Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

12 Issues per year

IMPACT FACTOR 2016: 3.432

CiteScore 2016: 2.21

SCImago Journal Rank (SJR) 2016: 1.000
Source Normalized Impact per Paper (SNIP) 2016: 1.112

See all formats and pricing
More options …
Volume 43, Issue 4 (Apr 2005)


How accurate are clinical activity indices for scoring of disease activity in inflammatory bowel disease (IBD)?

Lone G. M. Jørgensen / Lisbeth Fredholm / Per Hyltoft Petersen
  • Department of Clinical Biochemistry, Odense University Hospital, Odense C, Denmark and Norwegian Centre for External Quality Assurance of Primary Care Laboratories, University of Bergen, Bergen, Norway
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Henrik Hey / Pia Munkholm / Ivan Brandslund
Published Online: 2011-09-21 | DOI: https://doi.org/10.1515/CCLM.2005.073


Clinical activity indices are essential instruments in monitoring inflammatory bowel diseases such as Crohn's disease (CD) and ulcerative colitis (UC). To subclassify components of disease indices in CD and UC, investigate technical noise in estimation of the indices, establish a signal-to-noise ratio (SNR), evaluate correlation between indices and calculate the reference change value (RCV) for selected biochemical variables in individual cases, 50 patients with CD and 49 patients with UC were included in the study. Qualitative index variables were assessed for scoring errors. The standard deviation (SD) was estimated according to a rectangular model, while SD in biochemical variable scoring was estimated according to a Gaussian model; a combined SD was also calculated. These values were investigated for their individual contribution to variation. The 95% CI of an index value was based on ±1.96×SD combined and a change in separate biochemical variables was calculated as RCV 1.96×√2×SD combined. Correlation between different disease activity indices was assessed for unexplained variation. The Crohn's disease activity index (CDAI) had the highest variation compared to the van Hees (Hees) and the Harvey-Bradshaw index (HBI) in CD, but it also had the best SNR, whereas HBI had the lowest. In UC the clinical activity index (CAI) showed the highest variance, but the best SNR compared to Seo's activity index (AI). The 95% CI of the CDAI discriminatory activity sum of 150 in individual cases was 105–195, whereas the 95% interval for a change was ±62.4. Self-reported wellness contributed 40% to total variance in the CDAI. Factors of clinical importance increased errors in estimates and variance of the indices. Poor correlation was obtained between activity indices, with up to 70% unexplained variance. The SD combined for estimated errors was as high as 23 points, with the best SNR being approximately 20. Index factors increase the sensitivity of SNRs to errors and lower the disease specificity. Sensitivity optimisation may be achieved by standardisation of the variables and their use.

Keywords: activity index; biochemistry; inflammatory bowel disease; sensitivity; specificity


  • 1

    Munkholm P. Crohn's disease – occurrence, course and prognosis. An epidemiologic cohort-study [thesis]. Dan Med Bull 1997; 44: 287–302. Google Scholar

  • 2

    Kjeldsen J, Muckadell BS. Assessment of disease severity and activity in IBD. Scand J Gastroenterol 1993; 28: 1–9. CrossrefGoogle Scholar

  • 3

    Sandborn WJ, Feagan BG, Hanauer SB, Lochs H, Löfberg R, Modigliani R, et al. A review of activity indices and efficacy for clinical trials of medical therapy in adults with Crohn's disease. Gastroenterology 2002; 122: 512–30. CrossrefGoogle Scholar

  • 4

    Best WR, Becktel JM, Singleton JW, Kern F. Development of a Crohn's disease activity index. Gastroenterology 1976; 70: 439–44. Web of ScienceGoogle Scholar

  • 5

    van Hees PA, van Elteren PH, van Lier HJ, van Tongeren JH. An index of inflammatory activity in patients with Crohn's disease. Gut 1980; 21: 279–86. CrossrefGoogle Scholar

  • 6

    Harvey RF, Bradshaw JM. A simple index of Crohn's disease activity. Lancet 1980;514. CrossrefGoogle Scholar

  • 7

    Seo M, Okada M, Yao T, Okabe N, Maeda K, Oh K. An index of disease activity in patients with ulcerative colitis. Am J Gastroenterol 1992; 87: 971–6. Google Scholar

  • 8

    Seo M, Okada M, Yao T, Okabe N, Maeda K, Oh K. Evaluation of disease activity in patients with moderately active ulcerative colitis: comparisons between a new activity index and Truelove and Witts' classification. Am J Gastroenterol 1995; 90: 1759–63. Google Scholar

  • 9

    Travis SP, Farrant JM, Rickett C, Nolan DJ, Mortensen NM, Kettlewell MG, et al. Predicting outcome in severe ulcerative colitis. Gut 1996; 38: 905–10. CrossrefGoogle Scholar

  • 10

    Prantera C, Levenstein S, Andreoli A, Kohn A, Luzi C, Suriano G. Assessing disease activity in Crohn's disease: a comparison of two indices (is Best best?). Ital J Gastroenterol 1982; 14: 152–5. Google Scholar

  • 11

    Papi C, Ciaco A, Bianchi M, Montanti S, Koch M, Capurso L. Correlation of various Crohn's disease activity indexes in subgroups of patients with primarily inflammatory or fibrostenosing clinical characteristics. J Clin Gastroenterol 1996; 23: 40–3. CrossrefGoogle Scholar

  • 12

    Myren J, Bouchier IA, Watkinson G, Softley A, Clamp SE, De Dombal FT. The OMGE Multinational inflammatory bowel disease survey 1976–1982. Scand J Gastroenterol 1994; 19(Suppl 95): 1–27. Google Scholar

  • 13

    Van Deventer SJ, Elson CO, Fedorak RN. Multiple doses of intravenous interleukin 10 in steroid refractory Crohn's disease. Gastroenterology 1997; 113: 383–9. CrossrefGoogle Scholar

  • 14

    Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, Van Hogezand RA, et al. Infliximab for the treatment of fistulas in patients with Crohn's disease. N Engl J Med 1999; 340: 1398–405. CrossrefGoogle Scholar

  • 15

    Bauditz J, Haemling J, Ortner M, Lochs H, Raidler A, Schreiber S. Treatment with tumour necrosis factor inhibitor oxpentifylline does not improve corticosteroid dependent chronic active Crohn's disease. Gut 1997; 40: 470–4. CrossrefGoogle Scholar

  • 16

    Targan SR, Hanauer SB, Van Deventer SJ, Mayer L, Present DH, Braakman T, et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor α for Crohn's disease. N Engl J Med 1997; 337: 1029–35. CrossrefGoogle Scholar

  • 17

    Sands BE, Winston BD, Salzberg B, Safdi M, Barish C, Wruble L, et al., The Rhil-11 Crohn's Study Group. Randomized, controlled trial of recombinant human interleukin-11 in patients with active Crohn's disease. Aliment Pharmacol Ther 2002; 16: 399–406. CrossrefGoogle Scholar

  • 18

    Tremaine WJ, Hanauer SB, Katz S, Winston BD, Levine JG, Persson T, et al., Budesonide CIR United States Study Group. Budesonide CIR capsules (once or twice daily divided-dose) in active Crohn's disease: a randomized placebo-controlled study in the United States. Am J Gastroenterol 2002; 7: 1748–54. CrossrefGoogle Scholar

  • 19

    Dieckgraefe BK, Korzenik JR. Treatment of active Crohn's disease with recombinant human granolocyte macrophage colony-stimulating factor. Lancet 2002; 360: 1478–80. CrossrefGoogle Scholar

  • 20

    Kane SV, Schoenfeld P, Sandborn WJ, Tremaines W, Hofer T, Feagan BG. Systematic review: the effectiveness of budesonide therapy for Crohn's disease. Aliment Pharmacol Ther 2002; 16: 1509–17. CrossrefGoogle Scholar

  • 21

    Cellier C, Sahmoud T, Froguel E, Adenis A, Belaiche J, Bretagne J, et al. Correlation between clinical activity, endoscopic severity, and biological parameters in colonic or iliocolonic Crohn's disease. A prospective multicenter study of 121 cases. Gut 1994; 35: 231–5. CrossrefGoogle Scholar

  • 22

    Andre C, Descos L, Fermanian J. Assessment of appropriate laboratory measurements to supplement the Crohn's disease activity index. Gut 1981; 22: 571–4. CrossrefGoogle Scholar

  • 23

    Jensen KB, Jarnum S, Koudahl G, Kristensen M. Serum orosomucoid in ulcerative colitis. Scand J Gastroenterol 1976; 11: 177–83. Google Scholar

  • 24

    Pepys MB. C-Reactive protein fifty years on. Lancet 1881; 21: 653–6. Google Scholar

  • 25

    Buckell NA, Lennard-Jones JE, Hernandez MA, Kohn J, Riches PG, Wadsworth J. Measurement of serum proteins during attacks of ulcerative colitis as a guide to patient management. Gut 1979; 20: 22–7. CrossrefGoogle Scholar

  • 26

    Fagan EA, Dyck RF, Maton PN, Hudgson HJ, Chadwick VS, Petrie A, et al. Serum levels of C-reactive protein in Crohn's disease and ulcerative colitis. Eur J Clin Invest 1982; 12: 351–9. CrossrefGoogle Scholar

  • 27

    Andrè C, Descos L, Vignal J, Gillon J. C-reactive protein as a predictor of relapse in asymptomatic patients with Crohn's disease. Scott Med J 1983; 28: 26–9. CrossrefGoogle Scholar

  • 28

    Prantera C, Luzi C, Olivotto P, Levenstein S, Cerro P, Fanucci A. Relationship between clinical and laboratory parameters and length of lesion in Crohn's disease of small bowel. Dig Dis Sci 1984; 29: 1093–7. CrossrefGoogle Scholar

  • 29

    Shine B, Berghouse L, Jones JE, Landon J. C-reactive protein as an aid in the differentiation of functional and inflammatory bowel disorders. Clin Chim Acta 1985; 148: 105–9. CrossrefGoogle Scholar

  • 30

    Boirivant M, Leoni M, Tariciotti D, Fais S, Squarcia O, Pallone F. The clinical significance of serum C-reactive protein levels in Crohn's disease. Results of a prospective longitudinal study. J Clin Gastroenterol 1988; 10: 401–5. CrossrefGoogle Scholar

  • 31

    Mazlam MZ, Hodgson HJ. Why measure C-reactive protein? Gut 1994; 35: 5–7. CrossrefGoogle Scholar

  • 32

    Cellier C, Sahmoud T, Froguel E, Adenis A, Belaiche J, Bretagne J-F, et al., Groupe d'Études Thérapeutiques des Affections Imflammatoires Digestives. Correlations between clinical activity, endoscopic severity, and biological parameters in colonic or ileocolonic Crohn's disease. A prospective multicenter study of 121 cases. Gut 1994; 35: 231–5. CrossrefGoogle Scholar

  • 33

    Kjeldsen J. Biochemical parameters of disease activity in inflammatory bowel disease. PhD thesis, 1996:3–105. Google Scholar

  • 34

    Kjeldsen J, Lauritsen K, Muckadell BS. Serum Concentrations of orosomucoid: improved decision-making for tapering prednisolone therapy in patients with active inflammatory bowel disease? Scand J Gastroenterol 1997; 32: 933–41. CrossrefGoogle Scholar

  • 35

    Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 1999; 340: 449–54. Google Scholar

  • 36

    Biton A, Peppercorn MA, Antonioli DA, Niles JL, Shah S, Bousvaros A, et al. Clinical, biological and histologic parameters as predictors of relapse in ulcerative colitis. Gastroenterology 2001; 120: 13–20. CrossrefGoogle Scholar

  • 37

    Clark CM, Sheppard L, Fillenbaum GG, Galasko D, Morris JC, Koss E, et al. Variability in annual mini-mental state examination score in patients with probable Alzheimer disease. Arch Neurol 1999; 56: 857–62. CrossrefGoogle Scholar

  • 38

    ISO. Guide to expression of uncertainty in measurement. Geneva: ISO, 1995. Google Scholar

  • 39

    Ricos C, Alvarez V, Cava F, Garcia-Lario JV, Hernandez A, Jimenez CV, et al. Current database on biologic variation: pros, cons and progress. Scand J Clin Lab Invest 1999; 59: 491–500. (http://www.westgard.com/biodata-base1.htm). Google Scholar

  • 40

    Sebastio-Gambaro MA, Liron-Hernandez FJ, Fuentes-Arderiu X. Intra- and inter-individual biological variability data bank, part 1. http://www.westgard.com/intra-inter.htm Google Scholar

  • 41

    Jørgensen LG, Østerlind K, Genollá J, Gomm SA, Hernández JH, Johnson PW, et al. Serum neuron specific enolase (S-NSE) and the prognosis in small cell lung cancer (SCLC): a combined multivariable analysis on data from nine centres. Br J Cancer 1996; 74: 463–7. CrossrefGoogle Scholar

  • 42

    Sostegni R, Daperno M, Scaglione N, Lavagna A, Rocca R, Pera A. Review article: Crohn's disease: monitoring disease activity. Aliment Pharmacol Ther. 2003; 17(Suppl 2): 11–7. CrossrefGoogle Scholar

  • 43

    Hölzel WG. Intra-individual variation of some analytes in serum of patients with chronic renal failure. Clin Chem 1987; 33: 670–3. Google Scholar

  • 44

    Hölzel WG. Influence of hypertension and antihypertensive drugs on the biological intra-individual variation of electrolytes and lipids in serum. Clin Chem 1988; 34: 1485–8. Google Scholar

  • 45

    Lassen JF, Brandslund I, Antonsen S. International normalized ratio for prothrombin times in patients taking oral anticoagulants: critical difference and probability of significant change in consecutive measurements. Clin Chem 1995; 41: 444–7. Google Scholar

  • 46

    Canadell NI, Hyltoft Petersen P, Jensen E, Ricós C, Jørgensen PE. Reference change values and power functions. Clin Chem Lab Med 2004; 42: 415–22. CrossrefGoogle Scholar

  • 47

    The CDAI calculator for home use given by private organizations: http://www.ibdjohn.com/cdai/. Google Scholar

About the article

Corresponding author: Lone Jørgensen, The Laboratory Centre, Vejle County Hospital, 7100 Vejle, Denmark Phone: +45-79406505, +45 2140 5760,

Received: 2004-07-21

Accepted: 2005-02-11

Published Online: 2011-09-21

Published in Print: 2005-04-01

Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2005.073.

Export Citation

© by Walter de Gruyter Berlin New York. Copyright Clearance Center

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

Blair S Lewis
World Journal of Gastroenterology, 2008, Volume 14, Number 26, Page 4137
Ferenc Nagy, Tamás Molnár, Zoltán Szepes, Klaudia Farkas, Tibor Nyári, and János Lonovics
World Journal of Gastroenterology, 2008, Volume 14, Number 27, Page 4342
Dania Alrefai, Jennifer Jones, Wael El-Matary, Susan Whiting, Abdulrahman Aljebreen, Naghmeh Mirhosseini, and Hassan Vatanparast
Nutrients, 2017, Volume 9, Number 10, Page 1112
Anastassios C Manolakis, Gregory Christodoulidis, Andreas N Kapsoritakis, Panagiotis Georgoulias, Elisavet K Tiaka, Kostas Oikonomou, Varvara J Valotassiou, and Spyros P Potamianos
World Journal of Gastroenterology, 2017, Volume 23, Number 3, Page 437
A. Cholapranee, G. S Hazlewood, G. G. Kaplan, L. Peyrin-Biroulet, and A. N. Ananthakrishnan
Alimentary Pharmacology & Therapeutics, 2017, Volume 45, Number 10, Page 1291
Eran Zittan, Boyko Kabakchiev, Orlaith B. Kelly, Raquel Milgrom, Geoffrey C. Nguyen, Kenneth Croitoru, A. Hillary Steinhart, and Mark S. Silverberg
Journal of Crohn's and Colitis, 2016, Page jjw200
Zbigniew Serafin, Marcin Białecki, Agnieszka Białecka, Luca Maria Sconfienza, and Maria Kłopocka
Journal of Crohn's and Colitis, 2016, Volume 10, Number 3, Page 354
Laura Romanini, Matteo Passamonti, Mario Navarria, Francesco Lanzarotto, Vincenzo Villanacci, Luigi Grazioli, Fabrizio Calliada, and Roberto Maroldi
European Journal of Radiology, 2014, Volume 83, Number 8, Page 1317
Gerhard Rogler, Xavier Aldeguer, Wolfgang Kruis, Anders Lasson, Ulrich Mittmann, Ken Nally, Laurent Peyrin-Biroulet, Alain Schoepfer, Morten Vatn, Stephan Vavricka, and Robert Logan
Journal of Crohn's and Colitis, 2013, Volume 7, Number 8, Page 670
Shonit Punwani, Manuel Rodriguez-Justo, Alan Bainbridge, Rebecca Greenhalgh, Enrico De Vita, Stuart Bloom, Richard Cohen, Alastair Windsor, Austin Obichere, Anika Hansmann, Marco Novelli, Steve Halligan, and Stuart A. Taylor
Radiology, 2009, Volume 252, Number 3, Page 712
Severine Vermeire, Stefan Schreiber, William J. Sandborn, Cécile Dubois, and Paul Rutgeerts
Clinical Gastroenterology and Hepatology, 2010, Volume 8, Number 4, Page 357
Bernd B. Frericks, Anja A. Kühl, Christoph Loddenkemper, Andrea Stroux, Steffi Valdeig, Birgit Hotz, Bernd Misselwitz, Jörg C. Hoffmann, and Frank K. Wacker
Investigative Radiology, 2011, Volume 46, Number 8, Page 478
B. G. Feagan, S. B. Hanauer, G. Coteur, and S. Schreiber
Alimentary Pharmacology & Therapeutics, 2011, Volume 33, Number 10, Page 1143
Alimentary Pharmacology & Therapeutics, 2007, Volume 25, Number 8, Page 933
Alimentary Pharmacology & Therapeutics, 2007, Volume 27, Number 2, Page 146
Roberto Malagò, Riccardo Manfredi, Luigi Benini, Gianni D’Alpaos, and Roberto Pozzi Mucelli
Abdominal Imaging, 2008, Volume 33, Number 6, Page 669
Lone G. M. Jørgensen
Accreditation and Quality Assurance, 2006, Volume 11, Number 6, Page 297

Comments (0)

Please log in or register to comment.
Log in