K, Mikecz K, Glant TT (1995) Presentation of cartilage proteoglycan to a T cell hybridoma derived from a mouse with proteoglycan-induced arthritis. Clin Exp Immunol 100:104–110

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bretano F, Schorr O, Gay RE, Gay S, Kyburz D (2005) RNA released from necrotic synovial fluid in RA—evidence of an inhibitory effect on toll-like receptor signalling. Arthritis Rheum 52:2656–2665

    Article  CAS  Google Scholar 

  • British National Formulary 57 (2009) BMJ Group and RPS Publishing, London, p 566

  • Brocks DR, Mehvar R (2003) Stereoselectivity in the pharmacodynamics and pharmacokinetics of the chiral antimalarial drugs. Clin Pharmacokinet 42:1359–1382

    Article  CAS  PubMed  Google Scholar 

  • Brocks DR, Pasutto FM, Jamali F (1992) Analytical and semi-preparative high-performance liquid chromatographic separation and assay of hydroxychloroquine enantiomers. J Chromatogr 581:83–92

    Article  CAS  PubMed  Google Scholar 

  • Brown ND, Poon BT, Chulay JD (1985) Chloroquine metabolism in man: urinary excretion of 7-chloro-4-hydroxy-quinoline and 7-chloro-4-aminoquinoline metabolites. J Chromatogr 345:209–214

    Article  CAS  PubMed  Google Scholar 

  • Brucato A, Frassi M, Franceschini F, Cimaz R, Faden D, Pisoni MP, Muscarà M, Vignati G, Stramba-Badiale M, Catelli L, Lojacono A, Cavazzana I, Ghirardello A, Vescovi F, Gambari PF, Doria A, Meroni PL, Tincani A (2001) Risk of congenital complete heart block in newborns of mothers with anti-Ro/SSA antibodies detected by counter-immunoelectrophoresis: a prospective study of 100 women. Arthritis Rheum 44:1832–1835

    Article  CAS  PubMed  Google Scholar 

  • Bryant LR et al. (1995) Hydroxychloroquine in the treatment of erosive osteoarthritis. J Rheumatol 22:1527–1531

    CAS  PubMed  Google Scholar 

  • Bygbjerg IC, Theander TG, Andersen BJ, Flachs H, Jepsen S, Larsen PB (1986) In vitro effect of chloroquine, mefloquine and quinine on human lymphocyte proliferative responses to malaria antigens and other antigens/mitogens. Trop Med Parasit 37:245–247

    CAS  Google Scholar 

  • Bygbjerg IC, Svenson M, Theander TG, Bendtzen K (1987) Effect of antimalarial drugs on stimulation and interleukin 2 production of human lymphocytes. Int J Immunopharmacol 9:513–519

    Article  CAS  PubMed  Google Scholar 

  • Cameron MC, Word AP, Dominguez A (2014) Hydroxychloroquine-induced fatal toxic epidermal necrolysis complicated by angioinvasive rhizopus. Dermatol Online J 20 (pii: 13030/qt1q90q0h5)

  • Canadian Rheumatology Association (2000) Canadian Consensus Conference on hydroxychloroquine. J Rheumatol 27:2919–2921

    Google Scholar 

  • Cankaya H, Alpöz E, Karabulut G, Güneri P, Boyacioglu H, Kabasakal Y (2010) Effects of hydroxychloroquine on salivary flow rates and oral complaints of Sjögren patients: a prospective sample study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 110:62–67

    Article  PubMed  Google Scholar 

  • Cansu DU, Korkmaz C (2008) Hypoglycaemia induced by hydroxychloroquine in a non-diabetic patient treated for RA. Rheumatology (Oxford) 47:378–379

    Article  CAS  Google Scholar 

  • Carmichael SJ, Beal J, Day RO, Tett SE (2002) Combination therapy with methotrexate and hydroxychloroquine for rheumatoid arthritis increases exposure to methotrexate. J Rheumatol 29:2077–2083

    CAS  PubMed  Google Scholar 

  • Carmichael SJ, Charles B, Tett SE (2003) Population pharmacokinetics of hydroxychloroquine in patients with rheumatoid arthritis. Ther Drug Monit 25:671–681

    Article  CAS  PubMed  Google Scholar 

  • Carmichael SJ, Day RO, Tett SE (2013) A cross-ectional survey of hydroxychloroquine concentrations and effects in people with systemic lupus erythematosus. Intern Med J 43:547–553

    Article  CAS  PubMed  Google Scholar 

  • Cecchi E, Porzio F (1964) Affinité de l-hydroxychloroquine pour les tissues articulaires. Rhumatologie 16:399–400

    CAS  PubMed  Google Scholar 

  • Cervera R, Khamashta MA, Hughes GR (2009) The Euro-lupus project: epidemiology of systemic lupus erythematosus in Europe. Lupus 18:869–874

    Article  CAS  PubMed  Google Scholar 

  • Chafin CB, Regna NL, Hammanod SE, Reilly CM (2013) Cellular and urinary microRNA alterations in NZB/W mice with hydroxychloroquine and prednisone treatment. Int Immunopharmacol 17:894–906

    Article  CAS  PubMed  Google Scholar 

  • Chiang G, Sassaroli M, Louie M, Chen H, Stecher VJ, Sperber K (1996) Inhibition of HIV-1 replication by hydroxychloroquine: mechanism of action and comparison with zidovudine. Clin Ther 18:1080–1092

    Article  CAS  PubMed  Google Scholar 

  • Choi HK, Seeger JD, Kuntz KM (2000) A cost-effectiveness analysis of treatment options for patients with methotrexate-resistant rheumatoid arthritis. Arthritis Rheum 43:2316–2327

    Article  CAS  PubMed  Google Scholar 

  • Churchill FC, Mount DL, Schwartz IK (1983) Determination of chloroquine and its major metabolite in blood using perfluoroacylation followed by fused-silica capillary gas chromatography with nitrogen-sensitive detection. J Chromatogr 274:111–120

    Article  CAS  PubMed  Google Scholar 

  • Clarke AK (1998) Antimalarial drugs in the treatment of rheumatological diseases. Br J Rheumatol 37:580

    Article  CAS  PubMed  Google Scholar 

  • Clarke AK, Vernon-Roberts B, Currey HLF (1975) Assessment of anti-inflammatory drugs in the rat using subcutaneous implants of polyurethane foam impregnated with dead tubercule bacilli. Ann Rheum Dis 34:326–331

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Clegg DO, Dietz F, Duffy J, Willkens RF, Hurd E, Germain BF, Wall B, Wallace DJ, Bell CL, Sleckman J (1997) Safety and efficacy of hydroxychloroquine as maintenance therapy for rheumatoid arthritis after combination therapy with methotrexate and hydroxychloroquine. J Rheumatol 24:1896–1902

    CAS  PubMed  Google Scholar 

  • Colombo C, Butler M, Hickman L, Selwyn M, Chart J, Steinetz B (1983) A new model of osteoarthritis in rabbits. II. Evaluation of anti-osteoarthritic effects of selected antirheumatic drugs administered systemically. Arthritis Rheum 26:1132–1139

    Article  CAS  PubMed  Google Scholar 

  • Combe B, Guttierrez M, Anaya JM, Sany J (1993) Possible efficacy of hydroxychloroquine on accelerated nodulosis during methotrexate therapy for rheumatoid arthritis. J Rheumatol 20:755–756

    CAS  PubMed  Google Scholar 

  • Conaghan PG, Lehmann T, Brooks P (1997) Disease-modifying antirheumatic drugs. Curr Opin Rheumatol 9:183–190

    Article  CAS  PubMed  Google Scholar 

  • Connolly KM, Stecher VJ, Danis E, Pruden DJ, LaBrie T (1988) Alteration of interleukin-1 activity and the acute phase response in adjuvant arthritic rats treated with disease modifying antirheumatic drugs. Agents Actions 25:94–105

    Article  CAS  PubMed  Google Scholar 

  • Cook JA, Randinitis EJ, Bramson CR, Wesche DL (2006) Lack of a pharmacokinetic interaction between azithromycin and chloroquine. Am J Trop Med Hyg 74:407–412

    CAS  PubMed  Google Scholar 

  • Costedoat-Chalumeau N, Amoura Z, Aymard G, Le TH, Wechsler B, Vauthier D, Dermer ME, Darbois Y, Piette JC (2002) Evidence of transplacental passage of hydroxychloroquine in humans. Arthritis Rheum 46:1123–1124

    Article  PubMed  Google Scholar 

  • Costedoat-Chalumeau N, Amoura Z, Duhaut P, Huong DL, Sebbough D, Wechsler B, Vauthier D, Denjoy I, Lupoglazoff JM, Piette JC (2003) Safety of hydroxychloroquine in pregnant patients with connective tissue diseases: a study of one hundred thirty-three cases compared with a control group. Arthritis Rheum 48:3207–3211

    Article  CAS  PubMed  Google Scholar 

  • Cowey FK, Whitehouse MW (1966) Biochemical properties of anti-inflammatory drugs. VII. Inhibition of proteolytic enzymes in connective tissue by chloroquine (resorchin) and related antimalarial antirheumatic drugs. Biochem Pharmacol 15:1071–1084

    Article  CAS  PubMed  Google Scholar 

  • Cox A, Duff GW (1996) Cytokines as genetic modifying factors in immune and inflammatory diseases. J Pediatric Endocrinol Metab 9:129–132

    Article  Google Scholar 

  • Craig JC, Bhargava HN, Everhart ET, LaBelle B, Ohnsorge U, Webster RV (1988) Absolute configuration of the enantiomers of 7-chloro-4-[[4-diethylamino)-1-methylbutyl]amino]quinoline (chloroquine). J Org Chem 53:1167–1170

    Article  CAS  Google Scholar 

  • Crossley MJ, Spowage M, Hunneyball IM (1987) Studies on the effects of pharmacological agents on antigen-induced arthritis in BALB/c mice. Drugs Exp Clin Res 13:273–277

    CAS  PubMed  Google Scholar 

  • Csuka M, Carrera GF, McCarty DJ (1986) Treatment of intractable rheumatoid arthritis with combined cyclophosphamide, azathioprine, and hydroxychloroquine. A follow-up study. JAMA 255:2315–2319

    Article  CAS  PubMed  Google Scholar 

  • Cutler DJ (1993) Possible mechanisms of action of antimalarials in rheumatic disease. Agents Actions Suppl 44:139–143

    CAS  PubMed  Google Scholar 

  • Cutler DJ, MacIntyre AC, Tett SE (1988) Pharmacokinetics and cellular uptake of 4-aminoquinoline antimalarials. Agents Actions Suppl 24:142–157

    CAS  PubMed  Google Scholar 

  • Das SK, Pareek A, Mathur DS, Wanchu A, Srivastava R, Agarwal GG, Chauhan RS (2002) Efficacy and safety of hydroxychloroquine sulphate in rheumatoid arthritis: a randomized, double-blind, placebo controlled clinical trial—an Indian experience. Curr Med Res Opin 23:2227–2234

    Article  CAS  Google Scholar 

  • Das SK, Pareek A, Mathur DS, Wanchu A, Srivastava R, Agarwal GG, Chauhan RS (2007) Efficacy and safety of hydroxychloroquine sulphate in rheumatoid arthritis: a randomized, double-blind, placebo controlled clinical trial–an Indian experience. Curr Med Res Opin 23:2227–2234

    Article  CAS  PubMed  Google Scholar 

  • Davila L, Ranganathan P (2011) Pharmacogenetics: implications for therapy in rheumatic diseases. Nat Rev Rheumatol 7:537–550

    Article  CAS  PubMed  Google Scholar 

  • Davis MJ, Woolf AD (1996) Role of antimalarials in rheumatoid arthritis–the British experience. Lupus 5(Suppl 1):S37–S40

    Article  CAS  PubMed  Google Scholar 

  • Dawson LJ, Caulfield VL, Stanbury JB, Field AE, Christmas SE, Smith PM (2005) Hydroxychloroquine therapy in patients with primary Sjögren’s syndrome may improve salivary gland hypofunction by inhibition of glandular cholinesterase. Rheumatology 44:449–455

    Article  CAS  PubMed  Google Scholar 

  • Detert J, Klaus P, Listing J, Höhne-Zimmer V, Braun T, Wassenberg S, Rau R, Buttgereit F, Burmester GR (2014) Hydroxychloroquine in patients with inflammatory and erosive osteoarthritis of the hands (OA TREAT): study protocol for a randomized controlled trial. Trials 15:412. doi:10.1186/1745-6215-15-412

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • De Duve C (1965) The separation and characterization of subcellular particles. Harvey Lect 59:49–87

    PubMed  Google Scholar 

  • de Oliveira AR, Cardoso CD, Bonato PS (2007) Stereoselective determination of hydroxychloroquine and its metabolites in human urine by liquid-phase microextraction and CE. Electrophoresis 28:1081–1091

    Article  PubMed  CAS  Google Scholar 

  • Derksen RH, de Groot PG (2010) Towards evidence-based treatment of thrombotic antiphospholipid syndrome. Lupus 19:470–474

    Article  CAS  PubMed  Google Scholar 

  • Descloux E, Durieu I, Cochat P, Vital-Durand D, Ninet J, Fabien N, Cimaz R (2009) Influence of age at disease onset in the outcome of paediatric systemic lupus erythematosus. Rheumatology 48:779–784

    Article  PubMed  Google Scholar 

  • Dixon JS, Pickup ME, Bird HA, Lee MR (1981) Biochemical indices of response to hydroxychloroquine and sodium aurothiomalate in rheumatoid arthritis. Ann Rheum Dis 40:480–488

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Dubois EL (1967) Management and prognosis of systemic lupus erythematosus. Bull Rheum Dis 18:477–482

    CAS  PubMed  Google Scholar 

  • Dubois EL (1978) Antimalarials in the management of discoid and systemic lupus erythematosus. Semin Arthritis Rheum 8:33–51

    Article  CAS  PubMed  Google Scholar 

  • Ducharme J, Farinotti R (1996) Clinical pharmacokinetics and metabolism of chloroquine. Focus on recent advancements. Clin Pharmacokinet 31:257–274

    Article  CAS  PubMed  Google Scholar 

  • Ducharme J, Fieger H, Ducharme MP, Khalil SK, Wainer IW (1995) Enantioselective disposition of hydroxychloroquine after a single oral dose of the racemate to healthy subjects. Br J Clin Pharmacol 40:127–133

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Duve De, Wattiaux R, Wibo M (1962) Effects of fat-soluble compounds on lysosomes in vitro. Biochem Pharmacol 9:97–116

    Article  Google Scholar 

  • Easterbrook M (1990) Is corneal disposition of anti-malarials any indication of retinal toxicity? Can J Opthal 25:249–251

    CAS  Google Scholar 

  • Easterbrook M (2002) Screening for antimalarial toxicity: current concepts. Can J Ophthalmol. 37:325–358 (331–334)

    Article  PubMed  Google Scholar 

  • Edmead CE, Patel YI, Wilson A, Boulougouris G, Hall ND, Ward SG, Sansom DM (1996) Induction of activator protein (AP)-1 and nuclear factor-κB by CD28 stimulation involves both phosphoinositol-3-kinase and acidic sphingomyelinase signals. J Immunol 157:3290–3297

    CAS  PubMed  Google Scholar 

  • Edstein MD, Veenendaal JR, Newman K, Hyslop R (1986) Excretion of chloroquine, dapsone and pyrimethamine in human milk. Br J Clin Pharmacol 22:733–735

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Edwards MH, Pierangeli S, Liu XW, Barker JH, Anderson G, Harris EN (1997) Hydroxychloroquine reverses thrombogenic properties of antiphospholipid antibodies in mice. Circulation 96:4380–4384

    Article  CAS  PubMed  Google Scholar 

  • Eklund KK, Leirisalo-Repo M, Ranta P, Mäki T, Kautiainen H, Hannonen P, Korpela M, Hakala M, Järvinen P, Möttönen T (2007) Serum IL-1beta levels are associated with the presence of erosions in recent onset rheumatoid arthritis. Clin Exp Rheumatol 25:684–689

    CAS  PubMed  Google Scholar 

  • Emami J, Pasutto FM, Jamali F (1998) Effect of experimental diabetes mellitus and arthritis on the pharmacokinetics of hydroxychloroquine enantiomers in rats. Pharm Res 15:897–903

    Article  CAS  PubMed  Google Scholar 

  • Emami J, Gerstein HC, Pasutto FM, Jamali F (1999a) Insulin-sparing effect of hydroxychloroquine in diabetic rats is concentration dependent. Can J Physiol Pharmacol 77:118–123

    Article  CAS  PubMed  Google Scholar 

  • Emami J, Pasutto FM, Mercer JR, Jamali F (1999b) Inhibition of insulin metabolism by hydroxychloroquine and its enantiomers in cytosolic fraction of liver homogenates from healthy and diabetic rats. Life Sci 64:325–335

    Article  CAS  PubMed  Google Scholar 

  • Estrada C, Gómez C, Martin C, Moncada S, González C (1992) Nitric oxide mediates tumor necrosis factor-α cytotoxicity in endothelial cells. Biochem Biophys Res Commun 186:475–482

    Article  CAS  PubMed  Google Scholar 

  • Etherington DJ, Pugh D, Silver IA (1981) Collagen degradation in an experimental inflammatory lesion: studies on the role of the macrophage. Acta Biol Med Ger 40:1625–1636

    CAS  PubMed  Google Scholar 

  • Ette EI, Brorm-Awala EA, Essien EE (1987a) Effect of ranitidine on chloroquine disposition. Drug Intell Clin Pharm 21:732–734

    CAS  PubMed  Google Scholar 

  • Ette EI, Essien EE, Ogonor JI, Brown-Awala EA (1987b) Chloroquine in human milk. J Clin Pharmacol 27:499–502

    Article  CAS  PubMed  Google Scholar 

  • Ette EI, Brown-Awala EA, Essien EE (1987c) Chloroquine elimination in humans: effect of low-dose cimetidine. J Clin Pharmacol 27:813–816

    Article  CAS  PubMed  Google Scholar 

  • Evans D, Williamson WRN (1987) Chemistry of clinically active anti-inflammatory compounds. In: Williamson WRN (ed) Anti-inflammatory compounds. Marcel Dekker, New York, pp 193–302

    Google Scholar 

  • Famaey JP, Fontaine J (1980) Prevention by chloroquine of hexosamine cartilage depletion by E-prostaglandins. Arthritis Rheum 23:780–781

    Article  CAS  PubMed  Google Scholar 

  • Farrante A, Rowan-Kelly B, Seow WK, Thong YH (1986) Depression of human polymorphonuclear leucocyte function by anti-malarial drugs. Immunology 58:125–130

    Google Scholar 

  • Finbloom DS, Silver K, Newsome DA, Gunkel R (1985) Comparison of hydroxychloroquine and chloroquine use and the development of retinal toxicity. J Rheumatol 12:692–694

    CAS  PubMed  Google Scholar 

  • Fosdyke DR (1975) Evidence for a relationship between chloroquine and complement from studies with lymphocyte mitogens: possible implications for the mechanism of chloroquine in disease. Can J Microbiol 21:1581–1586

    Article  Google Scholar 

  • Fox RI (1993) Mechanism of action of hydroxychloroquine as an antirheumatic drug. Semin Arthritis Rheum 23:82–91

    Article  CAS  PubMed  Google Scholar 

  • Fox R (1996) Anti-malarial drugs: possible mechanisms of action in autoimmune disease and prospects for drug development. Lupus 5(Suppl 1):S4–S10

    Article  CAS  PubMed  Google Scholar 

  • Fox RI, Dixon R, Guarrasi V, Krubel S (1996) Treatment of primary Sjogren’s syndrome with hydroxychloroquine: a retrospective, open-label study. Lupus 5(Suppl 1):S31–S36

    Article  PubMed  Google Scholar 

  • French JK, Hurst NP, O’Donnell ML, Betts WH (1987) Uptake of chloroquine and hydroxychloroquine by human blood leucocytes in vitro: relation to cellular concentrations during antirheumatic therapy. Ann Rheum Dis 46:42–45

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fryauff DJ, Richards AL, Baird JK, Richie TL, Mouzin E, Tjitra E, Sutamihardja MA, Ratiwayanto S, Hadiputranto H, Larasati RP, Pudjoprawoto N, Subianto B, Hoffman SL (1996) Lymphocyte proliferative response and subset profiles during extended periods of chloroquine or primaquine prophylaxis. Antimicrob Agents Chemother 40:2737–2742

    PubMed Central  CAS  PubMed  Google Scholar 

  • Fu S, Björkman A, Wåhlin B, Ofori-Adjei D, Ericsson O, Sjöqvist F (1986) In vitro activity of chloroquine, the two enantiomers of chloroquine, desethylchloroquine and pyronaridine against Plasmodium falciparum. Br J Clin Pharmacol 22:93–96

    PubMed Central  CAS  PubMed  Google Scholar 

  • Fulkerson JP, Ladenbauer-Bellis IM, Chrisman OD (1979) In vitro hexosamine depletion of intact articular cartilage by E-prostaglandins: prevention by chloroquine. Arthritis Rheum 22:1117–1121

    Article  CAS  PubMed  Google Scholar 

  • Furst DE (1993) Optimizing combination chemotherapy for rheumatoid arthritis. Ann N Y Acad Sci 696:285–291

    Article  CAS  PubMed  Google Scholar 

  • Furst DE (1996) Pharmacokinetics of hydroxychloroquine and chloroquine during treatment of rheumatic diseases. Lupus 5(Suppl 1):S11–S15

    Article  CAS  PubMed  Google Scholar 

  • Furst DE, Lindsley H, Baethge B, Botstein GR, Caldwell J, Dietz F, Ettlinger R, Golden HE, McLaughlin GE, Moreland LW, Roberts WN, Rooney TW, Rothschild B, Sack M, Sebba AI, Weisman M, Welch KE, Yocum D (1999) Dose-loading with hydroxychloroquine improves the rate of response in early, active rheumatoid arthritis: a randomized, double-blind six-week trial with eighteen-week extension. Arthritis Rheum 42:357–365

    Article  CAS  PubMed  Google Scholar 

  • Gallus AS (1979) Antiplatelet drugs: clinical pharmacology and therapeutic use. Drugs 18:439–477

    Article  CAS  PubMed  Google Scholar 

  • Geamănu-Pancă A, Popa-Cheracheanu A, Marinescu B, Geamănu CD, Voinea LM (2014) Retinal toxicity associated with chronic exposure to hydroxychloroquine and its ocular screening. Review. J Med Life 7:322–326

    PubMed Central  PubMed  Google Scholar 

  • Gendrel D, Verdier F, Richard-Lenoble D, Nardou M (1990) Interaction of cholestyramine and chloroquine. Arch Fr Pediatr 47:387–388

    CAS  PubMed  Google Scholar 

  • Gerstein HC, Thorpe KE, Taylor DW, Haynes RB (2002) The effectiveness of hydroxychloroquine in patients with type 2 diabetes mellitus who are refractory to sulfonylureas—a randomized trial. Diabetes Res Clin Pract 55:209–219

    Article  CAS  PubMed  Google Scholar 

  • Gil JP, Gil Berglund E (2007) CYP2C8 and antimalarial drug efficacy. Pharmacogenomics 8:187–198

    Article  CAS  PubMed  Google Scholar 

  • Ginsburg H, Geary TG (1987) Current concepts and new ideas on the mechanism of action of quinoline-containing antimalarials. Biochem Pharmacol 36:1567–1576

    Article  CAS  PubMed  Google Scholar 

  • Girart MV, Fuertes MB, Domaica CI, Rossi LE, Zwirner NW (2007) Engagement of TLR3, TLR7, and NKG2D regulate IFN-gamma secretion but not NKG2D-mediated cytotoxicity by human NK cells stimulated with suboptimal doses of IL-12. J Immunol 179:3472–3479

    Article  CAS  PubMed  Google Scholar 

  • Gladman DD, Blake R, Brubacher B, Farewell VT (1992) Chloroquine therapy in psoriatic arthritis. J Rheumatol 19:1724–1726

    CAS  PubMed  Google Scholar 

  • Glaumann H, Ahlberg J, Berkenstam A (1985) Rapid isolation of rat liver secondary lysosomes—autophagic vacuoles—following chloroquine administration. Exp Cell Res 163:151–158

    Article  Google Scholar 

  • Goekoop YP, Allaart CF, Breedveld FC, Dijkmans BA (2001) Combination therapy in rheumatoid arthritis. Curr Opin Rheumatol 13:177–183

    Article  CAS  PubMed  Google Scholar 

  • Goldman FD, Gilman AL, Hollenback C, Kato RM, Premack BA, Rawlings DJ (2000) Hydroxychloroquine inhibits calcium signals in T cells: a new mechanism to explain its immunomodulatory properties. Blood 95:3460–3466

    CAS  PubMed  Google Scholar 

  • Gordon D, Lewis GP (1984) Effects of piroxicam on mononuclear cells. Comparison with other antiarthritic drugs. Inflammation 8(Suppl):S87–S102

    Article  CAS  PubMed  Google Scholar 

  • Gottenberg JE, Ravaud P, Puéchal X, Le Guern V, Sibilia J, Goeb V, Larroche C, Dubost JJ, Rist S, Saraux A, Devauchelle-Pensec V, Morel J, Hayem G, Hatron P, Perdriger A, Sene D, Zarnitsky C, Batouche D, Furlan V, Benessiano J, Perrodeau E, Seror R, Mariette X (2014) Effects of hydroxychloroquine on symptomatic improvement in primary Sjögren syndrome: the JOQUER randomized clinical trial. JAMA 312:249–258

    Article  PubMed  CAS  Google Scholar 

  • Gräbner R, Meerbach W (1983) Imipramine and chloroquine induce alterations in phospholipid content of rat lung. Exp Path 24:253–259

    Article  Google Scholar 

  • Grierson DJ (1997) Hydroxychloroquine and visual screening in a rheumatology outpatient clinic. Ann Rheum Dis 56:188–190

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gupta JD, Gruca M, Ablett W (1979) Effect of other drugs and chemicals on the degradation of aspirin in vitro: possible extrapolation to in vivo metabolism of aspirin. Eur J Drug Metab Pharmacokinet 4:103–108

    Article  CAS  PubMed  Google Scholar 

  • Haberkorn A, Kraft HP, Blaschke G (1979) Antimalarial activity of the optical isomers of chloroquine diphosphate. Tropenmed Parasitol 30:308–312

    CAS  PubMed  Google Scholar 

  • Hage MP, Al-Badri MR, Azar ST (2014) A favourable effect of hydroxychloroquine on glucose and lipid metabolism beyond its anti-inflammatory role. Ther Adv Endocronol Metab 5:77–85

    Article  CAS  Google Scholar 

  • Hanna B, Holdeman NR, Tang RA, Schiffman JS (2008) Retinal toxicity secondary to Plaquenil therapy. Optometry 79:90–94

    Article  PubMed  Google Scholar 

  • Hedin U, Thyberg J (1985) Receptor-mediated endocytosis of immunoglobulin-coated colloidal gold particles in cultured mouse peritoneal macrophages. Chloroquine and monensin inhibit transfer of the ligand from endocytic vesicles to lysosomes. Eur J Cell Biology 39:130–135

    CAS  Google Scholar 

  • Hereng T, Lambert M, Hachulla E, Samor M, Dubucquoi S, Caron C, Launay D, Morell-Dubois S, Queyrel V, Hatron PY (2008) Influence of aspirin on the clinical outcomes of 103 anti-phospholipid antibodies-positive patients. Lupus 17:11–15

    Article  CAS  PubMed  Google Scholar 

  • Hobbs HE, Sorsby A, Freeman A (1959) Retinopathy following chloroquine therapy. Lancet 2:478–480

    Article  CAS  PubMed  Google Scholar 

  • Homewood CA, Warhurst DC, Peters W, Baggaly VC (1972) Lysosomes, pH and the anti-malarial action of chloroquine. Nature 235:50–52

    Article  CAS  PubMed  Google Scholar 

  • Hostetler KY, Richman DD (1982) Studies on the mechanism of phospholipid storage induced by amantadine and chloroquine in Madin Darby canine kidney cells. Biochem Pharmacol 31:3795–3799

    Article  CAS  PubMed  Google Scholar 

  • Hugosson E, Bjökman A, Troye-Blomberg M (2002) Chloroquine enhances the number of IL-10 producing cells and the expression of B7-2 and ICAM in in vitro-cultured PBMC. Scan J Immunol 55:399–402

    Article  CAS  Google Scholar 

  • Hunneyball IM, Crossley MJ, Spowage M (1986) Pharmacological studies of antigen-induced arthritis in BALB/c mice. II. The effects of second-line antirheumatic drugs and cytotoxic agents on the histopathological changes. Agents Actions 18:394–400

    Article  CAS  PubMed  Google Scholar 

  • Hurst NP, French JK, Gorjatsschko L, Betts WH (1987) Studies on the mechanism of inhibition of chemotactic tripeptide stimulated human neutrophil polymorphonuclear leucocyte superoxide production by chloroquine and hydroxychloroquine. Ann Rheum Dis 46:750–756

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hurst NP, French JK, Gorjatschko L, Betts WH (1988) Chloroquine and hydroxychloroquine inhibit multiple sites in metabolic pathways leading to neutrophil superoxide release. J Rheumatol 15:23–27

    CAS  PubMed  Google Scholar 

  • Hurvitz D, Hurschhorn K (1965) Suppression of in vitro lymphocyte responses by chloroquine. New Engl J Med 273:23–26

    Article  CAS  PubMed  Google Scholar 

  • Ignarro LJ (1971) Dissimilar effects of anti-inflammatory drugs on stability of lysosomes from peritoneal and circulating leukocytes and liver. Biochem Pharmacol 20:2861–2870

    Article  CAS  PubMed  Google Scholar 

  • Ignarro LJ (1974) Release of neutral protease and beta-glucuronidase from human neutrophils in the presence of cartilage treated with various immunologic reactants. J Immunol 113:298–308

    CAS  PubMed  Google Scholar 

  • Ignarro LJ, Colombo C (1972) Enzyme release from guinea-pig polymorphonuclear leucocyte lysosomes inhibited in vitro by anti-inflammatory drugs. Nat New Biol 239:155–157

    Article  CAS  PubMed  Google Scholar 

  • Ilo EC, Orisakwe OE, Ilondu NA, Okwoli N, Brown SA, Elo-Ilo J, Agbasi PU (2006) Effect of chloroquine on the bioavailability of ciprofloxacin in man. J Control Release 116:e109–e110

    Article  CAS  PubMed  Google Scholar 

  • Ilo CE, Ezejiofor NA, Agbakoba N, Brown SA, Maduagwuna CA, Agbasi PU, Orisakwe OE (2008) Effect of chloroquine on the urinary excretion of ciprofloxacin. Am J Ther 15:419–422

    Article  PubMed  Google Scholar 

  • Iredale J, Fieger H, Wainer IW (1993) Determination of the stereoisomers of hydroxychloroquine and its major metabolites in plasma and urine following a single oral administration of racemic hydroxychloroquine. Semin Arthritis Rheum 23:74–81

    Article  CAS  PubMed  Google Scholar 

  • Izmirly PM, Kim MY, Llanos C, Le PU, Guerra MM, Askanase AD, Salmon JE, Buyon JP (2010) Evaluation of the risk of anti-SSA/Ro-SSB/La antibody-associated cardiac manifestations of neonatal lupus in fetuses of mothers with systemic lupus erythematosus exposed to hydroxychloroquine. Ann Rheum Dis 69:1827–1830

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jang C-H, Choi J-H, Byun M-S, Jue D-M (2006) Chloroquine inhibits production of TNF-α, IL-1β and IL-6 from lipopolysaccharide-stimulated human monocytes/macrophages by different modes. Rheumatology 45:703–710

    Article  CAS  PubMed  Google Scholar 

  • Järvinen K, Vuolteenaho K, Nieminen R, Moilanen T, Knowles RG, Moilanen E (2008) Selective iNOS inhibitor 1400 W enhances anti-catabolic IL-10 and reduces destructive MMP-10 in OA cartilage. Survey of the effects of 1400 W on inflammatory mediators produced by OA cartilage as etected by protein antibody array. Clin Exp Rheumatol 26:275–282

    PubMed  Google Scholar 

  • Jarzyna R, Kiersztan A, Lisowa O, Bryła J (2001) The inhibition of gluconeogenesis by chloroquine contributes to its hypoglycaemic action. Eur J Pharmacol 428:381–388

    Article  CAS  PubMed  Google Scholar 

  • Jokar M et al. (2013) The effect of hydroxychloroquine on symptoms of knee osteoarthritis: a double-blind randomized controlled clinical trial. Iran J Med Sci 38(3):221–226

    PubMed Central  PubMed  Google Scholar 

  • Jones CJP, Jayson MIV (1984) Chloroquine: its effect on leucocyte auto- and heterophagocytosis. Ann Rheum Dis 43:205–212

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jones CJP, Salisbury RS, Jayson MIV (1984) The presence of abnormal lysosomes in lymphocytes and neutrophils during chloroquine therapy: a quantitative ultrastructural study. Ann Rheum Dis 43:710–715

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jover JA, Leon L, Pato E, Loza E, Rosales Z, Matias MA, Mendez-Fernandez R, Díaz-Valle D, Benitez-Del-Castillo JM, Abasolo L (2012) Long-term use of antimalarial drugs in rheumatic diseases. Clin Exp Rheumatol 30:380–387

    CAS  PubMed  Google Scholar 

  • Julkunen H, Rokkanen P, Laine H (1976) Chloroquine treatment and bone changes in rheumatoid arthritis. Scand J Rheumatol 5:36–38

    CAS  PubMed  Google Scholar 

  • Jung H, Bobba R, Su J, Shariati-Sarabi Z, Gladman DD, Urowitz M, Lou W, Fortin PR (2010) The protective effect of antimalarial drugs on thrombovascular events in systemic lupus erythematosus. Arthritis Rheum 62:863–868

    Article  CAS  PubMed  Google Scholar 

  • Kalmanson GM, Guze LB (1963) Effects of hydroxyl-chloroquine on immune mechanisms. Clin Res 11:106

    Google Scholar 

  • Kamal M, Bassiouni M (1992) Chloroquine inhibits elastase enzyme activity in vitro. Clin Exp Rheumatol 10:99–104

    Google Scholar 

  • Kamal MA, Jusko WJ (2004) Interactions of prednisolone and other immunosuppressants used in dual treatment of systemic lupus erythematosus in lymphocyte proliferation assays. J Clin Pharmacol 44:1034–1045

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kao KJ (1988) Selective elution of HLA antigens and β2-microglobulin from human platelets by chloroquine diphosphate. Transfusion 28:14–17

    Article  CAS  PubMed  Google Scholar 

  • Kaplan MJ, Lewis EE, Shelden EA, Somers E, Pavlic R, McCune WJ, Richardson BC (2002) The apoptotic ligands, TRAIL, TWEAK, and Fas ligand mediate monocyte death induced by autologous lupus T cells. J Immunol 169:6020–6029

    Article  CAS  PubMed  Google Scholar 

  • Karres I, Kremer JP, Dietl I, Steckholzer U, Jochum M, Ertel W (1998) Chloroquine inhibits roinflammatory cytokine release into human whole blood. Am J Physiol 274:R1058–R1064

    CAS  PubMed  Google Scholar 

  • Katchamart W, Trudeau J, Phumethum V, Bombardier C (2009) Efficacy and toxicity of methotrexate (MTX) monotherapy versus MTX combination therapy with non-biological disease-modifying antirheumatic drugs in rheumatoid arthritis: a systematic review and meta-analysis. Ann Rheum Dis 68:1105–1112

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Katz SJ, Russell AS (2011) Re-evaluation of antimalarials in treating rheumatic diseases: re-appreciation and insights into new mechanisms of action. Curr Opin Rheumatol 23:278–281

    Article  CAS  PubMed  Google Scholar 

  • Kelman SM, Sullivan SG, Stern A (1981) Chloroquine- and primaquiine-induced alterations of glucose metabolism in the uninfected red cell. Biochem Pharmacol 30:81–87

    Article  CAS  PubMed  Google Scholar 

  • Kheirkhah A, Amoli FA, Azari AA, Molaei S, Roozbahani M (2012) Conjunctival nodule in rheumatoid arthritis. Int Ophthalmol 32:81–83

    Article  PubMed  Google Scholar 

  • Khraishi MM, Singh G (1996) The role of anti-malarials in rheumatoid arthritis—the American experience. Lupus 5(Suppl 1):S41–S44

    Article  CAS  PubMed  Google Scholar 

  • Kingsbury SR et al. (2013) Hydroxychloroquine effectiveness in reducing symptoms of hand osteoarthritis (HERO): study protocol for a randomized controlled trial. Trials 14:64

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kim KA, Park JY, Lee JS, Lim S (2003) Cytochrome P450 2C8 and CYP3A4/5 are involved in chloroquine metabolism in human liver microsomes. Arch Pharm Res 26:631–637

    Article  CAS  PubMed  Google Scholar 

  • Klinefelter HF, Achurra A (1973) Effect of gold salts and antimalarials on the rheumatoid factor in rheumatoid arthritis. Scand J Rheumatol 2:177–182

    Article  CAS  PubMed  Google Scholar 

  • Knutson VP, Ronnett GV, Lane MD (1985) The effects of cycloheximide and chloroquine on insulin receptor metabolism. J Biol Chem 260:14180–14188

    CAS  PubMed  Google Scholar 

  • Köppel C, Tenczer J, Ibe K (1987) Urinary metabolism of chloroquine. Arzneim Forsch 37:208–211

    Google Scholar 

  • Korpela M, Laasonen L, Hannonen P, Kautiainen H, Leirisalo-Repo M, Hakala M, Paimela L, Blafield H, Puolakka K, Mottonen T, FIN-RACo Trial Group (2004) Retardation of joint damage in patients with early rheumatoid arthritis by initial aggressive treatment with disease-modifying antirheumatic drugs: five-year experience from the FIN-RACo study. Arthritis Rheum 50:2072–2081

    Article  CAS  PubMed  Google Scholar 

  • Krane SM, Amento EP, Goldring SR (1986) Cellular interactions in tissue breakdown in rheumatoid arthritis. Adv Inflamm Res 11:1–12

    Google Scholar 

  • Kruize AA, Hene RJ, Kallenberg CG, van Bijsterveld OP, van der Heide A, Kater L, Bijlsma JW (1993) Hydroxychloroquine treatment for primary Sjögren’s syndrome: a two year double blind crossover trial. Ann Rheum Dis 52:360–364

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kubo M, Hostettler KY (1980) Mechanism of cationic amphiphilic drug inhibition of purified lysosomal phospholipase A1. Biochemistry 24:6515–6520

    Article  Google Scholar 

  • Kull FC Jr, Besterman JM (1990) Drug-induced alterations of tumour necrosis factor-mediated cytotoxicity: discrimination of early versus late stage action. J Cell Biochem 42:1–12

    Article  CAS  PubMed  Google Scholar 

  • Kyburz D, Bretano F, Gay S (2006) Mode of action of hydroxychloroquine in RA—evidence of an inhibitory effect on toll-like signalling. Nature Clin Pract Rheumatol 2:458–459

    Article  Google Scholar 

  • Laaksonen AL, Koskiahde V, Juva K (1974) Dosage of antimalarial drugs for children with juvenile rheumatoid arthritis and systemic lupus erythematosus. A clinical study with determination of serum concentrations of chloroquine and hydroxychloroquine. Scand J Rheumatol 3:103–108

    Article  CAS  PubMed  Google Scholar 

  • Lafyatis R, York M, Marshak-Rothstein A (2006) Antimalarial agents: closing the gate on toll-like receptors. Arthritis Rheum 54:3068–3070

    Article  CAS  PubMed  Google Scholar 

  • Lai J-H, Ho L-J, Lu K-C, Chang D-M, Shaio M-F, Han S-H (2001) Western and Chinese antirheumatic drug-induced T cell apoptotic DNA damage uses different caspases cascades and is independent of Fas/Fas ligand interaction. J Immunol 166:6914–6924

    Article  CAS  PubMed  Google Scholar 

  • Landewe RBM, Miltenburg AMM, Verdonk MJA, Verweij CL, Breedveld FC, Daha MR, Dijkmans BAC (1995) Chloroquine inhibits T cell proliferation by interfering with IL-2 production and responsiveness. Clin Exp Immunol 102:144–151

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Leoni A (1955) Gli effetti della chlorochina sulla riposte eritematosa al fenolo nei portatori di eritematode cronico. Minerva Derm 30:410–411

    CAS  PubMed  Google Scholar 

  • Li XQ, Björkman A, Andersson TB, Gustafsson LL, Masimirembwa CM (2003) Identification of human cytochrome P(450)s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data. Eur J Clin Pharmacol 59:429–442

    Article  CAS  PubMed  Google Scholar 

  • Lim HS, Im JS, Cho JY, Bae KS, Klein TA, Yeom JS, Kim TS, Choi JS, Jang IJ, Park JW (2009) Pharmacokinetics of hydroxychloroquine and its clinical implications in chemoprophylaxis against malaria caused by Plasmodium vivax. Antimicrob Agents Chemother 53:1468–1475

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lipsky PE (1986) Natural killer cell function in rheumatoid arthritis. Clin Exp Rheumatol 4:303–305

    CAS  PubMed  Google Scholar 

  • Littler TR (1990) Anti-rheumatic drugs. In: Orme M (ed) Anti-rheumatic drugs. Pergamon Press, New York, pp 189–216

    Google Scholar 

  • Lomater G, Gattinara M, Gerloni V, Zeni S, Fantini F (1994) Combination therapy of juvenile rheumatoid arthritis with hydroxychloroquine-gold-methotrexate: a pilot study. Acta Univ Carol Med (Praha) 40:109–112

    CAS  Google Scholar 

  • Lowe JS, Turner EH (1973) The effect of adjuvant arthritis and drugs on the ability of rat plasma to inhibit the triton X-100 induced lysis of rabbit polymorphonuclear leucocyte granules. Biochem Pharmacol 22:2069–2078

    Article  CAS  PubMed  Google Scholar 

  • Lullmann-Rauch R, Pods R, von Witzendorff B (1996) The antimalarials quinacrine and chloroquine induce weak lysosomal storage of sulphated glycosaminoglycans in cell culture and in vivo. Toxicology 110:27–37

    Article  CAS  PubMed  Google Scholar 

  • MacIntyre AC, Cutler DJ (1986) In vitro binding of chloroquine to rat muscle preparations. J Pharm Sci 75:1068–1070

    Article  CAS  PubMed  Google Scholar 

  • MacIntyre AC, Cutler DJ (1988) Role of lysosomes in hepatic accumulation of chloroquine. J Pharm Sci 77:196–199

    Article  CAS  PubMed  Google Scholar 

  • Mackenzie AH (1970) An appraisal of chloroquine. Arthritis Rheum 13:280–291

    Article  CAS  PubMed  Google Scholar 

  • Mackenzie AH (1983a) Antimalarial drugs for rheumatoid arthritis. Am J Med 75:48–58

    Article  CAS  PubMed  Google Scholar 

  • Mackenzie AH (1983b) Pharmacologic actions of 4-aminoquinoline compounds. Am J Med 75(1A):5–10

    Article  CAS  PubMed  Google Scholar 

  • Mackenzie AH (1983c) Dose refinements in long-term therapy of rheumatoid arthritis with antimalarials. Am J Med 75(1A):40–45

    Article  CAS  PubMed  Google Scholar 

  • Maksymowych W, Russell AS (1987) Antimalarials in rheumatology: efficacy and safety. Semin Arthritis Rheum 16:206–221

    Article  CAS  PubMed  Google Scholar 

  • Malbica JO, Hart LG (1971) Effect of adenosine triphosphate and some anti-inflammatory agents on a purified lysosomal fraction having high acid phosphatase and labile β-glucuronidase activity. Biochem Pharmacol 20:2017–2026

    Article  CAS  PubMed  Google Scholar 

  • Manku MS, Horrobin DF (1976) Chloroquine, quinacrine, procaine, quinidine and clomipramine are prostanglandin agonsist and antagonists. Prostaglandins 12:789–801

    Article  CAS  PubMed  Google Scholar 

  • Marmor MF (2004) Hydroxychloroquine at the recommended dose (<or = 6.5 mg/kg/day) is safe for the retina in patients with rheumatoid arthritis and systemic lupus erythematosus. Clin Exp Rheumatol 22:143–144

    PubMed  Google Scholar 

  • Marmor MF, Carr RE, Easterbrook M, Farjo AA, Mieler WF, American Academy of Ophthalmology (2002) Recommendations on screening for chloroquine and hydroxychloroquine retinopathy: a report by the American Academy of Ophthalmology. Ophthalmology 109:1377–1382

    Article  PubMed  Google Scholar 

  • Martínez-Costa L, Victoria Ibañez M, Murcia-Bello C, Epifanio I, Verdejo-Gimeno C, Beltrán-Catalán E, Marco-Ventura P (2013) Use of microperimetry to evaluate hydroxychloroquine and chloroquine retinal toxicity. Can J Ophthalmol 48:400–405

    Article  PubMed  Google Scholar 

  • Mary CF, Legros J (1987) Experimental study of ocular effects of hydroxychloroquine in the rat: influence of oxidiser status. Br J Clin Pract 41(Suppl 52):46–49

    Google Scholar 

  • Matsuzawa Y, Hostettler KY (1980) Inhibition of lysosomal phospholipase A and phospholipase C by chloroiquine and 4,4′-bis(diethylaminoethoxy)α, β-diethyldiphenylethane. J Biol Chem 255:5190–5194

    CAS  PubMed  Google Scholar 

  • McCarty DJ, Carrera GF (1982) Intractable rheumatoid arthritis. Treatment with combined cyclophosphamide, azathioprine, and hydroxychloroquine. J Am Med Assn 248:1718–1723

    Article  CAS  Google Scholar 

  • McChesney EW (1983) Animal toxicity and pharmacokinetics of hydroxychloroquine sulphate. Am J Med 75(6A):11–18

    Article  CAS  PubMed  Google Scholar 

  • McChesney EW, Fitch CD (1984) 4-Aminoquinolines. In: Peters W, Richards WHG (eds) Antimalarial drugs II. Springer, Berlin, pp 3–60

    Chapter  Google Scholar 

  • McChesney EW, Banks WF Jr, Sullivan DJ (1965) Metabolism of chloroquine and hydroxychloroquine in albino and pigmented rats. Toxicol Appl Pharmacol 7:627–636

    Article  CAS  PubMed  Google Scholar 

  • McChesney EW, Conway WD, Banks WF Jr, Rogers JE, Shekosky JM (1966) Studies on the metabolism of some compounds of the 4-amino-7-chloroquinoline series. J Pharmacol Exp Ther 151:482–493

    CAS  PubMed  Google Scholar 

  • McChesney EW, Banks WF Jr, Fabian RJ (1967a) Tissue distribution of chloroquine, hydroxychloroquine, and desethylchloroquine. Toxicol Appl Pharmacol 10:501–513

    Article  CAS  PubMed  Google Scholar 

  • McChesney EW, Fasco MJ, Banks WF (1967b) The metabolism of chloroquine in man after repeated oral dosage. J Pharmacol Exp Ther 158:323–331

    CAS  PubMed  Google Scholar 

  • McElnay JC, Sidahmed AM, D’Arcy PF, McQuade RD (1985) Chloroquine-digoxin interaction. Int J Pharm 1985:267–274

    Article  Google Scholar 

  • McGettigan P, Henry D (2006) Cardiovascular risk and inhibition of cyclooxygenase: asystematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2. J Am Med Assn 296:1633–1644

    Article  CAS  Google Scholar 

  • McKendry RJR et al. (2001) Hydroxychloroquine (HCQ) versus acetaminophen (ACM) versus placebo (PL) in the treatment of nodal osteoarthritis (NOA) of the hands. J Rheumatol 28:1421–1421

    Google Scholar 

  • McLachlan AJ, Tett SE, Cutler DJ, Day RO (1993) Disposition of the enantiomers of hydroxychloroquine in patients with rheumatoid arthritis following multiple doses of the racemate. Br J Clin Pharmacol 36:78–81

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • McLachlan AJ, Tett SE, Cutler DJ, Day RO (1994) Disposition and absorption of hydroxychloroquine enantiomers following a single dose of the racemate. Chirality 6:360–364

    Article  CAS  PubMed  Google Scholar 

  • Meller S, Gerber PA, Homey B (2008) Clinical image: blonde by prescription. Arthritis Rheum 58:2286

    Article  PubMed  Google Scholar 

  • Midha KK, McKay G, Rawson MJ, Hubbard JW (1998) The impact of stereoisomerism in bioequivalence studies. J Pharm Sci 87:797–802

    Article  CAS  PubMed  Google Scholar 

  • Migkos MP, Markatseli TE, Iliou C, Voulgari PV, Drosos AA (2014) Effect of hydroxychloroquine on the lipid profile of patients with Sjögren syndrome. J Rheumatol 41:902–908

    Article  CAS  PubMed  Google Scholar 

  • Miller LC (1995) Cytokines in rheumatic diseases. Biotherapy 8:99–111

    Article  Google Scholar 

  • Minta JO, Williams MD (1986) Interactions of antirheumatic drugs with the superoxide generation system of activated human polymorphonuclear leukocytes. J Rheumatol 13:498–504

    CAS  PubMed  Google Scholar 

  • Miyachi Y, Yoshioka A, Imamura S, Niwa Y (1986) Antioxidant action of antimalarials. Ann Rheum Dis 45:244–248

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mottonen T, Hannonen P, Korpela M, Nissila M, Kautiainen H, Ilonen J, Laasonen L, Kaipiainen-Seppanen O, Franzen P, Helve T, Koski J, Gripenberg-Gahmberg M, Myllykangas-Luosujarvi R, Leirisalo-Repo M, the FIN-RACo Trial Group (2002) FINnish Rheumatoid Arthritis Combination therapy. Delay to institution of therapy and induction of remission using single-drug or combination-disease-modifying antirheumatic drug therapy in early rheumatoid arthritis. Arthritis Rheum 46:894–898

    Article  CAS  PubMed  Google Scholar 

  • Muller-Peddinghaus R, Wurl M (1987) The amplified chemiluminescence test to characterize antirheumatic drugs as oxygen radical scavengers. Biochem Pharmacol 36:1125–1132

    Article  CAS  PubMed  Google Scholar 

  • Mullié C, Jonet A, Desgrouas C, Taudon N, Sonnet P (2012) Differences in anti-malarial activity of 4-aminoalcohol quinoline enantiomers and investigation of the presumed underlying mechanism of action. Malar J 11:65

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Munster T, Gibbs JP, Shen D, Baethge BA, Botstein GR, Caldwell J, Dietz F, Ettlinger R, Golden HE, Lindsley H, McLaughlin GE, Moreland LW, Roberts WN, Rooney TW, Rothschild B, Sack M, Sebba AI, Weisman M, Welch KE, Yocum D, Furst DE (2002) Hydroxychloroquine concentration-response relationships in patients with rheumatoid arthritis. Arthritis Rheum 46:1460–1469

    Article  CAS  PubMed  Google Scholar 

  • Namazi MR (2009) The potential negative impact of proton pump inhibitors on the immunopharmacologic effects of chloroquine and hydroxychloroquine. Lupus 18:104–105

    Article  CAS  PubMed  Google Scholar 

  • Nation RL, Hackett LP, Dusci LJ, Ilett KF (1984) Excretion of hydroxychloroquine in human milk. Br J Clin Pharmacol 17:368–369

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nayak V, Esdaile JM (1996) The efficacy of antimalarials in systemic lupus erythematosus. Lupus 5(Suppl 1):S23–S27

    Article  CAS  PubMed  Google Scholar 

  • Neal TM, Vissers MC, Winterbourn CC (1987) Inhibition by nonsteroidal anti-inflammatory drugs of superoxide production and granule enzyme release by polymorphonuclear leukocytes stimulated with immune complexes or formyl-methionyl-leucyl-phenylalanine. Biochem Pharmacol 36:2511–2517

    Article  CAS  PubMed  Google Scholar 

  • Nebbioso M, Livani ML, Steigerwalt RD, Panetta V, Rispoli E (2011) Retina in rheumatic diseases: standard full field and multifocal electroretinography in hydroxychloroquine retinal dysfunction. Clin Exp Optom 94:276–283

    Article  PubMed  Google Scholar 

  • Neidel J, Zeidler U (1993) Independent effects of interleukin 1 on proteoglycan synthesis and proteoglycan breakdown of bovine articular cartilage in vitro. Agents Actions 39:82–90

    Article  CAS  PubMed  Google Scholar 

  • Neil HA, Perera R, Armitage JM, Farmer AJ, Mant D, Durrington PN (2008) Estimated 10-year cardiovascular risk in a British population: results of a national screening project. Int J Clin Pract 62:1322–1331

    Article  CAS  PubMed  Google Scholar 

  • Neill WA, Panayi GS, Duthie JJR (1973) Action of chloroquine phosphate in rheumatoid arthritis. 2. Chromosome damaging effect. Ann Rheum Dis 32:547–550

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Newbold BB (1963) Chemotherapy of arthritis induced in rats by mycobacterial adjuvant. Br J Pharmacol Chemother 21:127–136

    Article  Google Scholar 

  • Northover BJ (1977) Effect of indomethacin and related drugs on the calcium ion-dependent secretion of lysosomal and other enzymes by neutrophil polymorphonuclear leucocytes in vitro. Br J Pharmacol 59:253–259

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Novikoff AB, Beafay H, De Duve C (1956) Electron microscopy of lysosome rich fractions from rat liver. J Biophys Biochem Cytol 25(4 Suppl):179–184

    Article  Google Scholar 

  • Obua C, Ntale M, Lundblad MS, Mahindi M, Gustafsson LL, Ogwal-Okeng JW, Anokbonggo WW, Hellgren U (2006) Pharmacokinetic interactions between chloroquine, sulfadoxine and pyrimethamine and their bioequivalence in a generic fixed-dose combination in healthy volunteers in Uganda. Afr Health Sci 6:86–92

    PubMed Central  CAS  PubMed  Google Scholar 

  • O’Dell JR (1998) Triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine in patients with rheumatoid arthritis. Rheum Dis Clin North Am 24:465–477

    Article  PubMed  Google Scholar 

  • O’Dell JR (1999) Combination DMARD therapy with hydroxychloroquine, sulfasalazine, and methotrexate. Clin Exp Rheumatol 17:S53–S58

    PubMed  Google Scholar 

  • O’Dell JR, Blakely KW, Mallek JA, Eckhoff PJ, Leff RD, Wees SJ, Sems KM, Fernandez AM, Palmer WR, Klassen LW, Paulsen GA, Haire CE, Moore GF (2001) Treatment of early seropositive rheumatoid arthritis: a two-year, double-blind comparison of minocycline and hydroxychloroquine. Arthritis Rheum 44:2235–2241

    Article  PubMed  Google Scholar 

  • O’Dell JR, Petersen K, Leff R, Palmer W, Schned E, Blakely K, Haire C, Fernandez A (2006) Etanercept in combination with sulfasalazine, hydroxychloroquine, or gold in the treatment of rheumatoid arthritis. J Rheumatol 33:213–218

    PubMed  Google Scholar 

  • Oforah E, Anyogo S (2000) The contributions of various chloroquine salts to the biliary and urinary execretion of hepatic paracetamol conjugation metabolites in the rat. Drug Metabol Drug Interact 16:129–141

    CAS  PubMed  Google Scholar 

  • Ogunbona FA, Onyeji CO, Bolaji OO, Torimiro SE (1987) Excretion of chloroquine and desethylchloroquine in human milk. Br J Clin Pharmacol 23:473–476

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ohsugi Y, Gershwin ME (1984) Inhibition by various antiarthritic agents of murine splenic B cell colony formation. Immunopharmacology 7:1–7

    Article  CAS  PubMed  Google Scholar 

  • Onyeji CO, Toriola TA, Ogunbona FA (1993) Lack of pharmacokinetic interaction between chloroquine and imipramine. Ther Drug Monit 15:43–46

    Article  CAS  PubMed  Google Scholar 

  • Østensen M, Brown ND, Chiang PK, Aarbakke J (1985) Hydroxychloroquine in human breast milk. Eur J Clin Pharmacol 28:357

    Article  PubMed  Google Scholar 

  • Padol IT, Hunt RH (2010) Association of myocardial infarctions with COX-2 inhibition may be related to immunomodulation towards a Th1 response resulting in atheromatous plaque instability: an evidence-based interpretation. Rheumatology 49:837–843

    Article  CAS  PubMed  Google Scholar 

  • Page F (1951) Treatment of lupus erythematosus with mepacrine. Lancet 2:755–758

    Article  CAS  PubMed  Google Scholar 

  • Panayi GS, Neill WA, Duthie JJR, McCormick JN (1973) Action of chloroquine phosphate in rheumatoid arthritis. 1. Immunosuppressive effect. Ann Rheum Dis 32:316

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Pappu A, Hauser G (1981) Changes in brain phosphoinositide metabolism induced by cationic amphiphilic drugs in vitro. Biochem Pharmacol 30:3234–3246

    Article  Google Scholar 

  • Parke AL (1993) Antimalarial drugs, pregnancy and lactation. Lupus 2(Suppl 1):S21–S23

    Article  PubMed  Google Scholar 

  • Pasternak RD, Marks RL, Hubbs SJ, DiPasquale G (1985) Effects of antirheumatic agents on the mitogen response of arthritic rat spleen cells. Rec Commun Chem Path Pharmacol 48:353–367

    CAS  Google Scholar 

  • Paulus HE (1988) Antimalarial agents compared with or in combination with other disease-modifying antirheumatic drugs. Am J Med 85:45–52

    Article  CAS  PubMed  Google Scholar 

  • Pavelka K Jr, Pavelka Sen K, Peliskova Z, Vacha J, Trnavsky K (1989) Hydroxychloroquine sulphate in the treatment of rheumatoid arthritis: a double blind comparison of two dose regimens. Ann Rheum Dis 48:542–546

    Article  PubMed Central  PubMed  Google Scholar 

  • Payne JP (1894) A lecture on lupus erythematosus. Clin J IV:223

    Google Scholar 

  • Penn SK, Kao AH, Schott LL, Elliott JR, Toledo FG, Kuller L, Manzi S, Wasko MC (2010) Hydroxychloroquine and glycemia in women with rheumatoid arthritis and systemic lupus erythematosus. J Rheumatol 37:1136–1142

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Perrin DD (1965) Dissociation constants of organic bases in aqueous solutions. Butterworths, London

    Google Scholar 

  • Petri M (1996) Hydroxychloroquine use in the Baltimore Lupus Cohort; effects on lipids, glucose and thrombosis. Lupus 5(Suppl 1):S16–S22

    Article  CAS  PubMed  Google Scholar 

  • Petri M (2005) Lupus in Baltimore: evidence-based ‘clinical pearls’ from the Hopkins Lupus Cohort. Lupus 14:970–973

    Article  CAS  PubMed  Google Scholar 

  • Petri M, Purvey S, Fang H, Magder LS (2012) Predictors of organ damage in systemic lupus erythematosus: the Hopkins Lupus Cohort. Arthritis Rheum 64:4021–4028

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Pettipher ER, Higgs GA, Henderson B (1986) Interleukin 1 induces leukocyte infiltration and cartilage proteoglycan degradation in the synovial joint. Proc Natl Acad Sci USA 1986(83):8749–8753

    Article  Google Scholar 

  • Pico S, Peyron F, Vuillez J-P, Polack B, Ambroise-Thomas P (1991) Chloroquine inhibits tumour necrosis factor production by human macrophages in vitro. J Infect Dis 164:830

    Article  Google Scholar 

  • Pons-Estel GJ, Alarcón GS, McGwin G Jr, Danila MI, Zhang J, Bastian HM, Reveille JD, Vilá LM, Lumina Study Group (2009) Protective effect of hydroxychloroquine on renal damage in patients with lupus nephritis: LXV, data from a multiethnic US cohort. Arthritis Rheum 61:830–839

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Projean D, Baune B, Farinotti R, Flinois JP, Beaune P, Taburet AM, Ducharme J (2003) In vitro metabolism of chloroquine: identification of CYP2C8, CYP3A4, and CYP2D6 as the main isoforms catalyzing N-desethylchloroquine formation. Drug Metab Dispos 31:748–754

    Article  CAS  PubMed  Google Scholar 

  • Punzi L et al. (1996) Soluble interleukin 2 receptors and treatment with hydroxychloroquine in erosive osteoarthritis. J Rheumatol 23:1477–1478

    CAS  PubMed  Google Scholar 

  • Pussard E, Verdier, Blayo M-C (1986) Simultaneous determination of chloroquine, amadiaquine and their metabolites in human plasma, red blood cells, and whole blood and urine by column liquid chromatography. J Chromatogr 374:111–118

    Article  CAS  PubMed  Google Scholar 

  • Raghoebar M, Peeters PA, van den Berg W, van Ginneken CA (1986) Mechanisms of cell association of chloroquine to leucocytes. J Pharmacol Exp Ther 238:302–306

    CAS  PubMed  Google Scholar 

  • Raina RK, Bano G, Amla V, Kapoor V, Gupta KL (1993) The effect of aspirin, paracetamol and analgin on pharmacokinetics of chloroquine. Indian J Physiol Pharmacol 37:229–231

    CAS  PubMed  Google Scholar 

  • Rainsford KD (1985) Effects of anti-inflammatory drugs on catabolin-induced cartilage destruction in vitro. Int J Tissue React 7:123–126

    CAS  PubMed  Google Scholar 

  • Rainsford KD (1986) Effects of antimalarial drugs on interleukin 1-induced cartilage proteoglycan degradation in-vitro. J Pharm Pharmacol 38:829–833

    Article  CAS  PubMed  Google Scholar 

  • Rainsford KD (1987) Effects of anti-inflammatory drugs on the release from synovial tissues of cartilage-resorbing (catabolin-like) activity in vitro: role of assay conditions and drug effects on eicosanoid metabolism. In: The control of tissue damage. The Strangeways Research Laboratory 75th Annual Symposium. Arthritis and Rheumatism Council for Research, p 130

  • Rainsford KD (1988) Inhibitors of prostaglandin and leukotriene production. In: Curtis-Prior PB (ed) Prostaglandins: biology and chemistry of prostaglandins and related eicosanoids. Churchill-Livingstone, London, pp 52–68

    Google Scholar 

  • Rainsford KD (1990) Analgesics vs. nonsteroidal anti-inflammatory drugs (NSAIDs): differences among NSAIDs. In: Brandt KD (ed) Cartilage changes in osteoarthritis. Indiana University School of Medicine, pp 129–136

  • Rainsford KD (1992). Effects of antimalarial drugs oin the progression of adjuvant induced arthritis in rats. Unpublished studies

  • Rainsford KD, Rashad SY, Revell PA, Low FM, Hemingway AP, Walker FS, Johnson D, Stetsko P, Ying C, Smith F (1992) Effects of NSAIDs on cartilage proteoglycan and synovial prostaglandin metabolism in relation to progression of joint deterioration in osteoarthritis. In: Bálint G, Gömör B, Hadinka L (eds) Rheumatology, state of the art. Elsevier, Amsterdam, pp 177–183

    Google Scholar 

  • Rand JH, Wu X-X, Quinn AS, Chen PP, Hathcock JJ, Taatjes DJ (2008) Hydroxychloroquine directly reduces the binding of anti-phospholipid antibody-β2-glycoprotein I complexes to phospholipid bilayers. Blood 112:1687–1695

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Räsänen L, Lehto M, Hyöty H, Leinikki P (1989) Collaboration between human blood dentritic cells and monocytes in antigen presentation. APMIS 97:981–986

    Article  PubMed  Google Scholar 

  • Riches DWH, Stanworth DR (1982) Weak-base induced lysosomal secretion by macrophages: an alternative trigger mechanism that is independent of complement activation. Adv Exp Biol 155:313–323

    Article  CAS  Google Scholar 

  • Riches DWH, Morris CJ, Stanworth DR (1981) Induction of selective acid hydrolase release from mouse macrophages during exposure to chloroquine and quinine. Biochem Pharmacol 30:629–634

    Article  CAS  PubMed  Google Scholar 

  • Robertson CR et al. (1993) Treatment of erosive osteoarthritis with hydroxychloroquine. Arthritis Rheum 36:S167

    Google Scholar 

  • Ruiz-Irastorza G, Khamashta MA (2008) Hydroxychloroquine: the cornerstone of lupus therapy. Lupus 17:271–273

    Article  CAS  PubMed  Google Scholar 

  • Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, Khamashta MA (2010) Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus. Ann Rheum Dis 69:20–28

    Article  CAS  PubMed  Google Scholar 

  • RxFiles Detailing Program (2008) Drug comparison charts, 7th edn. In: Jensen B, Regier LD (Eds). Saskatoon City Hospital, Saskatoon, p 62

  • Rynes RI (1988) Toxicity of antimalarial drugs in rheumatoid arthritis. Agents Actions Suppl 44:151–157

    Google Scholar 

  • Rynes RI (1992) Antimalarials. In: Dixon JS, Furst DE (eds) Second-line agents in the treatment of rheumatic diseases. Marcel Dekker, New York, pp 245–266

    Google Scholar 

  • Rynes RI (1997) Antimalarial drugs in the treatment of rheumatological diseases. Br J Rheumatol 36:799–805

    Article  CAS  PubMed  Google Scholar 

  • Saklatvala J, Sarsfield SJ (1988) How do interleukin-1 and tumour necrosis factor induce degradation of proteoglycan in cartilage? In: Glauert A (ed) The control of tissue damage. Elsevier, Amsterdam, pp 97–108

    Google Scholar 

  • Saklatvala J, Pilsworth LMC, Sarsfield SJ, Gavrilovic J, Health JK (1984) Pig catabolin is a form of interleukin 1. Cartilage and bone resorb, fibroblasts make prostaglandins and collagen, and thymocyte proliferation is augmented in response to one protein. Biochem J 224:461–466

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Salaffi F, Carotti M, Cervini C (1996) Combination therapy of cyclosporine A with methotrexate or hydroxychloroquine in refractory rheumatoid arthritis. Scand J Rheumatol 25:16–23

    Article  CAS  PubMed  Google Scholar 

  • Salmeron G, Lipsky PE (1983) Immunosuppressive potential of antimalarials. Am Med J 75(1A):19–24

    Article  CAS  Google Scholar 

  • Salton DJ (1987) Chloroquine and the eye. Br J Clin Pract 41(Suppl 52):50–55

    Google Scholar 

  • Sammaritano LR, Bermas BL (2014) Rheumatoid arthritis medications and lactation. Curr Opin Rheumatol 26:354–360

    Article  CAS  PubMed  Google Scholar 

  • Sams WM (1967) Chloroquine: mechanism of action. Mayo Clin Proc 42:300–309

    PubMed  Google Scholar 

  • Sanders M (2000) A review of controlled clinical trials examining the effects of antimalarial compounds and gold compounds on radiographic progression in rheumatoid arthritis. J Rheumatol 27:523–529

    CAS  PubMed  Google Scholar 

  • Saviola G et al. (2012) Clondronate and hydroxychloroquine in erosive osteoarthritis: a 24-month open randomized pilot study. Mod Rheumatol 22(2):256–263

    Article  CAS  PubMed  Google Scholar 

  • Scala G, Oppenheim JJ (1983) Antigen presentation by human monocytes: evidence for stimulant processing and requirement for interleuklin 1. J Immunol 131:1160–1166

    CAS  PubMed  Google Scholar 

  • Schug BS, Kalbhen DA (1995) Influence of chloroquine and other substances on the collagenolytic activity in human osteoarthritic cartilage in vitro. Arzneimittelforschung 45:285–289

    CAS  PubMed  Google Scholar 

  • Semrau K, Kuhn L, Kasonde P, Sinkala M, Kankasa C, Shutes E, Vwalika C, Ghosh M, Aldrovandi G, Thea DM (2006) Impact of chloroquine on viral load in breast milk. Trop Med Int Health 11:800–833

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Seror R, Theander E, Bootsma H, Bowman SJ, Tzioufas A, Gottenberg JE, Ramos-Casals M, Dörner T, Ravaud P, Mariette X, Vitali C (2014) Outcome measures for primary Sjögren’s syndrome: a comprehensive review. J Autoimmun 51:51–56

    Article  PubMed  Google Scholar 

  • Seror R, Theander E, Brun JG, Ramos-Casals M, Valim V, Dörner T, Bootsma H, Tzioufas A, Solans-Laqué R, Mandl T, Gottenberg JE, Hachulla E, Sivils KL, Ng WF, Fauchais AL, Bombardieri S, Valesini G, Bartoloni E, Saraux A, Tomsic M, Sumida T, Nishiyama S, Caporali R, Kruize AA, Vollenweider C, Ravaud P, Vitali C, Mariette X, Bowman SJ, Sjögren’s Task Force EULAR (2015) Validation of EULAR primary Sjögren’s syndrome disease activity (ESSDAI) and patient indexes (ESSPRI). Ann Rheum Dis 74:859–866

    Article  PubMed  Google Scholar 

  • Shearer RV, Dubois EL (1967) Ocular changes induced by long-term hydroxychloroquine (plaquenil) therapy. Am J Ophthalmol 64:245–252

    Article  CAS  PubMed  Google Scholar 

  • Sheppeard H, Pilsworth LM, Hazleman B, Dingle JT (1982) Effects of antirheumatoid drugs on the production and action of porcine catabolin. Ann Rheum Dis 41:463–468

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sibtain SK et al. (2007) Role of hydroxychloroquine in management of osteoarthritis. Rheumatology (Oxford) 46:i61–i61

    Google Scholar 

  • Silva MA, Ishii-Iwamoto EL, Bracht A, Caparroz-Assef SM, Kimura E, Cuman RK, Bersani-Amado CA (2005) Efficiency of combined methotrexate/chloroquine therapy in adjuvant-induced arthritis. Fundam Clin Pharmacol 19:479–489

    Article  CAS  PubMed  Google Scholar 

  • Sisó A, Ramos-Casals M, Bové A, Brito-Zerón P, Soria N, Muñoz S, Testi A, Plaza J, Sentís J, Coca A (2008) Previous antimalarial therapy in patients diagnosed with lupus nephritis: influence on outcomes and survival. Lupus 17:281–288

    Article  PubMed  Google Scholar 

  • Skinner-Adams TS, Andrews KT, Melville L, McCarthy J, Gardiner DL (2007) Synergistic interactions of the antiretroviral protease inhibitors saquinavir and ritonavir with chloroquine and mefloquine against Plasmodium falciparum in vitro. Antimicrob Agents Chemother 51:759–762

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Smith RJ (1977) Modulation of phagocytosis by and lysosomal enzyme secretion from guinea-pig neutrophils: effect of nonsteroid anti-inflammatory agents and prostaglandins. J Pharmacol Exp Ther 200:647–657

    CAS  PubMed  Google Scholar 

  • Sneader W (2005) Drug discovery. A history. John Wiley, Chichester

    Book  Google Scholar 

  • Somer M, Kallio J, Pesonen U, Pyykko K, Huupponen R, Scheinin M (2000) Influence of hydroxychloroquine on the bioavailability of oral metoprolol. Br J Clin Pharmacol 49:549–554

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Spaldin V, Madden S, Pool WF, Woolf TF, Park BK (1994) The effect of enzyme inhibition on the metabolism and activation of tacrine by human liver microsomes. Br J Clin Pharmacol 38:15–22

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sperber K, Quraishi H, Kalb TH, Stecher V, Mayer L (1993) Selective regulation of cytokine secretion by hydroxychloroquine: inhibition of interleukin 1 alpha (IL-1α) and IL-6 in human monocytes and T cells. J Rheumatol 20:813–818

    Google Scholar 

  • Stecher VJ, Connolly KM, Speicht PT (1987) Fibronectin and macrophages as parameters of disease-modifying antirheumatic activity. Br J Clin Practice 41(Suppl 52):64–71

    Google Scholar 

  • Stepien KB, Wilczok T (1982) Studies on the mechanism of chloroquine binding to synthetic DOPA-melanin. Biochem Pharmacol 31:3359–3365

    Article  CAS  PubMed  Google Scholar 

  • Stepien K, Porebska M, Wilczok T (1987) Interaction of chloroquine with melanosomes and model melanin complexes. Stud Biophys 122:165–174

    CAS  Google Scholar 

  • Stringer E, Bohnsack J, Bowyer SL, Griffin TA, Huber AM, Lang B, Lindsley CB, Ota S, Pilkington C, Reed AM, Scuccimarri R, Feldman BM (2010) Treatment approaches to juvenile dermatomyositis (JDM) across North America: the Childhood Arthritis and Rheumatology Research Alliance (CARRA) JDM Treatment Survey. J Rheumatol 37:1953–1961

    Article  CAS  PubMed  Google Scholar 

  • Sun S, Rao NL, Venable J, Thurmond R, Karlsson L (2007) TLR7/9 antagonists as therapeutics for immune-mediated inflammatory disorders. Inflamm Allergy Drug Targets 6:223–235

    Article  CAS  PubMed  Google Scholar 

  • Suzuki Y, Ito I, Ito M, Yamagami I (1973) Changes of mucopolysaccharase, protease and collagenolytic activities in rats with adjuvant arthritis and the effects of various anti-inflammatory drugs. Nippon Yakurigaku Zasshi 69:947–968 (in Japanese)

    Article  CAS  PubMed  Google Scholar 

  • Tagoe CN, Ofori-Adjei D (1995) Effects of chloroquine and its enantiomers on the development of rat embryos in vitro. Teratology 52:137–142

    Article  CAS  PubMed  Google Scholar 

  • Tang C, Godfrey T, Stawell R, Nikpour M (2012) Hydroxychloroquine in lupus: emerging evidence supporting multiple beneficial effects. Intern Med J 42:968–978

    CAS  PubMed  Google Scholar 

  • Tauber R, Heinze K, Reutter W (1985) Effect of chloroquine on the degradation of l-fucose and the polypeptide moiety of plasma membrane glycoproteins. Eur J Cell Biology 39:380–385

    Google Scholar 

  • Tehrani R, Ostrowski RA, Hariman R, Jay WM (2008) Ocular toxicity of hydroxychloroquine. Semin Ophthalmol 23:201–209

    Article  PubMed  Google Scholar 

  • Teitz CC, Chrisman OD (1975) The effect of salicylate and chloroquine on prostaglandin-induced articular damage in the rabbit knee. Clin Orthop Relat Res 12:264–274

    Article  Google Scholar 

  • Tejeswar Rao P (1977) Intra-articular chloroquine in rheumatoid and osteo-arthritis of knee joint. J Indian Med Assoc 69(9):193–195

    CAS  PubMed  Google Scholar 

  • Tett SE (1993) Clinical pharmacokinetics of slow-acting antirheumatic drugs. Clin Pharmacokinet 25:392–407

    Article  CAS  PubMed  Google Scholar 

  • Tett SE, Cutler DJ, Day RO, Brown KF (1989) Bioavailability of hydroxychloroquine tables in healthy volunteers. Br J Pharmacol 27:771–779

    Article  CAS  Google Scholar 

  • Tett S, Cutler D, Day R (1990) Antimalarials in rheumatic diseases. Bailliere’s Clin Rheumatol 4:467–489

    Article  CAS  Google Scholar 

  • Tett S, McLachlan A, Day R, Cutler D (1993) Insights from pharmacokinetic and pharmacodynamic studies of hydroxychloroquine. Agents Actions Suppl 44:145–190

    CAS  PubMed  Google Scholar 

  • Tett SE, McLachlan AJ, Cutler DJ, Day RO (1994) Pharmacokinetics and pharmacodynamics of hydroxychloroquine enantiomers in patients with rheumatoid arthritis receiving multiple doses of racemate. Chirality 6:355–359

    Article  CAS  PubMed  Google Scholar 

  • Thiele DL, Lipsky PE (1985a) Modulation of human natural killer cell function by l-leucine methyl ester: monocyte-dependent depletion from human peripheral blood mononuclear cells. J Immunol 134:786–793

    CAS  PubMed  Google Scholar 

  • Thiele DL, Lipsky PE (1985b) Regulation of cellular function by products of lysosomal enzyme activity: elimination of human natural killer cells by a dipeptide methyl ester generated from l-leucine methyl ester by monocytes or poplymorphonuclear leukocytes. Proc Nat Acad Sci USA 82:2468–2472

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Thompson GR, Bartholomew L (1964) The effect of chloroquine on antibody production. Univ Michigan Med Ctr J 30:227–230

    CAS  Google Scholar 

  • Thorens B, Vassalli P (1986) Chloroquine and ammonium chloride prevent terminal glycosylation of immunoglobulins in plasma cells without affecting secretion. Nature 321:618–620

    Article  CAS  PubMed  Google Scholar 

  • Titus EO (1989) Recent developments in the understanding of the phramacokinetics and mechanism of action of chloroquine. Ther Drug Monit 11:369–379

    Article  CAS  PubMed  Google Scholar 

  • Trnavská Z, Trnavský K (1967) Influence of anti-rheumatic drugs on urinary excretion of hydroxyproline in lathyrism. Nature 214:384

    Article  PubMed  Google Scholar 

  • Trnavsky K, Gatterova J, Linduskova M, Peliskova Z (1993) Combination therapy with hydroxychloroquine and methotrexate in rheumatoid arthritis. Z Rheumatol 52:292–296

    CAS  PubMed  Google Scholar 

  • Tzekov R (2005) Ocular toxicity due to chloroquine and hydroxychloroquine: electrophysiological and visual function correlates. Doc Ophthalmol 110:111–120

    Article  PubMed  Google Scholar 

  • Van Cauwenberge H, Lecomte J, Lapiere C (1958a) Influence de la chloroquine sur l’oedeme a la ovalbumine ou au dextran, et sur la test d’ambrose et de eds chez le rat. C R Soc Biol 152:1405–1408

    Google Scholar 

  • Van Cauwenberge H, Lecomte J, Lapiere C (1958b) Influence de la chloroquine sur le development du granulome a l’ouate et sur la poche granulomateuse. C R Soc Biol 152:1414–1417

    Google Scholar 

  • van den Borne BE, Landewe RB, Goei The HS, Rietveld JH, Zwinderman AH, Bruyn GA, Breedveld FC, Dijkmans BA (1998) Combination therapy in recent onset rheumatoid arthritis: a randomized double blind trial of the addition of low dose cyclosporine to patients treated with low dose chloroquine. J Rheumatol 25:1493–1498

    PubMed  Google Scholar 

  • van der Heijde DM, van Riel PL, Nuver-Zwart IH, Gribnau FW, vad de Putte LB (1989) Effects of hydroxychloroquine and sulphasalazine on progression of joint damage in rheumatoid arthritis. Lancet 1:1036–1038

    Article  PubMed  Google Scholar 

  • van Loenen HJ, Dijkmans BA, De Vries E (1990) Concentration dependency of cyclosporin and chloroquine as inhibitors of cell proliferation and immunoglobulin production upon mitogen stimulation of mononuclear cells. Clin Exp Rheumatol 1990(8):59–61

    Google Scholar 

  • Van Roon EN, van den Bemt PMLA, Jansen TLThA, Houtman NM, van de Laar MAFJ, Brouwers JRBJ (2009) An evidence-based assessment of the clinical significance between disease-modifying antirheumatic drugs and non-antirheumatic drugs according to rheumatologists and pharmacists. Clin Ther 31:1737–1746

    Article  CAS  PubMed  Google Scholar 

  • van Vollenhoven RF, Ernestam S, Geborek P, Petersson IF, Coster L, Waltbrand E, Zickert A, Theander J, Thorner A, Hellstrom H, Teleman A, Dackhammar C, Akre F, Forslind K, Ljung L, Oding R, Chatzidionysiou A, Wornert M, Bratt J (2009) Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to methotrexate in patients with early rheumatoid arthritis (Swefot trial): 1-year results of a randomised trial. Lancet 374:459–466

    Article  PubMed  CAS  Google Scholar 

  • Varga F (1968a) Tissue distribution of chloroquine in the rat. Acta Physiol Acad Sci Hung Tomus 34:319–325

    CAS  Google Scholar 

  • Varga F (1968b) Intracellular localization of chloroquine in the liver and kidney of the rat. Acta Physiol Acad Sci Hung Tomus 34:327–332

    CAS  Google Scholar 

  • Vayuvegula B, Ohira K, Gollapudi S, Gupta S (1990) Role of monocytes in anti-CD3—induced T-cell DNA synthesis: effect of chloroquine and monensin on anti-CD3—induced T-cell activation. J Clin Immunol 10:247–254

    Article  CAS  PubMed  Google Scholar 

  • Verstappen SM, Jacobs JW, Bijlsma JW, Heurkens AH, van Booma-Frankfort C, Borg EJ, Hofman DM, van der Veen MJ, the Utrecht Arthritis Cohort Study Group (2003) Five-year follow-up of rheumatoid arthritis patients after early treatment with disease-modifying antirheumatic drugs versus treatment according to the pyramid approach in the first year. Arthritis Rheum 48:1797–1807

    Article  PubMed  Google Scholar 

  • Vezmar M, Georges E (2000) Reversal of MRP-mediated doxorubicin resistance with quinoline-based drugs. Biochem Pharmacol 59:1245–1252

    Article  CAS  PubMed  Google Scholar 

  • Viala A, Deturmeny E, Aubert C, Estadieu M, Durnad A, Cano JP, Delmont J (1983) Determination of chloroquine and monodesethylchloroquine in hair. J Forensic Sci 28:922–928

    Article  CAS  PubMed  Google Scholar 

  • Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, Daniels TE, Fox PC, Fox RI, Kassan SS, Pillemer SR, Talal N, Weisman MH, European Study Group on Classification Criteria for Sjögren’s Syndrome (2002) Classification criteria for Sjögren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis 61:554–558

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Vitali C, Bootsma H, Bowman SJ, Dorner T, Gottenberg JE, Mariette X, Ramos-Casals M, Ravaud P, Seror R, Theander E, Tzioufas AG (2013) Classification criteria for Sjogren’s syndrome: we actually need to definitively resolve the long debate on the issue. Ann Rheum Dis 72:476–478

    Article  PubMed  Google Scholar 

  • Volastro PS, Malawista SE, Chrisman OD (1973) Chloroquine: protective and destructive effects on injured rabbit cartilage in vivo. Clin Orthop Relat Res 14:243–248

    Article  Google Scholar 

  • Vuolteenaho K, Moilanen T, Hämäläinen M, Moilanen E (2003) Regulation of nitric oxide production in osteoarthritic and rheumatoid cartilage. Role of endogenous IL-1 inhibitors. Scand J Rheumatol 32:19–24

    Article  PubMed  Google Scholar 

  • Vuolteenaho K, Kujala P, Moilanen T, Moilanen E (2005) Aurothiomalate and hydroxychloroquine inhibit nitric oxide production in chondrocytes and in human osteoarthritic cartilage. Scand J Rheumatol 34:475–479

    Article  CAS  PubMed  Google Scholar 

  • Wallace DJ (1996) The history of antimalarials. Lupus 5(Suppl 1):S2–S3

    Article  PubMed  Google Scholar 

  • Ward PA (1966) The chemosuppression of chemotaxis. J Exp Med 23:1038–1044

    Google Scholar 

  • Wei LC, Chen SN, Ho CL, Kuo YH, Ho JD (2001) Progression of hydroxychloroquine retinopathy after discontinuation of therapy: case report. Chang Gung Med J 24:329–334

    CAS  PubMed  Google Scholar 

  • Weissmann G (1984) Labilization and stabilization of lysosomes. Federation Proc 23:1038–1044

    Google Scholar 

  • White NJ (1985) Clinical pharmacokinetics of antimalarial drugs. Clin Pharmacokinet 10:187–215

    Article  CAS  PubMed  Google Scholar 

  • Whitehead RW, Hager JP (1954) The anti-inflammatory and anti-hyaluronidase effect of chloroquine diphosphate. J Pharmacol Exp Ther 110:52–53

    Google Scholar 

  • Whitehouse MW (1967) Evaluation of potential antirheumatic drugs in vitro using lymphocytes and epithelial cells. The selective action of indoxole, methyl glyoxal and chloroquine. J Pharm Pharmacol 19:590–595

    Article  CAS  PubMed  Google Scholar 

  • Whitehouse MW, Boström H (1962) The effect of some anti-rheumatic drugs on the metabolism of connective tissues. Biochem Pharmacol 11:1175–1201

    Article  CAS  PubMed  Google Scholar 

  • Whitehouse MW, Boström H (1965) Biochemical properties of anti-inflammatory drugs. VI. The effects of chloroquine (resochin), mepacrine (quinacrine) and some of their potential metabolites on cartilage metabolism and oxidative phosphorylation. Biochem Pharmacol 14:1173–1184

    Article  CAS  PubMed  Google Scholar 

  • Whitehouse MW, Cowley FK (1966) Inhibition of connective tissue proteases by antimalarials. Biochem J 98:118–120

    Google Scholar 

  • Wiegmann K, Schutze S, Machleidt T, Witte D, Kronke M (1994) Functional dichotomy of neutral and sphingomylinase in tumor necrosis factor signalling. Cell 78:1005

    Article  CAS  PubMed  Google Scholar 

  • Wildfeuer A (1983) Action of antirheumatic drugs on the function of human leucocytes. Arzneimittelforschung 33:780–783

    CAS  PubMed  Google Scholar 

  • Williams WR, Davidson LAG (1983) Effects of therapeutic drugs on lymphocyte transformation. Br J Clin Pharmacol 15:83–90

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Witiak DT, Grattan DA, Heaslip RJ, Rahwan RG (1981) Synthesis and preliminary pharmacological evaluation of asymmetric chloroquine analogues. J Med Chem 24:712–717

    Article  CAS  PubMed  Google Scholar 

  • Wolfe F, Michaud K (2008) The risk of myocardial infarction and pharmacologic and nonpharmacologic myocardial infarction predictors in rheumatoid arthritis: a cohort and nested case-control analysis. Arthritis Rheum 58:2612–2621

    Article  PubMed  Google Scholar 

  • Woo TY, Callen JP, Voorhees JJ, Bickers DR, Hanno R, Hawkins C (1984) Cutaneous lesions of dermatomyositis are improved by hydroxychloroquine. J Am Acad Dermatol 10:592–600

    Article  CAS  PubMed  Google Scholar 

  • Wozniacka A, Lesiak A, Boncela J, Smolarczyk K, McCauliffe DP, Sysa-Jedrzejowska A (2008) The influence of antimalarial treatment in IL-1β, IL-6 and TNF-α mRNA expression on UVB-irradiated skin in systemic lupus erythematosus. Br J Dematol 159:1124–1130

    CAS  Google Scholar 

  • Yanagishita M, Hascall VC (1984) Metabolism of proteoglycans in rat ovarian granulosa cell culture. Multiple intracellular degradative pathways and the effects of chloroquine. J Biol Chem 259:10270–10283

    CAS  PubMed  Google Scholar 

  • Yasuda T (2006) Cartilage destruction by matrix degradation products. Mod Rheumatol 16:197–205

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yi Q, Holm G, Lefvert AK (1996) Idiotype-induced T cell stimulation requires antigen presentation in association with HLA-DR molecules. Clin Exp Immunol 104:359–365

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zhang W, Doherty M, Leeb BF, Alekseeva L, Arden NK, Bijlsma JW, Dinçer F, Dziedzic K, Häuselmann HJ, Herrero-Beaumont G, Kaklamanis P, Lohmander S, Maheu E, Martín-Mola E, Pavelka K, Punzi L, Reiter S, Sautner J, Smolen J, Verbruggen G, Zimmermann-Górska I (2007) EULAR evidence based recommendations for the management of hand osteoarthritis: report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 66:377–388

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zhou D, Liu Y, Xu LH, Ouyang DY, Pan H, Zhang XY, Zhao GX, He XH (2015) Chloroquine differentially modulates inflammatory cytokine expression in RAW 264.7 cells in response to inactivated Staphylococcus aureus. Inflammation 38:745–755

    Article  CAS  PubMed  Google Scholar 

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The authors declare no financial interest or support from commercial organizations marketing antimalarials in preparing this review. This was entirely author-initiated research for publication.

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Rainsford, K.D., Parke, A.L., Clifford-Rashotte, M. et al. Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases. Inflammopharmacol 23, 231–269 (2015). https://doi.org/10.1007/s10787-015-0239-y

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