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United European Gastroenterology Week (UEGW)
Oral oligonucleotide shows efficacy, safety in Crohn’s
VIENNA – Fourteen days of daily treatment with mongersen, an oral, antisense oligonucleotide, safely produced remissions in two-thirds of patients with Crohn’s disease in a phase II study with a total of 163 patients.
The responses were also durable, with patients in remission continuing to show low disease activity at 10 weeks after they received their last dose of mongersen, Dr. Giovanni Monteleone reported at he United European Gastroenterology Global Congress.
The durability of patient response was not a surprise as similar findings occurred during phase I testing, he said. Mongensen “is not an anti-inflammatory drug. It removes a brake on the normal immunosupressant mechanism in the gut, and that is why the effect is long lasting. It allows TGF [transforming growth factor]-beta to work again [as an endogenous immunosuppressant] and promote healing,” said Dr. Monteleone, a professor of gastroenterology at the University of Rome Tor Vergata.
Dr. Silvio Danese, director of the IBD center at the Humanitis Research Hospital in Milan, said he was impressed by the frequent, durable, and apparently safe remissions achieved by mongensen treatment. “If the phase III studies show efficacy, mongersen will probably be a game changer” for treating inflammatory bowel disease, he commented.
Dr. Monteleone traced development on mongensen to work he published 13 years ago, which showed that oligonucleotide blockade of the production of the Smad7 intracellular protein prevented the inhibitory effect of Smad7 on TGF-beta and thus allowed TGF-beta to inhibit cytokine production and T lymphocyte signaling (J. Clin. Invest. 2001;108:601-9). His work also showed that patients with inflammatory bowel disease have elevated Smad7 levels in their intestinal mucosa, suggesting the potential for therapeutically cutting Smad7 levels in the gut of patients with inflammatory bowel disease.
The study he reported at the meeting included 163 patients with active Crohn’s disease at about a dozen hospitals in Italy. Patients had a Crohn’s disease activity index (CDAI) score of 221-400, were steroid dependent, steroid resistant, or both, and had documented lesions in their terminal ileum, right colon, or both. Patients randomized to active treatment received a daily pill for 14 days with one of three dosages of mongersen formulated into a tablet with a pH dependent coating designed to release the drug in the terminal ileum and right colon and avoid systemic absorption. The researchers then followed patients for an additional 70 days during which they received usual care but no additional treatment with mongersen or placebo.
The study’s primary endpoint was the frequency of remission, designed as a CDAI score of less than 150 on day 15 (the day after their last investigational dose) that was then maintained through day 28 of the study. This endpoint occurred in 65% of the 43 patients who received the highest mongersen dosage, 160 mg/day, in 55% of patients who received 40 mg/day of mongersen, in 12% of patients who received 10 mg/day of mongersen, and in 10% of placebo patients. The differences were statistically significant for the two highest drug dosages.
At 84 days into the study, 10 weeks after receiving their final dosage of mongersen, the rate of patients who were given the highest dosage and continued to have a CDAI of less than 150 stood at 67%, Dr. Monteleone reported. An additional analysis focused on the 61% of patients who entered the study with a C-reactive protein level greater than 3 mg/L. Within this subgroup, 68% of patients who received the highest mongersen dosage achieved remission compared with 12% of patients who received placebo, a statistically significant difference.
The safety analysis showed that mongersen was safe and well tolerated, with low rates of total and serious adverse events that were similar across all four treatment arms. Patient follow-up also showed no clinically meaningful changes in laboratory values, vital signs, physical findings, or strictures.
Celgene has stated that it will proceed into phase III testing of mongersen.
The study was sponsored by Nogra, and then subsequently by Celgene which acquired a license for morgensen from Nogra. Dr. Monteleone has received research support from Nogra and from several other companies and has been a speaker on behalf of AbbVie and Zambon. Dr. Danese has been a consultant to several drug companies.
On Twitter @mitchelzoler
VIENNA – Fourteen days of daily treatment with mongersen, an oral, antisense oligonucleotide, safely produced remissions in two-thirds of patients with Crohn’s disease in a phase II study with a total of 163 patients.
The responses were also durable, with patients in remission continuing to show low disease activity at 10 weeks after they received their last dose of mongersen, Dr. Giovanni Monteleone reported at he United European Gastroenterology Global Congress.
The durability of patient response was not a surprise as similar findings occurred during phase I testing, he said. Mongensen “is not an anti-inflammatory drug. It removes a brake on the normal immunosupressant mechanism in the gut, and that is why the effect is long lasting. It allows TGF [transforming growth factor]-beta to work again [as an endogenous immunosuppressant] and promote healing,” said Dr. Monteleone, a professor of gastroenterology at the University of Rome Tor Vergata.
Dr. Silvio Danese, director of the IBD center at the Humanitis Research Hospital in Milan, said he was impressed by the frequent, durable, and apparently safe remissions achieved by mongensen treatment. “If the phase III studies show efficacy, mongersen will probably be a game changer” for treating inflammatory bowel disease, he commented.
Dr. Monteleone traced development on mongensen to work he published 13 years ago, which showed that oligonucleotide blockade of the production of the Smad7 intracellular protein prevented the inhibitory effect of Smad7 on TGF-beta and thus allowed TGF-beta to inhibit cytokine production and T lymphocyte signaling (J. Clin. Invest. 2001;108:601-9). His work also showed that patients with inflammatory bowel disease have elevated Smad7 levels in their intestinal mucosa, suggesting the potential for therapeutically cutting Smad7 levels in the gut of patients with inflammatory bowel disease.
The study he reported at the meeting included 163 patients with active Crohn’s disease at about a dozen hospitals in Italy. Patients had a Crohn’s disease activity index (CDAI) score of 221-400, were steroid dependent, steroid resistant, or both, and had documented lesions in their terminal ileum, right colon, or both. Patients randomized to active treatment received a daily pill for 14 days with one of three dosages of mongersen formulated into a tablet with a pH dependent coating designed to release the drug in the terminal ileum and right colon and avoid systemic absorption. The researchers then followed patients for an additional 70 days during which they received usual care but no additional treatment with mongersen or placebo.
The study’s primary endpoint was the frequency of remission, designed as a CDAI score of less than 150 on day 15 (the day after their last investigational dose) that was then maintained through day 28 of the study. This endpoint occurred in 65% of the 43 patients who received the highest mongersen dosage, 160 mg/day, in 55% of patients who received 40 mg/day of mongersen, in 12% of patients who received 10 mg/day of mongersen, and in 10% of placebo patients. The differences were statistically significant for the two highest drug dosages.
At 84 days into the study, 10 weeks after receiving their final dosage of mongersen, the rate of patients who were given the highest dosage and continued to have a CDAI of less than 150 stood at 67%, Dr. Monteleone reported. An additional analysis focused on the 61% of patients who entered the study with a C-reactive protein level greater than 3 mg/L. Within this subgroup, 68% of patients who received the highest mongersen dosage achieved remission compared with 12% of patients who received placebo, a statistically significant difference.
The safety analysis showed that mongersen was safe and well tolerated, with low rates of total and serious adverse events that were similar across all four treatment arms. Patient follow-up also showed no clinically meaningful changes in laboratory values, vital signs, physical findings, or strictures.
Celgene has stated that it will proceed into phase III testing of mongersen.
The study was sponsored by Nogra, and then subsequently by Celgene which acquired a license for morgensen from Nogra. Dr. Monteleone has received research support from Nogra and from several other companies and has been a speaker on behalf of AbbVie and Zambon. Dr. Danese has been a consultant to several drug companies.
On Twitter @mitchelzoler
VIENNA – Fourteen days of daily treatment with mongersen, an oral, antisense oligonucleotide, safely produced remissions in two-thirds of patients with Crohn’s disease in a phase II study with a total of 163 patients.
The responses were also durable, with patients in remission continuing to show low disease activity at 10 weeks after they received their last dose of mongersen, Dr. Giovanni Monteleone reported at he United European Gastroenterology Global Congress.
The durability of patient response was not a surprise as similar findings occurred during phase I testing, he said. Mongensen “is not an anti-inflammatory drug. It removes a brake on the normal immunosupressant mechanism in the gut, and that is why the effect is long lasting. It allows TGF [transforming growth factor]-beta to work again [as an endogenous immunosuppressant] and promote healing,” said Dr. Monteleone, a professor of gastroenterology at the University of Rome Tor Vergata.
Dr. Silvio Danese, director of the IBD center at the Humanitis Research Hospital in Milan, said he was impressed by the frequent, durable, and apparently safe remissions achieved by mongensen treatment. “If the phase III studies show efficacy, mongersen will probably be a game changer” for treating inflammatory bowel disease, he commented.
Dr. Monteleone traced development on mongensen to work he published 13 years ago, which showed that oligonucleotide blockade of the production of the Smad7 intracellular protein prevented the inhibitory effect of Smad7 on TGF-beta and thus allowed TGF-beta to inhibit cytokine production and T lymphocyte signaling (J. Clin. Invest. 2001;108:601-9). His work also showed that patients with inflammatory bowel disease have elevated Smad7 levels in their intestinal mucosa, suggesting the potential for therapeutically cutting Smad7 levels in the gut of patients with inflammatory bowel disease.
The study he reported at the meeting included 163 patients with active Crohn’s disease at about a dozen hospitals in Italy. Patients had a Crohn’s disease activity index (CDAI) score of 221-400, were steroid dependent, steroid resistant, or both, and had documented lesions in their terminal ileum, right colon, or both. Patients randomized to active treatment received a daily pill for 14 days with one of three dosages of mongersen formulated into a tablet with a pH dependent coating designed to release the drug in the terminal ileum and right colon and avoid systemic absorption. The researchers then followed patients for an additional 70 days during which they received usual care but no additional treatment with mongersen or placebo.
The study’s primary endpoint was the frequency of remission, designed as a CDAI score of less than 150 on day 15 (the day after their last investigational dose) that was then maintained through day 28 of the study. This endpoint occurred in 65% of the 43 patients who received the highest mongersen dosage, 160 mg/day, in 55% of patients who received 40 mg/day of mongersen, in 12% of patients who received 10 mg/day of mongersen, and in 10% of placebo patients. The differences were statistically significant for the two highest drug dosages.
At 84 days into the study, 10 weeks after receiving their final dosage of mongersen, the rate of patients who were given the highest dosage and continued to have a CDAI of less than 150 stood at 67%, Dr. Monteleone reported. An additional analysis focused on the 61% of patients who entered the study with a C-reactive protein level greater than 3 mg/L. Within this subgroup, 68% of patients who received the highest mongersen dosage achieved remission compared with 12% of patients who received placebo, a statistically significant difference.
The safety analysis showed that mongersen was safe and well tolerated, with low rates of total and serious adverse events that were similar across all four treatment arms. Patient follow-up also showed no clinically meaningful changes in laboratory values, vital signs, physical findings, or strictures.
Celgene has stated that it will proceed into phase III testing of mongersen.
The study was sponsored by Nogra, and then subsequently by Celgene which acquired a license for morgensen from Nogra. Dr. Monteleone has received research support from Nogra and from several other companies and has been a speaker on behalf of AbbVie and Zambon. Dr. Danese has been a consultant to several drug companies.
On Twitter @mitchelzoler
AT UEG WEEK VIENNA 2014
Key clinical point: Mongersen may prove to be an effective oral therapy that can be used on a short-term basis to produce durable remissions in Crohn’s.
Major finding: Two weeks of oral treatment with mongersen produced remissions in 65% of Crohn’s disease patients while the remission rate was 10% in placebo-treated controls.
Data source: A multicenter, placebo-controlled phase II study that included 163 patients.
Disclosures: The study was sponsored by Nogra, and then subsequently by Celgene which acquired a license for morgensen from Nogra. Dr. Monteleone has received research support from Nogra and from several other companies and has been a speaker on behalf of AbbVie and Zambon. Dr. Danese has been a consultant to several drug companies.
Psoriasiform lesions linked to anti-TNF treatment
VIENNA – Patients treated with an anti–tumor necrosis factor drug had a 5% annual rate of developing one or more psoriasiform skin lesions in a review of more than 400 patients who received these drugs to treat inflammatory bowel disease at a single center in Rome.
The cohort review confirmed prior reports that smoking is a risk factor for the appearance of psoriasislike skin lesions on patients being treated with an anti–tumor necrosis factor (TNF) drug, such as infliximab (Remicade) or adalimumab (Humira). The Rome experience also showed that in 28 of the 42 patients who developed a psoriasiform lesion, the eruption responded to topical treatment without need to stop or change the anti-TNF regimen. Ten of the 42 patients ultimately had to stop their anti-TNF regimen, Dr. Daniela Pugliese said at the United European Gastroenterology Global Congress.
“There have been several case reports of this, but this is the largest cohort review yet reported by one center,” said Dr. Pugliese, a gastroenterologist in the inflammatory bowel disease (IBD) unit of Complesso Integrato Columbus, Catholic University in Rome.
The review included 402 patients treated with an anti-TNF drug at the unit during 2008-2013, with a median follow-up of 17 months. During follow-up, 42 patients developed a psoriasiform lesion with a biopsy-proven diagnosis, a rate of 5 cases/100 person-years on anti-TNF treatment. The IBD patients averaged 40 years old, and 60% had Crohn’s disease and 40% had ulcerative colitis. About 60% received infliximab treatment, and 40% adalimumab. Most lesions appeared in predilection sites, as well as on palmoplantar surfaces or on the scalp; nearly half the patients had lesions in two or more locations.
A multivariate regression analysis that assessed several demographic and clinical features of all 402 patients identified two parameters that significantly linked with lesion development. Smoking linked with a greater than twofold increased risk for having a psoriasiform lesion (78 of the patients, 19%, smoked), and concurrent treatment with a thiopurine such as azathioprine, linked with a 67% reduced rate of lesion development (85 patients, 21%, were on concurrent thiopurine treatment). All IBD patients seen at the Rome unit who smoked were counseled regarding smoking cessation, Dr. Pugliese said in an interview.
Among the patients who did not respond to topical treatment, four received some benefit from starting treatment with ustekinumab (Stelara), which especially benefited patients who were otherwise difficult to treat, Dr. Pugliese said. Other patients benefited from starting treatment with cyclosporine, methotrexate, or a transient treatment with an oral steroid. Two patients who developed lesions on infliximab switched to adalimumab, and two other patients who had lesions on adalimumab switched to infliximab.
Dr. Pugliese and her associates did not have a good explanation of why patients on anti-TNF drugs develop these lesions, which Dr. Pugliese called “paradoxical.” One possible etiology is that inhibition of TNF-alpha results in uncontrolled production of interferon-alpha by plasmacytoid dendritic cells and this then triggers the psoriasiform eruptions.
A key element in managing these lesions may be early detection and topical treatment while they remain small, commented Dr. C. Janneke van der Woude, head of the IBD unit at Erasmus University Medical Center in Rotterdam, the Netherlands. “Every time we see an IBD patient who is on an anti-TNF drug, we ask whether they have had any itching, allergic reaction, arthritis, eye problem, or headache,” to facilitate early detection of an adverse effect from treatment, she said in an interview.
Dr. Pugliese had no disclosures. Dr. van der Woude said that she has been an adviser to Dr Falk, AbbVie, Janssen, Johnson & Johnson, and Cosmo.
On Twitter@mitchelzoler
VIENNA – Patients treated with an anti–tumor necrosis factor drug had a 5% annual rate of developing one or more psoriasiform skin lesions in a review of more than 400 patients who received these drugs to treat inflammatory bowel disease at a single center in Rome.
The cohort review confirmed prior reports that smoking is a risk factor for the appearance of psoriasislike skin lesions on patients being treated with an anti–tumor necrosis factor (TNF) drug, such as infliximab (Remicade) or adalimumab (Humira). The Rome experience also showed that in 28 of the 42 patients who developed a psoriasiform lesion, the eruption responded to topical treatment without need to stop or change the anti-TNF regimen. Ten of the 42 patients ultimately had to stop their anti-TNF regimen, Dr. Daniela Pugliese said at the United European Gastroenterology Global Congress.
“There have been several case reports of this, but this is the largest cohort review yet reported by one center,” said Dr. Pugliese, a gastroenterologist in the inflammatory bowel disease (IBD) unit of Complesso Integrato Columbus, Catholic University in Rome.
The review included 402 patients treated with an anti-TNF drug at the unit during 2008-2013, with a median follow-up of 17 months. During follow-up, 42 patients developed a psoriasiform lesion with a biopsy-proven diagnosis, a rate of 5 cases/100 person-years on anti-TNF treatment. The IBD patients averaged 40 years old, and 60% had Crohn’s disease and 40% had ulcerative colitis. About 60% received infliximab treatment, and 40% adalimumab. Most lesions appeared in predilection sites, as well as on palmoplantar surfaces or on the scalp; nearly half the patients had lesions in two or more locations.
A multivariate regression analysis that assessed several demographic and clinical features of all 402 patients identified two parameters that significantly linked with lesion development. Smoking linked with a greater than twofold increased risk for having a psoriasiform lesion (78 of the patients, 19%, smoked), and concurrent treatment with a thiopurine such as azathioprine, linked with a 67% reduced rate of lesion development (85 patients, 21%, were on concurrent thiopurine treatment). All IBD patients seen at the Rome unit who smoked were counseled regarding smoking cessation, Dr. Pugliese said in an interview.
Among the patients who did not respond to topical treatment, four received some benefit from starting treatment with ustekinumab (Stelara), which especially benefited patients who were otherwise difficult to treat, Dr. Pugliese said. Other patients benefited from starting treatment with cyclosporine, methotrexate, or a transient treatment with an oral steroid. Two patients who developed lesions on infliximab switched to adalimumab, and two other patients who had lesions on adalimumab switched to infliximab.
Dr. Pugliese and her associates did not have a good explanation of why patients on anti-TNF drugs develop these lesions, which Dr. Pugliese called “paradoxical.” One possible etiology is that inhibition of TNF-alpha results in uncontrolled production of interferon-alpha by plasmacytoid dendritic cells and this then triggers the psoriasiform eruptions.
A key element in managing these lesions may be early detection and topical treatment while they remain small, commented Dr. C. Janneke van der Woude, head of the IBD unit at Erasmus University Medical Center in Rotterdam, the Netherlands. “Every time we see an IBD patient who is on an anti-TNF drug, we ask whether they have had any itching, allergic reaction, arthritis, eye problem, or headache,” to facilitate early detection of an adverse effect from treatment, she said in an interview.
Dr. Pugliese had no disclosures. Dr. van der Woude said that she has been an adviser to Dr Falk, AbbVie, Janssen, Johnson & Johnson, and Cosmo.
On Twitter@mitchelzoler
VIENNA – Patients treated with an anti–tumor necrosis factor drug had a 5% annual rate of developing one or more psoriasiform skin lesions in a review of more than 400 patients who received these drugs to treat inflammatory bowel disease at a single center in Rome.
The cohort review confirmed prior reports that smoking is a risk factor for the appearance of psoriasislike skin lesions on patients being treated with an anti–tumor necrosis factor (TNF) drug, such as infliximab (Remicade) or adalimumab (Humira). The Rome experience also showed that in 28 of the 42 patients who developed a psoriasiform lesion, the eruption responded to topical treatment without need to stop or change the anti-TNF regimen. Ten of the 42 patients ultimately had to stop their anti-TNF regimen, Dr. Daniela Pugliese said at the United European Gastroenterology Global Congress.
“There have been several case reports of this, but this is the largest cohort review yet reported by one center,” said Dr. Pugliese, a gastroenterologist in the inflammatory bowel disease (IBD) unit of Complesso Integrato Columbus, Catholic University in Rome.
The review included 402 patients treated with an anti-TNF drug at the unit during 2008-2013, with a median follow-up of 17 months. During follow-up, 42 patients developed a psoriasiform lesion with a biopsy-proven diagnosis, a rate of 5 cases/100 person-years on anti-TNF treatment. The IBD patients averaged 40 years old, and 60% had Crohn’s disease and 40% had ulcerative colitis. About 60% received infliximab treatment, and 40% adalimumab. Most lesions appeared in predilection sites, as well as on palmoplantar surfaces or on the scalp; nearly half the patients had lesions in two or more locations.
A multivariate regression analysis that assessed several demographic and clinical features of all 402 patients identified two parameters that significantly linked with lesion development. Smoking linked with a greater than twofold increased risk for having a psoriasiform lesion (78 of the patients, 19%, smoked), and concurrent treatment with a thiopurine such as azathioprine, linked with a 67% reduced rate of lesion development (85 patients, 21%, were on concurrent thiopurine treatment). All IBD patients seen at the Rome unit who smoked were counseled regarding smoking cessation, Dr. Pugliese said in an interview.
Among the patients who did not respond to topical treatment, four received some benefit from starting treatment with ustekinumab (Stelara), which especially benefited patients who were otherwise difficult to treat, Dr. Pugliese said. Other patients benefited from starting treatment with cyclosporine, methotrexate, or a transient treatment with an oral steroid. Two patients who developed lesions on infliximab switched to adalimumab, and two other patients who had lesions on adalimumab switched to infliximab.
Dr. Pugliese and her associates did not have a good explanation of why patients on anti-TNF drugs develop these lesions, which Dr. Pugliese called “paradoxical.” One possible etiology is that inhibition of TNF-alpha results in uncontrolled production of interferon-alpha by plasmacytoid dendritic cells and this then triggers the psoriasiform eruptions.
A key element in managing these lesions may be early detection and topical treatment while they remain small, commented Dr. C. Janneke van der Woude, head of the IBD unit at Erasmus University Medical Center in Rotterdam, the Netherlands. “Every time we see an IBD patient who is on an anti-TNF drug, we ask whether they have had any itching, allergic reaction, arthritis, eye problem, or headache,” to facilitate early detection of an adverse effect from treatment, she said in an interview.
Dr. Pugliese had no disclosures. Dr. van der Woude said that she has been an adviser to Dr Falk, AbbVie, Janssen, Johnson & Johnson, and Cosmo.
On Twitter@mitchelzoler
AT UEG WEEK VIENNA 2014
Key clinical point: Inflammatory bowel disease patients on anti–tumor necrosis factor treatment often develop psoriasiform skin lesions.
Major finding: Patients receiving an anti-TNF drug developed psoriasiform lesions at an annual rate of 5%.
Data source: Retrospective review of 402 patients with inflammatory bowel disease treated with an anti-TNF drug at one center in Rome.
Disclosures: Dr. Pugliese had no disclosures. Dr. van der Woude said that she has been an adviser to Dr Falk, AbbVie, Janssen, Johnson & Johnson, and Cosmo.
Uncomplicated diverticulitis patients safely avoid routine antibiotics
VIENNA – Patients with first-episode, uncomplicated diverticulitis can safely be managed by observation alone without routine antibiotic treatment, based on results from a prospective, controlled, multicenter Dutch trial with 528 patients.
Coupled with similar results from a 2012 Swedish randomized trial, the new findings show that an observational approach without up-front antibiotic treatment is safe and effective for routine practice for patients with a modified Hinchey stage 1 classification, the most common diverticulitis presentation, Dr. Lidewine Daniels said at the United European Gastroenterology Global Congress.
The 2012 trial, done in Sweden and Iceland, randomized 623 patients with acute, uncomplicated diverticulitis, and found no statistically significant difference in the rate of recovery without complications during 12 months of follow-up, regardless of whether or not patients received routine antibiotic treatment at the time of initial diagnosis (Br. J. Surg. 2012;99:532-9).
This approach “can now be adopted into guidelines,” said Dr. Daniels, a researcher in the surgery department at the Academic Medical Center in Amsterdam. This would shift current practice recommendations, such as those published earlier this year by the American College of Colon and Rectal Surgeons (Dis. Colon Rectum 2014;57:284-94), which have generally called for routine antibiotic management of these types of diverticulitis patients, Dr. Daniels said.
The DIABOLO (Multicenter Randomized Clinical Trial Investigating the Cost-effectiveness of Treatment Strategies With or Without Antibiotics for Uncomplicated Acute Diverticulitis) trial enrolled patients with CT-proven, left-sided, first-episode, uncomplicated diverticulitis at 22 Dutch centers. All patients were classified as having stage 1 disease by the modified Hinchey criteria (Int. J. Colorectal Dis. 2012;27:207-14), with about 92% of patients classified as Hinchey 1a.
The 266 patients randomized to initial antibiotic treatment began at least 2 days on intravenous treatment with amoxicillin and clavulanic acid, followed by a switch to oral delivery of the same combination when appropriate for a total of 10 days on the antibiotic.
Patients remained hospitalized until they switched from intravenous to oral treatment. The 262 patients randomized to no initial antibiotic treatment were hospitalized and observed, and received supportive treatment until they were judged ready for discharge by being able to eat a normal diet, had a temperature of less than 38 °C, and had a self-rated pain score of less than 4 on a visual analog scale of 0-10 without use of pain medication; in addition, the patient’s agreement was needed for discharge.
During 6 months of follow-up, the median time to complete recovery – defined as the criteria for hospital discharge plus a return to normal activity – occurred after a median of 12 days among patients in the antibiotic group and 14 days among those in the observation group, a difference that was not statistically significant for the study’s primary endpoint.
The results also showed no statistically significant differences between the two study arms for almost all the other outcomes assessed, including need for readmission, complications, need for surgery, morbidities, serious morbidities, and deaths. The only significant differences in outcomes were a decreased rate of hospitalization at the time of initial treatment among patients in the observation-only arm, and fewer hospitalized days among the observation-only patients.
“Observational treatment is without short- or long-term repercussions,” Dr. Daniels concluded.
Dr. Daniels had no disclosures.
On Twitter @mitchelzoler
VIENNA – Patients with first-episode, uncomplicated diverticulitis can safely be managed by observation alone without routine antibiotic treatment, based on results from a prospective, controlled, multicenter Dutch trial with 528 patients.
Coupled with similar results from a 2012 Swedish randomized trial, the new findings show that an observational approach without up-front antibiotic treatment is safe and effective for routine practice for patients with a modified Hinchey stage 1 classification, the most common diverticulitis presentation, Dr. Lidewine Daniels said at the United European Gastroenterology Global Congress.
The 2012 trial, done in Sweden and Iceland, randomized 623 patients with acute, uncomplicated diverticulitis, and found no statistically significant difference in the rate of recovery without complications during 12 months of follow-up, regardless of whether or not patients received routine antibiotic treatment at the time of initial diagnosis (Br. J. Surg. 2012;99:532-9).
This approach “can now be adopted into guidelines,” said Dr. Daniels, a researcher in the surgery department at the Academic Medical Center in Amsterdam. This would shift current practice recommendations, such as those published earlier this year by the American College of Colon and Rectal Surgeons (Dis. Colon Rectum 2014;57:284-94), which have generally called for routine antibiotic management of these types of diverticulitis patients, Dr. Daniels said.
The DIABOLO (Multicenter Randomized Clinical Trial Investigating the Cost-effectiveness of Treatment Strategies With or Without Antibiotics for Uncomplicated Acute Diverticulitis) trial enrolled patients with CT-proven, left-sided, first-episode, uncomplicated diverticulitis at 22 Dutch centers. All patients were classified as having stage 1 disease by the modified Hinchey criteria (Int. J. Colorectal Dis. 2012;27:207-14), with about 92% of patients classified as Hinchey 1a.
The 266 patients randomized to initial antibiotic treatment began at least 2 days on intravenous treatment with amoxicillin and clavulanic acid, followed by a switch to oral delivery of the same combination when appropriate for a total of 10 days on the antibiotic.
Patients remained hospitalized until they switched from intravenous to oral treatment. The 262 patients randomized to no initial antibiotic treatment were hospitalized and observed, and received supportive treatment until they were judged ready for discharge by being able to eat a normal diet, had a temperature of less than 38 °C, and had a self-rated pain score of less than 4 on a visual analog scale of 0-10 without use of pain medication; in addition, the patient’s agreement was needed for discharge.
During 6 months of follow-up, the median time to complete recovery – defined as the criteria for hospital discharge plus a return to normal activity – occurred after a median of 12 days among patients in the antibiotic group and 14 days among those in the observation group, a difference that was not statistically significant for the study’s primary endpoint.
The results also showed no statistically significant differences between the two study arms for almost all the other outcomes assessed, including need for readmission, complications, need for surgery, morbidities, serious morbidities, and deaths. The only significant differences in outcomes were a decreased rate of hospitalization at the time of initial treatment among patients in the observation-only arm, and fewer hospitalized days among the observation-only patients.
“Observational treatment is without short- or long-term repercussions,” Dr. Daniels concluded.
Dr. Daniels had no disclosures.
On Twitter @mitchelzoler
VIENNA – Patients with first-episode, uncomplicated diverticulitis can safely be managed by observation alone without routine antibiotic treatment, based on results from a prospective, controlled, multicenter Dutch trial with 528 patients.
Coupled with similar results from a 2012 Swedish randomized trial, the new findings show that an observational approach without up-front antibiotic treatment is safe and effective for routine practice for patients with a modified Hinchey stage 1 classification, the most common diverticulitis presentation, Dr. Lidewine Daniels said at the United European Gastroenterology Global Congress.
The 2012 trial, done in Sweden and Iceland, randomized 623 patients with acute, uncomplicated diverticulitis, and found no statistically significant difference in the rate of recovery without complications during 12 months of follow-up, regardless of whether or not patients received routine antibiotic treatment at the time of initial diagnosis (Br. J. Surg. 2012;99:532-9).
This approach “can now be adopted into guidelines,” said Dr. Daniels, a researcher in the surgery department at the Academic Medical Center in Amsterdam. This would shift current practice recommendations, such as those published earlier this year by the American College of Colon and Rectal Surgeons (Dis. Colon Rectum 2014;57:284-94), which have generally called for routine antibiotic management of these types of diverticulitis patients, Dr. Daniels said.
The DIABOLO (Multicenter Randomized Clinical Trial Investigating the Cost-effectiveness of Treatment Strategies With or Without Antibiotics for Uncomplicated Acute Diverticulitis) trial enrolled patients with CT-proven, left-sided, first-episode, uncomplicated diverticulitis at 22 Dutch centers. All patients were classified as having stage 1 disease by the modified Hinchey criteria (Int. J. Colorectal Dis. 2012;27:207-14), with about 92% of patients classified as Hinchey 1a.
The 266 patients randomized to initial antibiotic treatment began at least 2 days on intravenous treatment with amoxicillin and clavulanic acid, followed by a switch to oral delivery of the same combination when appropriate for a total of 10 days on the antibiotic.
Patients remained hospitalized until they switched from intravenous to oral treatment. The 262 patients randomized to no initial antibiotic treatment were hospitalized and observed, and received supportive treatment until they were judged ready for discharge by being able to eat a normal diet, had a temperature of less than 38 °C, and had a self-rated pain score of less than 4 on a visual analog scale of 0-10 without use of pain medication; in addition, the patient’s agreement was needed for discharge.
During 6 months of follow-up, the median time to complete recovery – defined as the criteria for hospital discharge plus a return to normal activity – occurred after a median of 12 days among patients in the antibiotic group and 14 days among those in the observation group, a difference that was not statistically significant for the study’s primary endpoint.
The results also showed no statistically significant differences between the two study arms for almost all the other outcomes assessed, including need for readmission, complications, need for surgery, morbidities, serious morbidities, and deaths. The only significant differences in outcomes were a decreased rate of hospitalization at the time of initial treatment among patients in the observation-only arm, and fewer hospitalized days among the observation-only patients.
“Observational treatment is without short- or long-term repercussions,” Dr. Daniels concluded.
Dr. Daniels had no disclosures.
On Twitter @mitchelzoler
AT UEG WEEK VIENNA 2014
Key clinical point: Observation-only worked as well as routine antibiotic treatment for patients with uncomplicated diverticulitis.
Major finding: Median time to full recovery was 12 days for antibiotic-treated patients and 14 days for observation-only patients.
Data source: The DIABOLO study, which randomized 528 patients with first-time, CT-proven, acute, uncomplicated diverticulitis at 22 Dutch centers.
Disclosures: Dr. Daniels had no disclosures.
