Cimzia's setback paves way for other TNF inhibitors in Crohn's disease

e18010 Background: Inhibitors of tumor necrosis factor alpha (anti-TNF agents) are commonly used in Crohn’s disease and rheumatoid arthritis. Relationship between TNF inhibitors and development of malignancy, e.g., lymphoma and solid tumors, is defined recently. However, a few authors reported leukemia. Crohn’s disease and also azothioprine may also be associated with leukemia. Here, we are presenting two acute myeloid leukemia (AML) cases using azothioprine and anti-TNF inhibitors for Crohn’s disease. Methods: Observational case report. Results: Case 1: A 56-year-old male patient with active Crohn’s disease for 4 years was refractory to first line mesalazine, corticosteroid and azothioprine treatment. So, anti-TNF monoclonal antibody (moAb) (Adalimumab) had been given. After second dose of adalimumab treatment AML (AML-M2 as FAB) developed. Case 2: A 38-year-old male had been diagnosed with ankylosing spondylitis for 7 years and Crohn’s disease for 2 years. He had been treated with salazopyrin and indomethacin. Anti-TNF etanercept (50 mg/wk) was started 30 months ago due to severe active pulmonary disease. After 1 year, he developed active Crohn’s disease. So, the treatment changed to infliximab. Also, mesalazine and azothioprine were added to treatment. On the 18th month of the infliximab t(15;17) positive acute promyelocytic leukemia were developed in the patient. Conclusions: Blocking TNF with anti TNF agents may cause blocking apoptosis and inhibit natural killer activity. So, antitumoral activity of natural killer cells is blocked by these agents. TNF alpha gene mutation has been associated with CLL, lymphoma, myelodysplastic syndrome and secondary AML. Azothioprine may also increase leukemia, lymphoma and solid tumors risk at patient on anti TNF treatment. Following the diagnosis of Crohn’s disease without immunomodulator treatment a case had developed acute leukemia in the literature. In our patients, anti-TNF, azothioprine and inflammatory bowel disease may be cause acute leukemia cumulatively. Physicians should be careful and regularly check the patients using anti-TNF agents in considering of malignancy development. In conclusion, the pathogenesis of leukemia development after TNF blockage should be clarified.

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Clinical Practice of Adalimumab and Infliximab Biosimilar Treatment in Adult Patients With Crohn’s Disease

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa078 ◽

2020 ◽

Vol 27 (1) ◽

pp. 106-122

Author(s):

Walter Reinisch ◽

Krisztina Gecse ◽

Jonas Halfvarson ◽

Peter M Irving ◽

Jørgen Jahnsen ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Symptomatic Relief ◽

Certolizumab Pegol ◽

Tnf Inhibitors ◽

Treatment Algorithms ◽

Monitoring Tools ◽

Clinical Scenarios ◽

Endoscopic Remission ◽

Evidence Based Guidelines

Abstract The introduction of tumor necrosis factor (TNF) inhibitors has significantly changed the treatment landscape in Crohn’s disease (CD). The overall therapeutic achievements with TNF inhibitors such as infliximab, adalimumab, and certolizumab pegol paved the way to push the boundaries of treatment goals beyond symptomatic relief and toward cessation of objective signs of inflammation, including endoscopic remission. Even though these agents are widely used for the treatment of moderate to severe CD, heterogeneity still exists in translating evidence-based guidelines on the use of anti-TNF agents into actual treatment algorithms in CD. This might be due to several reasons including disparities in health expenditure policies; lack of harmonization between countries; and variations in assessment of disease severity, use of disease monitoring tools, or application of treatment targets by physicians. With the advent of biosimilars, patent-free versions of reference biologics are now available to minimize health inequalities in drug availability. In this context, this article aims to provide practical clinical guidance for the use of infliximab and adalimumab biosimilars in patients with moderate to severe CD by outlining different clinical scenarios that patients may encounter during their treatment journey.

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DOP070 Endoscopic response to induction therapy with TNF inhibitors is the best predictor of long term mucosal healing in Crohn's disease

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjx002.107 ◽

2017 ◽

Vol 11 (suppl_1) ◽

pp. S67-S68

Author(s):

I. Alfaro ◽

M. Masamunt ◽

N. Planell ◽

A. Lόpez-García ◽

J. Castro ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Induction Therapy ◽

Mucosal Healing ◽

Tnf Inhibitors

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New Onset, Aggravation and Recurrence of Crohn's Disease upon Treatment with Three Different Tumor Necrosis Factor Inhibitors

Case Reports in Gastroenterology ◽

10.1159/000381637 ◽

2015 ◽

Vol 9 (1) ◽

pp. 106-112 ◽

Cited By ~ 5

Author(s):

Jonas Zeitz ◽

Susann Enderlin ◽

Luc Biedermann ◽

Matthias Turina ◽

Sebastian Leibl ◽

...

Keyword(s):

Crohn’S Disease ◽

Tumor Necrosis Factor ◽

Crohn's Disease ◽

Tumor Necrosis ◽

Tnf Inhibitors ◽

Etanercept Treatment ◽

Abdominal Symptoms ◽

Long Term Treatment ◽

Tnf Inhibition ◽

Necrosis Factor

Tumor necrosis factor (TNF) is a major cytokine in the pathogenesis of inflammatory bowel disease (IBD), and TNF inhibition is a cornerstone of contemporary IBD therapy. However, paradoxical induction of IBD has recently been reported upon treatment of rheumatologic disorders with TNF inhibitors. In previous cases, induction of IBD was associated with one single drug and IBD was successfully managed by switching TNF inhibitors. We report the case of a patient with juvenile rheumatoid arthritis under long-term treatment with etanercept. After switching TNF inhibition to adalimumab, symptoms of Crohn's disease (CD) occurred and the diagnosis of CD was established by endoscopy. Further treatment with adalimumab and subsequently infliximab aggravated the abdominal symptoms, necessitating ileocecal resection, after which symptoms resolved for several months. Etanercept treatment due to recurrent rheumatologic symptoms was followed by recurrent CD symptoms and findings, which resolved upon discontinuation of etanercept. This case suggests that induction, aggravation and recurrence of IBD can be rare class effects of TNF inhibition.

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