Use of Intravenous Immunoglobulin for Patients with Inflammatory Bowel Disease with Contraindications or Who Are Unresponsive to Conventional Treatments

Merkley, Scott; Beaulieu, Dawn B.; Horst, Sara; Duley, Caroline; Annis, Kim; Nohl, Anne; Schwartz, David A.

doi:10.1097/mib.0000000000000456

Cited by 25 publications

(18 citation statements)

References 15 publications

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“…Of these, 9 of 23 received rescue therapy (4 ciclosporin, 2 tacrolimus, 2 infliximab, and 1 patient received IV Immunoglobulin). 20 21 Sixteen of 23 patients underwent surgery, including 2 after rescue therapy.…”

Section: Resultsmentioning

confidence: 99%

Are Truelove and Witts criteria for diagnosing acute severe colitis relevant for the Indian population? A prospective study

et al. 2018

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Background/AimsTruelove and Witts criteria have been used to define acute severe colitis since the 1950s. However, hemoglobin (an additional criterion of the definition) levels in the general population in developing countries are lower than in the population of developed countries. We aimed to determine the relevance of Truelove and Witts criteria in the Indian population.MethodsConsecutive patients with acute severe colitis satisfying the Truelove and Witts criteria, hospitalized at a single center between April 2015 and December 2016 were included. All patients received intravenous corticosteroids and 16 required colectomy. The hemoglobin levels at admission were subsequently excluded from the classification criteria, and the effect this had on the criteria for diagnosis was determined.ResultsOut of 61 patients of acute severe colitis diagnosed according to the original Truelove and Witts criteria, 12 patients (20%) had 1 additional criterion, 33 (54%) had 2 additional criteria and 16 (26%) had 3 or more additional criteria in addition to 6 or more blood stained stools on admission. On excluding hemoglobin as an additional criterion from the Truelove and Witts definition, all patients still met the criteria for acute severe colitis.ConclusionsTruelove and Witts criteria can be used to define acute severe colitis in India, despite lower mean hemoglobin in the native population.

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Section: Resultsmentioning

confidence: 99%

Are Truelove and Witts criteria for diagnosing acute severe colitis relevant for the Indian population? A prospective study

et al. 2018

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“…IVIg treatment reduces serum TNF and IL‐1β in people with Guillain‐Barré syndrome, although IL‐10 levels were not measured 13 . Importantly, IVIg has been used safely in the past 20 years to treat some people with IBD; efficacy has been noted in people with IBD, who were receiving IVIg for other reasons, were treatment refractory, or had contraindications for conventional treatments, such as respiratory fungal infections . In a retrospective chart review of 24 people, who were difficult to treat, IVIg induced remission or clinical improvement in 79% of people with IBD and 62.5% of people showed endoscopic improvement .…”

Section: Discussionmentioning

confidence: 99%

Intravenous immunoglobulin (IVIg) or IVIg‐treated macrophages reduce DSS‐induced colitis by inducing macrophage IL‐10 production

et al. 2019

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Intravenous immunoglobulin (IVIg) is used to treat immune‐mediated diseases but its mechanism of action is poorly understood. We have reported that co‐treatment with IVIg and lipopolysaccharide activates macrophages to produce large amounts of anti‐inflammatory IL‐10 in vitro. Thus, we asked whether IVIg‐treated macrophages or IVIg could reduce intestinal inflammation in mice during dextran sulfate sodium (DSS)‐induced colitis by inducing macrophage IL‐10 production in vivo. Adoptive transfer of IVIg‐treated macrophages reduces intestinal inflammation in mice and collagen accumulation post‐DSS. IVIg treatment also reduces DSS‐induced intestinal inflammation and its activity is dependent on the Fc portion of the antibody. Ex vivo, IVIg induces IL‐10 production and reduces IL‐12/23p40 and IL‐1β production in colon explant cultures. Co‐staining tissues for mRNA, we demonstrate that macrophages are the source of IL‐10 in IVIg‐treated mice; and using IL‐10‐GFP reporter mice, we demonstrate that IVIg induces IL‐10 production by intestinal macrophages. Finally, IVIg‐mediated protection is lost in mice deficient in macrophage IL‐10 production (LysMcre+/−IL‐10fl/fl mice). Together, our data demonstrate a novel, in vivo mechanism of action for IVIg. IVIg‐treated macrophages or IVIg could be used to treat people with intestinal inflammation and may be particularly useful for people with inflammatory bowel disease, who are refractory to therapy.

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“…It is dose-related, i.e., the magnitude increases with antibody dose, and is conceivably a genuine therapeutic effect. Intravenous immunoglobulin therapy (IVIG) is a recognized treatment for IBD 27 and it is possible that in this context, the isotype control antibodies are having some level of IVIG-like effect.…”

Section: Discussionmentioning

confidence: 99%

An anti-TL1A antibody for the treatment of asthma and inflammatory bowel disease

Clarke

Poulton

Shim

et al. 2018

mAbs

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TL1A is an attractive therapeutic target for the treatment of mucosal inflammation associated with inflammatory bowel disease (IBD) and asthma. Blockade of the TL1A pathway has been shown to reduce inflammatory responses while leaving baseline immunity intact, and to be beneficial in animal models of colitis and asthma. Given the therapeutic potential of blocking this pathway in IBD and asthma, we developed C03V, a human antibody that binds with high affinity to soluble and membrane-bound TL1A. In an assay measuring apoptosis induced by exogenous TL1A, C03V was 43-fold more potent than the next most potent anti-TL1A antibody analyzed. C03V also potently inhibited endogenous TL1A activity in a primary cell-based assay. This potency was linked to the C03V-binding epitope on TL1A, encompassing the residue R32. This residue is critical for the binding of TL1A to its signaling receptor DR3 but not to its decoy receptor DcR3, and explains why C03V inhibited TL1A-DR3 binding to a much greater extent than TL1A-DcR3 binding. This characteristic may be advantageous to preserve some of the homeostatic functions of DcR3, such as TL1A antagonism. In colitis models, C03V significantly ameliorated microscopic, macroscopic and clinical aspects of disease pathology, and in an asthma model it significantly reduced airways inflammation. Notable in both types of disease model was the reduction in fibrosis observed after C03V treatment. C03V has the potential to address unmet medical needs in asthma and IBD.

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Use of Intravenous Immunoglobulin for Patients with Inflammatory Bowel Disease with Contraindications or Who Are Unresponsive to Conventional Treatments

Abstract: IVIg is safe and effective in the short-term management of patients with IBD when standard therapies are contraindicated.

Cited by 25 publications

References 15 publications

Are Truelove and Witts criteria for diagnosing acute severe colitis relevant for the Indian population? A prospective study

Are Truelove and Witts criteria for diagnosing acute severe colitis relevant for the Indian population? A prospective study

Intravenous immunoglobulin (IVIg) or IVIg‐treated macrophages reduce DSS‐induced colitis by inducing macrophage IL‐10 production

An anti-TL1A antibody for the treatment of asthma and inflammatory bowel disease

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