TNF Inhibitors and Risk of Malignancy in Patients with Inflammatory Bowel Diseases: A Systematic Review

Background and Aims: The association between tumour necrosis factor inhibitors [TNFi] and malignancy in patients with inflammatory bowel disease [IBD] is not well understood. Our aim was to systematically evaluate the impact of TNFi use on risk of malignancy in IBD patients in daily clinical practice. Methods: We searched Pubmed, Embase and Scopus until March 1, 2020 for observational cohort studies on adult IBD patients reporting malignancy occurrence and TNFi use. Results: Twenty-eight studies [20 retrospective and eight prospective] were included, involving 298 717 IBD patients. Mean age at inclusion ranged from 28 to >65 years. Mean follow-up varied from 7 to 80 months. Infliximab was the most frequently usedTNFi [13/28 studies, 46.4%], followed by adalimumab [3/28, 10.7%], while both infliximab and adalimumab were evaluated in five studies [17.8%]. In total, 692 malignancies were diagnosed in IBD patients treated withTNFi, accounting for an overall occurrence of 1.0%. The most frequent malignancies were non-melanoma skin cancers [123/692, 17.8%], digestive malignancies [120/692, 17.3%] and haematological malignancies [106/692, 15.3%]. The association between TNFi and malignancy was evaluated in 11 studies [39.3%]: no significant association was found in ten studies, while an increased risk of lymphoma in patients exposed to TNFi was reported in one study. Conclusion: TNFi treatment is not associated with an increased risk of malignancy in IBD patients in real-life settings. Further large studies are needed to assess the prognosis of patients exposed to TNFi and risk of recurrence or new cancers in subjects with personal malignancy history.