Index

A1298C polymorphism 185 aura nofin (AF) 9, 38, 302 abnormal color vision 87 aurocyanide 8, 9 12 aurosome 134 ACR20 28, 204 auroth ioglucose 136 ACR20 responder rate 204 aurothi omalate 7- 9 ACR50 28 autoimmune disease 210 ACR70 28 autoimmun e disorders, with anti TNF-a ACR response criteria 179 therapy 272 activator protein 1 (AP-l) 70-72, 75 AV block 86 adalimumab 265 4, 5, 163-1 70, 294 adenosine 177, 178 azathiop rine, and allopurinol 4 adhesion molecule 135 azathioprine, and hypoxanthin e guanine adjuvant arthritis 134 phosphoribosyl transferase 4 adverse reactions, due to 15 azathiop rine, and 6-mercaptopurine 4, 5 agranulocytosis 150 azathioprine, and thiopurin e methyl­ alcohol intake 192 transferase 4 allopurinol 4 azathiopr ine, and xanthine oxidase 4 alopecia 210 azathioprine, comparison with other aminosalicylate 15, 16 DMARDs 166 amodiaquine 2 azathioprine, metabolism 4, 5 anakinra 279-289 azathioprine, structur e 5 angiogenesis 135 antibody deficiency 134 betamethasone 19 antigen processing 134 bioavailability 83, 175,202,222 antigenicity, anti TNF-a therap y 271 bioavailability, oral or parente ral 175 anti-inflammatory actions of 202 biologic agents 69 anti-TNF-a therapy 265-267,270-274 bisdesthylchloroquine 83 AP-l 70- 72,75 bucillamine 12, 13 aplastic anemia 150 apoptosis 178 C677T polymorphism 185 ASPIRE 306 calcineurin 7, 222

337 Index

captopril 13 cortisone 19 cardiomyopathy 86 cost of illness (COl) 57 CDI4+ monocyte 134 cost-effectiveness 50,60, 192 1-4, 81, 82,293 cost-effectiveness analysis 50,51,57, 60 chloroquine, and amodiaquine 2 cost-effectiveness ratio 50 chloroquine, and lysosomes 3 cough 191 chloroquine, and mepacrine 1 CTLM-Ig 309 chloroquine, and quinacrine 3 cyclophosphamid e 294 chloroquine, chiral centre 3 cyclosporin 6,7,186,221-231,301,307,310 chloroquine, enantiomers 3, 4 cyclosporin, absorption 6 chloroquine, half life 3 cyclosporin, and calcineurin 7 chloroquine, ionisation 2, 3 cyclosporin, and cyclophilin A 7 chloroquine, lipid solubility cyclosporin, and cytochrome p450 7 chloroquine, log D 2, 3 cyclosporin, and 186 chloroquine, log P 3 cyclosporin, structure 6 chloroquine, passive diffusion 2 cyclosporin A (CsA) 77,221,303 chloroquine, tissue binding 3 cyclosporin A, absorption of 222 chloroquine, volume of distribution 3 cyclosporin A, adverse effects of 228, 229 cholesterol 211 cyclosporin A, bioavailability of 222 cholestyramine 203 cyclosporin A, combination therapy with 225, chronic renal impairment 176 230 chrysiasis 150 cyclosporin A, distribution of 223 chrysotherapy 136 cyclosporin A, drug interactions with 223, 224 cirrhosis 190 cyclosporin A, efficacy of 224 clinical efficacy 137, 203 cyclosporin A, hypertension and 228 clinical improvement, with methotrexate 179 cyclosporin A, infection and 229 clinical pharmacology, anti TNF-a therapy 266 cyclosporin A, international guidelines for the clinical practice guidelines 38 use of 224, 230 COBRA 300 cyclosporin A, malignancy and 229 collagen-induced arthritis 134,310 cyclosporin A, monitoring of 230 color vision, abnormal 87 cyclosporin A, monotherapy of 225, 226, 230 combination of infliximab and leflunomide 209 cyclosporin A, nephrotoxicity 224 combination of leflunomide and methotrexate cyclosporin A, renal disfunction with 228 208 cyclosporin A, toxicity of 227,228 combination therapy 168, 186-188,208,209, cytochrome P450 7,223 225,230 cytokine production 133, 134 computer-based decision-support sytem 39 conception, methotrexate 191 DAS28 55 congestive heart failure (CHF), with anti TNF-a decision analysis 49 therapy 273 decision-making 26,36,37,49 corneal deposits 87 demyelinating syndrome, with anti TNF-a corticosteroids 18-21 therapy 273

338 Index

depression, mood disorder due to sulfasalazine folate supplementation 189 120 folic acid 10,11, 177, 190 dermatitis 149 functional capacity/disability 142 dermatological adverse events 89 functional disability 142,153 desethylchloroquine 83 desethylhydroxychloroquine 83 gastrointestinal adverse events, leflunomide 210 dexamethasone 19 gastrointestinal hyper sensitivity reaction 169 dihydrofolate reductase (DHFR) 175, 177 gastrointestinal side effect, dihydroorotate dehydrogenase 200 85,86 disability 142,153,179,183,184 gastrointestinal toxicity 189 disease models, RA 51 gingival hyperplasia 229 dizziness 86 gold 7-10,133-155,293,304 drug interaction 83 gold, absorption 7, 9 duration of treatment, gold 155 gold, and 9 gold, and aurocyanide 8, 9 early RA 298 gold, and aurothiomalate 7-9 efficacy 30,84,98,100,101,122,267 gold, and lactoperoxidase 8, 9 efficacy study 30 gold, and myeloperoxidase 8, 9 efficacy, anti-TNF-a therapy 267 gold, aurosomes 8 efficacy, of sulfasalazine 98, 100, 101, 122 gold, mechanism of action 133 elimination, methotrexate 176 gold, metabolism 8, 9 elimination half-life, hydroxychloroquine 83 gold, pharmacology 136 end stage renal failure 203 gold, 7-9, 134 enterocolitis 151 gold, stereochemistry 7 enterohepatic circulation 176 gold, structure 8, 9 enterohepatic recirculation 202 gold complexes 7-10 eosinophilia 150 gold distribution 136 erosion and joint space narrowing 182 gold dosing 154 c-selccrin 74, 77 gold nephropathy 150 established RA 302 gold treatment, combination with methotrexate established active RA 212 145 etanercept 265, 305-307, 309 gold treatment, history 133 evidence based medicine (EBM) 26, 152 gold treatment, lactation 151 exfoliative dermatitis 149 gold treatment, liver toxicity 151 extracellular signal regulated kinase (ERK) gold treatment, pregnancy 151 70-73 Golgi complex 82 graft rejection 210 Felty's syndrome 210 GSTM (gold sodium thiomalate) 134 fertility, influence of sulfasalazine 121 fibroblast 135 hair bleaching 89 FIN-RACo 300 hair loss 89, 150 fludrocortisone 21 headache 86

339 Index

Health Assessment Questionnaire (HAQ) 55, interactions, pharmacological of sulfasalazine 142, 183 97 health-related quality of life 205 interleukin converting enzyme (ICE) 78 hematuria 150 interstitial lung injury 191 hepatotoxicity 187,211 intra-articular methotrexate 176 HLA region 35 intra-articular steroid 301 humoral immunity 134 intracellular folate 177 hydroxychloroquine (HQ) 1-4, 81-89, 187, intracellular signaling molecules 70 295,300 intracellular signaling pathways 69 hydroxychloroquine, and amodiaquine 2 intrahepatic cholestasis 151 hydroxychloroquine, and Iysosomes 3 hydroxychloroquine, and mepacrine 1 Janus kinase (JAK) 77 hydroxychloroquine, and methotrexate 187 joint space narrowing 182 hydroxychloroquine, and quinacrine 3 Jun N-terminal kinase (JNK) 70-73, 75 hydroxychloroquine, chiral centre 3 hydroxychloroquine, dose 87 knockout mouse, ICE 78 hydroxychloroquine, enantiomers 3, 4 hydroxychloroquine, ionisation 2, 3 lab monitoring 89 hydroxychloroquine, lipid solubility 1 lactoperoxidase 8, 9 hydroxychloroquine, log D 2, 3 leflunomide 10,187,199-213,304,307 hydroxychloroquine, log P 3 leflunomide, half life 10, 203 hydroxychloroquine, passive diffusion 2 leflunomide, metabolism 10 hydroxychloroquine, structure 2 leucopenia 119, 150 hypertension 210,228 leucopenia, due to sulfasalazine treatment 119 hypertrichosis 229 liposome encapsulated GSTM 134 hypoxanthine guanine phosphoribosyl liver biopsy 190 transferase 4 liver necrosis 151 long-term efficacy, leflunomide 204 ICE knockout mouse 78 long-term observational study, gold 140 IgM 134 long-term outcome, treatment with sulfasalazine IKK 76 104 Il-1~ 82 Lyell's syndrome 149 immunoglobulin 134 lymphocyte 134 infection 169,210,229,271 lysosome 3, 134 infection , in anti TNF-a therapy 271 infliximab 209,265,306,307 macrophage 134 infusion reactions/injection site reactions, malformations in pregnancy, hydroxy­ anti TNF-a therapy 270 chloroquine 87 inhibition of progression, TNF blockers malignancy, in anti TNF-a therapy 272 153 MAPK activated protein kinase (MAPKAP K) inhibitor of nuclear factor KB inducing kinase 72, 73 (IKB) 75,76 MAPK kinase kinase (MAPKKK) 72

340 Index

marrow suppression, azathioprine 168 NF-AT 71 matrix metalloproteinase (MMP) 135,237 NF-KB 71-76,133,134 mechanims of action, anti-TNF-a therap y 265 NF-KB dimer 75 mechanism of action, of sulfasalazine 93 NF-KB inducing kinase (NIK) 75 membranous glomerulonephritis 150 NF-KB inhibitors 76 mepacrine 1 nitritoid reactions 151 mercaptopurine 4, 5 non-steroidal anti-inflammatory drugs (NSAIDs) mesalazine 15, 16 177 methotrexate (MTX) 10, 11, 83, 139, 145, nuclear factor of activated T cells (NFAT) 76, 175-192,208,300-304,307 77 methotrexate, and folic acid 10, 11 number needed to harm (NNH) 29 methotrexate, and cyclosporin 186 number needed to treat (NNT) 29,32 methotrexate, and hydroxychloroquine 187 methotrexate, and leflunomide 187 olsalazine 15 methotrexate, cellular effects 177 oral bioavailability, methotrexate 179 methotrexate, dosage 179 oral folic acid 190 methotrexate, log P 10 osteoclast differentiation 75 methotrexate, polyglutamation 10 oxygen radicals 135 methotrexate induced nodulosis 190 methylprednisolone 20 p38 MAPK 70, 71, 75 methylprednisolone acetate 20 p38 MAPK family 72-75 methylprednisolone sodium succcinate 20 p38 MAPK inhibitor 73-75 metoprolol 83 pancytopenia 150, 273 minocycline 16-18,239 pancytopenia, with anti TNF-a therapy 273 minocycline, half life 18 patient preferences 36, 37 minocycline, ionisation 17-18 11-15 minocycline, log P 18 d-penicillamine 295 minocycline, structure 17 penicillamine pKa 11 minocycline, volume of distribution 18 penicillamine, and acetylcysteine 12 mitogen activated protein kinase (MAI'K) penicillamine, and bucillamine 12, 13 70-75 penicillamine, and captopril 13 mode of action, leflunomide 200 penicillamine, and cysteine 11 monitoring 88, 154, 170, 191,212,271 penicillamine, and pentopril 14 monitoring, anti TNF-a therapy 274 penicillamine, and pyrithioxine 13 mood disorder, sulfasalazine 120 penicillamine, and thiopronine 13 MTX/LEF combination 187 penicillamine, and thiopy ridoxine 13 mucositis 150 penicillamine, configuration 11 mye1operoxidase 8, 9 penicillamine, thiol group 11 myopathy 86 pentopril 14 P-glycoprotein 223 Neoral® 222 pharmacokinetics, of sulfasalazine 95 nephrotric syndrome 150 pigmentous changes, hydroxychloroquine 89

341 Index

platelet activation in SLE 82 Sandimmune® 222 pneumonitis 191 sarcoidosis 210 polyglutamate-MTX 176 scotomata 87 post-injection reactions, gold 151 SF36 183 predictors for lung injury 191 Sharp score 181,207 predictors of therapeutic response 34 signal transducers and activators of transcription prednisolone 18, 19, 300 (STAT) 71, 77 prednisolone, structure 19 skin, adverse reactions 116, 120 prednisone 19,307 skin psoriasis 209 prednisone, metabolism 19 small molecules 69, 74, 79 pregnancy 87, 121, 123, 169 socioeconomic impacts 38 prognostic factors 34 sodium aurothiomalate (GST) 7-9, 136 progressive vision loss 87 SP100030 76 proinflammatory cytokine 134 SP600125 72 protein uria 150 standard methods for pharmacoeconomic psoriatic arthritis 85, 168,209 evaluation 55 pyridinylimidazole 73, 74 stomatitis 149 pyrimidine 200 subcutaneous administration 179 pyrithioxine 13 sulfasalazine 15,16,93-123,140,300-302, 306 quality of life 143,153,183 sulfasalazine, and aminosalicylate 15, 16 Quality-Adjusted Life-Years (QALYs) 50 sulfasalazine, and mesalazine 15, 16 quinacrine 3, 82 sulfasalazine, and olsalazine 15 quinine 2,3 sulfasalazine, and sulphamethoxazole 15 quinine, ionization 3 sulfasalazine, and sulphapyridine 15, 16 quinine, structure 2 sulfasalazine, structure 15 synovial membrane 134 radiographic progression 143-145,167,168, systemic lupus erythematosus 82, 210 180-183,206 radiographical outcome, of sulfasalazine treatment T cell activation, inhibition of 221 in clinical trials 103 T lymphocytes 224 randomised clinical trial (ReT) 26, 27 tacrolimus 304 rash 86,210 targeted small molecule inhibitors 79 receptor activator of NF-KB ligand (RANKL) 75 TEMPO 306 reference case recommendation 56 teratogenic effect 211 renal failure, and stage 203 tetracycline 16,18,237-241 renal functions, monitoring of 224 tetrahydrofolate (THF) 177 renal side effect 86 Thl cell 134 resistance to MTX therapy 185 Th2 cell 134 reticuloendothelial system 136 thiopronine 13 retinopathy 86, 87, 89 methyltransferase (TPMT) 4, 164, rituximab 307 165

342 Index

thiopyridoxine 13 triamcinolone, structure 21 third degree AV block 86 triamcinolone acetonide 20,21 thresholds for cost-effectiveness analyses 51 triamcinolone hexaceton ide 20,21 thrombocytopenia 150 triamcinolone hexaceton ide, structure 21 th ymidylate synthase 177 triple therapy 187 tissue gold concentrations 136 tyrosine kinase inhibition 201 TNF-i nhibitors 265- 274 TNF-a 71- 73, 76, 78, 82,265-267,270-274 upper respiratory tract infection 210 TNF-a converting enzyme (TACE) 78 user's guides for economic analysis 57 toxicity 85, 148, 188 toxicity index 85 vascular cell adhesion molecule-I (VCAM-I) 74 toxicity, anti-TNF-a therapy 270 vasculitis 210 toxicity, of sulfasalazine 114, 118, 122 vision loss, progressive 87 transcription as a therapeutic target 77 transcription factor families as therapeutic weight loss 211 targets 70-77 transcription factors, substrates of p38 MAPK xanthine oxidase 4, 164, 165 73

343 The PIR-Series Progress in Inflammation Research

Homepage: http://www.birkhauser.ch

Up-to-date information on the latest developments in the pathology, mechanisms and therapy of inflammatory disease are provided in this monograph series . Areas covered inclu­ de vascular responses, skin inflammation, pain, neuroinflammation, arthritis cartilage and bone, airways inflammation and asthma, allergy, cytokines and inflammatory mediators, cell signalling, and recent advances in drug therapy. Each volume is edited by acknowledged experts providing succinct overviews on specific topics intended to inform and explain . The series is of interest to academic and industrial biomedical researchers, drug development personnel and rheumatologists, allergists, pathologists, dermatologists and other clinicians requiring regular scientific updates.

Available volumes: T Cells in Arthritis, P. M iossec, W. van den Berg, G. Firestein (Editors), 1998 Chemokines and Skin, E. Kownatzki, J. Norgauer (Editors), 1998 Medicinal Fatty Acids, J. Kremer (Editor) , 1998 Inducible Enzymes in the Inflammatory Response , DA Willoughby, A Tomlinson (Editors), 1999 Cytokines in Severe Sepsis and Septic Shock, H. Redl, G. Schlag (Editors), 1999 Fatty Acids and Inflammatory Skin Diseases, J.-M . Schroder (Editor), 1999 Immunomodulatory Agents from Plants, H. Wagner (Editor), 1999 Cytokines and Pain, L. Watkins , S. Maier (Editors), 1999 In Vivo Models of Inflammation, D. Morgan, L. Marshall (Editors), 1999 Pain and Neurogenic Inflammation, S.D. Brain, P. Moore (Editors), 1999 Anti-Inflammatory Drugs in Asthma, AP. Sampson, M .K. Church (Editors), 1999 Novel Inhibitors of Leukotrienes, G. Folco, B. Samuelsson, R.C. Murphy (Editors), 1999 Vascular Adhesion Molecules and Inflammation, J.D. Pearson (Editor), 1999 Metalloproteinases as Targets for Anti-Inflammatory Drugs, K.M.K. Bottomley, D. Bradshaw, J.S. Nixon (Editors), 1999 Free Radicals and Inflammation, P.G. Winyard, D.R. Blake, C.H. Evans (Editors), 1999 Gene Therapy in Inflammatory Diseases, C.H. Evans, P. Robbins (Editors), 2000 New Cytokines as Potential Drugs, S. K. Narula, R. Coffmann (Editors), 2000 High Throughput Screening for Novel Anti-inflammatories, M. Kahn (Editor), 2000 Immunology and Drug Therapy of Atopic Skin Diseases, CAF. Bruijnzeel-Komen, E.F. Knol (Editors), 2000 Novel Cytokine Inhibitors, GA Higgs, B. Henderson (Editors), 2000 Inflammatory Processes. Molecular Mechanisms and Therapeutic Opportunities, L.G. Letts, D.W. Morgan (Editors), 2000 Backlist

Cellular Mechanisms in Airways Inflammation, C. Page, K. Banner,D. Spina (Editors), 2000 Inflammatory and Infectious Basis of Atherosclerosis, J.L. Mehta (Editor), 2001 Muscarinic Receptors in Airways Diseases, J. Zaagsma, H. Meurs, AF. RoffeI (Editors), 2001 TGF-{3 and Related Cytokines in Inflammation, S.N. Breit, S. Wahl (Editors), 2001 Nitric Oxide and Inflammation, D. Salvemini, T.R. Billiar, Y. Vodovotz (Editors), 2001 Neuroinflammatory Mechanisms in Alzheimer's Disease. Basic and Clinical Research, J. Rogers (Editor), 2001 Disease-modifying Therapy in Vasculitides, C.G.M. Kallenberg, l.W Cohen Tervaert (Editors), 2001 Inflammation and Stroke, G.Z. Feuerstein (Editor), 2001 NMDA Antagonists as Potential Analgesic Drugs, D.J.5. Sirinathsinghji, R.G. Hill (Editors), 2002 Migraine: A Neuroinflammatory Disease? E.L.H. Spierings, M. Sanchez del Rio (Editors), 2002 Mechanisms and Mediators of Neuropathic pain , AB. Malmberg, S.R. Chaplan (Editors), 2002 Bone Morphogenetic Proteins. From Laboratory to Clinical Practice, S. Vukicevic, K.T. Sampath (Editors), 2002 The Hereditary Basisof Allergic Diseases, J. Holloway, S. Holgate (Editors), 2002 Inflammation and Cardiac Diseases, G.Z. Feuerstein, P. Libby, D.L. Mann (Editors), 2003 Mind over Matter - Regulation of Peripheral Inflammation by the CNS, M. Schafer, C. Stein (Editors), 2003 Heat Shock Proteins and Inflammation, W van Eden (Editor), 2003 Pharmacotherapy of Gastrointestinal Inflammation, A Guglietta (Editor), 2004 Arachidonate Remodeling and Inflammation, AN. Fonteh, R.L. Wykle (Editors), 2004 Recent Advances in Pathophysiology of COPD, P.J. Barnes, TT Hansel (Editors), 2004 Cytokines and Joint tniut», WB. van den Berg, P. Miossec (Editors), 2004 Cancer and Inflammation, D.W Morgan, U. Forssmann , M.T. Nakada (Editors), 2004 Bone Morphogenetic Proteins: Bone Regeneration and Beyond, S. Vukicevic, K.T. Sam path (Editors), 2004 Antibiotics as Anti-Inflammatory and Immunomodulatory Agents, B.K. Rubin, J. Tamaoki (Editors), 2005