Cancer in Crohnʼs Disease patients treated with infliximab: A long-term multicenter matched pair study

Biancone, Livia; Petruzziello, C.; Orlando, Ambrogio; Kohn, Anna; Ardizzone, Sandro; Daperno, Marco; Angelucci, E.; Castiglione, Fabiana; D’Incà, R.; Zorzi, Francesca; Papi, Claudio; Meucci, G.; Riegler, G.; Sica, Giuseppe; Rizzello, Fernando; Mocciaro, Filippo; Onali, S.; Calabrese, Emma; Cottone, Mario; Pallone, Francesco

doi:10.1002/ibd.21416

Cited by 44 publications

(29 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For instance, the risk of developing lymphoma and non-melanoma cutaneous tumors is increasing over time under azathioprine treatment. [15][16][17][18] Trials investigating the consequences of immunosuppressive or biological therapy withdrawal 12,14,29 have defined the background relapse risk and related factors. The time limit of four years suggested to the panellists' assessment was set in analogy to studies evaluating the outcome after withdrawal of azathioprine.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, safety issues such as infections and neoplasia in the context of long-term immunomodulatory and anti-TNF, mostly in the case of combination therapy, 4 are still of significant concern to both patients and physicians. Hence, higher risks of lymphoproliferative disorders [15][16][17] and non-melanoma skin cancer 18 have been documented in patients receiving long-term immunosuppressive drugs. 19 Furthermore, the significant cost of anti-TNF treatment is of increasing concern in the current climate of budget constraints in healthcare systems.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

When do we dare to stop biological or immunomodulatory therapy for Crohn's disease? Results of a multidisciplinary European expert panel

Pittet

Froehlich

Maillard

et al. 2013

Journal of Crohn's and Colitis

View full text Add to dashboard Cite

Background: Safety and economic issues have increasingly raised concerns about the long term use of immunomodulators or biologics as maintenance therapies for Crohn's disease (CD). Despite emerging evidence suggesting that stopping therapy might be an option for low risk patients, criteria identifying target groups for this strategy are missing, and there is a lack of recommendations regarding this question. Methods: Multidisciplinary European expert panel (EPACT-II Update) rated the appropriateness of stopping therapy in CD patients in remission. We used the RAND/UCLA Appropriateness Method, and included the following variables: presence of clinical and/or endoscopic remission, CRP level, fecal calprotectin level, prior surgery for CD, and duration of remission (1, 2 or 4 years). Results: Before considering withdrawing therapy, the prerequisites of a C-reactive protein (CRP) and fecal calprotectin measurement were rated as "appropriate" by the panellists, whereas a radiological evaluation was considered as being of "uncertain" appropriateness. Ileo-colonoscopy was considered appropriate 1 year after surgery or after 4 years in the absence of prior surgery. Stopping azathioprine, 6-mercaptopurine or methotrexate mono-therapy was judged appropriate after 4 years of clinical remission. Withdrawing anti-TNF mono-therapy was judged appropriate after 2 years in case of clinical and endoscopic remission, and after 4 years of clinical remission. In case of combined therapy, anti-TNF withdrawal, while continuing the immunomodulator, was considered appropriate after two years of clinical remission. Conclusion: A multidisciplinary European expert panel proposed for the first time treatment stopping rules for patients in clinical and/or endoscopic remission, with normal CRP and fecal calprotectin levels.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

When do we dare to stop biological or immunomodulatory therapy for Crohn's disease? Results of a multidisciplinary European expert panel

Pittet

Froehlich

Maillard

et al. 2013

Journal of Crohn's and Colitis

View full text Add to dashboard Cite

show abstract

“…45 However, Infliximab must be administered systemically and its use is limited owing to serious side effects, including acute or delayed infusion reactions, leukopenia, serious infection, antichimeric antibody formation, increased risk of malignancy and lymphoma as well as psoriasis. [46][47][48][49][50][51][52][53] Thus, there is an unmet need for a carrier system capable of specifically and exclusively delivering drugs to the inflamed regions for a prolonged period of time. Such a system could significantly reduce side effects of existing, otherwise effective, treatments.…”

Section: Micheliolide and Colitis-associated Cancer E Viennois Et Almentioning

confidence: 99%

Micheliolide, a new sesquiterpene lactone that inhibits intestinal inflammation and colitis-associated cancer

Viennois

Xiao

Ayyadurai

et al. 2014

Laboratory Investigation

View full text Add to dashboard Cite

Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal (GI) tract associated with an increased risk of colorectal cancer (CRC). Current treatments for both IBD and colitis-associated CRC suffer from numerous side effects. Parthenolide (PTL) is a sesquiterpene lactone with anti-inflammatory activity, and previous studies have demonstrated that PTL is a potent inhibitor of the NF-kB pathway. Micheliolide (MCL), substantially more stable than PTL in vivo, was recently developed, and this study aimed to decipher its suitability as therapeutic tool for IBD and IBDassociated diseases. Similar to PTL, MCL inhibited NF-kB activation and subsequent pro-inflammatory pathways activation in vitro. Pro-drug forms of both compounds inhibited the DSS-induced colitis when administrated intraperitoneally or encapsulated in a polysaccharide gel designed to release drugs in the colon. Interestingly, MCL was found to attenuate carcinogenesis in AOM/DSS-induced CRC, thus providing new candidate for the treatment of inflammatory bowel disease and CRC.Laboratory Investigation (2014) 94, 950-965;

show abstract

“…Though it is now firmly established that thiopurines are associated with an increased lymphoma risk and a nonmelanoma skin cancer risk, similar associations with TNF-α inhibitors have been less consistent [55,60,61,62,63]. Subgroup analysis of 9 randomized clinical trials on infliximab, adalimumab and certolizumab pegol in IBD as well as a meta-analysis of 10 randomized clinical trials on infliximab use in IBD, showed no increase in lymphoma risk; likewise, data from the TREAT database on infliximab use in IBD have been unable to identify any increased risk of lymphoma development [55,64,65].…”

Section: Concerns About Biological Agents Regarding Infections and Mamentioning

confidence: 99%

“…Most of the patients who developed lymphomas were on combination therapy with thiopurines, and it is therefore currently not clarified if the increased lymphoma risk can be attributed to the TNF-α blockers, the thiopurines or both. The risk of developing solid tumors in patients in anti-TNF-α therapy is poorly investigated in CD but seems to not actually be greater [61]. …”

Section: Concerns About Biological Agents Regarding Infections and Mamentioning

confidence: 99%

Biological Treatment of Crohn’s Disease

Nielsen

Bjerrum²,

Seidelin³

et al. 2012

Dig Dis

View full text Add to dashboard Cite

Introduction of biological agents for the treatment of Crohn’s disease (CD) has led to a transformation of the treatment paradigm. Several biological compounds have been approved for patients with CD refractory to conventional treatment: infliximab, adalimumab and certolizumab pegol (and natalizumab in several countries outside the European Union). However, despite the use of biologics for more than a decade, questions still remain about the true efficacy and the best treatment regimens – especially about when to discontinue treatment. Furthermore, a need for optimizing treatment with biologics still exists, as 20–40% of patients with CD (depending on selection criteria) do not have any relevant response to the current biological agents (i.e. primary failures). A better patient selection might maximize the clinical outcome while minimizing the complications associated with this type of therapy. However, the clinical tools capable of identifying such patients are still unavailable, and the trough level strategy may help the clinician to optimize therapy and to avoid loss of response and/or immunogenicity (i.e. a low but measurable antibody level exists just before the periodic administration of the biological agent). On the other hand, peak levels and average levels should not exceed concentrations associated with increased toxicity. Randomized, controlled studies focusing on trough levels and antibodies towards the biological agent in routine clinical situations may add important pieces to the puzzle for a more rational treatment algorithm of CD patients. In some situations, the risks (i.e. immunogenicity, serious infections and the promotion of neoplasia) may, however, not outweigh the benefits of biological treatment.

show abstract

Cancer in Crohnʼs Disease patients treated with infliximab: A long-term multicenter matched pair study

Abstract: The frequency of neoplasia was comparable in an adult population of CD patients treated or not with infliximab, matched for clinical variables and followed up for a median of 6 years.

Cited by 44 publications

References 32 publications

When do we dare to stop biological or immunomodulatory therapy for Crohn's disease? Results of a multidisciplinary European expert panel

When do we dare to stop biological or immunomodulatory therapy for Crohn's disease? Results of a multidisciplinary European expert panel

Micheliolide, a new sesquiterpene lactone that inhibits intestinal inflammation and colitis-associated cancer

Biological Treatment of Crohn’s Disease

Contact Info

Product

Resources

About