Abstract
Purpose
Mesalazine and sulfasalazine are commonly used drugs for the treatment of inflammatory bowel disease. However, there have been few reports with a strict statistical analysis comparing the effects of mesalazine and sulfasalazine on laboratory test results. Therefore, we designed a retrospective cohort study to investigate whether or not differences in clinical laboratory parameters exist between mesalazine and sulfasalazine users.
Methods
We used data from the Clinical Data Warehouse of Nihon University School of Medicine to identify cohorts of new mesalazine users (n = 303) and sulfasalazine users (n = 67). We used a multivariate regression model and regression adjustment with the propensity score to adjust for differences in baseline covariates between mesalazine and sulfasalazine users, and compared serum levels of creatinine, urea nitrogen, aspartate aminotransferase, alanine aminotransferase, and hematological parameters including red and white blood cell counts and platelet count.
Results
After adjustment, in sulfasalazine users, the mean values for all tests showed no significant change between baseline and during the exposure period. In contrast, in mesalazine users, the mean WBC and platelet counts during the exposure period were significantly lower than those at baseline. Furthermore, mean serum urea nitrogen level during the exposure period was significantly higher than that at baseline. In terms of mean changes in laboratory test values during the exposure period compared with baseline, the reduction of platelet count in mesalazine users was significant in comparison to that in sulfasalazine users.
Conclusion
Our findings suggested that the hematological adverse effects of mesalazine treatment might be greater than those of sulfasalazine treatment.
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References
Rijk MC, van Schaik A, van Tongeren JH (1988) Disposition of 5-aminosalicylic acid by 5-aminosalicylic acid-delivering compounds. Scand J Gastroenterol 23(1):107–111
Sandborn WJ, Hanauer SB (2003) Systematic review: the pharmacokinetic profiles of oral mesalazine formulations and mesalazine pro-drugs used in the management of ulcerative colitis. Aliment Pharmacol Ther 17(1):29–42
Das KM, Eastwood MA, McManus JP, Sircus W (1973) Adverse reactions during salicylazosulfapyridine therapy and the relation with drug metabolism and acetylator phenotype. N Engl J Med 289(10):491–495
Riley SA, Mani V, Goodman MJ, Herd ME, Dutt S, Turnberg LA (1988) Comparison of delayed release 5 aminosalicylic acid (mesalazine) and sulphasalazine in the treatment of mild to moderate ulcerative colitis relapse. Gut 29(5):669–674
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(4):536–553
Hopkinson ND, Saiz Garcia F, Gumpel JM (1989) Haematological side-effects of sulphasalazine in inflammatory arthritis. Br J Rheumatol 28(5):414–417
Farr M, Tunn EJ, Symmons DP, Scott DG, Bacon PA (1989) Sulphasalazine in rheumatoid arthritis: haematological problems and changes in haematological indices associated with therapy. Br J Rheumatol 28(2):134–138
McKenna KE, Burrows D (1994) Leucopenia, thrombocytopenia and lymphadenopathy associated with sulphasalazine. Clin Exp Dermatol 19(5):419–420
Daneshmend TK (1991) Mesalazine-associated thrombocytopenia. Lancet 337(8752):1297–1298
Casellas F, Vallano A, Malagelada JR (1996) Leukopenia and thrombocytopenia as adverse effects of treatment with 5-aminosalicylic suppositories. J Clin Gastroenterol 22(2):160–161
Farrell RJ, Peppercorn MA, Fine SN, Michetti P (1999) Mesalamine-associated thrombocytopenia. Am J Gastroenterol 94(8):2304–2306
Laidlaw ST, Reilly JT (1994) Antilymphocyte globulin for mesalazine-associated aplastic anaemia. Lancet 343(8903):981–982
Mulder CJ, Tytgat GN, Weterman IT, Dekker W, Blok P, Schrijver M, van der Heide H (1988) Double-blind comparison of slow-release 5-aminosalicylate and sulfasalazine in remission maintenance in ulcerative colitis. Gastroenterology 95(6):1449–1453
Hanauer SB, Verst-Brasch C, Regalli G (1997) Renal safety of long-term mesalamine therapy in inflammatory bowel disease. Gastroenterology 112 [Suppl A]:991
Takahashi Y, Nishida Y, Nakayama T, Asai S (2011) Adverse effect profile of trichlormethiazide: a retrospective observational study. Cardiovasc Diabetol 10:45
Nishida Y, Takahashi Y, Nakayama T, Soma M, Asai S (2011) Comparative effect of olmesartan and candesartan on lipid metabolism and renal function in patients with hypertension: a retrospective observational study. Cardiovasc Diabetol 10:74
Nishida Y, Takahashi Y, Nakayama T, Soma M, Kitamura N, Asai S (2010) Effect of candesartan monotherapy on lipid metabolism in patients with hypertension: a retrospective longitudinal survey using data from electronic medical records. Cardiovasc Diabetol 9:38
Kitamura N, Takahashi Y, Yamadate S, Asai S (2007) Angiotensin II receptor blockers decreased blood glucose levels: a longitudinal survey using data from electronic medical records. Cardiovasc Diabetol 6:26
Rubin DB (1979) Using multivariate matched sampling and regression adjustment to control bias in observational studies. J Am Stat Assoc 74:318–324
D'Agostino RB Jr (1998) Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med 17(19):2265–2281
Wu AH, Aaronson KD, Bolling SF, Pagani FD, Welch K, Koelling TM (2005) Impact of mitral valve annuloplasty on mortality risk in patients with mitral regurgitation and left ventricular systolic dysfunction. J Am Coll Cardiol 45(3):381–387
Cunliffe RN, Scott BB (2002) Review article: monitoring for drug side-effects in inflammatory bowel disease. Aliment Pharmacol Ther 16(4):647–662
Jick H, Myers MW, Dean AD (1995) The risk of sulfasalazine- and mesalazine-associated blood disorders. Pharmacotherapy 15(2):176–181
Garcia-Diaz M, Nevado L, Berenguer A, Bureo JC, Bureo P, Saenz de Santamaria J (1995) Acute renal failure associated with 5-aminosalicylic acid in inflammatory bowel disease. Gastroenterol Hepatol 18(1):18–21
Hamling J, Raedler A, Helmchen U, Schreiber S (1997) 5-Aminosalicylic acid-associated renal tubular acidosis with decreased renal function in Crohn's disease. Digestion 58(3):304–307
Alivanis P, Aperis G, Lambrianou F, Zervos A, Paliouras C, Karvouniaris N, Arvanitis A (2010) Reversal of refractory sulfasalazine-related renal failure after treatment with corticosteroids. Clin Ther 32(11):1906–1910
Kreisel W, Wolf LM, Grotz W, Grieshaber M (1996) Renal tubular damage: an extraintestinal manifestation of chronic inflammatory bowel disease. Eur J Gastroenterol Hepatol 8(5):461–468
Gran JT, Myklebust G (1993) Toxicity of sulphasalazine in rheumatoid arthritis. Possible protective effect of rheumatoid factors and corticosteroids. Scand J Rheumatol 22(5):229–232
Rogler G (2010) Gastrointestinal and liver adverse effects of drugs used for treating IBD. Best Pract Res Clin Gastroenterol 24(2):157–165
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Masuda, H., Takahashi, Y., Nishida, Y. et al. Comparison of the effect of mesalazine and sulfasalazine on laboratory parameters: a retrospective observational study. Eur J Clin Pharmacol 68, 1549–1555 (2012). https://doi.org/10.1007/s00228-012-1289-3
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DOI: https://doi.org/10.1007/s00228-012-1289-3