PDF herunterladen
Z Gastroenterol 2017; 55(05): 461-465
DOI: 10.1055/s-0043-106310
Originalarbeit
© Georg Thieme Verlag KG Stuttgart · New York

Azathioprine allows glucocorticoid withdrawal – post hoc results of a prospective study in patients with inflammatory bowel diseases

Azathioprin erlaubt das Absetzen von Cortikosteroiden – post hoc Ergebnisse einer prospektiven Studie bei Patienten mit CED
Niels Teich
1   Internistische Gemeinschaftspraxis für Verdauungs- und Stoffwechselkrankheiten, Leipzig, Germany
,
Wolfgang Mohl
2   Gemeinschaftspraxis – Endoskopiezentrum, Saarbrücken, Germany
,
Bernd Bokemeyer
3   Gastroenterologische Gemeinschaftspraxis Minden, Germany
,
Burkhard Bündgens
4   Schwerpunktpraxis CED, Eschweiler, Germany
,
Jürgen Büning
5   Medical Department I, Gastroenterology, University Hospital of Schleswig-Holstein, Campus Lübeck, Germany
,
Stephan Miehlke
6   Center for Digestive Diseases, Cooperation of Internal Medicine Eppendorf, Hamburg, Germany
,
Dietrich Hüppe
7   Gastroenterologische Praxis, Herne, Germany
,
Christian Maaser
8   MVZ Gastroenterologie am Klinikum Lüneburg, Lüneburg, Germany
,
Britta Siegmund
9   Medizinische Klinik für Gastroenterologie, Charite, CBF, Berlin, Germany
,
Carsten Schmidt
10   Klinik für Innere Medizin IV, Universitätsklinikum Jena, Germany
,
Andreas Stallmach
10   Klinik für Innere Medizin IV, Universitätsklinikum Jena, Germany
,
on behalf of the German IBD Study group › Institutsangaben
Weitere Informationen

Publikationsverlauf

09. November 2016

12. März 2017

Publikationsdatum:
12. Mai 2017 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Abstract

Background Azathioprine is recommended as first-line immunosuppressant in patients with steroid-dependent inflammatory bowel diseases (IBDs). However, data on steroid withdrawal after induction therapy in IBD patients are sparse.

Methods In this post-hoc analysis of a prospective multicenter study, we analyzed the proportion and clinical characteristics of 324 azathioprine-tolerant patients as to whether they could terminate the glucocorticoid therapy after initiation of treatment with azathioprine.

Results Systemic steroid therapy was required in 190 patients (58.6 %) at baseline and in 40 patients (12.3 %) at the end of the follow-up period (p < 0.001). The median daily dose was 30 mg at baseline and 10 mg at follow-up. At baseline, only 122 patients (37.2 %) were advised to take at least the lowest recommended dose of 2 mg/kg per day. At follow-up, 221 patients (68.2 %) were prescribed at least the recommended maintenance dosage.

Conclusion The majority of patients with thiopurine-naïve IBDs that needed systemic steroids at baseline were able to discontinue steroids after 3 – 6 months of azathioprine therapy. These data support the continued high value of azathioprine in the immunosuppressive therapy of IBD.

Zusammenfassung

Hintergrund Azathioprin wird als Erstinien-Immunsuppressivum bei Patienten mit steroidabhängigen chronisch entzündlichen Darmerkrankungen (CED) empfohlen. Es existieren jedoch kaum Daten über die Möglichkeit des Absetzens von Glukokortikoiden nach der Induktionstherapie mit Azathioprin.

Methoden In dieser posthoc-Analyse einer prospektiven multizentrischen Studie analysierten wir den Anteil und die klinischen Charakteristika von 324 Azathioprin-toleranten Patienten hinsichtlich der Frage, ob sie die nach Therapiebeginn mit Azathioprin die Glukokortikoidtherapie beenden konnten.

Ergebnisse Eine systemische Steroidtherapie war bei 190 Patienten (58,6 %) zu Beginn und bei 40 Patienten (12,3 %) am Ende der Nachbeobachtungszeit (p < 0,001) erforderlich. Die mittlere Tagesdosis betrug 30 mg zu Beginn und 10 mg bei Nachuntersuchung. Zu Studienbeginn wurde 122 Patienten (37,2 %) empfohlen, mindestens die empfohlene Mindestdosis von 2 mg/kg pro Tag zu nehmen. Bei der Nachuntersuchung wurde hingegen bereits 221 Patienten (68,2 %) die empfohlene Mindestdosis verordnet.

Schlussfolgerung Die meisten Thiopurin-naiven CED-Patienten, die zu Studienbeginn eine systemische Glukokortikoidtherapie benötigten, konnten diese nach 3 – 6 Monaten Azathioprin-Einnahme absetzen. Diese Daten unterstützen die weiterhin hohe Wertigkeit von Azathioprin in der immunsuppressiven Therapie der CED.

Schlüsselwörter

Morbus Crohn - Colitis ulcerosa - Steroidtherapie - chronisch entzündliche Darmerkrankung

Keywords

crohn’s disease - ulcerative colitis - steroid therapy - inflammatory bowel disease
 

  • References

  • 1 Bowen GE. Irons Jr GV. Rhodes JB. et al. Early experiences with azathioprine in ulcerative colitis; a note of caution. JAMA 1966; 195: 460-464
    CrossrefPubMedSuche in Google Scholar
  • 2 Brooke BN. Hoffmann DC. Swarbrick ET. Azathioprine for Crohn's disease. Lancet 1969; 2: 612-614
    PubMedSuche in Google Scholar
  • 3 Travis SP. Stange EF. Lémann M. et al. European evidence-based consensus on the management of ulcerative colitis: Current management. J Crohns Colitis 2008; 2: 24-62
    CrossrefPubMedSuche in Google Scholar
  • 4 Dignass A. van Assche G. Lindsay JO. et al. The second European evidence-based consensus on the diagnosis and management of Crohn’s disease: current management. J Crohns Colitis 2010; 4: 28-62
    CrossrefPubMedSuche in Google Scholar
  • 5 Dignass A. Preiss JC. Aust DE. et al. Updated German guideline on diagnosis and treatment of ulcerative colitis. Z Gastroenterol 2011; 49: 1276-1341
    Thieme ConnectPubMedSuche in Google Scholar
  • 6 Preiß JC. Bokemeyer B. Buhr HJ. et al. Updated German clinical practice guideline on "Diagnosis and treatment of Crohn's disease" 2014. Z Gastroenterol 2014; 52: 1431-1484
    Thieme ConnectPubMedSuche in Google Scholar
  • 7 Chande N. Patton PH. Tsoulis DJ. et al. Azathioprine or 6‑mercaptopurine for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev 2015; 10: CD000067
    PubMedSuche in Google Scholar
  • 8 Timmer A. McDonald JW. Tsoulis DJ. et al. Azathioprine and 6‑mercaptopurine for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev 2012; 9: CD000478
    PubMedSuche in Google Scholar
  • 9 Cosnes J. Bourrier A. Laharie D. et al. Early administration of azathioprine vs conventional management of Crohn's Disease: a randomized controlled trial. Gastroenterology 2013; 145: 758-765
    CrossrefPubMedSuche in Google Scholar
  • 10 Panés J. López-Sanromán A. Bermejo F. et al. Early azathioprine therapy is no more effective than placebo for newly diagnosed Crohn's disease. Gastroenterology 2013; 145: 766-774
    CrossrefPubMedSuche in Google Scholar
  • 11 Schmidt C. Herrlinger K. Siegmund B. et al. Azathioprine in Crohn's disease therapy-guidance against the background of recent studies. Z Gastroenterol 2014; 52: 1423-1430
    PubMedSuche in Google Scholar
  • 12 Teich N. Mohl W. Bokemeyer B. et al. Azathioprine-induced acute pancreatitis in patients with inflammatory bowel diseases – a prospective study on incidence and severity. J Crohns Colitis 2016; 10: 61-68
    CrossrefPubMedSuche in Google Scholar
  • 13 Parkes GC. Whelan K. Lindsay JO. Smoking in inflammatory bowel disease: impact on disease course and insights into the aetiology of its effect. J Crohns Colitis 2014; 8: 717-725
    CrossrefPubMedSuche in Google Scholar
  • 14 Boyle BM. Kappelman MD. Colletti RB. et al. Routine use of thiopurines in maintaining remission in pediatric Crohn's disease. World J Gastroenterol 2014; 20: 9185-9190
    PubMedSuche in Google Scholar
  • 15 Lémann M. Mary JY. Colombel JF. et al. A randomized, double-blind, controlled withdrawal trial in Crohn's disease patients in long-term remission on azathioprine. Gastroenterology 2005; 128: 1812-1818
    CrossrefPubMedSuche in Google Scholar
  • 16 Vilien M. Dahlerup JF. Munck LK. et al. Randomized controlled azathioprine withdrawal after more than two years treatment in Crohn's disease: increased relapse rate the following year. Aliment Pharmacol Ther 2004; 19: 1147-1152
    CrossrefPubMedSuche in Google Scholar
  • 17 Magro F. Santos-Antunes J. Vilas-Boas F. et al. Crohn's disease outcome in patients under azathioprine: a tertiary referral center experience. J Crohns Colitis 2014; 8: 617-625
    CrossrefPubMedSuche in Google Scholar
  • 18 Pinto AL. Chebli LA. Ribeiro MS. et al. Azathioprine therapy in steroid-dependent patients with Crohn disease: results of a 10-year longitudinal follow-up study. Med Sci Monit 2009; 15: PI19- PI26
    PubMedSuche in Google Scholar
  • 19 Domènech E. Carrión S. Garcia-Planella E. et al. Smoking status and response to thiopurines in steroid-dependent inflammatory bowel disease. Inflamm Bowel Dis 2011; 17: 971-975
    CrossrefPubMedSuche in Google Scholar
  • 20 Chebli LA. Chaves LD. Pimentel FF. et al. Azathioprine maintains long-term steroid-free remission through 3 years in patients with steroid-dependent ulcerative colitis. Inflamm Bowel Dis 2010; 16: 613-619
    CrossrefPubMedSuche in Google Scholar