Respiratory Medicine
Volume 103, Issue 7 , Pages 975-994 , July 2009

The cumulative burden of oral corticosteroid side effects and the economic implications of steroid use

  • Stephanie C. Manson

      Affiliations

    • United BioSource Corporation, 20 Bloomsbury Square, London WCIA 2NS, UK
    • Corresponding Author InformationCorresponding author. Tel.: +44 207 299 4596.
    • ,
  • Ruth E. Brown

      Affiliations

    • United BioSource Corporation, 20 Bloomsbury Square, London WCIA 2NS, UK
    • ,
  • Annamaria Cerulli

      Affiliations

    • Novartis Pharma AG, Basel, Switzerland
    • ,
  • Carlos Fernandez Vidaurre

      Affiliations

    • Novartis Pharma AG, East Hanover, NJ, USA

Received 18 June 2008 ,Accepted 5 January 2009.

References 

  1. van Staa TP, Leufkens HG, Abenhaim L, Begaud B, Zhang B, Cooper C. Use of oral corticosteroids in the United Kingdom. QJM. Feb 2000;93(2):105–111
  2. Adcock IM, Ito K. Molecular mechanisms of corticosteroid actions. Monaldi Arch Chest Dis. Jun 2000;55(3):256–266
  3. Jones MA, Wagener JS. Managing acute pediatric asthma: keeping it short. J Pediatr. Jul 2001;139(1):3–5
  4. Munkholm P, Langholz E, Davidsen M, Binder V. Frequency of glucocorticoid resistance and dependency in Crohn's disease. Gut. Mar 1994;35(3):360–362
  5. Walsh LJ, Wong CA, Oborne J, et al. Adverse effects of oral corticosteroids in relation to dose in patients with lung disease. Thorax. Apr 2001;56(4):279–284
  6. Donnan PT, Libby G, Boyter AC, Thompson P. The population risk of fractures attributable to oral corticosteroids. Pharmacoepidemiol Drug Saf. Mar 2005;14(3):177–186
  7. Tattersfield AE, Harrison TW, Hubbard RB, Mortimer K. Safety of inhaled corticosteroids. Proc Am Thorac Soc. 2004;1(3):171–175
  8. Perry I, Neuberger J. Immunosuppression: towards a logical approach in liver transplantation. Clin Exp Immunol. Jan 2005;139(1):2–10
  9. Hailey D, Ohinmaa A, Roine R. Study quality and evidence of benefit in recent assessments of telemedicine. J Telemed Telecare. 2004;10(6):318–324
  10. Kamada AK, Szefler SJ. Glucocorticoids and growth in asthmatic children. Pediatr Allergy Immunol. 1995 Aug;6(3):145–154
  11. Kim SM, Lee HS, Hann SK. The efficacy of low-dose oral corticosteroids in the treatment of vitiligo patients. Int J Dermatol. 1999 Jul;38(7):546–550
  12. de Vries F, Bracke M, Leufkens HG, Lammers JW, Cooper C, Van Staa TP. Fracture risk with intermittent high-dose oral glucocorticoid therapy. Arthritis Rheum. Jan 2007;56(1):208–214
  13. estergaard P, Rejnmark L, Mosekilde L. Fracture risk associated with systemic and topical corticosteroids. J Intern Med. Apr 2005;257(4):374–384
  14. Steinbuch M, Youket TE, Cohen S. Oral glucocorticoid use is associated with an increased risk of fracture. Osteoporos Int. Apr 2004;15(4):323–328
  15. van Staa TP, Laan RF, Barton IP, Cohen S, Reid DM, Cooper C. Bone density threshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy. Arthritis Rheum. Nov 2003;48(11):3224–3229
  16. van Staa TP, Cooper C, Leufkens HG, Bishop N. Children and the risk of fractures caused by oral corticosteroids. J Bone Miner Res. May 2003;18(5):913–918
  17. Walsh LJ, Lewis SA, Wong CA, et al. The impact of oral corticosteroid use on bone mineral density and vertebral fracture. Am J Respir Crit Care Med. Sep 1 2002;166(5):691–695
  18. van Staa TP, Abenhaim L, Cooper C, Zhang B, Leufkens HG. Public health impact of adverse bone effects of oral corticosteroids. Br J Clin Pharmacol. Jun 2001;51(6):601–607
  19. Zonana-Nacach A, Barr SG, Magder LS, Petri M. Damage in systemic lupus erythematosus and its association with corticosteroids. Arthritis Rheum. Aug 2000;43(8):1801–1808
  20. van Staa TP, Geusens P, Pols HA, de Laet C, Leufkens HG, Cooper C. A simple score for estimating the long-term risk of fracture in patients using oral glucocorticoids. QJM. Mar 2005;98(3):191–198
  21. Gurwitz JH, Bohn RL, Glynn RJ, Monane M, Mogun H, Avorn J. Glucocorticoids and the risk for initiation of hypoglycemic therapy. Arch Intern Med. Jan 10 1994;154(1):97–101
  22. Garbe E, LeLorier J, Boivin JF, Suissa S. Risk of ocular hypertension or open-angle glaucoma in elderly patients on oral glucocorticoids. Lancet. Oct 4 1997;350(9083):979–982
  23. Decramer M, Lacquet LM, Fagard R, Rogiers P. Corticosteroids contribute to muscle weakness in chronic airflow obstruction. Am J Respir Crit Care Med. 1994 Jul;150(1):11–16
  24. Varas-Lorenzo C, Rodriguez LA, Maguire A, Castellsague J, Perez-Gutthann S. Use of oral corticosteroids and the risk of acute myocardial infarction. Atherosclerosis. 2007 Jun;192(2):376–383
  25. Huiart L, Ernst P, Ranouil X, Suissa S. Oral corticosteroid use and the risk of acute myocardial infarction in chronic obstructive pulmonary disease. Can Respir J. Apr 2006;13(3):134–138
  26. Souverein PC, Berard A, Van Staa TP, et al. Use of oral glucocorticoids and risk of cardiovascular and cerebrovascular disease in a population based case-control study. Heart. Aug 2004;90(8):859–865
  27. Curtis JR, Westfall AO, Allison J, et al. Population-based assessment of adverse events associated with long-term glucocorticoid use. Arthritis Rheum. Jun 15 2006;55(3):420–426
  28. Rothberg AD, Matshidze PK. Monitoring and management of bone status in patients on chronic glucocorticoid treatment – the Medscheme experience. S Afr Med J. Nov 2000;90(11):1125–1129
  29. Kumagai S, Kawano S, Atsumi T, et al. Vertebral fracture and bone mineral density in women receiving high dose glucocorticoids for treatment of autoimmune diseases. J Rheumatol. May 2005;32(5):863–869
  30. Piper JM, Ray WA, Daugherty JR, Griffin MR. Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs. Ann Intern Med. May 1 1991;114(9):735–740
  31. Kanis JA, Stevenson M, McCloskey EV, Davis S, Lloyd-Jones M. Glucocorticoid-induced osteoporosis: a systematic review and cost-utility analysis. Health Technol Assess. Mar 2007;11(7):iii–iv, ix-xi, p. 1–231
  32. Sorensen HT, Mellemkjaer L, Nielsen GL, Baron JA, Olsen JH, Karagas MR. Skin cancers and non-hodgkin lymphoma among users of systemic glucocorticoids: a population-based cohort study. J Natl Cancer Inst. May 5 2004;96(9):709–711
  33. Blackburn D, Hux J, Mamdani M. Quantification of the risk of corticosteroid-induced diabetes mellitus among the elderly. J Gen Intern Med. Sep 2002;17(9):717–720
  34. Evans JM, Barnett KN, Ogston SA, Morris AD. Increasing prevalence of type 2 diabetes in a Scottish population: effect of increasing incidence or decreasing mortality?. Diabetologia. 2007 Apr;50(4):729–732
  35. Office for National Statistics. Cancer statistics registrations: registrations of cancer diagnosed in 2004, England. Series MB1 no.35; 2007.
  36. Welsh Cancer Intelligence and Surveillance Unit. Cancer registrations in Wales 2004; 2007.
  37. ISD Online. Cancer incidence, mortality and survival; 2007.
  38. Northern Ireland Cancer Registry. Cancer registrations in Northern Ireland, 2004; 2007.
  39. Incidence of Myocardial Infarction . British Heart Foundation Statistics Website. <http://www.heartstats.org/datapage.asp?id=1085>[accessed 20.11.07]
  40. The Royal College of Ophthalmologists . Cataract surgery guidelines. <www.rcophth.ac.uk>2004;[accessed 06.09.07]
  41. Kang JY, Tinto A, Higham J, Majeed A. Peptic ulceration in general practice in England and Wales 1994–98: period prevalence and drug management. Aliment Pharmacol Ther. 2002 Jun;16(6):1067–1074
  42. Carroll K, Murad S, Eliahoo J, Majeed A. Stroke incidence and risk factors in a population-based prospective cohort study. Health Stat Q. 2001;12:18–26
  43. Johansen A, Evans RJ, Stone MD, Richmond PW, Lo SV, Woodhouse KW. Fracture incidence in England and Wales: a study based on the population of Cardiff. Injury. 1997 Nov–Dec;28(9–10):655–660
  44. Sancar M, Izzettin FV, Apikoglu-Rabus S, Besisik F, Tozun N, Dulger G. Pharmacoeconomic comparison of Helicobacter pylori eradication regimens. Pharm World Sci. 2006 Aug;28(4):207–214
  45. NHS Trust Reference Cost Index 2005–06 . <http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_062884>[accessed 20.11.07]
  46. Plosker GL, Figgitt DP. Repaglinide: a pharmacoeconomic review of its use in type 2 diabetes mellitus. Pharmacoeconomics. 2004;22(6):389–411
  47. Knight C, Hind D, Brewer N, Abbott V. Rituximab (MabThera) for aggressive non-Hodgkin's lymphoma: systematic review and economic evaluation. Health Technol Assess. 2004 Sep;8(37):iii, ix–xi, p. 1–82
  48. Youman P, Wilson K, Harraf F, Kalra L. The economic burden of stroke in the United Kingdom. Pharmacoeconomics. 2003;21(Suppl. 1):43–50
  49. Dolan P, Torgerson DJ. The cost of treating osteoporotic fractures in the United Kingdom female population. Osteoporos Int. 1998;8(6):611–617
  50. Cresswell PA, Allen ED, Tomkinson J, Chapman FM, Pickering S, Donaldson LJ. Cost effectiveness of a single-function treatment center for cataract surgery. J Cataract Refract Surg. 1996 Sep;22(7):940–946
  51. Simon D, Fernando C, Czernichow P, Prieur AM. Linear growth and final height in patients with systemic juvenile idiopathic arthritis treated with longterm glucocorticoids. J Rheumatol. Jun 2002;29(6):1296–1300
  52. Allen DB, Mullen M, Mullen B. A meta-analysis of the effect of oral and inhaled corticosteroids on growth. J Allergy Clin Immunol. Jun 1994;93(6):967–976
  53. Slobbe L, Medlicott N, Lockhart E, et al. A prolonged immune response to antigen delivered in poly (epsilon-caprolactone) microparticles. Immunol Cell Biol. Jun 2003;81(3):185–191
  54. Kutikova L, Bowman L, Chang S, Long SR, Arning M, Crown WH. Medical costs associated with non-Hodgkin's lymphoma in the United States during the first two years of treatment. Leuk Lymphoma. Aug 2006;47(8):1535–1544
  55. de Vries F, Pouwels S, Lammers JW, et al. Use of inhaled and oral glucocorticoids, severity of inflammatory disease and risk of hip/femur fracture: a population-based case-control study. J Intern Med. Feb 2007;261(2):170–177
  56. Mortimer KJ, Tata LJ, Smith CJ, et al. Oral and inhaled corticosteroids and adrenal insufficiency: a case-control study. Thorax. May 2006;61(5):405–408
  57. Syed MI, Patel NA, Jan S, Shaikh A, Grunden B, Morar K. Symptomatic refractures after vertebroplasty in patients with steroid-induced osteoporosis. AJNR Am J Neuroradiol. Oct 2006;27(9):1938–1943
  58. Nagasawa K, Tada Y, Koarada S, et al. Very early development of steroid-associated osteonecrosis of femoral head in systemic lupus erythematosus: prospective study by MRI. Lupus. 2005;14(5):385–390
  59. Patel RS, Shaw SR, Wallace AM, McGarry GW. Efficacy and systemic tolerability of mometasone furoate and betamethasone sodium phosphate. J Laryngol Otol. Nov 2004;118(11):866–871
  60. van der Voort DJ, Geusens PP, Dinant GJ. A cross-sectional study of postmenopausal women found an association between osteoporosis and past gastric surgery or oral corticosteroids. J Clin Epidemiol. May 2004;57(5):533–538
  61. Joly P, Roujeau JC, Benichou J, et al. A comparison of oral and topical corticosteroids in patients with bullous pemphigoid. N Engl J Med. Jan 31 2002;346(5):321–327
  62. Lazenby JP, Guzzo MR, Harding SM, Patterson PE, Johnson LF, Bradley LA. Oral corticosteroids increase esophageal acid contact times in patients with stable asthma. Chest. Feb 2002;121(2):625–634
  63. Maltais F, Ostinelli J, Bourbeau J, et al. Comparison of nebulized budesonide and oral prednisolone with placebo in the treatment of acute exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial. Am J Respir Crit Care Med. Mar 1 2002;165(5):698–703
  64. van Everdingen AA, Jacobs JW, Siewertsz Van Reesema DR, Bijlsma JW. Low-dose prednisone therapy for patients with early active rheumatoid arthritis: clinical efficacy, disease-modifying properties, and side effects: a randomized, double-blind, placebo-controlled clinical trial. Ann Intern Med. Jan 1 2002;136(1):1–12
  65. van Staa TP, Leufkens HG, Cooper C. The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int. Oct 2002;13(10):777–787
  66. Levine A, Broide E, Stein M, Bujanover Y, Weizman Z, Dinari G, et al. Evaluation of oral budesonide for treatment of mild and moderate exacerbations of Crohn's disease in children. J Pediatr. 2002 Jan;140(1):75–80
  67. Marcocci C, Bartalena L, Tanda ML, et al. Comparison of the effectiveness and tolerability of intravenous or oral glucocorticoids associated with orbital radiotherapy in the management of severe Graves' ophthalmopathy: results of a prospective, single-blind, randomized study. J Clin Endocrinol Metab. Aug 2001;86(8):3562–3567
  68. Oinuma K, Harada Y, Nawata Y, et al. Osteonecrosis in patients with systemic lupus erythematosus develops very early after starting high dose corticosteroid treatment. Ann Rheum Dis. Dec 2001;60(12):1145–1148
  69. Nishimura K, Nonomura N, Yasunaga Y, et al. Low doses of oral dexamethasone for hormone-refractory prostate carcinoma. Cancer. Dec 15 2000;89(12):2570–2576
  70. van Staa TP, Leufkens HG, Abenhaim L, Zhang B, Cooper C. Oral corticosteroids and fracture risk: relationship to daily and cumulative doses. Rheumatology (Oxford). Dec 2000;39(12):1383–1389
  71. van Staa TP, Leufkens HG, Abenhaim L, Zhang B, Cooper C. Use of oral corticosteroids and risk of fractures. J Bone Miner Res. Jun 2000;15(6):993–1000
  72. Dasgupta B, Dolan AL, Panayi GS, Fernandes L. An initially double-blind controlled 96 week trial of depot methylprednisolone against oral prednisolone in the treatment of polymyalgia rheumatica. Br J Rheumatol. Feb 1998;37(2):189–195
  73. Sartor O, Weinberger M, Moore A, Li A, Figg WD. Effect of prednisone on prostate-specific antigen in patients with hormone-refractory prostate cancer. Urology. Aug 1998;52(2):252–256
  74. Sharma VK, Muralidhar S. Treatment of widespread alopecia areata in young patients with monthly oral corticosteroid pulse. Pediatr Dermatol. Jul–Aug 1998;15(4):313–317
  75. Borgna-Pignatti C, Rugolotto S, Nobili B, et al. A trial of high-dose dexamethasone therapy for chronic idiopathic thrombocytopenic purpura in childhood. J Pediatr. Jan 1997;130(1):13–16
  76. Campieri M, Ferguson A, Doe W, Persson T, Nilsson LG. Oral budesonide is as effective as oral prednisolone in active Crohn's disease. The Global Budesonide Study Group. Gut. Aug 1997;41(2):209–214
  77. Ginsberg L, Caine SE, Valentine AR. Corticosteroids and the prevention of adverse reactions to myelography. Br J Neurosurg. Jun 1996;10(3):285–287
  78. Howland WC, Dockhorn R, Gillman S, et al. A comparison of effects of triamcinolone acetonide aqueous nasal spray, oral prednisone, and placebo on adrenocortical function in male patients with allergic rhinitis. J Allergy Clin Immunol. Jul 1996;98(1):32–38
  79. Naber D, Sand P, Heigl B. Psychopathological and neuropsychological effects of 8-days' corticosteroid treatment. A prospective study. Psychoneuroendocrinology. Jan 1996;21(1):25–31
  80. Ziv Y, Church JM, Fazio VW, King TM, Lavery IC. Effect of systemic steroids on ileal pouch-anal anastomosis in patients with ulcerative colitis. Dis Colon Rectum. May 1996;39(5):504–508
  81. Scarfone RJ, Loiselle JM, Wiley JF, Decker JM, Henretig FM, Joffe MD. Nebulized dexamethasone versus oral prednisone in the emergency treatment of asthmatic children. Ann Emerg Med. Oct 1995;26(4):480–486
  82. Blanchette V, Imbach P, Andrew M, et al. Randomised trial of intravenous immunoglobulin G, intravenous anti-D, and oral prednisone in childhood acute immune thrombocytopenic purpura. Lancet. Sep 10 1994;344(8924):703–707
  83. Saag KG, Koehnke R, Caldwell JR, et al. Low dose long-term corticosteroid therapy in rheumatoid arthritis: an analysis of serious adverse events. Am J Med. Feb 1994;96(2):115–123
  84. Blanchette VS, Luke B, Andrew M, et al. A prospective, randomized trial of high-dose intravenous immune globulin G therapy, oral prednisone therapy, and no therapy in childhood acute immune thrombocytopenic purpura. J Pediatr. Dec 1993;123(6):989–995
  85. Chrousos GA, Kattah JC, Beck RW, Cleary PA. Side effects of glucocorticoid treatment. Experience of the optic neuritis treatment trial. JAMA. Apr 28 1993;269(16):2110–2112
  86. Olgaard K, Storm T, van Wowern N, et al. Glucocorticoid-induced osteoporosis in the lumbar spine, forearm, and mandible of nephrotic patients: a double-blind study on the high-dose, long-term effects of prednisone versus deflazacort. Calcif Tissue Int. Jun 1992;50(6):490–497
  87. Ramond MJ, Poynard T, Rueff B, et al. A randomized trial of prednisolone in patients with severe alcoholic hepatitis. N Engl J Med. Feb 20 1992;326(8):507–512
  88. Sanders BP, Portman RJ, Ramey RA, Hill M, Strunk RC. Hypertension during reduction of long-term steroid therapy in young subjects with asthma. J Allergy Clin Immunol. Apr 1992;89(4):816–821
  89. Fechner PU, Wichmann W. Retarded corneoscleral wound healing associated with high preoperative doses of systemic steroids in glaucoma surgery. Refract Corneal Surg. Mar–Apr 1991;7(2):174–176
  90. Anderson KD, Rouse TM, Randolph JG. A controlled trial of corticosteroids in children with corrosive injury of the esophagus. N Engl J Med. Sep 6 1990;323(10):637–640

PII: S0954-6111(09)00003-1

doi: 10.1016/j.rmed.2009.01.003

Respiratory Medicine
Volume 103, Issue 7 , Pages 975-994 , July 2009

Article Tools

* Image Usage & Resolution