IBD & Intestinal Disorders

Introduction

Inpatient management of acute ulcerative colitis (UC) flares can be challenging because of the multiple patient and disease-related factors influencing therapeutic decision making. The clinical course during the first 24-72 hours of the hospitalization will likely guide the decision between rescue medical and surgical therapy. Using available evidence from clinical practice guidelines, we present a day-by-day guide to managing most hospitalized UC patients.

Day 0 – The emergency department (ED)

When an UC patient presents to the ED for evaluation, the initial assessments should focus on the acuity and severity of the flare. Key clinical features of disease severity include the presence of fever, tachycardia, hypotension, or weight loss in addition to worsened gastrointestinal symptoms of stool frequency relative to baseline, rectal bleeding, and abdominal pain. Acute severe ulcerative colitis (ASUC) is often defined using the modified Truelove and Witts criteria.¹ A patient meets criteria for ASUC if they have at least six bloody stools per day and at least one sign of systemic toxicity, such as heart rate greater than 90 bpm, temperature at or above 37.8° C, hemoglobin level below 10.5 g/dL, or elevated inflammatory markers.

Initial laboratory assessments should include complete blood counts to identify anemia, potential superimposed infection, or toxicity and a comprehensive metabolic profile to evaluate for dehydration, electrolyte abnormalities, hepatic injury or hypoalbuminemia (an important predictor of surgery), as well as assessment of response to treatment and readmission.^2,3 An evaluation at admission of C-reactive protein (CRP) is crucial because changes from the initial value will determine steroid response and predict need for surgical intervention or rescue therapy. A baseline fecal calprotectin can serve as a noninvasive marker that can be followed after discharge to monitor response to therapy.

Clostridioides difficile infection (CDI) must be ruled out in all patients presenting with ASUC regardless of history of antibiotic use or prior negative testing. Concomitant UC and CDI are associated with a four- to sixfold increased risk of in-hospital mortality and a two- to sixfold increased risk of bowel surgery.^4-6 Immunoassay testing is inexpensive and fast with a high specificity but has low sensitivity; nucleic acid amplification testing with polymerase chain reaction has a high sensitivity and specificity.⁷ Knowing which testing algorithm the hospital lab uses helps guide interpretation of results.

For patients meeting criteria for ASUC, obtaining at least an abdominal x-ray is important to assess for colonic dilation to further stratify the patient by risk. Colonic dilation, defined as a transverse colon diameter greater than 5.5 cm, places the patient in the category of fulminant colitis and colorectal surgical consultation should be obtained.⁸ A CT scan is often ordered first because it can provide a rapid assessment of intra-abdominal processes but is not routinely needed unless hemodynamic instability, an acute abdomen, or markedly abnormal laboratory testing (specifically white blood cell count with bandemia) is present as these can be indicators of toxic megacolon or perforation.^8-10

Day 1 – Assess disease severity and assemble the team

Obtaining a thorough clinical history is essential to classify disease severity and identify potential triggers for the acute exacerbation. Potential triggers may include infections, new medications, recent antibiotic use, recent travel, sick contacts, or cessation of treatments. Standard questions include asking about the timing of onset of symptoms, bowel movements during a 24-hour period, and particularly the presence of nocturnal bowel movements. If patients report bloody stools, inquire how often they see blood relative to the total number of bowel movements. The presence and nature of abdominal pain should be elicited, particularly changes in abdominal pain and comparison with previous disease flares. These clinical parameters are used to assess response to treatment; therefore, ask patients to keep a log of their stool frequency, consistency, rectal urgency, and bleeding each day to report to the team during daily rounds.

Once disease severity has been determined, intravenous corticosteroid therapy may be initiated, ideally once CDI and CMV have been excluded. The recommended dosing of intravenous corticosteroids is methylprednisolone 20 mg IV every 8 hours or equivalent. There is no evidence to support additional benefit for doses exceeding these amounts.⁸ Prior to starting parenteral corticosteroids, it is important to keep in mind the possible need for rescue therapy during the admission. Recommended testing includes hepatitis B surface antigen and antibody, hepatitis B core antibody and tuberculosis testing if there is no documented negative testing within the past 6-12 months. These labs should be drawn prior to steroid treatment to avoid delays in care and indeterminate results. Finally, a lipid profile is recommended for patients who may be cyclosporine candidates pending response to intravenous corticosteroids. Unless the patient has been admitted with a bowel obstruction, which should raise the suspicion that the diagnosis is actually Crohn’s disease, enteral feeding is preferred for UC patients even if they may have significant food aversion. The early involvement of a registered dietitian is valuable to guide dietary choices and recommend appropriate enteral nutrition supplements. During acute flares, patients may find a low-residue diet to be less stimulating to their gut while their acute flare is being treated. Electrolyte abnormalities should be repleted and consistently monitored during the hospitalization. Providing parenteral intravenous iron for anemic patients will expedite correction of the anemia alongside treatment of the underlying UC.

Day 3 – Assessing response to corticosteroids

In addition to daily symptom assessments, a careful abdominal exam should be performed every day with the understanding that steroids (and also narcotics) may mask perforation or pain. Any abrupt decrease or cessation of bowel movements, increasing abdominal distention, or a sudden increase in abdominal pain or tenderness may require abdominal imaging to ensure no interim perforation or severe colonic dilation has occurred while receiving steroid therapy. In these circumstances, the addition of broad spectrum intravenous antibiotics should be considered, particularly if hemodynamic instability (such as tachycardia) is present.

Patients should be assessed for response to intravenous steroid therapy after 3 days of treatment. A meaningful response to corticosteroids is present if the patient has had more than 50% improvement in symptoms, particularly rectal bleeding and stool frequency. A more than 75% improvement in CRP should also be noted from admission to day 3 with an overall trend of improvement.^2,21 Additionally, patients should be afebrile, require minimal to no narcotic usage, tolerating oral intake, and be ambulatory. If the patient has met all these parameters, it is reasonable to transition to oral corticosteroids, such as prednisone 40-60 mg daily after a course of 3-5 days of intravenous corticosteroids. Ideally, patients should be observed for 24-48 hours in the hospital after transitioning to oral corticosteroids to make sure that symptoms do not worsen with the switch.

Patients with more than eight bowel movements per day, CRP greater than 4.5 g/dL, deep ulcers on endoscopy, or albumin less than 3.0 g/dL have a higher likelihood of failing intravenous corticosteroid therapy, and these patients should be prepared for rescue therapy.^2,21 A patient has failed intravenous corticosteroids by day 3 if they have sustained fever in the absence of an infection, continued CRP elevation or lack of CRP decrease, or ongoing high stool frequency, bleeding, and pain with less than 50% improvement from baseline on admission.⁸ In the setting of nonresponse to intravenous corticosteroids, it is prudent to involve colorectal surgery to discuss colectomy as an option of equal merit to medical salvage therapies such as infliximab or cyclosporine.

Infliximab is the most readily available rescue therapy for steroid-refractory patients and has been shown to increase colectomy-free survival in patients with ASUC.⁸ However, patients with the same predictors for intravenous steroid failures (low albumin, high CRP, and/or deep ulcers on endoscopy) are also at the highest risk for infliximab nonresponse. These factors are important to discuss with the patients and colorectal surgery teams when providing the options of treatment strategy, particularly with medication dosing. ASUC with more severe disease biochemically (low albumin, elevated CRP, possibly bandemia) benefit from a higher dose of infliximab at 10 mg/kg, given the likelihood of increased drug clearance in this situation.^22,23

From a practical standpoint, it is important to confirm the patient’s insurance status prior to medication administration to make sure therapy can be continued after hospital discharge. Early involvement of the social workers and case coordinators is key to ensuring timely administration of the next dose of treatment. Patients who receive infliximab rescue therapy should be monitored for an additional 1-2 days after administration to ensure they are responding to this therapy with continued monitoring of CRP and symptoms during this period. If there is no response at this point, an additional dose of infliximab may be considered but surgery should not be delayed if there is no meaningful response after the first dose.

Another option for intravenous corticosteroid nonresponders is intravenous cyclosporine because treatment failure rates for cyclosporine and infliximab were similar in head-to-head studies.²⁴ However, patient selection is key to successful utilization of this agent. Unlike infliximab, cyclosporine is primarily an induction agent for steroid nonresponders rather than a maintenance strategy. Therefore, in patients in whom cyclosporine is being considered, thiopurines or vedolizumab are potential options for maintenance therapy. If the patient has poor renal function, low cholesterol, advanced age, significant comorbidities, or a history of nonadherence to therapy, cyclosporine should not be given. Additionally, clinical experience with intravenous cyclosporine administration and monitoring both during inpatient and outpatient care settings should be factored into the decision making for infliximab versus cyclosporine.⁸
 

Day 5 and beyond – Discharge planning

Patients who have responded to the initial intravenous steroid course by hospital day 5 should have successfully transitioned to oral steroids with plans to start an appropriate steroid-sparing therapy shortly after discharge. Treatment planning should commence prior to discharge and should be communicated with the outpatient GI team to ensure a smooth transition to the ambulatory care setting, primarily to begin insurance authorizations as soon as possible. If the patient has had a meaningful response to infliximab rescue therapy (improvement by more than 50% in bowel frequency, amount of blood, abdominal pain), discharge planning needs to prioritize obtaining authorization for the second dose within 2 weeks of the initial infusion. These patients are high risk for readmission, and close outpatient follow-up by the ambulatory GI care team is necessary to help direct the tapering of steroids and monitor response to treatment.

If the patient has not responded to intravenous steroid therapy, infliximab, or cyclosporine by day 5-7, then surgery should be strongly considered. Delaying surgery may worsen outcomes as patients become more malnourished, anemic, and continue to receive intravenous steroids. Additional preoperative optimization may be required depending on the patient’s course up to this point (Table 2).
 

Summary

The cornerstones of inpatient UC management center on a thorough initial evaluation including imaging and endoscopy as appropriate, establishment of baseline parameters, and daily assessment of response to therapy through a combination of patient-reported outcomes and biomarkers of inflammation. With this strategy in mind, practitioners and care teams can manage these complex patients using a consistent strategy focusing on multidisciplinary, evidence-based care.

References

1. Truelove SC et al. Br Med J. 1955 Oct 23;2(4947):1041-8.

2. Ho GT et al. Aliment Pharmacol Ther. 2004 May 15;19(10):1079-87.


3. Tinsley A et al. Scand J Gastroenterol. 2015;50(9):1103-9.

4. Issa M et al. Clin Gastroenterol Hepatol. 2007 Mar;5(3):345-51.

5. Ananthakrishnan AN et al. Gut. 2008 Feb;57(2):205-10.

6. Negron ME et al. Am J Gastroenterol. 2016 May;111(5):691-704.

7. Taylor KN et al. Gynecol Oncol. 2017 Feb;144(2):428-37.

8. Rubin DT et al. Am J Gastroenterol. 2019 Mar;114(3):384-413.

9. Jalan KN et al. Gastroenterology. 1969 Jul;57(1):68-82.

10. Gan SI et al. Am J Gastroenterol. 2003 Nov;98(11):2363-71.

11. Makkar R et al. Gastroenterol Hepatol (N Y). 2013 Sep;9(9):573-83.

12. Hindryckx P et al. Nat Rev Gastroenterol Hepatol. 2016 Nov;13(11):654-64.

13. Yerushalmy-Feler A et al. Curr Infect Dis Rep. 2019 Feb 15;21(2):5.

14. Shukla T et al. J Clin Gastroenterol. 2017 May/Jun;51(5):394-401.

15. McCurdy JD et al. Clin Gastroenterol Hepatol. 2015 Jan;13(1):131-7; quiz e7.

16. Cottone M et al. Am J Gastroenterol. 2001 Mar;96(3):773-5.

17. Nguyen GC et al. Gastroenterology. 2014 Mar;146(3):835-48 e6.

18. Limsrivilai J et al. Clin Gastroenterol Hepatol. 2017 Mar;15(3):385-92 e2.

19. Targownik LE et al. Am J Gastroenterol. 2014 Oct;109(10):1613-20.

20. Takeuchi K et al. Clin Gastroenterol Hepatol. 2006 Feb;4(2):196-202.

21. Travis SP et al. Gut. 1996 Jun;38(6):905-10.

22. Syal G et al. Mo1891 - Gastroenterology. 2018;154:S841.

23. Ungar B et al. Aliment Pharmacol Ther. 2016 Jun;43(12):1293-9.

24. Laharie D et al. Lancet 2012 Dec 1;380(9857):1909-15.
 

Dr. Chiplunker is an advanced inflammatory bowel disease fellow; Dr. Ha is associate professor of medicine at the Inflammatory Bowel Disease Center at Cedars-Sinai Medical Center, Los Angeles.

Introduction

Inpatient management of acute ulcerative colitis (UC) flares can be challenging because of the multiple patient and disease-related factors influencing therapeutic decision making. The clinical course during the first 24-72 hours of the hospitalization will likely guide the decision between rescue medical and surgical therapy. Using available evidence from clinical practice guidelines, we present a day-by-day guide to managing most hospitalized UC patients.

Day 0 – The emergency department (ED)

When an UC patient presents to the ED for evaluation, the initial assessments should focus on the acuity and severity of the flare. Key clinical features of disease severity include the presence of fever, tachycardia, hypotension, or weight loss in addition to worsened gastrointestinal symptoms of stool frequency relative to baseline, rectal bleeding, and abdominal pain. Acute severe ulcerative colitis (ASUC) is often defined using the modified Truelove and Witts criteria.¹ A patient meets criteria for ASUC if they have at least six bloody stools per day and at least one sign of systemic toxicity, such as heart rate greater than 90 bpm, temperature at or above 37.8° C, hemoglobin level below 10.5 g/dL, or elevated inflammatory markers.

Initial laboratory assessments should include complete blood counts to identify anemia, potential superimposed infection, or toxicity and a comprehensive metabolic profile to evaluate for dehydration, electrolyte abnormalities, hepatic injury or hypoalbuminemia (an important predictor of surgery), as well as assessment of response to treatment and readmission.^2,3 An evaluation at admission of C-reactive protein (CRP) is crucial because changes from the initial value will determine steroid response and predict need for surgical intervention or rescue therapy. A baseline fecal calprotectin can serve as a noninvasive marker that can be followed after discharge to monitor response to therapy.

Clostridioides difficile infection (CDI) must be ruled out in all patients presenting with ASUC regardless of history of antibiotic use or prior negative testing. Concomitant UC and CDI are associated with a four- to sixfold increased risk of in-hospital mortality and a two- to sixfold increased risk of bowel surgery.^4-6 Immunoassay testing is inexpensive and fast with a high specificity but has low sensitivity; nucleic acid amplification testing with polymerase chain reaction has a high sensitivity and specificity.⁷ Knowing which testing algorithm the hospital lab uses helps guide interpretation of results.

For patients meeting criteria for ASUC, obtaining at least an abdominal x-ray is important to assess for colonic dilation to further stratify the patient by risk. Colonic dilation, defined as a transverse colon diameter greater than 5.5 cm, places the patient in the category of fulminant colitis and colorectal surgical consultation should be obtained.⁸ A CT scan is often ordered first because it can provide a rapid assessment of intra-abdominal processes but is not routinely needed unless hemodynamic instability, an acute abdomen, or markedly abnormal laboratory testing (specifically white blood cell count with bandemia) is present as these can be indicators of toxic megacolon or perforation.^8-10

Day 1 – Assess disease severity and assemble the team

Obtaining a thorough clinical history is essential to classify disease severity and identify potential triggers for the acute exacerbation. Potential triggers may include infections, new medications, recent antibiotic use, recent travel, sick contacts, or cessation of treatments. Standard questions include asking about the timing of onset of symptoms, bowel movements during a 24-hour period, and particularly the presence of nocturnal bowel movements. If patients report bloody stools, inquire how often they see blood relative to the total number of bowel movements. The presence and nature of abdominal pain should be elicited, particularly changes in abdominal pain and comparison with previous disease flares. These clinical parameters are used to assess response to treatment; therefore, ask patients to keep a log of their stool frequency, consistency, rectal urgency, and bleeding each day to report to the team during daily rounds.

Once disease severity has been determined, intravenous corticosteroid therapy may be initiated, ideally once CDI and CMV have been excluded. The recommended dosing of intravenous corticosteroids is methylprednisolone 20 mg IV every 8 hours or equivalent. There is no evidence to support additional benefit for doses exceeding these amounts.⁸ Prior to starting parenteral corticosteroids, it is important to keep in mind the possible need for rescue therapy during the admission. Recommended testing includes hepatitis B surface antigen and antibody, hepatitis B core antibody and tuberculosis testing if there is no documented negative testing within the past 6-12 months. These labs should be drawn prior to steroid treatment to avoid delays in care and indeterminate results. Finally, a lipid profile is recommended for patients who may be cyclosporine candidates pending response to intravenous corticosteroids. Unless the patient has been admitted with a bowel obstruction, which should raise the suspicion that the diagnosis is actually Crohn’s disease, enteral feeding is preferred for UC patients even if they may have significant food aversion. The early involvement of a registered dietitian is valuable to guide dietary choices and recommend appropriate enteral nutrition supplements. During acute flares, patients may find a low-residue diet to be less stimulating to their gut while their acute flare is being treated. Electrolyte abnormalities should be repleted and consistently monitored during the hospitalization. Providing parenteral intravenous iron for anemic patients will expedite correction of the anemia alongside treatment of the underlying UC.

Day 3 – Assessing response to corticosteroids

In addition to daily symptom assessments, a careful abdominal exam should be performed every day with the understanding that steroids (and also narcotics) may mask perforation or pain. Any abrupt decrease or cessation of bowel movements, increasing abdominal distention, or a sudden increase in abdominal pain or tenderness may require abdominal imaging to ensure no interim perforation or severe colonic dilation has occurred while receiving steroid therapy. In these circumstances, the addition of broad spectrum intravenous antibiotics should be considered, particularly if hemodynamic instability (such as tachycardia) is present.

Patients should be assessed for response to intravenous steroid therapy after 3 days of treatment. A meaningful response to corticosteroids is present if the patient has had more than 50% improvement in symptoms, particularly rectal bleeding and stool frequency. A more than 75% improvement in CRP should also be noted from admission to day 3 with an overall trend of improvement.^2,21 Additionally, patients should be afebrile, require minimal to no narcotic usage, tolerating oral intake, and be ambulatory. If the patient has met all these parameters, it is reasonable to transition to oral corticosteroids, such as prednisone 40-60 mg daily after a course of 3-5 days of intravenous corticosteroids. Ideally, patients should be observed for 24-48 hours in the hospital after transitioning to oral corticosteroids to make sure that symptoms do not worsen with the switch.

Patients with more than eight bowel movements per day, CRP greater than 4.5 g/dL, deep ulcers on endoscopy, or albumin less than 3.0 g/dL have a higher likelihood of failing intravenous corticosteroid therapy, and these patients should be prepared for rescue therapy.^2,21 A patient has failed intravenous corticosteroids by day 3 if they have sustained fever in the absence of an infection, continued CRP elevation or lack of CRP decrease, or ongoing high stool frequency, bleeding, and pain with less than 50% improvement from baseline on admission.⁸ In the setting of nonresponse to intravenous corticosteroids, it is prudent to involve colorectal surgery to discuss colectomy as an option of equal merit to medical salvage therapies such as infliximab or cyclosporine.

Infliximab is the most readily available rescue therapy for steroid-refractory patients and has been shown to increase colectomy-free survival in patients with ASUC.⁸ However, patients with the same predictors for intravenous steroid failures (low albumin, high CRP, and/or deep ulcers on endoscopy) are also at the highest risk for infliximab nonresponse. These factors are important to discuss with the patients and colorectal surgery teams when providing the options of treatment strategy, particularly with medication dosing. ASUC with more severe disease biochemically (low albumin, elevated CRP, possibly bandemia) benefit from a higher dose of infliximab at 10 mg/kg, given the likelihood of increased drug clearance in this situation.^22,23

From a practical standpoint, it is important to confirm the patient’s insurance status prior to medication administration to make sure therapy can be continued after hospital discharge. Early involvement of the social workers and case coordinators is key to ensuring timely administration of the next dose of treatment. Patients who receive infliximab rescue therapy should be monitored for an additional 1-2 days after administration to ensure they are responding to this therapy with continued monitoring of CRP and symptoms during this period. If there is no response at this point, an additional dose of infliximab may be considered but surgery should not be delayed if there is no meaningful response after the first dose.

Another option for intravenous corticosteroid nonresponders is intravenous cyclosporine because treatment failure rates for cyclosporine and infliximab were similar in head-to-head studies.²⁴ However, patient selection is key to successful utilization of this agent. Unlike infliximab, cyclosporine is primarily an induction agent for steroid nonresponders rather than a maintenance strategy. Therefore, in patients in whom cyclosporine is being considered, thiopurines or vedolizumab are potential options for maintenance therapy. If the patient has poor renal function, low cholesterol, advanced age, significant comorbidities, or a history of nonadherence to therapy, cyclosporine should not be given. Additionally, clinical experience with intravenous cyclosporine administration and monitoring both during inpatient and outpatient care settings should be factored into the decision making for infliximab versus cyclosporine.⁸
 

Day 5 and beyond – Discharge planning

Patients who have responded to the initial intravenous steroid course by hospital day 5 should have successfully transitioned to oral steroids with plans to start an appropriate steroid-sparing therapy shortly after discharge. Treatment planning should commence prior to discharge and should be communicated with the outpatient GI team to ensure a smooth transition to the ambulatory care setting, primarily to begin insurance authorizations as soon as possible. If the patient has had a meaningful response to infliximab rescue therapy (improvement by more than 50% in bowel frequency, amount of blood, abdominal pain), discharge planning needs to prioritize obtaining authorization for the second dose within 2 weeks of the initial infusion. These patients are high risk for readmission, and close outpatient follow-up by the ambulatory GI care team is necessary to help direct the tapering of steroids and monitor response to treatment.

If the patient has not responded to intravenous steroid therapy, infliximab, or cyclosporine by day 5-7, then surgery should be strongly considered. Delaying surgery may worsen outcomes as patients become more malnourished, anemic, and continue to receive intravenous steroids. Additional preoperative optimization may be required depending on the patient’s course up to this point (Table 2).
 

Summary

The cornerstones of inpatient UC management center on a thorough initial evaluation including imaging and endoscopy as appropriate, establishment of baseline parameters, and daily assessment of response to therapy through a combination of patient-reported outcomes and biomarkers of inflammation. With this strategy in mind, practitioners and care teams can manage these complex patients using a consistent strategy focusing on multidisciplinary, evidence-based care.

References

1. Truelove SC et al. Br Med J. 1955 Oct 23;2(4947):1041-8.

2. Ho GT et al. Aliment Pharmacol Ther. 2004 May 15;19(10):1079-87.


3. Tinsley A et al. Scand J Gastroenterol. 2015;50(9):1103-9.

4. Issa M et al. Clin Gastroenterol Hepatol. 2007 Mar;5(3):345-51.

5. Ananthakrishnan AN et al. Gut. 2008 Feb;57(2):205-10.

6. Negron ME et al. Am J Gastroenterol. 2016 May;111(5):691-704.

7. Taylor KN et al. Gynecol Oncol. 2017 Feb;144(2):428-37.

8. Rubin DT et al. Am J Gastroenterol. 2019 Mar;114(3):384-413.

9. Jalan KN et al. Gastroenterology. 1969 Jul;57(1):68-82.

10. Gan SI et al. Am J Gastroenterol. 2003 Nov;98(11):2363-71.

11. Makkar R et al. Gastroenterol Hepatol (N Y). 2013 Sep;9(9):573-83.

12. Hindryckx P et al. Nat Rev Gastroenterol Hepatol. 2016 Nov;13(11):654-64.

13. Yerushalmy-Feler A et al. Curr Infect Dis Rep. 2019 Feb 15;21(2):5.

14. Shukla T et al. J Clin Gastroenterol. 2017 May/Jun;51(5):394-401.

15. McCurdy JD et al. Clin Gastroenterol Hepatol. 2015 Jan;13(1):131-7; quiz e7.

16. Cottone M et al. Am J Gastroenterol. 2001 Mar;96(3):773-5.

17. Nguyen GC et al. Gastroenterology. 2014 Mar;146(3):835-48 e6.

18. Limsrivilai J et al. Clin Gastroenterol Hepatol. 2017 Mar;15(3):385-92 e2.

19. Targownik LE et al. Am J Gastroenterol. 2014 Oct;109(10):1613-20.

20. Takeuchi K et al. Clin Gastroenterol Hepatol. 2006 Feb;4(2):196-202.

21. Travis SP et al. Gut. 1996 Jun;38(6):905-10.

22. Syal G et al. Mo1891 - Gastroenterology. 2018;154:S841.

23. Ungar B et al. Aliment Pharmacol Ther. 2016 Jun;43(12):1293-9.

24. Laharie D et al. Lancet 2012 Dec 1;380(9857):1909-15.
 

Dr. Chiplunker is an advanced inflammatory bowel disease fellow; Dr. Ha is associate professor of medicine at the Inflammatory Bowel Disease Center at Cedars-Sinai Medical Center, Los Angeles.

Introduction

Inpatient management of acute ulcerative colitis (UC) flares can be challenging because of the multiple patient and disease-related factors influencing therapeutic decision making. The clinical course during the first 24-72 hours of the hospitalization will likely guide the decision between rescue medical and surgical therapy. Using available evidence from clinical practice guidelines, we present a day-by-day guide to managing most hospitalized UC patients.

Day 0 – The emergency department (ED)

When an UC patient presents to the ED for evaluation, the initial assessments should focus on the acuity and severity of the flare. Key clinical features of disease severity include the presence of fever, tachycardia, hypotension, or weight loss in addition to worsened gastrointestinal symptoms of stool frequency relative to baseline, rectal bleeding, and abdominal pain. Acute severe ulcerative colitis (ASUC) is often defined using the modified Truelove and Witts criteria.¹ A patient meets criteria for ASUC if they have at least six bloody stools per day and at least one sign of systemic toxicity, such as heart rate greater than 90 bpm, temperature at or above 37.8° C, hemoglobin level below 10.5 g/dL, or elevated inflammatory markers.

Initial laboratory assessments should include complete blood counts to identify anemia, potential superimposed infection, or toxicity and a comprehensive metabolic profile to evaluate for dehydration, electrolyte abnormalities, hepatic injury or hypoalbuminemia (an important predictor of surgery), as well as assessment of response to treatment and readmission.^2,3 An evaluation at admission of C-reactive protein (CRP) is crucial because changes from the initial value will determine steroid response and predict need for surgical intervention or rescue therapy. A baseline fecal calprotectin can serve as a noninvasive marker that can be followed after discharge to monitor response to therapy.

Clostridioides difficile infection (CDI) must be ruled out in all patients presenting with ASUC regardless of history of antibiotic use or prior negative testing. Concomitant UC and CDI are associated with a four- to sixfold increased risk of in-hospital mortality and a two- to sixfold increased risk of bowel surgery.^4-6 Immunoassay testing is inexpensive and fast with a high specificity but has low sensitivity; nucleic acid amplification testing with polymerase chain reaction has a high sensitivity and specificity.⁷ Knowing which testing algorithm the hospital lab uses helps guide interpretation of results.

For patients meeting criteria for ASUC, obtaining at least an abdominal x-ray is important to assess for colonic dilation to further stratify the patient by risk. Colonic dilation, defined as a transverse colon diameter greater than 5.5 cm, places the patient in the category of fulminant colitis and colorectal surgical consultation should be obtained.⁸ A CT scan is often ordered first because it can provide a rapid assessment of intra-abdominal processes but is not routinely needed unless hemodynamic instability, an acute abdomen, or markedly abnormal laboratory testing (specifically white blood cell count with bandemia) is present as these can be indicators of toxic megacolon or perforation.^8-10

Day 1 – Assess disease severity and assemble the team

Obtaining a thorough clinical history is essential to classify disease severity and identify potential triggers for the acute exacerbation. Potential triggers may include infections, new medications, recent antibiotic use, recent travel, sick contacts, or cessation of treatments. Standard questions include asking about the timing of onset of symptoms, bowel movements during a 24-hour period, and particularly the presence of nocturnal bowel movements. If patients report bloody stools, inquire how often they see blood relative to the total number of bowel movements. The presence and nature of abdominal pain should be elicited, particularly changes in abdominal pain and comparison with previous disease flares. These clinical parameters are used to assess response to treatment; therefore, ask patients to keep a log of their stool frequency, consistency, rectal urgency, and bleeding each day to report to the team during daily rounds.

Once disease severity has been determined, intravenous corticosteroid therapy may be initiated, ideally once CDI and CMV have been excluded. The recommended dosing of intravenous corticosteroids is methylprednisolone 20 mg IV every 8 hours or equivalent. There is no evidence to support additional benefit for doses exceeding these amounts.⁸ Prior to starting parenteral corticosteroids, it is important to keep in mind the possible need for rescue therapy during the admission. Recommended testing includes hepatitis B surface antigen and antibody, hepatitis B core antibody and tuberculosis testing if there is no documented negative testing within the past 6-12 months. These labs should be drawn prior to steroid treatment to avoid delays in care and indeterminate results. Finally, a lipid profile is recommended for patients who may be cyclosporine candidates pending response to intravenous corticosteroids. Unless the patient has been admitted with a bowel obstruction, which should raise the suspicion that the diagnosis is actually Crohn’s disease, enteral feeding is preferred for UC patients even if they may have significant food aversion. The early involvement of a registered dietitian is valuable to guide dietary choices and recommend appropriate enteral nutrition supplements. During acute flares, patients may find a low-residue diet to be less stimulating to their gut while their acute flare is being treated. Electrolyte abnormalities should be repleted and consistently monitored during the hospitalization. Providing parenteral intravenous iron for anemic patients will expedite correction of the anemia alongside treatment of the underlying UC.

Day 3 – Assessing response to corticosteroids

In addition to daily symptom assessments, a careful abdominal exam should be performed every day with the understanding that steroids (and also narcotics) may mask perforation or pain. Any abrupt decrease or cessation of bowel movements, increasing abdominal distention, or a sudden increase in abdominal pain or tenderness may require abdominal imaging to ensure no interim perforation or severe colonic dilation has occurred while receiving steroid therapy. In these circumstances, the addition of broad spectrum intravenous antibiotics should be considered, particularly if hemodynamic instability (such as tachycardia) is present.

Patients should be assessed for response to intravenous steroid therapy after 3 days of treatment. A meaningful response to corticosteroids is present if the patient has had more than 50% improvement in symptoms, particularly rectal bleeding and stool frequency. A more than 75% improvement in CRP should also be noted from admission to day 3 with an overall trend of improvement.^2,21 Additionally, patients should be afebrile, require minimal to no narcotic usage, tolerating oral intake, and be ambulatory. If the patient has met all these parameters, it is reasonable to transition to oral corticosteroids, such as prednisone 40-60 mg daily after a course of 3-5 days of intravenous corticosteroids. Ideally, patients should be observed for 24-48 hours in the hospital after transitioning to oral corticosteroids to make sure that symptoms do not worsen with the switch.

Patients with more than eight bowel movements per day, CRP greater than 4.5 g/dL, deep ulcers on endoscopy, or albumin less than 3.0 g/dL have a higher likelihood of failing intravenous corticosteroid therapy, and these patients should be prepared for rescue therapy.^2,21 A patient has failed intravenous corticosteroids by day 3 if they have sustained fever in the absence of an infection, continued CRP elevation or lack of CRP decrease, or ongoing high stool frequency, bleeding, and pain with less than 50% improvement from baseline on admission.⁸ In the setting of nonresponse to intravenous corticosteroids, it is prudent to involve colorectal surgery to discuss colectomy as an option of equal merit to medical salvage therapies such as infliximab or cyclosporine.

Infliximab is the most readily available rescue therapy for steroid-refractory patients and has been shown to increase colectomy-free survival in patients with ASUC.⁸ However, patients with the same predictors for intravenous steroid failures (low albumin, high CRP, and/or deep ulcers on endoscopy) are also at the highest risk for infliximab nonresponse. These factors are important to discuss with the patients and colorectal surgery teams when providing the options of treatment strategy, particularly with medication dosing. ASUC with more severe disease biochemically (low albumin, elevated CRP, possibly bandemia) benefit from a higher dose of infliximab at 10 mg/kg, given the likelihood of increased drug clearance in this situation.^22,23

From a practical standpoint, it is important to confirm the patient’s insurance status prior to medication administration to make sure therapy can be continued after hospital discharge. Early involvement of the social workers and case coordinators is key to ensuring timely administration of the next dose of treatment. Patients who receive infliximab rescue therapy should be monitored for an additional 1-2 days after administration to ensure they are responding to this therapy with continued monitoring of CRP and symptoms during this period. If there is no response at this point, an additional dose of infliximab may be considered but surgery should not be delayed if there is no meaningful response after the first dose.

Another option for intravenous corticosteroid nonresponders is intravenous cyclosporine because treatment failure rates for cyclosporine and infliximab were similar in head-to-head studies.²⁴ However, patient selection is key to successful utilization of this agent. Unlike infliximab, cyclosporine is primarily an induction agent for steroid nonresponders rather than a maintenance strategy. Therefore, in patients in whom cyclosporine is being considered, thiopurines or vedolizumab are potential options for maintenance therapy. If the patient has poor renal function, low cholesterol, advanced age, significant comorbidities, or a history of nonadherence to therapy, cyclosporine should not be given. Additionally, clinical experience with intravenous cyclosporine administration and monitoring both during inpatient and outpatient care settings should be factored into the decision making for infliximab versus cyclosporine.⁸
 

Day 5 and beyond – Discharge planning

Patients who have responded to the initial intravenous steroid course by hospital day 5 should have successfully transitioned to oral steroids with plans to start an appropriate steroid-sparing therapy shortly after discharge. Treatment planning should commence prior to discharge and should be communicated with the outpatient GI team to ensure a smooth transition to the ambulatory care setting, primarily to begin insurance authorizations as soon as possible. If the patient has had a meaningful response to infliximab rescue therapy (improvement by more than 50% in bowel frequency, amount of blood, abdominal pain), discharge planning needs to prioritize obtaining authorization for the second dose within 2 weeks of the initial infusion. These patients are high risk for readmission, and close outpatient follow-up by the ambulatory GI care team is necessary to help direct the tapering of steroids and monitor response to treatment.

If the patient has not responded to intravenous steroid therapy, infliximab, or cyclosporine by day 5-7, then surgery should be strongly considered. Delaying surgery may worsen outcomes as patients become more malnourished, anemic, and continue to receive intravenous steroids. Additional preoperative optimization may be required depending on the patient’s course up to this point (Table 2).
 

Summary

The cornerstones of inpatient UC management center on a thorough initial evaluation including imaging and endoscopy as appropriate, establishment of baseline parameters, and daily assessment of response to therapy through a combination of patient-reported outcomes and biomarkers of inflammation. With this strategy in mind, practitioners and care teams can manage these complex patients using a consistent strategy focusing on multidisciplinary, evidence-based care.

References

1. Truelove SC et al. Br Med J. 1955 Oct 23;2(4947):1041-8.

2. Ho GT et al. Aliment Pharmacol Ther. 2004 May 15;19(10):1079-87.


3. Tinsley A et al. Scand J Gastroenterol. 2015;50(9):1103-9.

4. Issa M et al. Clin Gastroenterol Hepatol. 2007 Mar;5(3):345-51.

5. Ananthakrishnan AN et al. Gut. 2008 Feb;57(2):205-10.

6. Negron ME et al. Am J Gastroenterol. 2016 May;111(5):691-704.

7. Taylor KN et al. Gynecol Oncol. 2017 Feb;144(2):428-37.

8. Rubin DT et al. Am J Gastroenterol. 2019 Mar;114(3):384-413.

9. Jalan KN et al. Gastroenterology. 1969 Jul;57(1):68-82.

10. Gan SI et al. Am J Gastroenterol. 2003 Nov;98(11):2363-71.

11. Makkar R et al. Gastroenterol Hepatol (N Y). 2013 Sep;9(9):573-83.

12. Hindryckx P et al. Nat Rev Gastroenterol Hepatol. 2016 Nov;13(11):654-64.

13. Yerushalmy-Feler A et al. Curr Infect Dis Rep. 2019 Feb 15;21(2):5.

14. Shukla T et al. J Clin Gastroenterol. 2017 May/Jun;51(5):394-401.

15. McCurdy JD et al. Clin Gastroenterol Hepatol. 2015 Jan;13(1):131-7; quiz e7.

16. Cottone M et al. Am J Gastroenterol. 2001 Mar;96(3):773-5.

17. Nguyen GC et al. Gastroenterology. 2014 Mar;146(3):835-48 e6.

18. Limsrivilai J et al. Clin Gastroenterol Hepatol. 2017 Mar;15(3):385-92 e2.

19. Targownik LE et al. Am J Gastroenterol. 2014 Oct;109(10):1613-20.

20. Takeuchi K et al. Clin Gastroenterol Hepatol. 2006 Feb;4(2):196-202.

21. Travis SP et al. Gut. 1996 Jun;38(6):905-10.

22. Syal G et al. Mo1891 - Gastroenterology. 2018;154:S841.

23. Ungar B et al. Aliment Pharmacol Ther. 2016 Jun;43(12):1293-9.

24. Laharie D et al. Lancet 2012 Dec 1;380(9857):1909-15.
 

Dr. Chiplunker is an advanced inflammatory bowel disease fellow; Dr. Ha is associate professor of medicine at the Inflammatory Bowel Disease Center at Cedars-Sinai Medical Center, Los Angeles.

Two cases of bacteremia have been described in two patients who received fecal microbiota transplants from the same donor.

Writing in the New England Journal of Medicine, researchers reported the two case studies of extended-spectrum beta-lactamase (ESBL)–producing Escherichia coli bacteremia, one of which ended in the death of the patient. These cases were previously announced by the Food and Drug Administration in a June 2019 safety alert.

Zachariah DeFilipp, MD, from Massachusetts General Hospital at Harvard Medical School, Boston, and coauthors wrote that fecal microbiota transplantation is rarely associated with complications. Placebo-controlled trials and a systematic review have found similar rates of complications in immunocompromised and immunocompetent recipients. Only four cases of gram-negative bacteremia previously have been reported, and in three of these, there was a plausible alternative explanation for the bacteremia.

In this paper, both patients received fecal microbiota transplantation via frozen oral capsules containing donor stool. These capsules were prepared prior to the implementation of screening for ESBL-producing organisms at the institution, and were not retrospectively tested since this expanded donor screening.

The first patient was a 69-year-old man with liver cirrhosis attributed to hepatitis C infection who was enrolled in a trial of fecal microbiota transplantation via oral capsules to treat hepatic encephalopathy. The first sign of the adverse event was a fever and cough, which developed 17 days after the final dose of 15 capsules. He was treated for pneumonia but failed to improve after 2 days, at which time gram-negative rods were discovered in blood cultures taken at the initial presentation.

After admission and further treatment, blood cultures were found to have ESBL-producing E. coli, and after further treatment, the patient was clinically stable. A stool sample taken after treatment was negative for ESBL-producing E. coli.

The second case study was a 73-year-old man with therapy-related myelodysplastic syndrome who was undergoing allogeneic hematopoietic stem cell transplantation and was receiving fecal microbiota transplantation via oral capsule as part of a phase 2 trial.

Eight days after the last dose of oral capsules, and 5 days after the stem-cell infusion, the man developed a fever, chills, febrile neutropenia and showed altered mental status. He was treated with cefepime but developed hypoxia and labored breathing later that evening, which prompted clinicians to intubate and begin mechanical ventilation.

His blood culture results showed gram-negative rods, and meropenem was added to his antibiotic regimen. However, the patient’s condition worsened, and he died of severe sepsis 2 days later with blood cultures confirmed as positive for ESBL-producing E. coli.

A follow-up investigation revealed that both patients received stool from the same donor. Each lot of three capsules from that donor was found to contain ESBL-producing E. coli with a resistance pattern similar to that seen in the two recipients.

Twenty-two patients had received capsules from this donor. Researchers contacted all the recipients and offered them stool screening for ESBL-producing E. coli. Twelve underwent testing, which found that five had samples that grew on ESBL-producing E. coli–selective medium.

The remaining seven patients who had follow-up testing were receiving treatment for recurrent or refractory Clostridioides difficile infection, and four of these grew samples on the selective medium.

“When FMT is successful, the recipient’s metagenomic burden of antimicrobial resistance genes mimics that of the donor,” the authors wrote. “Although we cannot conclusively attribute positive screening results for ESBL-producing organisms in other asymptomatic recipients to FMT, the rates of positive tests are, in our opinion, unexpectedly high and probably represent transmission through FMT.”

The authors said the donor had no risk factors for carriage of multidrug-resistant organism and had previously donated fecal material before the introduction of routine screening for ESBL-producing organisms.

However, they noted that both patients had risk factors for bacteremia, namely advanced cirrhosis and allogeneic hematopoietic stem cell transplantation and they also received oral antibiotics around the time of the fecal microbiota transplantation.

“Despite the infectious complications reported here, the benefits of FMT should be balanced with the associated risks when considering treatment options for patients with recurrent or refractory C. difficile infection,” the authors wrote. “Ongoing assessment of the risks and benefit of FMT research is needed, as are continuing efforts to improve donor screening to limit transmission of microorganisms that could lead to adverse infectious events.”

The American Gastroenterological Association FMT National Registry is a critical effort to track short- and long-term patient outcomes and potential risks associated with FMT. The registry's goal is to track 4,000 patients for 10 years. If you perform FMT, please contribute to this important initiative. Learn more at www.gastro.org/FMTRegistry.

The study was supported by a grant from the American College of Gastroenterology. Three authors declared personal fees and grants from the medical sector outside the submitted work, and two were attached to a diagnostics company involved in the study.

SOURCE: DeFilipp Z et al. N Engl J Med. 2019 Oct 30. doi: 10.1056/NEJMoa1910437.

* This story was updated on Oct. 31, 2019.

Two cases of bacteremia have been described in two patients who received fecal microbiota transplants from the same donor.

Writing in the New England Journal of Medicine, researchers reported the two case studies of extended-spectrum beta-lactamase (ESBL)–producing Escherichia coli bacteremia, one of which ended in the death of the patient. These cases were previously announced by the Food and Drug Administration in a June 2019 safety alert.

Zachariah DeFilipp, MD, from Massachusetts General Hospital at Harvard Medical School, Boston, and coauthors wrote that fecal microbiota transplantation is rarely associated with complications. Placebo-controlled trials and a systematic review have found similar rates of complications in immunocompromised and immunocompetent recipients. Only four cases of gram-negative bacteremia previously have been reported, and in three of these, there was a plausible alternative explanation for the bacteremia.

In this paper, both patients received fecal microbiota transplantation via frozen oral capsules containing donor stool. These capsules were prepared prior to the implementation of screening for ESBL-producing organisms at the institution, and were not retrospectively tested since this expanded donor screening.

The first patient was a 69-year-old man with liver cirrhosis attributed to hepatitis C infection who was enrolled in a trial of fecal microbiota transplantation via oral capsules to treat hepatic encephalopathy. The first sign of the adverse event was a fever and cough, which developed 17 days after the final dose of 15 capsules. He was treated for pneumonia but failed to improve after 2 days, at which time gram-negative rods were discovered in blood cultures taken at the initial presentation.

After admission and further treatment, blood cultures were found to have ESBL-producing E. coli, and after further treatment, the patient was clinically stable. A stool sample taken after treatment was negative for ESBL-producing E. coli.

The second case study was a 73-year-old man with therapy-related myelodysplastic syndrome who was undergoing allogeneic hematopoietic stem cell transplantation and was receiving fecal microbiota transplantation via oral capsule as part of a phase 2 trial.

Eight days after the last dose of oral capsules, and 5 days after the stem-cell infusion, the man developed a fever, chills, febrile neutropenia and showed altered mental status. He was treated with cefepime but developed hypoxia and labored breathing later that evening, which prompted clinicians to intubate and begin mechanical ventilation.

His blood culture results showed gram-negative rods, and meropenem was added to his antibiotic regimen. However, the patient’s condition worsened, and he died of severe sepsis 2 days later with blood cultures confirmed as positive for ESBL-producing E. coli.

A follow-up investigation revealed that both patients received stool from the same donor. Each lot of three capsules from that donor was found to contain ESBL-producing E. coli with a resistance pattern similar to that seen in the two recipients.

Twenty-two patients had received capsules from this donor. Researchers contacted all the recipients and offered them stool screening for ESBL-producing E. coli. Twelve underwent testing, which found that five had samples that grew on ESBL-producing E. coli–selective medium.

The remaining seven patients who had follow-up testing were receiving treatment for recurrent or refractory Clostridioides difficile infection, and four of these grew samples on the selective medium.

“When FMT is successful, the recipient’s metagenomic burden of antimicrobial resistance genes mimics that of the donor,” the authors wrote. “Although we cannot conclusively attribute positive screening results for ESBL-producing organisms in other asymptomatic recipients to FMT, the rates of positive tests are, in our opinion, unexpectedly high and probably represent transmission through FMT.”

The authors said the donor had no risk factors for carriage of multidrug-resistant organism and had previously donated fecal material before the introduction of routine screening for ESBL-producing organisms.

However, they noted that both patients had risk factors for bacteremia, namely advanced cirrhosis and allogeneic hematopoietic stem cell transplantation and they also received oral antibiotics around the time of the fecal microbiota transplantation.

“Despite the infectious complications reported here, the benefits of FMT should be balanced with the associated risks when considering treatment options for patients with recurrent or refractory C. difficile infection,” the authors wrote. “Ongoing assessment of the risks and benefit of FMT research is needed, as are continuing efforts to improve donor screening to limit transmission of microorganisms that could lead to adverse infectious events.”

The American Gastroenterological Association FMT National Registry is a critical effort to track short- and long-term patient outcomes and potential risks associated with FMT. The registry's goal is to track 4,000 patients for 10 years. If you perform FMT, please contribute to this important initiative. Learn more at www.gastro.org/FMTRegistry.

The study was supported by a grant from the American College of Gastroenterology. Three authors declared personal fees and grants from the medical sector outside the submitted work, and two were attached to a diagnostics company involved in the study.

SOURCE: DeFilipp Z et al. N Engl J Med. 2019 Oct 30. doi: 10.1056/NEJMoa1910437.

* This story was updated on Oct. 31, 2019.

Two cases of bacteremia have been described in two patients who received fecal microbiota transplants from the same donor.

Writing in the New England Journal of Medicine, researchers reported the two case studies of extended-spectrum beta-lactamase (ESBL)–producing Escherichia coli bacteremia, one of which ended in the death of the patient. These cases were previously announced by the Food and Drug Administration in a June 2019 safety alert.

Zachariah DeFilipp, MD, from Massachusetts General Hospital at Harvard Medical School, Boston, and coauthors wrote that fecal microbiota transplantation is rarely associated with complications. Placebo-controlled trials and a systematic review have found similar rates of complications in immunocompromised and immunocompetent recipients. Only four cases of gram-negative bacteremia previously have been reported, and in three of these, there was a plausible alternative explanation for the bacteremia.

In this paper, both patients received fecal microbiota transplantation via frozen oral capsules containing donor stool. These capsules were prepared prior to the implementation of screening for ESBL-producing organisms at the institution, and were not retrospectively tested since this expanded donor screening.

The first patient was a 69-year-old man with liver cirrhosis attributed to hepatitis C infection who was enrolled in a trial of fecal microbiota transplantation via oral capsules to treat hepatic encephalopathy. The first sign of the adverse event was a fever and cough, which developed 17 days after the final dose of 15 capsules. He was treated for pneumonia but failed to improve after 2 days, at which time gram-negative rods were discovered in blood cultures taken at the initial presentation.

After admission and further treatment, blood cultures were found to have ESBL-producing E. coli, and after further treatment, the patient was clinically stable. A stool sample taken after treatment was negative for ESBL-producing E. coli.

The second case study was a 73-year-old man with therapy-related myelodysplastic syndrome who was undergoing allogeneic hematopoietic stem cell transplantation and was receiving fecal microbiota transplantation via oral capsule as part of a phase 2 trial.

Eight days after the last dose of oral capsules, and 5 days after the stem-cell infusion, the man developed a fever, chills, febrile neutropenia and showed altered mental status. He was treated with cefepime but developed hypoxia and labored breathing later that evening, which prompted clinicians to intubate and begin mechanical ventilation.

His blood culture results showed gram-negative rods, and meropenem was added to his antibiotic regimen. However, the patient’s condition worsened, and he died of severe sepsis 2 days later with blood cultures confirmed as positive for ESBL-producing E. coli.

A follow-up investigation revealed that both patients received stool from the same donor. Each lot of three capsules from that donor was found to contain ESBL-producing E. coli with a resistance pattern similar to that seen in the two recipients.

Twenty-two patients had received capsules from this donor. Researchers contacted all the recipients and offered them stool screening for ESBL-producing E. coli. Twelve underwent testing, which found that five had samples that grew on ESBL-producing E. coli–selective medium.

The remaining seven patients who had follow-up testing were receiving treatment for recurrent or refractory Clostridioides difficile infection, and four of these grew samples on the selective medium.

“When FMT is successful, the recipient’s metagenomic burden of antimicrobial resistance genes mimics that of the donor,” the authors wrote. “Although we cannot conclusively attribute positive screening results for ESBL-producing organisms in other asymptomatic recipients to FMT, the rates of positive tests are, in our opinion, unexpectedly high and probably represent transmission through FMT.”

The authors said the donor had no risk factors for carriage of multidrug-resistant organism and had previously donated fecal material before the introduction of routine screening for ESBL-producing organisms.

However, they noted that both patients had risk factors for bacteremia, namely advanced cirrhosis and allogeneic hematopoietic stem cell transplantation and they also received oral antibiotics around the time of the fecal microbiota transplantation.

“Despite the infectious complications reported here, the benefits of FMT should be balanced with the associated risks when considering treatment options for patients with recurrent or refractory C. difficile infection,” the authors wrote. “Ongoing assessment of the risks and benefit of FMT research is needed, as are continuing efforts to improve donor screening to limit transmission of microorganisms that could lead to adverse infectious events.”

The American Gastroenterological Association FMT National Registry is a critical effort to track short- and long-term patient outcomes and potential risks associated with FMT. The registry's goal is to track 4,000 patients for 10 years. If you perform FMT, please contribute to this important initiative. Learn more at www.gastro.org/FMTRegistry.

The study was supported by a grant from the American College of Gastroenterology. Three authors declared personal fees and grants from the medical sector outside the submitted work, and two were attached to a diagnostics company involved in the study.

SOURCE: DeFilipp Z et al. N Engl J Med. 2019 Oct 30. doi: 10.1056/NEJMoa1910437.

* This story was updated on Oct. 31, 2019.

The Food and Drug Administration has approved ustekinumab (Stelara) for the treatment of moderate to severe ulcerative colitis in adults aged 18 years and older, according to a release from Janssen. This is the human interleukin-12 and IL-23 antagonist’s fourth indication since it was first approved by the FDA in 2009.

Olivier Le Moal/Getty Images

The approval is based on findings from the phase 3 UNIFI clinical trial, which achieved its primary endpoint of clinical remission over the course of both induction and maintenance. The 8-week induction study saw 19% of patients achieve clinical remission and 58% demonstrating clinical response; at the 1 year mark, after 44 weeks of maintenance therapy, 43% of patients were in clinical remission without steroids. The trial also assessed a novel histologic-endoscopic mucosal improvement endpoint that examined cellular improvement through both histologic examination and images observed during colonoscopy; 17% of treated patients achieved this endpoint at week 8, and 44% had by 1 year.

“The FDA approval of Stelara for [ulcerative colitis] represents an exciting milestone, offering patients a new option that has demonstrated improvement of the histology and endoscopic appearance of the intestinal lining, while also offering patients the potential for response and remission without the need for steroids,” said William J. Sandborn, MD, chief of the division of gastroenterology and professor of medicine at University of California, San Diego, and a study investigator.

Because of ustekinumab’s effects on the immune system, it may increase the risk of serious infection; as such, patients and health care professionals should discuss any signs of infection before initiation and continue discussions afterward. There are also concerns about risks of cancers, serious allergic reactions, and lung inflammation.

Full prescribing information is available on the Janssen website, as is the full press release regarding the approval

[email protected]

The Food and Drug Administration has approved ustekinumab (Stelara) for the treatment of moderate to severe ulcerative colitis in adults aged 18 years and older, according to a release from Janssen. This is the human interleukin-12 and IL-23 antagonist’s fourth indication since it was first approved by the FDA in 2009.

Olivier Le Moal/Getty Images

The approval is based on findings from the phase 3 UNIFI clinical trial, which achieved its primary endpoint of clinical remission over the course of both induction and maintenance. The 8-week induction study saw 19% of patients achieve clinical remission and 58% demonstrating clinical response; at the 1 year mark, after 44 weeks of maintenance therapy, 43% of patients were in clinical remission without steroids. The trial also assessed a novel histologic-endoscopic mucosal improvement endpoint that examined cellular improvement through both histologic examination and images observed during colonoscopy; 17% of treated patients achieved this endpoint at week 8, and 44% had by 1 year.

“The FDA approval of Stelara for [ulcerative colitis] represents an exciting milestone, offering patients a new option that has demonstrated improvement of the histology and endoscopic appearance of the intestinal lining, while also offering patients the potential for response and remission without the need for steroids,” said William J. Sandborn, MD, chief of the division of gastroenterology and professor of medicine at University of California, San Diego, and a study investigator.

Because of ustekinumab’s effects on the immune system, it may increase the risk of serious infection; as such, patients and health care professionals should discuss any signs of infection before initiation and continue discussions afterward. There are also concerns about risks of cancers, serious allergic reactions, and lung inflammation.

Full prescribing information is available on the Janssen website, as is the full press release regarding the approval

[email protected]

The Food and Drug Administration has approved ustekinumab (Stelara) for the treatment of moderate to severe ulcerative colitis in adults aged 18 years and older, according to a release from Janssen. This is the human interleukin-12 and IL-23 antagonist’s fourth indication since it was first approved by the FDA in 2009.

Olivier Le Moal/Getty Images

The approval is based on findings from the phase 3 UNIFI clinical trial, which achieved its primary endpoint of clinical remission over the course of both induction and maintenance. The 8-week induction study saw 19% of patients achieve clinical remission and 58% demonstrating clinical response; at the 1 year mark, after 44 weeks of maintenance therapy, 43% of patients were in clinical remission without steroids. The trial also assessed a novel histologic-endoscopic mucosal improvement endpoint that examined cellular improvement through both histologic examination and images observed during colonoscopy; 17% of treated patients achieved this endpoint at week 8, and 44% had by 1 year.

“The FDA approval of Stelara for [ulcerative colitis] represents an exciting milestone, offering patients a new option that has demonstrated improvement of the histology and endoscopic appearance of the intestinal lining, while also offering patients the potential for response and remission without the need for steroids,” said William J. Sandborn, MD, chief of the division of gastroenterology and professor of medicine at University of California, San Diego, and a study investigator.

Because of ustekinumab’s effects on the immune system, it may increase the risk of serious infection; as such, patients and health care professionals should discuss any signs of infection before initiation and continue discussions afterward. There are also concerns about risks of cancers, serious allergic reactions, and lung inflammation.

Full prescribing information is available on the Janssen website, as is the full press release regarding the approval

[email protected]

A diet low in fermentable carbohydrates can reduce gut symptoms related to inflammatory bowel disease (IBD), according to a study by U.K. researchers.

Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) occur in a number of common foods, including certain fruits, vegetables, and dairy products. They can draw increased water to the gut, and through microbial fermentation increase hydrogen in the colon.

While previous research has shown that a low-FODMAP diet can relieve gut symptoms such as swelling and flatulence in people with irritable bowel syndrome, the diet has been little studied in IBD patients, for whom gut symptoms often persist even in the absence of gastrointestinal inflammation. In a study published in Gastroenterology, Selina Cox, MD, of King’s College, London, and colleagues randomized 52 people with ulcerative colitis or Crohn’s disease with persistent gut symptoms but without active inflammation to 4 weeks on a low-FODMAP diet (n = 27) or a control diet comprising sham dietary advice (n = 25). Investigators were not blinded to treatment allocation.

At 4 weeks, Dr. Cox and her colleagues reported more patients on the low-FODMAP diet reported “adequate” relief of gut symptoms (52% vs. 16%, P = .007), and saw slight improvements in health-related quality of life scores, compared with the control group. Patient-reported flatulence and bloating were significantly lower in the treatment group, while few other symptom-specific differences were seen between groups.

Stool samples collected at baseline and at the study’s endpoint showed significantly reduced abundance of three types of gut bacteria thought to have a role in immune response – Bifidobacterium adolescentis, B longum, and Faecalibacterium prausnitzii – compared with control subjects. But there were no significant between-group differences in bacterial diversity or in biomarkers of inflammation.

“A major strength of this trial is that low-FODMAP dietary advice was compared to sham dietary advice, providing the first placebo-controlled evidence of effectiveness in IBD,” the researchers wrote in their analysis. Weaknesses of the study include its single-blinded design and inability to control for nutritional alterations related to the low-FODMAP diet.

Ms. Cox and her colleagues recommended a 4-week low-FODMAP diet along with “expert advice and intensive follow-up” for the management of gut symptoms in IBD, but cautioned that longer-term use may not be appropriate.

The study was funded by the U.S.-based Kenneth Rainin Foundation. Two of Dr. Cox’s coauthors declared financial conflicts of interest from a patent on a mobile application to support the low-FODMAP diet; the study’s corresponding author, Kevin Whelan, PhD, additionally reported receiving fees or research support from food and nutrition firms.

SOURCE: Cox S et al. Gastroenterology 2019. doi: 10.1053/j.gastro.2019.09.024.

AGA’s patient education can help your patients better understand the low-FODMAP diet. Learn more at https://www.gastro.org/practice-guidance/gi-patient-center/topic/low-fodmap-diet.

A diet low in fermentable carbohydrates can reduce gut symptoms related to inflammatory bowel disease (IBD), according to a study by U.K. researchers.

Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) occur in a number of common foods, including certain fruits, vegetables, and dairy products. They can draw increased water to the gut, and through microbial fermentation increase hydrogen in the colon.

While previous research has shown that a low-FODMAP diet can relieve gut symptoms such as swelling and flatulence in people with irritable bowel syndrome, the diet has been little studied in IBD patients, for whom gut symptoms often persist even in the absence of gastrointestinal inflammation. In a study published in Gastroenterology, Selina Cox, MD, of King’s College, London, and colleagues randomized 52 people with ulcerative colitis or Crohn’s disease with persistent gut symptoms but without active inflammation to 4 weeks on a low-FODMAP diet (n = 27) or a control diet comprising sham dietary advice (n = 25). Investigators were not blinded to treatment allocation.

At 4 weeks, Dr. Cox and her colleagues reported more patients on the low-FODMAP diet reported “adequate” relief of gut symptoms (52% vs. 16%, P = .007), and saw slight improvements in health-related quality of life scores, compared with the control group. Patient-reported flatulence and bloating were significantly lower in the treatment group, while few other symptom-specific differences were seen between groups.

Stool samples collected at baseline and at the study’s endpoint showed significantly reduced abundance of three types of gut bacteria thought to have a role in immune response – Bifidobacterium adolescentis, B longum, and Faecalibacterium prausnitzii – compared with control subjects. But there were no significant between-group differences in bacterial diversity or in biomarkers of inflammation.

“A major strength of this trial is that low-FODMAP dietary advice was compared to sham dietary advice, providing the first placebo-controlled evidence of effectiveness in IBD,” the researchers wrote in their analysis. Weaknesses of the study include its single-blinded design and inability to control for nutritional alterations related to the low-FODMAP diet.

Ms. Cox and her colleagues recommended a 4-week low-FODMAP diet along with “expert advice and intensive follow-up” for the management of gut symptoms in IBD, but cautioned that longer-term use may not be appropriate.

The study was funded by the U.S.-based Kenneth Rainin Foundation. Two of Dr. Cox’s coauthors declared financial conflicts of interest from a patent on a mobile application to support the low-FODMAP diet; the study’s corresponding author, Kevin Whelan, PhD, additionally reported receiving fees or research support from food and nutrition firms.

SOURCE: Cox S et al. Gastroenterology 2019. doi: 10.1053/j.gastro.2019.09.024.

AGA’s patient education can help your patients better understand the low-FODMAP diet. Learn more at https://www.gastro.org/practice-guidance/gi-patient-center/topic/low-fodmap-diet.

A diet low in fermentable carbohydrates can reduce gut symptoms related to inflammatory bowel disease (IBD), according to a study by U.K. researchers.

Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) occur in a number of common foods, including certain fruits, vegetables, and dairy products. They can draw increased water to the gut, and through microbial fermentation increase hydrogen in the colon.

While previous research has shown that a low-FODMAP diet can relieve gut symptoms such as swelling and flatulence in people with irritable bowel syndrome, the diet has been little studied in IBD patients, for whom gut symptoms often persist even in the absence of gastrointestinal inflammation. In a study published in Gastroenterology, Selina Cox, MD, of King’s College, London, and colleagues randomized 52 people with ulcerative colitis or Crohn’s disease with persistent gut symptoms but without active inflammation to 4 weeks on a low-FODMAP diet (n = 27) or a control diet comprising sham dietary advice (n = 25). Investigators were not blinded to treatment allocation.

At 4 weeks, Dr. Cox and her colleagues reported more patients on the low-FODMAP diet reported “adequate” relief of gut symptoms (52% vs. 16%, P = .007), and saw slight improvements in health-related quality of life scores, compared with the control group. Patient-reported flatulence and bloating were significantly lower in the treatment group, while few other symptom-specific differences were seen between groups.

Stool samples collected at baseline and at the study’s endpoint showed significantly reduced abundance of three types of gut bacteria thought to have a role in immune response – Bifidobacterium adolescentis, B longum, and Faecalibacterium prausnitzii – compared with control subjects. But there were no significant between-group differences in bacterial diversity or in biomarkers of inflammation.

“A major strength of this trial is that low-FODMAP dietary advice was compared to sham dietary advice, providing the first placebo-controlled evidence of effectiveness in IBD,” the researchers wrote in their analysis. Weaknesses of the study include its single-blinded design and inability to control for nutritional alterations related to the low-FODMAP diet.

Ms. Cox and her colleagues recommended a 4-week low-FODMAP diet along with “expert advice and intensive follow-up” for the management of gut symptoms in IBD, but cautioned that longer-term use may not be appropriate.

The study was funded by the U.S.-based Kenneth Rainin Foundation. Two of Dr. Cox’s coauthors declared financial conflicts of interest from a patent on a mobile application to support the low-FODMAP diet; the study’s corresponding author, Kevin Whelan, PhD, additionally reported receiving fees or research support from food and nutrition firms.

SOURCE: Cox S et al. Gastroenterology 2019. doi: 10.1053/j.gastro.2019.09.024.

AGA’s patient education can help your patients better understand the low-FODMAP diet. Learn more at https://www.gastro.org/practice-guidance/gi-patient-center/topic/low-fodmap-diet.

An online assessment tool can be used to identify patients with inflammatory bowel disease (IBD) who are receiving an excess of corticosteroids, and a quality improvement plan lowered the use of excess corticosteroids, according to recent research in the journal Alimentary Pharmacology & Therapeutics.

Since measurement of excess corticosteroid use can be measured through an online assessment tool in clinical practice and long-term corticosteroid use is associated with adverse outcomes, it may be a quality marker for patients with IBD, wrote Christian P. Selinger, MD, from the Leeds (England) Gastroenterology Institute and colleagues. “Such key performance indicators have previously been lacking in IBD, unlike other disease areas such as diabetes and cardiovascular disease.”

Over a period of 3 months, Dr. Selinger and colleagues collected prospective data from 2,385 patients with IBD at 19 centers in England, Wales, and Scotland who had received steroids within the last year. The researchers divided the centers into groups based on whether they participated in the quality improvement program (7 centers), were new to the process of collecting data on steroid use (11 centers), or did not participate in the program (1 center). The seven centers that participated in the intervention were part of an audit that began in 2017, while the other centers were evaluated over a 3-month period between April and July 2017. Patients were asked questions about their steroid use, including whether the steroids were prescribed for their IBD, how long the course of steroids was, how many courses of steroids they received, and if they were able to stop using steroids without their symptoms returning.

The researchers found 14.8% of patients had an excess of steroids or were dependent on steroids, and patients at centers that participated in the quality improvement programs had a lower rate of exposure (23.8% vs. 31.0%; P less than .001) and a lower rate of steroid excess (11.5% vs. 17.1%; P less than .001) than did patients at sites that did not participate in the program. Centers with the improvement program also had steroid use decrease over time, from 30.0% in 2015 to 23.8% in 2017 (P = .003), and steroid excess also decreased from 13.8% at those centers to 11.5% during that time (P equals .17). The researchers noted that, in over half of cases (50.7%), the steroid excess was “avoidable.”

In patients with Crohn’s disease, those who had reduced steroid excess were more likely to be part of an intervention center (odds ratio, 0.72; 95% confidence interval, 0.46-0.97), at a center with a multidisciplinary team (OR, 0.54; 95% CI, 0.20-0.86), or receiving maintenance anti–tumor necrosis factor therapy (OR, 0.61; 95% CI, 0.24-0.95); in contrast, patients who received aminosalicylate were more likely to have steroid excess (OR, 1.72; 95% CI, 1.24-2.09). Steroid excess in ulcerative colitis (UC) patients was more likely among those receiving thiopurine monotherapy (OR, 1.97; 95% CI, 1.19‐3.01), while UC patients at an intervention center were less likely to have steroid excess (OR; 0.72; 95% CI, 0.45‐0.95).

The researchers said the online assessment is limited in assessing the reason for steroid excess and is unable to consider variables such as patient age, sex, IBD phenotype, and disease duration, but is a “simple, pragmatic tool” that can be used in real time in a clinical setting.

“This advances the case for steroid excess as a potential key performance indicator of quality in an IBD service, although in order for clinicians to benchmark their service and provide targets for improvements, any numerical goal attached to this key performance indicator would require consideration of case mix. Further data, including from national and international contexts, is needed,” concluded Dr. Selinger and colleagues.

The authors reported AbbVie provided the funding to develop the steroid assessment tool, as well as honoraria for invited attendees of the quality improvement plan, which the company also sponsored.

To help your patients better understand their treatment options, share AGA’s IBD patient education, which is online at www.gastro.org/practice-guidance/gi-patient-center/topic/inflammatory-bowel-disease. 

SOURCE: Selinger CP et al. Aliment Pharmacol Ther. 2019. doi: 10.1111/apt.15497.

An online assessment tool can be used to identify patients with inflammatory bowel disease (IBD) who are receiving an excess of corticosteroids, and a quality improvement plan lowered the use of excess corticosteroids, according to recent research in the journal Alimentary Pharmacology & Therapeutics.

Since measurement of excess corticosteroid use can be measured through an online assessment tool in clinical practice and long-term corticosteroid use is associated with adverse outcomes, it may be a quality marker for patients with IBD, wrote Christian P. Selinger, MD, from the Leeds (England) Gastroenterology Institute and colleagues. “Such key performance indicators have previously been lacking in IBD, unlike other disease areas such as diabetes and cardiovascular disease.”

Over a period of 3 months, Dr. Selinger and colleagues collected prospective data from 2,385 patients with IBD at 19 centers in England, Wales, and Scotland who had received steroids within the last year. The researchers divided the centers into groups based on whether they participated in the quality improvement program (7 centers), were new to the process of collecting data on steroid use (11 centers), or did not participate in the program (1 center). The seven centers that participated in the intervention were part of an audit that began in 2017, while the other centers were evaluated over a 3-month period between April and July 2017. Patients were asked questions about their steroid use, including whether the steroids were prescribed for their IBD, how long the course of steroids was, how many courses of steroids they received, and if they were able to stop using steroids without their symptoms returning.

The researchers found 14.8% of patients had an excess of steroids or were dependent on steroids, and patients at centers that participated in the quality improvement programs had a lower rate of exposure (23.8% vs. 31.0%; P less than .001) and a lower rate of steroid excess (11.5% vs. 17.1%; P less than .001) than did patients at sites that did not participate in the program. Centers with the improvement program also had steroid use decrease over time, from 30.0% in 2015 to 23.8% in 2017 (P = .003), and steroid excess also decreased from 13.8% at those centers to 11.5% during that time (P equals .17). The researchers noted that, in over half of cases (50.7%), the steroid excess was “avoidable.”

In patients with Crohn’s disease, those who had reduced steroid excess were more likely to be part of an intervention center (odds ratio, 0.72; 95% confidence interval, 0.46-0.97), at a center with a multidisciplinary team (OR, 0.54; 95% CI, 0.20-0.86), or receiving maintenance anti–tumor necrosis factor therapy (OR, 0.61; 95% CI, 0.24-0.95); in contrast, patients who received aminosalicylate were more likely to have steroid excess (OR, 1.72; 95% CI, 1.24-2.09). Steroid excess in ulcerative colitis (UC) patients was more likely among those receiving thiopurine monotherapy (OR, 1.97; 95% CI, 1.19‐3.01), while UC patients at an intervention center were less likely to have steroid excess (OR; 0.72; 95% CI, 0.45‐0.95).

The researchers said the online assessment is limited in assessing the reason for steroid excess and is unable to consider variables such as patient age, sex, IBD phenotype, and disease duration, but is a “simple, pragmatic tool” that can be used in real time in a clinical setting.

“This advances the case for steroid excess as a potential key performance indicator of quality in an IBD service, although in order for clinicians to benchmark their service and provide targets for improvements, any numerical goal attached to this key performance indicator would require consideration of case mix. Further data, including from national and international contexts, is needed,” concluded Dr. Selinger and colleagues.

The authors reported AbbVie provided the funding to develop the steroid assessment tool, as well as honoraria for invited attendees of the quality improvement plan, which the company also sponsored.

To help your patients better understand their treatment options, share AGA’s IBD patient education, which is online at www.gastro.org/practice-guidance/gi-patient-center/topic/inflammatory-bowel-disease. 

SOURCE: Selinger CP et al. Aliment Pharmacol Ther. 2019. doi: 10.1111/apt.15497.

An online assessment tool can be used to identify patients with inflammatory bowel disease (IBD) who are receiving an excess of corticosteroids, and a quality improvement plan lowered the use of excess corticosteroids, according to recent research in the journal Alimentary Pharmacology & Therapeutics.

Since measurement of excess corticosteroid use can be measured through an online assessment tool in clinical practice and long-term corticosteroid use is associated with adverse outcomes, it may be a quality marker for patients with IBD, wrote Christian P. Selinger, MD, from the Leeds (England) Gastroenterology Institute and colleagues. “Such key performance indicators have previously been lacking in IBD, unlike other disease areas such as diabetes and cardiovascular disease.”

Over a period of 3 months, Dr. Selinger and colleagues collected prospective data from 2,385 patients with IBD at 19 centers in England, Wales, and Scotland who had received steroids within the last year. The researchers divided the centers into groups based on whether they participated in the quality improvement program (7 centers), were new to the process of collecting data on steroid use (11 centers), or did not participate in the program (1 center). The seven centers that participated in the intervention were part of an audit that began in 2017, while the other centers were evaluated over a 3-month period between April and July 2017. Patients were asked questions about their steroid use, including whether the steroids were prescribed for their IBD, how long the course of steroids was, how many courses of steroids they received, and if they were able to stop using steroids without their symptoms returning.

The researchers found 14.8% of patients had an excess of steroids or were dependent on steroids, and patients at centers that participated in the quality improvement programs had a lower rate of exposure (23.8% vs. 31.0%; P less than .001) and a lower rate of steroid excess (11.5% vs. 17.1%; P less than .001) than did patients at sites that did not participate in the program. Centers with the improvement program also had steroid use decrease over time, from 30.0% in 2015 to 23.8% in 2017 (P = .003), and steroid excess also decreased from 13.8% at those centers to 11.5% during that time (P equals .17). The researchers noted that, in over half of cases (50.7%), the steroid excess was “avoidable.”

In patients with Crohn’s disease, those who had reduced steroid excess were more likely to be part of an intervention center (odds ratio, 0.72; 95% confidence interval, 0.46-0.97), at a center with a multidisciplinary team (OR, 0.54; 95% CI, 0.20-0.86), or receiving maintenance anti–tumor necrosis factor therapy (OR, 0.61; 95% CI, 0.24-0.95); in contrast, patients who received aminosalicylate were more likely to have steroid excess (OR, 1.72; 95% CI, 1.24-2.09). Steroid excess in ulcerative colitis (UC) patients was more likely among those receiving thiopurine monotherapy (OR, 1.97; 95% CI, 1.19‐3.01), while UC patients at an intervention center were less likely to have steroid excess (OR; 0.72; 95% CI, 0.45‐0.95).

The researchers said the online assessment is limited in assessing the reason for steroid excess and is unable to consider variables such as patient age, sex, IBD phenotype, and disease duration, but is a “simple, pragmatic tool” that can be used in real time in a clinical setting.

“This advances the case for steroid excess as a potential key performance indicator of quality in an IBD service, although in order for clinicians to benchmark their service and provide targets for improvements, any numerical goal attached to this key performance indicator would require consideration of case mix. Further data, including from national and international contexts, is needed,” concluded Dr. Selinger and colleagues.

The authors reported AbbVie provided the funding to develop the steroid assessment tool, as well as honoraria for invited attendees of the quality improvement plan, which the company also sponsored.

To help your patients better understand their treatment options, share AGA’s IBD patient education, which is online at www.gastro.org/practice-guidance/gi-patient-center/topic/inflammatory-bowel-disease. 

SOURCE: Selinger CP et al. Aliment Pharmacol Ther. 2019. doi: 10.1111/apt.15497.

At least 50% of patients with irritable bowel syndrome (IBS) described their condition as “extremely bothersome” based on survey data from 3,254 individuals. However, differences in the nature of other symptoms among IBS subtypes, namely IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C), have not been well studied, wrote Sarah Ballou, PhD, of Beth Israel Deaconess Medical Center, Boston, and colleagues.

Source: American Gastroenterological Association

In a study published in Clinical Gastroenterology and Hepatology, the researchers reviewed survey results from 1,587 individuals with IBS-D and 1,667 with IBS-C. The average age of the patients was 47 years, 81% were female, and 90% were white.

Approximately 84% of patients with IBS-C and 93% of those with IBS-D reported abdominal pain, the most common symptom in both groups. Overall, 36% of the 1,885 patients employed or in school reported decreased productivity in those settings.

IBS-C patients were significantly more likely to report that their symptoms caused them to avoid sex, feel self-conscious about their bodies, have trouble concentrating, and feel “not like myself,” compared with IBS-D patients (P less than .004 for all).

IBS-D patients were significantly more likely to report that their symptoms caused them to avoid traveling in general, avoid places without bathrooms, avoid leaving the house, and have trouble making plans, compared with IBS-C patients (P less than .004 for all).

The survey also asked respondents what they would give up for 1 month in exchange for 1 month of relief from IBS symptoms. Overall, approximately 60% said they would give up alcohol, 55% said they would give up caffeine, 40% would give up sex, 24.5% would give up their cell phones, and 21.5% would give up the internet, the researchers wrote.

The study findings were limited by several factors, including the absence of survey respondents with mixed-type IBS, the reliance on self-reports, and the potential for recall bias. Also, the study was not designed to assess the impact of other comorbidities and did not include non-IBS controls, the researchers noted.

However, the results suggest that patients with different IBS subtypes struggle differently in areas of daily function, which has implications for treatment, they wrote.

“This study highlights important differences between IBS-C and IBS-D, which could impact the development and refinement of mind-body therapies for IBS, with tailored treatment goals for each IBS subtype. For example, treatment tailored specifically for IBS-D may be more behaviorally focused (e.g., exposure to specific situations outside the home) while treatment for IBS-C may be more cognitively focused (e.g., evaluating self-esteem and beliefs about self and others) in addition to targeting the bowel dysfunction and pain,” they concluded.

The researchers had no financial conflicts to disclose.

SOURCE: Ballou S et al. Clin Gastroenterol Hepatol. 2019 Aug 13. doi: 10.1016/j.cgh.2019.08.016.

At least 50% of patients with irritable bowel syndrome (IBS) described their condition as “extremely bothersome” based on survey data from 3,254 individuals. However, differences in the nature of other symptoms among IBS subtypes, namely IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C), have not been well studied, wrote Sarah Ballou, PhD, of Beth Israel Deaconess Medical Center, Boston, and colleagues.

Source: American Gastroenterological Association

In a study published in Clinical Gastroenterology and Hepatology, the researchers reviewed survey results from 1,587 individuals with IBS-D and 1,667 with IBS-C. The average age of the patients was 47 years, 81% were female, and 90% were white.

Approximately 84% of patients with IBS-C and 93% of those with IBS-D reported abdominal pain, the most common symptom in both groups. Overall, 36% of the 1,885 patients employed or in school reported decreased productivity in those settings.

IBS-C patients were significantly more likely to report that their symptoms caused them to avoid sex, feel self-conscious about their bodies, have trouble concentrating, and feel “not like myself,” compared with IBS-D patients (P less than .004 for all).

IBS-D patients were significantly more likely to report that their symptoms caused them to avoid traveling in general, avoid places without bathrooms, avoid leaving the house, and have trouble making plans, compared with IBS-C patients (P less than .004 for all).

The survey also asked respondents what they would give up for 1 month in exchange for 1 month of relief from IBS symptoms. Overall, approximately 60% said they would give up alcohol, 55% said they would give up caffeine, 40% would give up sex, 24.5% would give up their cell phones, and 21.5% would give up the internet, the researchers wrote.

The study findings were limited by several factors, including the absence of survey respondents with mixed-type IBS, the reliance on self-reports, and the potential for recall bias. Also, the study was not designed to assess the impact of other comorbidities and did not include non-IBS controls, the researchers noted.

However, the results suggest that patients with different IBS subtypes struggle differently in areas of daily function, which has implications for treatment, they wrote.

“This study highlights important differences between IBS-C and IBS-D, which could impact the development and refinement of mind-body therapies for IBS, with tailored treatment goals for each IBS subtype. For example, treatment tailored specifically for IBS-D may be more behaviorally focused (e.g., exposure to specific situations outside the home) while treatment for IBS-C may be more cognitively focused (e.g., evaluating self-esteem and beliefs about self and others) in addition to targeting the bowel dysfunction and pain,” they concluded.

The researchers had no financial conflicts to disclose.

SOURCE: Ballou S et al. Clin Gastroenterol Hepatol. 2019 Aug 13. doi: 10.1016/j.cgh.2019.08.016.

At least 50% of patients with irritable bowel syndrome (IBS) described their condition as “extremely bothersome” based on survey data from 3,254 individuals. However, differences in the nature of other symptoms among IBS subtypes, namely IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C), have not been well studied, wrote Sarah Ballou, PhD, of Beth Israel Deaconess Medical Center, Boston, and colleagues.

Source: American Gastroenterological Association

In a study published in Clinical Gastroenterology and Hepatology, the researchers reviewed survey results from 1,587 individuals with IBS-D and 1,667 with IBS-C. The average age of the patients was 47 years, 81% were female, and 90% were white.

Approximately 84% of patients with IBS-C and 93% of those with IBS-D reported abdominal pain, the most common symptom in both groups. Overall, 36% of the 1,885 patients employed or in school reported decreased productivity in those settings.

IBS-C patients were significantly more likely to report that their symptoms caused them to avoid sex, feel self-conscious about their bodies, have trouble concentrating, and feel “not like myself,” compared with IBS-D patients (P less than .004 for all).

IBS-D patients were significantly more likely to report that their symptoms caused them to avoid traveling in general, avoid places without bathrooms, avoid leaving the house, and have trouble making plans, compared with IBS-C patients (P less than .004 for all).

The survey also asked respondents what they would give up for 1 month in exchange for 1 month of relief from IBS symptoms. Overall, approximately 60% said they would give up alcohol, 55% said they would give up caffeine, 40% would give up sex, 24.5% would give up their cell phones, and 21.5% would give up the internet, the researchers wrote.

The study findings were limited by several factors, including the absence of survey respondents with mixed-type IBS, the reliance on self-reports, and the potential for recall bias. Also, the study was not designed to assess the impact of other comorbidities and did not include non-IBS controls, the researchers noted.

However, the results suggest that patients with different IBS subtypes struggle differently in areas of daily function, which has implications for treatment, they wrote.

“This study highlights important differences between IBS-C and IBS-D, which could impact the development and refinement of mind-body therapies for IBS, with tailored treatment goals for each IBS subtype. For example, treatment tailored specifically for IBS-D may be more behaviorally focused (e.g., exposure to specific situations outside the home) while treatment for IBS-C may be more cognitively focused (e.g., evaluating self-esteem and beliefs about self and others) in addition to targeting the bowel dysfunction and pain,” they concluded.

The researchers had no financial conflicts to disclose.

SOURCE: Ballou S et al. Clin Gastroenterol Hepatol. 2019 Aug 13. doi: 10.1016/j.cgh.2019.08.016.

Clinical evidence supporting the use of alternative biologic treatments and regimens for ulcerative colitis in patients who are unable to receive anti–tumor necrosis factor (TNF) therapies is beginning to emerge.

In one of two such trials published in The New England Journal of Medicine on Sept. 26, 2019, researchers led by Bruce E. Sands, MD, of the Icahn School of Medicine at Mount Sinai, New York, and associates evaluated ustekinumab as an 8-week induction therapy and a 44-week maintenance therapy in patients with moderate to severe ulcerative colitis (N Engl J Med 2019 Sep 25 doi: 10/1056/NEJMoa1900750). For the phase 3 trial, known as UNIFI, researchers randomly assigned 961 patients to receive an intravenous induction dose of ustekinumab over the course of 8 weeks (320 to a dose of 130 mg and 322 to a weight-range–based dose that approximated 6 mg per kilogram of body weight), while the remaining 319 received placebo. Patients who responded to induction therapy were randomly assigned to a 44-week maintenance phase in which they received subcutaneous maintenance injections of 90 mg of ustekinumab (172 to injections every 12 weeks, 176 to injections every 8 weeks, and 175 to placebo). The primary endpoint for both phases of the trial was clinical remission, defined as a total score of 2 or lower on the Mayo scale, and no subscore greater than 1 on any of the four Mayo scale components.

Dr. Sands and his colleagues found that at week 8, clinical remission was achieved in 15.6% of patients in the 130-mg ustekinumab infusion group, compared with 15.5% in the 6-mg per kg of body weight group, and 5.3% of those in the placebo group. “The percentages of patients who met major secondary endpoints or had histo-endoscopic mucosal healing were significantly higher in both ustekinumab groups than in the placebo group,” the researchers wrote. “Through week 8, the median changes from baseline in the IBDQ [Inflammatory Bowel Disease Questionnaire] score were significantly greater in both ustekinumab groups than in the placebo group.”

Meanwhile, at week 44, clinical remission was achieved in 38.4% of patients in the group receiving 90-mg subcutaneous ustekinumab every 12 weeks, compared with 43.8% of those in the group receiving 90 mg every 8 weeks, and 24% of those in the placebo group. “The percentages of patients with maintenance of clinical response through week 44, endoscopic improvement at week 44, or corticosteroid-free clinical remission (with either definition of clinical remission) at week 44 were significantly higher in both ustekinumab groups than in the placebo group,” the researchers wrote.

When they evaluated other endpoints, Dr. Sands and his colleagues observed that improvements in partial Mayo scores and reductions in serum and fecal concentrations of inflammatory biomarkers that occurred with induction were sustained through week 44. “Although our findings suggest that ustekinumab was effective in patients with or without previous treatment failure with biologics for both induction and maintenance therapy, the percentages of patients in whom each endpoint was achieved were lower across groups with previous treatment failure with biologics,” they wrote.

In the second study, known as VARSITY, researchers led by Dr. Sands conducted a randomized, phase 3b, head-to-head trial comparing vedolizumab with adalimumab in 769 adults with moderate to severe ulcerative colitis, in an effort to determine if vedolizumab is superior after 52 weeks of treatment (N Engl J Med 2019 Sep 25. doi: 10/1056/NEJMoa1905725). They assigned patients to receive IV infusions of 300 mg of vedolizumab on day 1 and at weeks 2, 6, 14, 22, 30, 38, and 46 (plus injections of placebo) or subcutaneous injections of 40 mg of adalimumab, with a total dose of 160 mg at week 1, 80 mg at week 2, and 40 mg every 2 weeks thereafter until week 50 (plus infusions of placebo). The primary endpoint was clinical remission, defined as a total score of 2 or lower on the Mayo scale, and no subscore greater than 1 on any of the four Mayo scale components.

At week 52, the researchers found that 31.3% of patients in the vedolizumab group achieved clinical remission, compared with 22.5% of those in the adalimumab group, while a higher percentage of patients in the vedolizumab group demonstrated endoscopic involvement (the first secondary outcome), compared with their counterparts in the adalimumab group (39.7% vs. 27.7%, respectively). Treatment effects were more pronounced in patients who had not previously used a TNF inhibitor.

In contrast, Dr. Sands and colleagues reported that at week 52, corticosteroid-free clinical remission was observed in 12.6% of patients in the vedolizumab group, compared with 21.8% of their counterparts in the adalimumab group. “It is difficult to explain the inconsistency of the results between this secondary remission outcome and the primary remission outcome,” they wrote. “The trial did not require a specific schedule for corticosteroid tapering, which can vary among practitioners. However, this limitation should not have resulted in differential effects in the two treatment groups.”

They noted that dosing regimens used in VARSITY were based on a conservative approach and use according to U.S. labels. “Real-world studies have shown improved efficacy outcomes after dose intensification in both adalimumab and vedolizumab therapies,” they wrote. “Data from ongoing trials of adalimumab (NCT02065622) and vedolizumab (NCT03029143) may further characterize the effect of higher doses on efficacy outcomes.”

UNIFI was funded by Janssen Research and Development. Dr. Sands disclosed that the Icahn School of Medicine received an institutional grant from Janssen to conduct the study. VARSITY was funded with support from Takeda. Dr. Sands reported that he received grant support and consulting fees from Takeda. Dr. Sands and coauthors reported having financial ties to many other companies in the pharmaceutical and biotechnology industries.

[email protected]

SOURCE: Sands B et al. N Engl J Med. 2019 Sep 25 doi: 10/1056/NEJMoa1900750; N Engl J Med. 2019 Sep 25 doi:.10/1056/NEJMoa1905725.

Clinical evidence supporting the use of alternative biologic treatments and regimens for ulcerative colitis in patients who are unable to receive anti–tumor necrosis factor (TNF) therapies is beginning to emerge.

In one of two such trials published in The New England Journal of Medicine on Sept. 26, 2019, researchers led by Bruce E. Sands, MD, of the Icahn School of Medicine at Mount Sinai, New York, and associates evaluated ustekinumab as an 8-week induction therapy and a 44-week maintenance therapy in patients with moderate to severe ulcerative colitis (N Engl J Med 2019 Sep 25 doi: 10/1056/NEJMoa1900750). For the phase 3 trial, known as UNIFI, researchers randomly assigned 961 patients to receive an intravenous induction dose of ustekinumab over the course of 8 weeks (320 to a dose of 130 mg and 322 to a weight-range–based dose that approximated 6 mg per kilogram of body weight), while the remaining 319 received placebo. Patients who responded to induction therapy were randomly assigned to a 44-week maintenance phase in which they received subcutaneous maintenance injections of 90 mg of ustekinumab (172 to injections every 12 weeks, 176 to injections every 8 weeks, and 175 to placebo). The primary endpoint for both phases of the trial was clinical remission, defined as a total score of 2 or lower on the Mayo scale, and no subscore greater than 1 on any of the four Mayo scale components.

Dr. Sands and his colleagues found that at week 8, clinical remission was achieved in 15.6% of patients in the 130-mg ustekinumab infusion group, compared with 15.5% in the 6-mg per kg of body weight group, and 5.3% of those in the placebo group. “The percentages of patients who met major secondary endpoints or had histo-endoscopic mucosal healing were significantly higher in both ustekinumab groups than in the placebo group,” the researchers wrote. “Through week 8, the median changes from baseline in the IBDQ [Inflammatory Bowel Disease Questionnaire] score were significantly greater in both ustekinumab groups than in the placebo group.”

Meanwhile, at week 44, clinical remission was achieved in 38.4% of patients in the group receiving 90-mg subcutaneous ustekinumab every 12 weeks, compared with 43.8% of those in the group receiving 90 mg every 8 weeks, and 24% of those in the placebo group. “The percentages of patients with maintenance of clinical response through week 44, endoscopic improvement at week 44, or corticosteroid-free clinical remission (with either definition of clinical remission) at week 44 were significantly higher in both ustekinumab groups than in the placebo group,” the researchers wrote.

When they evaluated other endpoints, Dr. Sands and his colleagues observed that improvements in partial Mayo scores and reductions in serum and fecal concentrations of inflammatory biomarkers that occurred with induction were sustained through week 44. “Although our findings suggest that ustekinumab was effective in patients with or without previous treatment failure with biologics for both induction and maintenance therapy, the percentages of patients in whom each endpoint was achieved were lower across groups with previous treatment failure with biologics,” they wrote.

In the second study, known as VARSITY, researchers led by Dr. Sands conducted a randomized, phase 3b, head-to-head trial comparing vedolizumab with adalimumab in 769 adults with moderate to severe ulcerative colitis, in an effort to determine if vedolizumab is superior after 52 weeks of treatment (N Engl J Med 2019 Sep 25. doi: 10/1056/NEJMoa1905725). They assigned patients to receive IV infusions of 300 mg of vedolizumab on day 1 and at weeks 2, 6, 14, 22, 30, 38, and 46 (plus injections of placebo) or subcutaneous injections of 40 mg of adalimumab, with a total dose of 160 mg at week 1, 80 mg at week 2, and 40 mg every 2 weeks thereafter until week 50 (plus infusions of placebo). The primary endpoint was clinical remission, defined as a total score of 2 or lower on the Mayo scale, and no subscore greater than 1 on any of the four Mayo scale components.

At week 52, the researchers found that 31.3% of patients in the vedolizumab group achieved clinical remission, compared with 22.5% of those in the adalimumab group, while a higher percentage of patients in the vedolizumab group demonstrated endoscopic involvement (the first secondary outcome), compared with their counterparts in the adalimumab group (39.7% vs. 27.7%, respectively). Treatment effects were more pronounced in patients who had not previously used a TNF inhibitor.

In contrast, Dr. Sands and colleagues reported that at week 52, corticosteroid-free clinical remission was observed in 12.6% of patients in the vedolizumab group, compared with 21.8% of their counterparts in the adalimumab group. “It is difficult to explain the inconsistency of the results between this secondary remission outcome and the primary remission outcome,” they wrote. “The trial did not require a specific schedule for corticosteroid tapering, which can vary among practitioners. However, this limitation should not have resulted in differential effects in the two treatment groups.”

They noted that dosing regimens used in VARSITY were based on a conservative approach and use according to U.S. labels. “Real-world studies have shown improved efficacy outcomes after dose intensification in both adalimumab and vedolizumab therapies,” they wrote. “Data from ongoing trials of adalimumab (NCT02065622) and vedolizumab (NCT03029143) may further characterize the effect of higher doses on efficacy outcomes.”

UNIFI was funded by Janssen Research and Development. Dr. Sands disclosed that the Icahn School of Medicine received an institutional grant from Janssen to conduct the study. VARSITY was funded with support from Takeda. Dr. Sands reported that he received grant support and consulting fees from Takeda. Dr. Sands and coauthors reported having financial ties to many other companies in the pharmaceutical and biotechnology industries.

[email protected]

SOURCE: Sands B et al. N Engl J Med. 2019 Sep 25 doi: 10/1056/NEJMoa1900750; N Engl J Med. 2019 Sep 25 doi:.10/1056/NEJMoa1905725.

Clinical evidence supporting the use of alternative biologic treatments and regimens for ulcerative colitis in patients who are unable to receive anti–tumor necrosis factor (TNF) therapies is beginning to emerge.

In one of two such trials published in The New England Journal of Medicine on Sept. 26, 2019, researchers led by Bruce E. Sands, MD, of the Icahn School of Medicine at Mount Sinai, New York, and associates evaluated ustekinumab as an 8-week induction therapy and a 44-week maintenance therapy in patients with moderate to severe ulcerative colitis (N Engl J Med 2019 Sep 25 doi: 10/1056/NEJMoa1900750). For the phase 3 trial, known as UNIFI, researchers randomly assigned 961 patients to receive an intravenous induction dose of ustekinumab over the course of 8 weeks (320 to a dose of 130 mg and 322 to a weight-range–based dose that approximated 6 mg per kilogram of body weight), while the remaining 319 received placebo. Patients who responded to induction therapy were randomly assigned to a 44-week maintenance phase in which they received subcutaneous maintenance injections of 90 mg of ustekinumab (172 to injections every 12 weeks, 176 to injections every 8 weeks, and 175 to placebo). The primary endpoint for both phases of the trial was clinical remission, defined as a total score of 2 or lower on the Mayo scale, and no subscore greater than 1 on any of the four Mayo scale components.

Dr. Sands and his colleagues found that at week 8, clinical remission was achieved in 15.6% of patients in the 130-mg ustekinumab infusion group, compared with 15.5% in the 6-mg per kg of body weight group, and 5.3% of those in the placebo group. “The percentages of patients who met major secondary endpoints or had histo-endoscopic mucosal healing were significantly higher in both ustekinumab groups than in the placebo group,” the researchers wrote. “Through week 8, the median changes from baseline in the IBDQ [Inflammatory Bowel Disease Questionnaire] score were significantly greater in both ustekinumab groups than in the placebo group.”

Meanwhile, at week 44, clinical remission was achieved in 38.4% of patients in the group receiving 90-mg subcutaneous ustekinumab every 12 weeks, compared with 43.8% of those in the group receiving 90 mg every 8 weeks, and 24% of those in the placebo group. “The percentages of patients with maintenance of clinical response through week 44, endoscopic improvement at week 44, or corticosteroid-free clinical remission (with either definition of clinical remission) at week 44 were significantly higher in both ustekinumab groups than in the placebo group,” the researchers wrote.

When they evaluated other endpoints, Dr. Sands and his colleagues observed that improvements in partial Mayo scores and reductions in serum and fecal concentrations of inflammatory biomarkers that occurred with induction were sustained through week 44. “Although our findings suggest that ustekinumab was effective in patients with or without previous treatment failure with biologics for both induction and maintenance therapy, the percentages of patients in whom each endpoint was achieved were lower across groups with previous treatment failure with biologics,” they wrote.

In the second study, known as VARSITY, researchers led by Dr. Sands conducted a randomized, phase 3b, head-to-head trial comparing vedolizumab with adalimumab in 769 adults with moderate to severe ulcerative colitis, in an effort to determine if vedolizumab is superior after 52 weeks of treatment (N Engl J Med 2019 Sep 25. doi: 10/1056/NEJMoa1905725). They assigned patients to receive IV infusions of 300 mg of vedolizumab on day 1 and at weeks 2, 6, 14, 22, 30, 38, and 46 (plus injections of placebo) or subcutaneous injections of 40 mg of adalimumab, with a total dose of 160 mg at week 1, 80 mg at week 2, and 40 mg every 2 weeks thereafter until week 50 (plus infusions of placebo). The primary endpoint was clinical remission, defined as a total score of 2 or lower on the Mayo scale, and no subscore greater than 1 on any of the four Mayo scale components.

At week 52, the researchers found that 31.3% of patients in the vedolizumab group achieved clinical remission, compared with 22.5% of those in the adalimumab group, while a higher percentage of patients in the vedolizumab group demonstrated endoscopic involvement (the first secondary outcome), compared with their counterparts in the adalimumab group (39.7% vs. 27.7%, respectively). Treatment effects were more pronounced in patients who had not previously used a TNF inhibitor.

In contrast, Dr. Sands and colleagues reported that at week 52, corticosteroid-free clinical remission was observed in 12.6% of patients in the vedolizumab group, compared with 21.8% of their counterparts in the adalimumab group. “It is difficult to explain the inconsistency of the results between this secondary remission outcome and the primary remission outcome,” they wrote. “The trial did not require a specific schedule for corticosteroid tapering, which can vary among practitioners. However, this limitation should not have resulted in differential effects in the two treatment groups.”

They noted that dosing regimens used in VARSITY were based on a conservative approach and use according to U.S. labels. “Real-world studies have shown improved efficacy outcomes after dose intensification in both adalimumab and vedolizumab therapies,” they wrote. “Data from ongoing trials of adalimumab (NCT02065622) and vedolizumab (NCT03029143) may further characterize the effect of higher doses on efficacy outcomes.”

UNIFI was funded by Janssen Research and Development. Dr. Sands disclosed that the Icahn School of Medicine received an institutional grant from Janssen to conduct the study. VARSITY was funded with support from Takeda. Dr. Sands reported that he received grant support and consulting fees from Takeda. Dr. Sands and coauthors reported having financial ties to many other companies in the pharmaceutical and biotechnology industries.

[email protected]

SOURCE: Sands B et al. N Engl J Med. 2019 Sep 25 doi: 10/1056/NEJMoa1900750; N Engl J Med. 2019 Sep 25 doi:.10/1056/NEJMoa1905725.

The subcutaneous (SC) form of vedolizumab is effective, generally safe, and well tolerated as maintenance treatment following intravenous vedolizumab induction in patients with moderately to severely active ulcerative colitis, results from a phase 3, double-blind trial demonstrated.

“The route of drug administration can be an important determinant of a patient’s treatment experience, particularly for chronic diseases such as UC [ulcerative colitis],” investigators led by William J. Sandborn, MD, of the division of gastroenterology and hepatology at the University of California, San Diego, wrote in a study published online in Gastroenterology (doi: 10/1053/j.gastro.2019.08.027). “Intravenous administration of a biologic treatment requires the patient to set time aside and travel to a treatment center for an infusion. In addition, the greater use of a health care facility increases the direct costs of care. Some studies show that even with the option of self-injection some patients may still prefer an IV route of administration for the reassurance provided by the opportunity for interacting with a health care professional or because they are averse to self-injection. The availability of both an SC and IV injection of vedolizumab will enable patients to choose the route of administration for maintenance treatment.”

Between Dec. 18, 2015, and Aug. 21, 2018, Dr. Sandborn and colleagues at 141 sites in 29 countries enrolled 353 patients with moderate to severely active UC to receive IV vedolizumab 300 mg at weeks 0 and 2. At week 6, 216 patients who demonstrated clinical response were randomly assigned to maintenance treatment: 106 to SC vedolizumab 108 mg every 2 weeks, 54 to IV vedolizumab 300 mg every 8 weeks, and 56 to placebo. The study’s primary endpoint was clinical remission at week 52, which was defined as a total Mayo score of 2 or lower and no subscore greater than 1.

The mean age of patients was 40 years and 60% were male, and they had UC for a mean of 8 years. At week 52, the researchers found that clinical remission was achieved by 46.2% of patients in the SC vedolizumab group, compared with 42.6% of patients in the IV vedolizumab group and 14.3% of patients in the placebo group. In addition, patients in the SC vedolizumab group experienced significantly greater rates of endoscopic improvement and durable clinical response compared with those in the placebo group (P less than .001).

In terms of safety, injection-site reactions were noted by 10.4% of patients in the SC vedolizumab group (mostly rash, swelling, erythema, and pruritus), compared with 1.9% of patients in the IV vedolizumab group and in no patients in the placebo group. “No serious cases were reported for the AEs of special interest: hypersensitivity (including injection site reactions or infusion-related AEs), malignancies, and liver injury,” the researchers wrote. “There were no cases of PML [progressive multifocal leukoencephalopathy] and no deaths.” They acknowledged that the study’s sample size was smaller than the previous GEMINI pivotal trial for vedolizumab IV in ulcerative colitis (N Engl J Med 2013;369:699-710). “This limitation may have contributed to the findings of numerically greater but not statistically significant differences between treatment arms for some secondary endpoints such as durable clinical remission and corticosteroid-free clinical remission,” they wrote.

Takeda sponsored the study. Dr. Sandborn and coauthors reported having numerous financial ties to industry.

[email protected]

SOURCE: Sandborn WJ et al. Gastroenterol 2019 Aug. 27. doi: 10/1053/j.gastro.2019.08.027.

The subcutaneous (SC) form of vedolizumab is effective, generally safe, and well tolerated as maintenance treatment following intravenous vedolizumab induction in patients with moderately to severely active ulcerative colitis, results from a phase 3, double-blind trial demonstrated.

“The route of drug administration can be an important determinant of a patient’s treatment experience, particularly for chronic diseases such as UC [ulcerative colitis],” investigators led by William J. Sandborn, MD, of the division of gastroenterology and hepatology at the University of California, San Diego, wrote in a study published online in Gastroenterology (doi: 10/1053/j.gastro.2019.08.027). “Intravenous administration of a biologic treatment requires the patient to set time aside and travel to a treatment center for an infusion. In addition, the greater use of a health care facility increases the direct costs of care. Some studies show that even with the option of self-injection some patients may still prefer an IV route of administration for the reassurance provided by the opportunity for interacting with a health care professional or because they are averse to self-injection. The availability of both an SC and IV injection of vedolizumab will enable patients to choose the route of administration for maintenance treatment.”

Between Dec. 18, 2015, and Aug. 21, 2018, Dr. Sandborn and colleagues at 141 sites in 29 countries enrolled 353 patients with moderate to severely active UC to receive IV vedolizumab 300 mg at weeks 0 and 2. At week 6, 216 patients who demonstrated clinical response were randomly assigned to maintenance treatment: 106 to SC vedolizumab 108 mg every 2 weeks, 54 to IV vedolizumab 300 mg every 8 weeks, and 56 to placebo. The study’s primary endpoint was clinical remission at week 52, which was defined as a total Mayo score of 2 or lower and no subscore greater than 1.

The mean age of patients was 40 years and 60% were male, and they had UC for a mean of 8 years. At week 52, the researchers found that clinical remission was achieved by 46.2% of patients in the SC vedolizumab group, compared with 42.6% of patients in the IV vedolizumab group and 14.3% of patients in the placebo group. In addition, patients in the SC vedolizumab group experienced significantly greater rates of endoscopic improvement and durable clinical response compared with those in the placebo group (P less than .001).

In terms of safety, injection-site reactions were noted by 10.4% of patients in the SC vedolizumab group (mostly rash, swelling, erythema, and pruritus), compared with 1.9% of patients in the IV vedolizumab group and in no patients in the placebo group. “No serious cases were reported for the AEs of special interest: hypersensitivity (including injection site reactions or infusion-related AEs), malignancies, and liver injury,” the researchers wrote. “There were no cases of PML [progressive multifocal leukoencephalopathy] and no deaths.” They acknowledged that the study’s sample size was smaller than the previous GEMINI pivotal trial for vedolizumab IV in ulcerative colitis (N Engl J Med 2013;369:699-710). “This limitation may have contributed to the findings of numerically greater but not statistically significant differences between treatment arms for some secondary endpoints such as durable clinical remission and corticosteroid-free clinical remission,” they wrote.

Takeda sponsored the study. Dr. Sandborn and coauthors reported having numerous financial ties to industry.

[email protected]

SOURCE: Sandborn WJ et al. Gastroenterol 2019 Aug. 27. doi: 10/1053/j.gastro.2019.08.027.

The subcutaneous (SC) form of vedolizumab is effective, generally safe, and well tolerated as maintenance treatment following intravenous vedolizumab induction in patients with moderately to severely active ulcerative colitis, results from a phase 3, double-blind trial demonstrated.

“The route of drug administration can be an important determinant of a patient’s treatment experience, particularly for chronic diseases such as UC [ulcerative colitis],” investigators led by William J. Sandborn, MD, of the division of gastroenterology and hepatology at the University of California, San Diego, wrote in a study published online in Gastroenterology (doi: 10/1053/j.gastro.2019.08.027). “Intravenous administration of a biologic treatment requires the patient to set time aside and travel to a treatment center for an infusion. In addition, the greater use of a health care facility increases the direct costs of care. Some studies show that even with the option of self-injection some patients may still prefer an IV route of administration for the reassurance provided by the opportunity for interacting with a health care professional or because they are averse to self-injection. The availability of both an SC and IV injection of vedolizumab will enable patients to choose the route of administration for maintenance treatment.”

Between Dec. 18, 2015, and Aug. 21, 2018, Dr. Sandborn and colleagues at 141 sites in 29 countries enrolled 353 patients with moderate to severely active UC to receive IV vedolizumab 300 mg at weeks 0 and 2. At week 6, 216 patients who demonstrated clinical response were randomly assigned to maintenance treatment: 106 to SC vedolizumab 108 mg every 2 weeks, 54 to IV vedolizumab 300 mg every 8 weeks, and 56 to placebo. The study’s primary endpoint was clinical remission at week 52, which was defined as a total Mayo score of 2 or lower and no subscore greater than 1.

The mean age of patients was 40 years and 60% were male, and they had UC for a mean of 8 years. At week 52, the researchers found that clinical remission was achieved by 46.2% of patients in the SC vedolizumab group, compared with 42.6% of patients in the IV vedolizumab group and 14.3% of patients in the placebo group. In addition, patients in the SC vedolizumab group experienced significantly greater rates of endoscopic improvement and durable clinical response compared with those in the placebo group (P less than .001).

In terms of safety, injection-site reactions were noted by 10.4% of patients in the SC vedolizumab group (mostly rash, swelling, erythema, and pruritus), compared with 1.9% of patients in the IV vedolizumab group and in no patients in the placebo group. “No serious cases were reported for the AEs of special interest: hypersensitivity (including injection site reactions or infusion-related AEs), malignancies, and liver injury,” the researchers wrote. “There were no cases of PML [progressive multifocal leukoencephalopathy] and no deaths.” They acknowledged that the study’s sample size was smaller than the previous GEMINI pivotal trial for vedolizumab IV in ulcerative colitis (N Engl J Med 2013;369:699-710). “This limitation may have contributed to the findings of numerically greater but not statistically significant differences between treatment arms for some secondary endpoints such as durable clinical remission and corticosteroid-free clinical remission,” they wrote.

Takeda sponsored the study. Dr. Sandborn and coauthors reported having numerous financial ties to industry.

[email protected]

SOURCE: Sandborn WJ et al. Gastroenterol 2019 Aug. 27. doi: 10/1053/j.gastro.2019.08.027.

The Food and Drug Administration has approved tenapanor (Ibsrela) for adults with irritable bowel syndrome with constipation (IBS-C), according to a release from the drug’s developer, Ardelyx. The approval is based on a pair of phase 3, randomized, double-blind, placebo-controlled trials in patients meeting the Rome III criteria for IBS-C. Both trials had identical 12-week treatment phases, while trial 1 had a 14-week continuation phase, and trial 2 included a 4-week withdrawal period. The primary endpoint was proportion of responders in the 12-week treatment period; this was defined as a 30% reduction in abdominal pain score and an increase of at least one complete spontaneous bowel movement on average weekly for at least 6 of the first 12 treatment weeks, compared with placebo. Both trials met this endpoint, with trial 1 showing a 37% response rate with treatment versus 24% with placebo, and trial 2 showing rates of 27% and 19%, respectively. Improvements were seen as early as week 1 and were maintained through the end of treatment.

Olivier Le Moal/Getty Images

The most common treatment-related adverse event was diarrhea, with severe diarrhea reported in 2.5% of treated patients versus 0.2% of placebo patients. Discontinuation rates were low. Tenapanor is contraindicated in IBS-C patients younger than 6 years because of concerns about dehydration, and use should be avoided in patients aged 6-12 years. Safety and efficacy has not been established in patients younger than 18 years. Tenapanor is also contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.

The full prescribing information can be found on the FDA website.

[email protected]

The Food and Drug Administration has approved tenapanor (Ibsrela) for adults with irritable bowel syndrome with constipation (IBS-C), according to a release from the drug’s developer, Ardelyx. The approval is based on a pair of phase 3, randomized, double-blind, placebo-controlled trials in patients meeting the Rome III criteria for IBS-C. Both trials had identical 12-week treatment phases, while trial 1 had a 14-week continuation phase, and trial 2 included a 4-week withdrawal period. The primary endpoint was proportion of responders in the 12-week treatment period; this was defined as a 30% reduction in abdominal pain score and an increase of at least one complete spontaneous bowel movement on average weekly for at least 6 of the first 12 treatment weeks, compared with placebo. Both trials met this endpoint, with trial 1 showing a 37% response rate with treatment versus 24% with placebo, and trial 2 showing rates of 27% and 19%, respectively. Improvements were seen as early as week 1 and were maintained through the end of treatment.

Olivier Le Moal/Getty Images

The most common treatment-related adverse event was diarrhea, with severe diarrhea reported in 2.5% of treated patients versus 0.2% of placebo patients. Discontinuation rates were low. Tenapanor is contraindicated in IBS-C patients younger than 6 years because of concerns about dehydration, and use should be avoided in patients aged 6-12 years. Safety and efficacy has not been established in patients younger than 18 years. Tenapanor is also contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.

The full prescribing information can be found on the FDA website.

[email protected]

The Food and Drug Administration has approved tenapanor (Ibsrela) for adults with irritable bowel syndrome with constipation (IBS-C), according to a release from the drug’s developer, Ardelyx. The approval is based on a pair of phase 3, randomized, double-blind, placebo-controlled trials in patients meeting the Rome III criteria for IBS-C. Both trials had identical 12-week treatment phases, while trial 1 had a 14-week continuation phase, and trial 2 included a 4-week withdrawal period. The primary endpoint was proportion of responders in the 12-week treatment period; this was defined as a 30% reduction in abdominal pain score and an increase of at least one complete spontaneous bowel movement on average weekly for at least 6 of the first 12 treatment weeks, compared with placebo. Both trials met this endpoint, with trial 1 showing a 37% response rate with treatment versus 24% with placebo, and trial 2 showing rates of 27% and 19%, respectively. Improvements were seen as early as week 1 and were maintained through the end of treatment.

Olivier Le Moal/Getty Images

The most common treatment-related adverse event was diarrhea, with severe diarrhea reported in 2.5% of treated patients versus 0.2% of placebo patients. Discontinuation rates were low. Tenapanor is contraindicated in IBS-C patients younger than 6 years because of concerns about dehydration, and use should be avoided in patients aged 6-12 years. Safety and efficacy has not been established in patients younger than 18 years. Tenapanor is also contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.

The full prescribing information can be found on the FDA website.

[email protected]

Hospitalized patients with inflammatory bowel diseases (IBD) are most likely to be readmitted for venous thromboembolism (VTE) within 60 days of discharge, according to a new study that analyzed 5 years of U.S. readmissions data.

“Given increased thrombotic risk postdischarge, as well as overall safety of VTE prophylaxis, extending prophylaxis for those at highest risk may have significant benefits,” wrote Adam S. Faye, MD, of Columbia University, and coauthors. The study was published in Clinical Gastroenterology and Hepatology.

To determine which IBD patients would be most in need of postdischarge VTE prophylaxis, as well as when to administer it, the researchers analyzed 2010-2014 data from the Nationwide Readmissions Database (NRD). They found a total of 872,122 index admissions for IBD patients; 4% of those patients had a prior VTE. Of the index admissions, 1,160 led to a VTE readmission within 90 days. Readmitted patients had a relatively equal proportion of ulcerative colitis (n = 522) and Crohn’s disease (n = 638).

More than 90% of VTE readmissions occurred within 60 days of discharge; the risk was highest over the first 10 days and then decreased in each ensuing 10-day period until a slight increase at the 81- to 90-day period. All patients over age 30 had higher rates of readmission than those of patients under age 18, with the highest risk in patients between the ages of 66 and 80 years (risk ratio 4.04; 95% confidence interval, 2.54-6.44, P less than .01). Women were at lower risk (RR 0.82; 95% CI, 0.73-0.92, P less than .01). Higher risks of readmission were also associated with being on Medicare (RR 1.39; 95% CI, 1.23-1.58, P less than .01) compared with being on private insurance and being cared for at a large hospital (RR 1.26; 95% CI, 1.04-1.52, P = .02) compared with a small hospital.

The highest risk of VTE readmission was associated with a prior history of VTE (RR 2.89; 95% CI, 2.40-3.48, P less than .01), having two or more comorbidities (RR 2.57; 95% CI, 2.11-3.12, P less than .01) and having a Clostridioides difficile infection as of index admission (RR 1.90; 95% CI, 1.51-2.38, P less than .01). In addition, increased risk was associated with being discharged to a nursing or care facility (RR 1.85; 95% CI, 1.56-2.20, P less than .01) or home with health services (RR 2.05; 95% CI, 1.78-2.38, P less than .01) compared with a routine discharge.

In their multivariable analysis, similar factors such as a history of VTE (adjusted RR 2.41; 95% CI, 1.99-2.90, P less than .01), two or more comorbidities (aRR 1.78; 95% CI, 1.44-2.20, P less than .01) and C. difficile infection (aRR 1.47; 95% CI, 1.17-1.85, P less than.01) continued to be associated with higher risk of VTE readmission.

SOURCE: Faye AS et al. Clin Gastroenterol Hepatol. 2019 July 20. doi: 10.1016/j.cgh.2019.07.028.

Hospitalized patients with inflammatory bowel diseases (IBD) are most likely to be readmitted for venous thromboembolism (VTE) within 60 days of discharge, according to a new study that analyzed 5 years of U.S. readmissions data.

“Given increased thrombotic risk postdischarge, as well as overall safety of VTE prophylaxis, extending prophylaxis for those at highest risk may have significant benefits,” wrote Adam S. Faye, MD, of Columbia University, and coauthors. The study was published in Clinical Gastroenterology and Hepatology.

To determine which IBD patients would be most in need of postdischarge VTE prophylaxis, as well as when to administer it, the researchers analyzed 2010-2014 data from the Nationwide Readmissions Database (NRD). They found a total of 872,122 index admissions for IBD patients; 4% of those patients had a prior VTE. Of the index admissions, 1,160 led to a VTE readmission within 90 days. Readmitted patients had a relatively equal proportion of ulcerative colitis (n = 522) and Crohn’s disease (n = 638).

More than 90% of VTE readmissions occurred within 60 days of discharge; the risk was highest over the first 10 days and then decreased in each ensuing 10-day period until a slight increase at the 81- to 90-day period. All patients over age 30 had higher rates of readmission than those of patients under age 18, with the highest risk in patients between the ages of 66 and 80 years (risk ratio 4.04; 95% confidence interval, 2.54-6.44, P less than .01). Women were at lower risk (RR 0.82; 95% CI, 0.73-0.92, P less than .01). Higher risks of readmission were also associated with being on Medicare (RR 1.39; 95% CI, 1.23-1.58, P less than .01) compared with being on private insurance and being cared for at a large hospital (RR 1.26; 95% CI, 1.04-1.52, P = .02) compared with a small hospital.

The highest risk of VTE readmission was associated with a prior history of VTE (RR 2.89; 95% CI, 2.40-3.48, P less than .01), having two or more comorbidities (RR 2.57; 95% CI, 2.11-3.12, P less than .01) and having a Clostridioides difficile infection as of index admission (RR 1.90; 95% CI, 1.51-2.38, P less than .01). In addition, increased risk was associated with being discharged to a nursing or care facility (RR 1.85; 95% CI, 1.56-2.20, P less than .01) or home with health services (RR 2.05; 95% CI, 1.78-2.38, P less than .01) compared with a routine discharge.

In their multivariable analysis, similar factors such as a history of VTE (adjusted RR 2.41; 95% CI, 1.99-2.90, P less than .01), two or more comorbidities (aRR 1.78; 95% CI, 1.44-2.20, P less than .01) and C. difficile infection (aRR 1.47; 95% CI, 1.17-1.85, P less than.01) continued to be associated with higher risk of VTE readmission.

SOURCE: Faye AS et al. Clin Gastroenterol Hepatol. 2019 July 20. doi: 10.1016/j.cgh.2019.07.028.

Hospitalized patients with inflammatory bowel diseases (IBD) are most likely to be readmitted for venous thromboembolism (VTE) within 60 days of discharge, according to a new study that analyzed 5 years of U.S. readmissions data.

“Given increased thrombotic risk postdischarge, as well as overall safety of VTE prophylaxis, extending prophylaxis for those at highest risk may have significant benefits,” wrote Adam S. Faye, MD, of Columbia University, and coauthors. The study was published in Clinical Gastroenterology and Hepatology.

To determine which IBD patients would be most in need of postdischarge VTE prophylaxis, as well as when to administer it, the researchers analyzed 2010-2014 data from the Nationwide Readmissions Database (NRD). They found a total of 872,122 index admissions for IBD patients; 4% of those patients had a prior VTE. Of the index admissions, 1,160 led to a VTE readmission within 90 days. Readmitted patients had a relatively equal proportion of ulcerative colitis (n = 522) and Crohn’s disease (n = 638).

More than 90% of VTE readmissions occurred within 60 days of discharge; the risk was highest over the first 10 days and then decreased in each ensuing 10-day period until a slight increase at the 81- to 90-day period. All patients over age 30 had higher rates of readmission than those of patients under age 18, with the highest risk in patients between the ages of 66 and 80 years (risk ratio 4.04; 95% confidence interval, 2.54-6.44, P less than .01). Women were at lower risk (RR 0.82; 95% CI, 0.73-0.92, P less than .01). Higher risks of readmission were also associated with being on Medicare (RR 1.39; 95% CI, 1.23-1.58, P less than .01) compared with being on private insurance and being cared for at a large hospital (RR 1.26; 95% CI, 1.04-1.52, P = .02) compared with a small hospital.

The highest risk of VTE readmission was associated with a prior history of VTE (RR 2.89; 95% CI, 2.40-3.48, P less than .01), having two or more comorbidities (RR 2.57; 95% CI, 2.11-3.12, P less than .01) and having a Clostridioides difficile infection as of index admission (RR 1.90; 95% CI, 1.51-2.38, P less than .01). In addition, increased risk was associated with being discharged to a nursing or care facility (RR 1.85; 95% CI, 1.56-2.20, P less than .01) or home with health services (RR 2.05; 95% CI, 1.78-2.38, P less than .01) compared with a routine discharge.

In their multivariable analysis, similar factors such as a history of VTE (adjusted RR 2.41; 95% CI, 1.99-2.90, P less than .01), two or more comorbidities (aRR 1.78; 95% CI, 1.44-2.20, P less than .01) and C. difficile infection (aRR 1.47; 95% CI, 1.17-1.85, P less than.01) continued to be associated with higher risk of VTE readmission.

SOURCE: Faye AS et al. Clin Gastroenterol Hepatol. 2019 July 20. doi: 10.1016/j.cgh.2019.07.028.