Featured Publications

“Prior Antibodies to Infliximab or Adalimumab Are Related to Immunogenicity to Vedolizumab in Patients with Inflammatory Bowel Disease”

Papamichael K, Vande Casteele N, Abraham BP, Ritter T, Jain A, Cheifetz AS. Prior Antibodies to Infliximab or Adalimumab Are Related to Immunogenicity to Vedolizumab in Patients With Inflammatory Bowel Disease. Clin Gastroenterol Hepatol. 2022 Nov 11:S1542-3565(22)01053-9. doi: 10.1016/j.cgh.2022.10.037

Biologic therapies with various mechanisms of action have proven effective in treating inflammatory bowel disease (IBD), but some patients develop antidrug antibodies (ADAb), or immunogenicity, and thus do not respond or lose response to therapy over time. Previous research suggests that patients who develop ADAb to an anti-tumor necrosis factor (anti-TNF) agent have a greater risk of immunogenicity to other anti-TNFs, but data are limited for patients who switch to a different class of therapeutic. Bincy Abraham, MD, and colleagues analyzed a large commercial database to investigate rates of immunogenicity to the anti-integrin agent vedolizumab and the anti-interleukin 12/23 agent ustekinumab in patients with previous exposure to anti-TNFs. They found that ADAb to the anti-TNFs infliximab and adalimumab were associated with immunogenicity to vedolizumab. These findings will help inform the choice of appropriate biologic agents for patients who do not respond or have lost response to anti-TNF therapy.

“Randomised clinical trial: efficacy and safety of the live biotherapeutic product MRx1234 in patients with irritable bowel syndrome”

Quigley EMM, Markinson L, Stevenson A, Treasure FP, Lacy BE. Randomised clinical trial: efficacy and safety of the live biotherapeutic product MRx1234 in patients with irritable bowel syndrome. Aliment Pharmacol Ther. 2023 Jan;57(1):81-93. doi: 10.1111/apt.17310

The novel live biotherapeutic product MRx1234, which contains a strain of the probiotic Blautia hydrogenotrophica, is in development for the treatment of irritable bowel syndrome (IBS). Eamonn M. M. Quigley, MD, and colleagues conducted a multicenter, randomized, double-blind, placebo-controlled phase 2 clinical trial to assess the efficacy and safety of MRx1234 in patients with IBS with predominant constipation (IBS-C) or diarrhea (IBS-D). They found that significantly more patients on MRx1234 than placebo reported improvement in bowel habit (stool frequency for IBS-C; stool consistency for IBS-D), a component of the primary efficacy endpoint, and patients in all cohorts reported improvements in abdominal pain. The safety profile of MRx1234 was similar to placebo. These results indicate that MRx1234 has the potential to become a novel, safe treatment option for patients with IBS.

“Impact of pre-operative transjugular intrahepatic portosystemic shunt on post-operative outcomes following non-transplant surgeries in patients with decompensated cirrhosis”

Patel P, Irani M, Graviss EA, Nguyen DT, Quigley EMM, Victor DW 3rd. Impact of pre-operative transjugular intrahepatic portosystemic shunt on post-operative outcomes following non-transplant surgeries in patients with decompensated cirrhosis. Transl Gastroenterol Hepatol. 2023 Jan 25;8:9. doi: 10.21037/tgh-21-133

Patients with liver cirrhosis have a high risk of morbidity and mortality when undergoing abdominal surgery. Elective transjugular intrahepatic portosystemic shunt (TIPS) placement prior to surgery has been reported to improve perioperative outcomes, but available data come from case reports and small case series. To improve the evidence base for this procedure, Dr. David Victor and colleagues in the Underwood Center conducted a retrospective chart review comparing 30-day and 1-year mortality in patients with cirrhosis who underwent abdominal surgeries with or without elective TIPS. They identified 38 patients with cirrhosis who underwent abdominal surgery at Houston Methodist Hospital between January 2013 and January 2018, 20 of whom underwent pre-operative TIPS placement. Dr. Victor and colleagues found no statistically significant differences in mortality between groups at 30 days or one year. More evidence is needed from prospective randomized trials to determine the role of TIPS placement in improving perioperative morbidity and mortality in patients with cirrhosis.

“Hyperphosphorylation of hepatic proteome characterizes nonalcoholic fatty liver disease in S-adenosylmethionine deficiency”

Robinson AE, Binek A, Ramani K, Sundararaman N, Barbier-Torres L, Murray B, Venkatraman V, Kreimer S, Ardle AM, Noureddin M, Fernández-Ramos D, Lopitz-Otsoa F, Gutiérrez de Juan V, Millet O, Mato JM, Lu SC, Van Eyk JE. Hyperphosphorylation of hepatic proteome characterizes nonalcoholic fatty liver disease in S-adenosylmethionine deficiency. iScience. 2023 Jan 14;26(2):105987. doi: 10.1016/j.isci.2023.105987

Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide due to the global rise in obesity, and it can progress to nonalcoholic steatohepatitis (NASH), liver cirrhosis, and even hepatocellular carcinoma. Currently, there are no FDA-approved treatments for NASH. To understand the progression of NASH in humans and to identify molecular targets for future drug development, Mazen Noureddin, MD, and colleagues analyzed changes in the proteome (protein quantity) and phosphoproteome (site-specific phosphorylation quantity) signatures at different stages in the progression from NAFLD (pre-disease) to NASH in a mouse model. Their analyses identified a hyperphosphorylation signature that persisted from the pre-disease to the NASH state, and a hyperactive casein kinase 2α (CK2α) and AKT1 signature in the phosphoproteome. Both signatures were observed in human NAFLD as well. These findings have illuminated the pathophysiology of this disease and may have implications for the future development of therapeutics for NASH.