Risk of malignancies in patients with inflammatory bowel disease treated with thiopurines or anti-TNF alpha antibodies.
OBJECTIVE
We aimed to analyse malignancy rates and predictors for the development of malignancies in a large German inflammatory bowel disease (IBD) cohort treated with thiopurines and/or anti-tumour necrosis factor (TNF) antibodies.


METHODS
De novo malignancies in 666 thiopurine-treated and/or anti-TNF-treated IBD patients were analysed. Patients (n = 262) were treated with thiopurines alone and never exposed to anti-TNF antibodies (TP group). In addition, patients (n = 404) were exposed to anti-TNF antibodies (TNF+ group) with no (7.4%), discontinued (80.4%) or continued (12.1%) thiopurine therapy.


RESULTS
In the TP group, 20 malignancies were observed in 18 patients compared with 8 malignancies in 7 patients in the TNF+ group (hazard ratio 4.15; 95% CI 1.82-9.44; p = 0.0007; univariate Cox regression). Moreover, 18.2% of all patients in the TP group ≥50 years of age developed a malignancy, compared with 3.8% of all patients <50 years of age (p = 0.0008). In the TNF+ group, 6.5% of all patients ≥50 years of age developed malignancies compared with 0.3% of all patients <50 years of age (p = 0.0007). In both groups combined, thiopurine treatment duration ≥4 years was associated with the risk for skin cancer (p = 0.0024) and lymphoma (p = 0.0005).


CONCLUSIONS
Our data demonstrate an increased risk for the development of malignancies in IBD patients treated with thiopurines in comparison with patients treated with anti-TNF antibodies with or without thiopurines.
Department of Medicine II, University Hospital Munich-Grosshadern, Ludwig-Maximilians-University Munich, Munich, Germany.
Florian
F
Beigel
Anni
A
Steinborn
Fabian
F
Schnitzler
Cornelia
C
Tillack
Simone
S
Breiteneicher
Jestinah Mahachie
JM
John
Kristel
K
Van Steen
Rüdiger P
RP
Laubender
Burkhard
B
Göke
Julia
J
Seiderer
Stephan
S
Brand
Thomas
T
Ochsenkühn
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001379:Azathioprine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D001379:Azathioprine
adalimumab; anti-TNF antibodies; azathioprine; cancer; carcinoma; inflammatory bowel disease; infliximab; lymphoma; malignancy; melanoma; pharmacoepidemiology; skin cancer; thiopurines; tumor