• Cees J. Haagsma
Part of the Progress in Inflammation Research book series (PIR)


In 1942 Nanna Svartz [1] published an important paper that has since become the benchmark for the present development of drugs: designing antirheumatic drugs based on notions of pathogenesis. She tried to link an antibacterial to an antiinflammatory agent in order to achieve simultaneous elimination of a putative infectious organism causing rheumatoid arthritis (RA) and suppression of inflammation. A number of compounds were developed and the one containing the antibiotic sulfapyridine and the anti-inflammatory salicylate 5-aminosalicylic acid linked by an azo bond (Structure 1) appeared to be the most promising.


Rheumatoid Arthritis Early Rheumatoid Arthritis Acetylator Phenotype Early Rheumatoid Arthritis Patient Intramuscular Gold 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Svartz N (1942) Salazopyrin, a new sulfanilamide preparation: a. therapeutic results in rheumatic polyarthritis; b. therapeutic results in ulcerative colitis; c. toxic manifestations in treatment with sulfanilamide preparations. Acta Med Scand 110: 577–598Google Scholar
  2. 2.
    McConkey B, Amos RS, Butler EP, Crockson RA, Crockson AP, Walsh L (1978) Salazopyrin in rheumatoid arthritis. Agents Actions 8: 438–441PubMedCrossRefGoogle Scholar
  3. 3.
    Smedegård G, Björk J (1995) Sulphasalazine: mechanism of action in rheumatoid arthritis. Br J Rheumatol 34(Suppl 2): 7–15PubMedGoogle Scholar
  4. 4.
    Rozin A, Schapira D, Braun-Moscovici Y, Nahir AM (2001) Cotrimoxazole treatment for rheumatoid arthritis. Semin Arthritis Rheum 31: 133–141PubMedCrossRefGoogle Scholar
  5. 5.
    Wahl C, Lipty S, Adler G, Schmid RM (1998) Sulfasalazine, a potent and specific inhibitor of nuclear factor kappa B. J Clin Invest 47: 323Google Scholar
  6. 6.
    Rodenburg RJT, Ganga A, van Lent PLEM, van de Putte LBA, van Venrooij WJ (2000) The antiinflammatory drug sulfasalazine inhibits tumor necrosis factor a expression in macrophages by inducing apoptosis. Arthritis Rheum 43: 1941–1950PubMedCrossRefGoogle Scholar
  7. 7.
    Pullar T, Hunter JA, Capell HA (1985) Which component of sulphasalazine is active in rheumatoid arthritis? Br Med J 290: 1535–1538CrossRefGoogle Scholar
  8. 8.
    Neumann VC, Taggart AJ, LeGallez P, Astbury C, Hill J, Bird HA (1986) A study to determine the active moiety of sulphasalazine in rheumatoid arthritis. J Rheumatol 13: 285–287PubMedGoogle Scholar
  9. 9.
    Astbury C, Hill J, Bird HA (1988) Co-trimoxazole in rheumatoid arthritis: a comparison with sulphapyridine. Ann Rheum Dis 47: 323–327PubMedCrossRefGoogle Scholar
  10. 10.
    Klotz U (1985) Clinical pharmacokinetics of sulphasalazine, its metabolites and other prodrugs of 5-aminosalicylic acid. Clin Pharmacokinet 10: 285–302PubMedCrossRefGoogle Scholar
  11. 11.
    Tett SE (1993) Clinical pharmacokinetics of slow-acting antirheumatic drugs. Clin Pharmacokinet 25: 392–407PubMedCrossRefGoogle Scholar
  12. 12.
    Rains CP, Noble S, Faulds D (1995) Sulfasalazine. A review of its pharmacological properties and therapeutic efficacy in the treatment of rheumatoid arthritis. Drugs 50: 137–156PubMedCrossRefGoogle Scholar
  13. 13.
    Farr M, Brodrick A, Bacon PA (1985) Plasma and synovial fluid concentrations of sulphasalazine and two of its metabolites in rheumatoid arthritis. Rheumatol Int 5: 247–251PubMedCrossRefGoogle Scholar
  14. 14.
    Haagsma CJ, Rüssel FGM, Vree TB, van Riel PLCM, van de Putte LBA (1996) Combination of methotrexate and sulphasalazine in patients with rheumatoid arthritis: pharmacokinetic analysis and relationship to clinical response. Br J Clin Pharmacol 42: 195–200PubMedCrossRefGoogle Scholar
  15. 15.
    Taggart AJ, McDermott BJ, Roberts SD (1992) The effect of age and acetylator phenotype on the pharmacokinetics of sulfasalazine in patients with rheumatoid arthritis. Clin Pharmacokinet 23: 311–320PubMedCrossRefGoogle Scholar
  16. 16.
    Astbury C, Taggart AJ, Juby L, Zebouni L, Bird HA (1990) Comparison of the single dose pharmacokinetics of sulphasalazine in rheumatoid arthritis and inflammatory bowel disease. Ann Rheum Dis 49: 587–590PubMedCrossRefGoogle Scholar
  17. 17.
    Schröder H, Price Evans DA (1972) Acetylator phenotype and adverse effects of sulphasalazine in healthy subjects. Gut 13: 278–284PubMedCrossRefGoogle Scholar
  18. 18.
    Rahav G, Zylber-Katz E, Rachmilewitz D, Levy M (1990) Relationship between the acetylator phenotype, plasma sulfapyridine levels and adverse effects during treatment with salicyazosulfapyridine in patients with chronic bowel diseases. Isr J Med Sei 26: 31–34Google Scholar
  19. 19.
    Pullar T, Hunter JA, Capell HA (1985) Effect of acetylator phenotype on efficacy and toxicity of sulphasalazine in rheumatoid arthritis. Ann Rheum Dis 44: 831–837PubMedCrossRefGoogle Scholar
  20. 20.
    Bax DE, Greaves MS, Amos RS (1986) Sulphasalazine for rheumatoid arthritis: relationship between dose, acetylator phenotype and response to treatment. Br J Rheumatol 25: 282–284PubMedCrossRefGoogle Scholar
  21. 21.
    Chalmers IM, Sitar DS, Hunter T (1990) A one-year, open, prospective study of sulfasalazine in the treatment of rheumatoid arthritis: adverse reactions and clinical response in relation to laboratory values, drug and metabolite serum levels, and acetylator status. J Rheumatol 17: 764–770PubMedGoogle Scholar
  22. 22.
    Tanaka E, Taniguchi A, Urano W, Nakajima H, Matsuda Y, Kitamura Y, Saito M, Yamanaka H, Saito T, Kamatani N (2002) Adverse effects of sulfasalazine in patients with rheumatoid arthritis are associated with diplotype configuration at the n-acetyl-transferase 2 gene. J Rheumatol 29: 2492–2499PubMedGoogle Scholar
  23. 23.
    Pullar T, Hunter JA, Capell HA (1985) Sulphasalazine in the treatment of rheumatoid arthritis: relationship of dose and serum levels to efficacy. Br J Rheumatol 24: 269–276PubMedCrossRefGoogle Scholar
  24. 24.
    Van Riel PLCM, van Gestel AM, van de Putte LBA (1995) Long-term usage and side-effect profile of sulphasalazine in rheumatoid arthritis. Br J Rheumatol 34 (Suppl 2): 40–42PubMedGoogle Scholar
  25. 25.
    Szumlanski CL, Weinshilboum RM (1995) Sulphasalazine inhibition of thiopurine methyltransferase: possible mechanism for interaction with 6-mercaptopurine and azathioprine. Br J Clin Pharmacol 39: 456–459PubMedGoogle Scholar
  26. 26.
    Lowry PW, Franklin CL, Weaver AL, Szumlanski CL, Mays DC, Loftus EV, Tremaine WJ, Lipsky JJ, Weinshilboum RM, Sandborn WJ (2001) Leucopenia resulting from a drug interaction between azathioprine or 6-mercaptopuine and mesalamine, sulphasalazine, or balsalazide. Gut 49: 656–664PubMedCrossRefGoogle Scholar
  27. 27.
    Waterworth RF (1989) The use of sulphasalazine and azathioprine in combination to treat rheumatoid arthritis. Br J Rheumatol 28: 456PubMedGoogle Scholar
  28. 28.
    Helliwell PS (1996) Combination therapy with sulphasalazine and azathioprine. Br J Rheumatol 35: 493–494PubMedCrossRefGoogle Scholar
  29. 29.
    Teefy AM, Martin JE, Kovacs MJ (2000) Warfarin resistance due to sulfasalazine. Ann Pharmacoter 34: 1165–1168CrossRefGoogle Scholar
  30. 30.
    Rodin SM, Johnson BF (1988) Pharmacokinetic interactions with digoxin. Clin Pharmacokinet 15: 227–244PubMedCrossRefGoogle Scholar
  31. 31.
    Felson DT, Anderson JJ, Meenan RT (1990) The comparative efficacy and toxicity of second-line drugs in rheumatoid arthritis. Results of two metaanalyses. Arthritis Rheum 33: 1449–1461PubMedCrossRefGoogle Scholar
  32. 32.
    Felson DT, Anderson JJ, Meenan RF (1992) Use of short-term efficacyJtoxicity tradeoffs to select second-line drugs in rheumatoid arthritis. A metaanalysis of published clinical trials. Arthritis Rheum 35: 1117–1125PubMedCrossRefGoogle Scholar
  33. 33.
    Suarez-Almazor ME, Beiseck E, Shea B, Wells G, Tugwell P (2002) Sulfasalazine for treating rheumatoid arthritis (Cochrane review). In: The Cochrane Library, Issue 4. Oxford: Update Software, OxfordGoogle Scholar
  34. 34.
    Ebringer R, Ahern M, Thomas D, Griffiths H, O’Callaghan J, Littlejohn G, Lewis D, Hazelton R, Barraclough D et al (1992) Sulfasalazine in early rheumatoid arthritis. The Australian Multicentre Clinical Trial Group. J Rheumatol 19: 1672–1677Google Scholar
  35. 35.
    Farr M, Waterhouse L, Johnson AE, Kitas GD, Jubb RW, Bacon PA (1995) A doubleblind controlled study comparing sulphasalazine with placebo in rheumatoid factor (RF)-negative rheumatoid arthritis. Clin Rheumatol 14: 531–536PubMedCrossRefGoogle Scholar
  36. 36.
    Hannonen P, Mottonen T, Hakola M, Oka M (1993) Sulfasalzine in early rheumatoid arthritis. A 48-week double-blind, prospective, placebo-controlled study. Arthritis Rheum 1501–1509Google Scholar
  37. 37.
    Pullar T, Hunter JA, Capell HA (1983) Sulphasalazine in early rheumatoid arthritis: a double blind comparison of sulphasalazine with placebo and sodium aurothiomalate. Br Med J (Clin Res Ed) 287: 1102–1104CrossRefGoogle Scholar
  38. 38.
    Skosey JL (1988) Comparison of responses to and adverse effects of graded doses of sulfasalazine in the treatment of rheumatoid arthritis. J Rheumatol (Suppl) 16: 5–8Google Scholar
  39. 39.
    Williams HJ, Ward JR, Dahl SL, Clegg DO, Willkens RF, Oglesby T, Weisman MH, Schlegel S, Michaels RM, Luggen ME et al (1988) A controlled trial comparing sulfasalazine, gold sodium thiomalate, and placebo in rheumatoid arthritis. Arthritis Rheum 31: 702–713PubMedCrossRefGoogle Scholar
  40. 40.
    Weinblatt ME, Reda D, Henderson W, Giobbie-Hurder A, Williams D, Diani A, Docsa S (1999) Sulfasalazine treatment for rheumatoid arthritis: a metaanalysis of 15 randomized trials. J Rheumatol 26: 2123–2130PubMedGoogle Scholar
  41. 41.
    Pinals RS, Kaplan SB, Lawson JG, Hepburn B (1986) Sulfasalazine in rheumatoid arthritis. A double-blind, placebo-controlled trial. Arthritis Rheum 29 (12): 1427–1434PubMedCrossRefGoogle Scholar
  42. 42.
    Nishioka K (1991) Double-blind comparative study of enteric salazosulfapyridine tablets (PJ-306) in the treatment of chronic rheumatoid arthritis. Ryumachi 31: 327–345PubMedGoogle Scholar
  43. 43.
    Nuver-Zwart IH, van Riel PLCM, van de Putte, Gribnau FWJ (1989) A double blind comparative study of sulphasalazine and hydroxychloroquine in rheumatoid arthritis: evidence of an earlier effect of sulphasalazine. Ann Rheum Dis 48: 389–395PubMedCrossRefGoogle Scholar
  44. 44.
    Van der Heijde DMFM, van Riel PLCM, Nuver-Zwart IH, Gribnau FWJ, van de Putte LBA (1989) Effects of hydroxychloroquine and sulphasalazine on progression of joint damage in rheumatoid arthritis. Lancet 333: 1036–1038CrossRefGoogle Scholar
  45. 45.
    Smolen JS, Kalden JR, Scott DL, Rozman B, Kvien TK, Larsen A, Loew-Friedrich I, Oed C, Rosenberg R (1999) European Leflunomide Study Group. Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double blind, randomised, multicentre trial. Lancet 353: 259–266PubMedCrossRefGoogle Scholar
  46. 46.
    Haagsma CJ, van Riel PLCM, de Jong AJL, van de Putte LBA (1997) Combination of sulphasalazine and methotrexate versus the single components in early rheumatoid arthritis: a randomized, controlled, doubl blind, 52 week clinical trial. Br J Rheumatol 36:1082–1088PubMedCrossRefGoogle Scholar
  47. 47.
    Dougados M, Combe B, Cantragel A, Goupille P, Olive P, Schattenkirchner M, Muesser S, Paimela L, Rau R, Zeidler H et al. (1999) Combination therapy in early rheumatoid arthritis: a randomised, controlled, double-blind 52 week clinical trial of sulpha-salazine and methotrexate compared with the single components. Ann Rheum Dis 58: 220–225PubMedCrossRefGoogle Scholar
  48. 48.
    Choy EH, Scott DL, Kingsley GH, Williams P, Wojtulewski J, Papasavvas G, Henderson E, Macfarlane D, Erhardt C, Young A et al (2002) Treating rheumatoid arthritis early with disease modifying drugs reduces joint damage: a randomised double blind trial of sulphasalazine versus diclofenac sodium. Clin Exp Rheumatol 20: 351–358PubMedGoogle Scholar
  49. 49.
    Sharp JT, Strand V, Leung H, Hurley F, Loew-Friedrich I (2000) Leflunomide Rheumatoid Arthritis Investigators Group. Treatment with leflunomide slows radiographic progression of rheumatoid arthritis. Arthritis Rheum 43: 495–505PubMedCrossRefGoogle Scholar
  50. 50.
    Larsen A, Kvien TK, Schattenkircher M, Rau R, Scott DL, Smolen JS, Rozman B, Westhovens R, Tikly M, Oed C, Rosenberg R (2001) The European Leflunomide Study Group. Slowing of disease progression in rheumatoid arthritis patients during long-term treatment with leflunomide or sulfasalazine. Scan J Rheumatol 30: 135–142CrossRefGoogle Scholar
  51. 51.
    Carroll GJ, Will RK, Breidahl PD, Tinsley LM (1989) Sulphasalazine versus penicillamine in the treatment of rheumatoid arthritis. Rheumatol Int 8: 251–255PubMedCrossRefGoogle Scholar
  52. 52.
    Pullar T, Hunter JA, Capell HA (1987) Effect of sulphasalazine on the radiological progression of rheumatoid arthritis. Ann Rheum Dis 46: 398–402PubMedCrossRefGoogle Scholar
  53. 53.
    Situnayake RD, McConkey B (1990) Clinical and laboratory effects of prolonged therapy with sulfasalazine, gold or penicillamine: the effects of disease duration on treatment response. J Rheumatol 17: 1268–1273PubMedGoogle Scholar
  54. 54.
    Situnayake RD, Grindulis KA, McConkey B (1987) Long-term treatment with sulphasalazine, gold or penicillamine: a comparison using life-table methods. Ann Rheum Dis 46: 177–183PubMedCrossRefGoogle Scholar
  55. 55.
    McEntegart A, Porter D, Capell HA, Thomson EA (1996) Sulfasalazine has a better efficacy/toxicity profile than auranofin — evidence from a 5 year prospective, randomized trial. J Rheumatol 23: 1887–1890PubMedGoogle Scholar
  56. 56.
    Capell HA, Maiden N, Madhok R, Hampson R, Thomson EA (1998) Intention-to-treat analysis of 200 patients with rheumatoid arthritis 12 years after random allocation to either sulfasalazine or penicillamine. J Rheumatol 25: 1880–1886PubMedGoogle Scholar
  57. 57.
    Scott DL, Smolen JS, Kalden JR, van de Putte LBA, Larsen A, Kvien TK, Schattenkircher M, Nash P, Oed C, Loew-Friedrich I (2001) European Leflunomide Study Group. Treatment of active rheumatoid arthritis with leflunomide: two year follow up of a double blind, placebo controlled trial versus sulfasalazine. Ann Rheum Dis 60: 913–923PubMedCrossRefGoogle Scholar
  58. 58.
    Utley M, Gallivan S, Young A, Cox N, Davies P, Dixey J, Emery P, Gough A, James D, Prouse P et al (2000) Potential bias in Kaplan-Meier survival analysis applied to rheumatology drug studies. Editorial. Rheumatology 39: 1–6Google Scholar
  59. 59.
    Jones E, Verrier Jones J, Woodbury JFL (1991) Response to sulfasalazine in rheumatoid arthritis: life table analysis of a 5-year follow up. J Rheumatol 18: 195–198PubMedGoogle Scholar
  60. 60.
    Wijnands MJH, van’t Hof MA, van Leeuwen MA, van Rijswijk MH, van de Putte LBA, van Riel PLCM (1992) Long-term second-line treatment: a prospective drug survival study. Br J Rheumatol 31: 253–258PubMedCrossRefGoogle Scholar
  61. 61.
    van der Heijde DMFM, van’t Hof MA, van Riel PLCM et al (1990) Judging disease activity in clinical practice in rheumatoid arthritis: first step in the development of each disease activity score. Ann Rheum Dis 49: 916–920PubMedCrossRefGoogle Scholar
  62. 62.
    Suarez-Almazor ME, Soskolne CL, Saunders D, Russell AS (1995) Use of second line drugs for the treatment of rheumatoid arthritis in Edmonton, Alberta. Patterns of prescription and long term effectiveness. J Rheumatol 22: 836–843PubMedGoogle Scholar
  63. 63.
    Galindo-Rodriguez G, Avina-Zubieta JA, Russell AS, Suarez-Almazor ME (1999) Dis-appointing long term results with disease modifying antirheumatic drugs. A practice based study. J Rheumatol 26: 2337–2343PubMedGoogle Scholar
  64. 64.
    Maetzel A, Wong A, Strand V, Tugwell P, Wells G, Bombardier C (2000) Meta-analysis of treatment termination rates among rheumatoid arthritis patients receiving diseasemodifying anti-rheumatic drugs. Rheumatology 39: 975–981PubMedCrossRefGoogle Scholar
  65. 65.
    Fries JF, Spitz P, Kraines RG, Holman HR (1980) Measurement of patient outcome in arthritis. Arthritis Rheum 23: 137–145PubMedCrossRefGoogle Scholar
  66. 66.
    Peliskova Z, Trnavsky K, Vacha J (1987) The use of the AIMS questionnaire in the evaluation of sulphasalazine treatment in rheumatoid arthritis. Z Rheumatol 46: 124–128PubMedGoogle Scholar
  67. 67.
    Van der Heijde DMFM, van Riel PLCM, van de Putte LBA (1990) Sensitivity of a Dutch Health Assessment Questionnaire in a trial comparing hydroxychloroquine versus sulphasalazine. Scand J Rheumatol 19: 407–412PubMedCrossRefGoogle Scholar
  68. 68.
    Fries JF, Williams CA, Morfeld D, Singh G, Sibley J (1996) Reduction in long-term disability in patients with rheumatoid arthritis by disease-modifying antirheumatic drugbased treatment strategies. Arthritis Rheum 39: 616–622PubMedCrossRefGoogle Scholar
  69. 69.
    Scott DL (1999) Leflunomide improves quality of life in rheumatoid arthritis. Scand J Rheumatol 28 (Suppl) 112: 23–29CrossRefGoogle Scholar
  70. 70.
    Smolen JS, Emery P (2000) Efficacy and safety of leflunomide in active rheumatoid arthritis. Rheumatology 39 (Suppl 1): 48–56PubMedGoogle Scholar
  71. 71.
    Kalden JR, Scott DL, Smoelen JS, Schattenkircher M, Rozman B, Williams BD, Kvien T, Jones P, Williams RB, Oed C et al (2001) European Leflunomide Study Group. Improved functional ability in patients with rheumatoid arthritis-long term treatment with leflunomide versus sulfasalazine. J Rheumatol 28: 1983–1991PubMedGoogle Scholar
  72. 72.
    Scott DL, Strand V (2002) The effects of disease-modifying anti-rheumatic drugs on the Health Assessment Questionnaire score. Lessons from the leflunomide clinical trials database. Rheumatology 41: 899–909PubMedCrossRefGoogle Scholar
  73. 73.
    Mcintosh E (1996) The costs of rheumatoid arthritis. Br J Rheumatol 35: 781–790PubMedCrossRefGoogle Scholar
  74. 74.
    Prashker M, Meenan RF (1995) The total cost of drug therapy for rheumatoid arthritis: a model based on costs of drug, monitoring, and toxicity. Arthritis Rheum 38: 318–325PubMedCrossRefGoogle Scholar
  75. 75.
    Verhoeven AC, Bibo JC, Boers M, Engel GL, van der Linden SJ (1998) Cost-effectiveness and cost-utility of combination therapy in early rheumatoid arthritis: randomized comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone. Br J Rheumatol 37: 1102–1109PubMedCrossRefGoogle Scholar
  76. 76.
    Hewitson PJ, DeBroe S, McBride A, Milne R (2000) Leflunomide and rheumatoid arthritis: a systematic review of effectiveness, safety and cost implications. J Clin Pharm Therap 25: 295–302CrossRefGoogle Scholar
  77. 77.
    Griffiths RI, Bar-Din M, MacLean C, Sullivan EM, Herbert RJ, Yelin EH (2001) Patterns of disease-modifying antirheumatic drug use, medical resource consumption, and costs among rheumatoid arthritis patients. Therap Apheresis 5: 92–104CrossRefGoogle Scholar
  78. 78.
    Ricart E, Taylor WR, Loftus EV, O’Kane D, Weinshilboum RM, Tremaine WJ, Harmsen WS, Zinsmeister AR, Sandborn WJ (2002) N-acetyltransferase 1 and 2 genotypes do not predict response or toxicity to treatment with mesalamine and sulfasalazine in patients with ulcerative colitis. Am J Gastroenterol 97 (7): 1763–1768PubMedCrossRefGoogle Scholar
  79. 79.
    Wijnands MJH, van’ t Hof MA, van de Putte LBA, van Riel PLCM (1993) Rheumatoid arthritis; a risk factor for sulphasalazine toxicity? A meta-analysis. Br J Rheumatol 32: 313–318PubMedCrossRefGoogle Scholar
  80. 80.
    Faarvang KL, Egsmose C, Kryger P, Podenphant J, Ingeman-Nielsen M, Hansen TM (1993) Hydroxychloroquine and sulphasalazine alone and in combination in rheumatoid arthritis: a randomised double blind trial. Ann Rheum Dis 52 (10): 711–715PubMedCrossRefGoogle Scholar
  81. 81.
    Amos RS, Pullar T, Bax DE, Situnayake D, Capell HA, McConkey B (1986) Sulphasalazine for rheumatoid arthritis: toxicity in 774 patients monitored for one to 11 years. BMJ 293: 420–423PubMedCrossRefGoogle Scholar
  82. 82.
    Marouf ES, Morris IM (1990) Neutropenia in patients with rheumatoid arthritis, treated with sulphasalazine. Br J Rheumatol 29: 407–409PubMedCrossRefGoogle Scholar
  83. 83.
    Ridley MG, Cheung NT, Myles AB (1989) Profound leucopenia with Salazopyrin EN. Br J Rheumatol 28: 364PubMedCrossRefGoogle Scholar
  84. 84.
    Capell HA, Pullar T, Hunter JA (1986) Comparison of white blood cell dyscrasias during sulphasalazine therapy of rheumatoid arthritis and inflammatory bowel disease. Drugs 32 (Suppl 1): 44–48PubMedCrossRefGoogle Scholar
  85. 85.
    Chakravarty K, Scott DGI, McCann BG (1992) Fatal neutropenic enterocolitis associated with sulphasalazine therapy for rheumatoid arthritis. Br J Rheumatol 31: 351–353PubMedCrossRefGoogle Scholar
  86. 86.
    Palmblad J, Jonson B, Kanerud L (1990) Treatment of drug-induced agranulocytosis with recombinant GM-CSF. J Intern Med 228: 537–539PubMedCrossRefGoogle Scholar
  87. 87.
    Kuipers EJ, Vellenga E, de Wolf JT, Hazenberg BP (1992) Sulfasalazine induced granulocytosis treated with granulocyte-macrophage colony stimulating factor. J Rheumatol 19: 621–622PubMedGoogle Scholar
  88. 88.
    Roddie P, Dorrance H, Cook MK, Rainey JB (1995) Treatment of sulphasalazineinduced agranulocytosis with granulocyte macrophage-colony stimulating factor. Aliment Pharmacol Ther 9: 711–712PubMedCrossRefGoogle Scholar
  89. 89.
    Wijnands MJ, Nuver-Zwart IH, van Riel PLCM, van’t Hof MA, Gribnau FW, van de Putte LB (1991) Hemolysis during low-dose sulfasalazine treatment in rheumatoid arthritis patients. Scand J Rheumatol 20: 52–57PubMedCrossRefGoogle Scholar
  90. 90.
    GGrindulis KA, McConkey AP (1985) Does sulphasalazine cause folate deficiency in rheumatoid arthritis? Scand J Rheumatol 14: 285–290CrossRefGoogle Scholar
  91. 91.
    Ralston SH, Willocks L, Shaw RW, Pitkeathly DA (1987) Macrocytosis and sulphasalazine treatment of rheumatoid arthritis. Br J Rheumatol 26: 472–473PubMedCrossRefGoogle Scholar
  92. 92.
    Prouse PJ, Shawe D, Gumpel JM (1986) Macrocytic anemia in patients treated with sulphasalazine for rheumatoid arthritis. Br Med J 293: 1047CrossRefGoogle Scholar
  93. 93.
    Farr M, Kitas GD, Tunn EJ, Bacon PA (1991) Immunodeficiencies associated with sulphasalazine therapy in inflammatory arthritis. Br J Rheumatol 30: 413–417PubMedCrossRefGoogle Scholar
  94. 94.
    Hamadeh MA, Atkinson J, Smith LJ (1992) Sulphasalazine-induced pulmonary disease. Chest 101: 1033–1037PubMedCrossRefGoogle Scholar
  95. 95.
    Parry SD, Barbatzas C, Peel ET, Barton JR (2002) Sulphasalazine and lung toxicity. Eur Respir J 19: 756–764PubMedCrossRefGoogle Scholar
  96. 96.
    Bashir RM, Lewis JH (1995) Hepatotoxicity of drugs used in the treatment of gastrointestinal disorders. Gastroenterol Clin North Am 24: 937–967PubMedGoogle Scholar
  97. 97.
    Haines JD Jr (1986) Hepatotoxicity after treatment with sulfasalazine. Postgrad Med 79: 193–194PubMedGoogle Scholar
  98. 98.
    Ransford RA, Langman MJ (2002) Sulphasalazine and mesalazine: serious adverse reactions re-evaluated on the basis of suspected adverse reaction reports to the Committee on Safety of Medicines. Gut 51: 536–539PubMedCrossRefGoogle Scholar
  99. 99.
    Helliwell PS (1995) Should tests for proteinuria be included in the monitoring schedule of sulphasalazine? Br J Rheumatol 34: 790–791PubMedCrossRefGoogle Scholar
  100. 100.
    Schiff MH, Whelton A (2000) Renal toxicity associated with disease-modifying antirheumatic drugs used for the treatment of rheumatoid arthritis. Semin Arthritis Rheum 30: 196–208PubMedCrossRefGoogle Scholar
  101. 101.
    Farr M, Scott DG, Bacon PA (1986) Side effect profile of 200 patients with inflammatory arthrititides treated with sulphasalazine. Drugs 32 (Suppl 1): 49–53PubMedCrossRefGoogle Scholar
  102. 102.
    Sherer J (1988) Depression induced by salazosulfapyridine in cyclothymia and Crohn disease. Nevenarzt 59: 371–373Google Scholar
  103. 103.
    Strom J (1969) Toxic epidermal necrolysis (Leyell’s syndrome). A report on four cases with three deaths. Scand J Infect Dis 1: 209–216PubMedGoogle Scholar
  104. 104.
    Vyse T, So AKL (1992) Sulphasalazine induced autoimmune syndrome. Br J Rheumatol 31: 115–116PubMedCrossRefGoogle Scholar
  105. 105.
    Gunnarson I, Kanerud L, Petterson E, Lundberg I, Lindblad S, Ringertz B (1997) Predisposing factors in sulphasalazine-induced systemic lupus erythematosus. Br J Rheumatol 36:1089–1094CrossRefGoogle Scholar
  106. 106.
    Gordon MM, Porter DR, Capell HA (1999) Does sulphasalazine cause drug induced systemic lupus erythematosus? No effect evident in a prospective randomised trial of 200 rheumatoid patients treated with sulphasalazine or auranofin over five years. Ann Rheum Dis 58: 288–290PubMedCrossRefGoogle Scholar
  107. 107.
    Hensleigh PA, Kauffman RE (1977) Maternal absorption and placental transfer of sulfasalazine. Am J Obstet Gynecol 27 (4): 443–444Google Scholar
  108. 108.
    Jarnerot G, Into-Malmberg MB, Esbjorner E (1981) Placental transfer of sulphasalazine and sulphapyridine and some of its metabolites. Scand J Gastroenterol 16 (5): 693–697PubMedCrossRefGoogle Scholar
  109. 109.
    Miller JP (1986) Inflammatory bowel disease in pregnancy: a review. J R Soc Med 79: 221–225PubMedGoogle Scholar
  110. 110.
    Mogadam M, Dobbins WO, Korelitz BI, Ahmed SW (1981) Pregnancy in inflammatory bowel disease: effect of sulphasalazine and corticosteroids on fetal outcome. Gastroenterology 80: 72–76PubMedGoogle Scholar
  111. 111.
    Ostensen M, Ramse-Goldman R (1998) Treatment of inflammatory rheumatic disorders in pregnancy: what are the safest treatment options? Drug Saf 19: 389–410PubMedCrossRefGoogle Scholar
  112. 112.
    Riley SA, Lecarpentier J, Mani V, Goodman MJ, Mandai BK, Turnberg LA (1987) Sulphasalazine induced seminal abnormalities in ulcerative colitis: results of mesalazine substitution. Gut 28: 1008–1012PubMedCrossRefGoogle Scholar
  113. 113.
    Kjaergaard N, Christensen LA, Lauritsen JG, Rasmussen SN, Hansen SH (1989) Effects of mesalazine substitution on salaicylazosulfapyridine-induced seminal abnormalities in men with ulcerative colitis. Scand J Gastroenterol 24: 891–896PubMedCrossRefGoogle Scholar
  114. 114.
    Zelissen PM, van Hattum J, Poen H, Schölten P, Gerritse R, te Velde ER (1988) Influence of salazosulphapyridine and 5-aminosalicylic acid on seminal qualities and male sex hormones. Scand J Gastroenterol 23: 1100–1104PubMedCrossRefGoogle Scholar
  115. 115.
    Purdy BH, Philips DM, Summers RW (1984) Desenstitization for sulfasalazine skin rash. Ann Intern Med 100: 512–514PubMedGoogle Scholar
  116. 116.
    Bax DE, Amos RS (1986) Sulphasalazine in rheumatoid arthritis: desensitising the patient with a skin rash. Ann Rheum Dis 45: 139–140PubMedCrossRefGoogle Scholar
  117. 117.
    Koski JM (1993) Desensitization to sulphasalazine in patients with arthritis. Clin Exp Rheumatol 11: 169–170PubMedGoogle Scholar
  118. 118.
    McCarthy C, Coughlan R (1994) Sulphasalazine desensitisation in patients with arthritis. Ir J Med Set 163: 238–239CrossRefGoogle Scholar
  119. 119.
    Di Paolo MC, Paoluzi OA, Pica R, Iacopini F, Crispino P, Rivera M, Spera G, Paoluzi P (2001) Sulphasalazine and 5-aminosalicylic acid in long-term treatment of ulcerative colitis: report on tolerance and side-effects. Dig Liver Dis 33: 563–569PubMedCrossRefGoogle Scholar
  120. 120.
    Mclnnes IB, Porter D, Murphy EA, Thomson EA, Madhok R, Hunter JA, Pullar T, Capell HA (1996) Low dose desensitisation does not reduce the toxicity of sulphasalazine in rheumatoid arthritis. Ann Rheum Dis 55: 328–330CrossRefGoogle Scholar
  121. 121.
    Cunliffe RN, Scott BB (2002) Review article: monitoring for drug side-effects in inflammatory bowel disease. Aliment Pharmacol Ther 16: 647–662PubMedCrossRefGoogle Scholar
  122. 122.
    Wijnands MJH, van Riel PLCM (1995) Management of adverse events of disease-modifying antirheumatic drugs. Drug Saf 13: 219–227PubMedCrossRefGoogle Scholar
  123. 123.
    (1995) Guidelines for monitoring drug therapy in rheumatoid arthritis. American College of Rheumatology ad hoc committee on clinical guidelines. Arthritis Rheum 39: 723–731Google Scholar
  124. 124.
    British Society for Rheumatology (2000) National guidelines for the monitoring of second line drugs. 2nd editionGoogle Scholar
  125. 125.
    Simon CH, Vliet Vlieland TP, Dijkmans BA, Bernelot Moens HJ, Janssen M, Hazes JM, Franken HC, Vandenbroucke JP, Breedveld FC (1998) Laboratory screening for side effects of disease modifying antirheumatic drugs in daily rheumatological practice. Scand J Rheumatol 27: 170–179PubMedCrossRefGoogle Scholar
  126. 126.
    Comer M, Scott DL, Doyle DV, Huskisson EC, Hopkins A (1995) Are slow-acting anti-rheumatic drugs monitored too often? An audit of current clinical practice. Br J Rheumatol 34: 966–970PubMedCrossRefGoogle Scholar
  127. 127.
    Boerbooms AMT, Kerstens PJSM, van Loenhout JWA, Mulder J, van de Putte LBA (1995) Infections during low-dose methotrexate treatment in rheumatoid arthritis. Semin Arthritis Rheum 24: 411–421PubMedCrossRefGoogle Scholar
  128. 128.
    Boers M, Verhoeven AC, Markusse HM, van de Laar MA, Westhovens R, van Denderen JC, van Zeben D, Dijkmans BAC, Peeters AJ, Jacobs P et al (1997) Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis. Lancet 350: 309–318PubMedCrossRefGoogle Scholar
  129. 129.
    Calguneri M, Pay S, Caliskaner Z, Apras S, Kiraz S, Ertenli I, Cobankara V (1999) Combination therapy versus monotherapy for the treatment of patients with rheumatoid arthritis. Clin Exp Rheumatol 17: 699–704PubMedGoogle Scholar
  130. 130.
    Möttönen T, Hannonen P, Leirisalo-Repo M, Nissila M, Kautainen H, Korpela M, Laasonen L, Julkunen H, Kuukkainen R, Vuori K et al (1999) Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomized trial. Lancet 353: 1568–1573PubMedCrossRefGoogle Scholar
  131. 131.
    O’Dell JR, Haire CE, Erikson N, Drymalski W, Palmer W, Eckhoff PJ, Garwood V, Maloley P, Klassen LW, Wees S et al (1996) Treatment of rheumatoid arthritis with methotrexate alone, sulfasalazine and hydroxychloroquine, or a combination of all three medications. N Engl J Med 334: 1287–1291PubMedCrossRefGoogle Scholar

Copyright information

© Birkhäuser Verlag Basel/Switzerland 2005

Authors and Affiliations

  • Cees J. Haagsma
    • 1
  1. 1.Twenteborg HospitalAlmeloThe Netherlands

Personalised recommendations