Chapters Transcript Video Update in Management of Acute Severe UC Dr. Matro reviews diagnosis, monitoring, and updates in management of acute severe ulcerative colitis. We're fortunate to have dr Rebecca made room at Scripps clinic. She follows primarily patients with inflammatory bowel diseases, both Crohn's and ulcerative colitis and she's going to give us an update on the management of acute severe ulcerative colitis. Thank you so much picky. Great thank you said I'm good afternoon everyone. I'm really pleased to talk to you about updates in the management of acute severe all sort of colitis. My objectives during this brief time or to review the diagnosis and monitoring strategies of acute severe all sort of colitis. And to discuss hospital management first we need to define it Acute severe you see is to find a six or is the presence of six or more bowel movements in 24 hours plus at least one systemic sign of toxicity. The care of the hospitalized patient with acute severity can be divided into three main goals, diagnosis preparation and management and while these are somewhat sequential there are many overlapping parts diagnosis includes making the diagnosis of acute severe you see and ruling out infection preparation prepares the patient for both steroids and possible rescue therapy and possible surgery and management can include both medical and surgical therapies on admission labs and stool studies should be obtained as well as any appropriate imaging to evaluate for Kalanick dilation, toxic mega colon abscess or perforation. It's essential to rule out c diff infection in any patient admitted with acute severe. You see several studies have shown increasing rates of C. D. I. Among IBD patients on the left. Uh this retrospective observational study showed an increasing proportion of IBD the patients with C. B. Compared to the total number of HIV infected patients With 4% in 2003 compared to 16% in 2005. The graph in the middle shows increasing rates of C. D. I. Among hospitalized IBD patients. The top two lines. And compared with non I. B. D. G. I. Patients and a representative sample of all hospital discharge. The bottom two lines Rates of C. D. I. Are highest among you see patients increasing to more than 50 cases per 1000 admissions. Uh We also know that there's a lot of adverse outcomes associated with C. D. I. A. Um Patients with uh I. B. D. And C. Diff are more likely to uh have flares of their disease, are more likely to fail. Medical therapy. Um Are more likely to need escalation of their IBD therapy and are more likely to have recurrence of C. Diff. They're more likely to have a longer hospital stays, increased health care costs, higher surgery rates and they have a four times higher mortality rate compared to patients with IBD alone. Yeah, endoscopy with a flexible sigmoidoscopy at the time of admission is important to assess disease activity and rule out CMB infection. The full colonoscopy is really not necessary and may be associated with higher rates of chronic dilation and perforation. There are several scoring systems that can be used. Um And they also predict the need for collect a me findings of deep ulceration is correlate with failure of steroid therapy and need for rescue therapy or collected me in order to prepare for treatment. Several tests are needed including tv testing. Hepatitis B and hepatitis B. Serology, ease colorectal surgery should be consulted as early in the hospital course as possible even if the patient does not end up needing surgery at that time. On admission any five S. E. S. And and said should be stopped, electrolytes should be repeated and I. V. Fluids given narcotics and anti coal energy mix should be limited. And prophylactic antibiotics are generally not recommended unless there are focal signs of infection. Concern for toxic mega colon or very high clinical suspicion for C. Diff infection. DVt prophylaxis should be started along with I. D. Steroids. Yeah pharmacologic dVt prophylaxis is essential for hospitalized IBD patients. This cohort study looked at the risk of the T. E. And IBD patients and match controls. Overall IBD patients had a significantly higher risk of developing V. T. E. And the risk was greatest during a flare. With the hazard ratio. Overall hazard racial 8.4. This increased risk was seen both in hospitalized patients and in outpatients and interestingly patients with chronic disease activity also had a very high risk of developing bte with a hazard ratio of 9.9 cortical steroids have been the mainstay of treatment for severe you see for decades. Um While there are no randomized controlled trials comparing steroid regimens there are several key points. The dough should be methylprednisolone, 60 mg A day or the equivalent. And there's really no incremental benefit to total doses more than 60 mg a day and no benefit to continuous I. V. Dose ng versus daily dose ng versus divided dozing Response is typically seen within 3-5 days and an additional response after seven days is unlikely. It's important to remember that 30% of patients will not respond to I. v. steroids after starting steroids. The patients should be monitored daily to assess response and this should include physical exam, symptom assessment and daily monitoring of labs particularly crp. Several factors have been shown to predict steroid failure and and these uh these uh indexes are listed up here. There's an 85% chance of failure at day three. If the patient is still having eight or more bowel movements a day or their crp is greater than 45 And there's a 60% failure rate at day seven. If they're still having more than three bowel movements a day or still have blood visible in their stool. The ho index on the right includes the number of bowel movements, albumin and presence of colonic dilation to predict steroid failure at day three. With an 85% failure rate with a score of four or higher and a 43% failure rate with a score of two or three day three of I. V. Steroids is essentially decision day. When you assess whether the patient is responding or not responding. Patients who are responding should continue I. V. Steroids for five days and then transition to oral predniSONE. Generally we like to observe them in the hospital for about 24 hours to make sure that they remain stable. And then a steroid sparing strategy can be started in the hospital or within 1-2 weeks of discharge for patients who are not responding. This is where we decide the next steps. Traditionally inflicts a mob or cyclosporin with transition to thio puritans have been the mainstays of medical treatment. However more options have recently shown good results. So options for steroid responders include are numerous. They include those listed on the on the slide and um can be considered based on um on prior history for steroid non responders. Inflicts a mob is effective for acute severe you see in this older important randomized controlled trial hospitalized you see patients who received inflicts a mob five mg per kilogram were more likely to avoid collecting me compared with patients who received placebo 71% versus 33%. And patients who do respond to respond and achieve remission with inflicts a mob should continue it for maintenance. More recently. Questions about whether standard induction dozing is sufficient and acute acute severe you see have been asked We know that accelerated clearance of inflicts a map is associated with treatment failure that fecal inflicts a mob levels are correlated with the lack of response and patients with severe inflammation lose more inflicts them out through the stool. And also that day 14 levels are significantly lower and severe you see. So it seems plausible that intensive dozing regimens may be more effective than standard induction. In the retrospective study on the left the hospital execute severe, you see patients who receive standard induction dozing or compared to those who received accelerated dozing or three doses within 24 days. Um accelerated dozing reduced the need for early collector me where patients had lower collectively rates at one month But collecting your rates were similar between the two groups 3 months on the right. This retrospective multi center study meta analysis compared accelerated dose sing higher dose or shorter interval dozing in the blue versus standard dozing in the orange and no difference in rates of collecting at any time point we're seeing. Um So currently the A. G. A. Guidelines make no recommendation on routine use of intensive versus standard and some out dozing cyclist born is an alternative rescue therapy and has been shown to be effective in treatment of acute severe you see um In the study on the left this is an older study patients who did not respond to I. V. Steroids who were randomized to cyclists, foreign four mg per kilogram Or to placebo. nine out of the 11 patients had a response at seven days and no placebo patients had a response. Um Later studies did show similar results with a two mg per kilogram dose so that doses generally favored. Um and then when comparing cyclosporin to inflict some ab several studies, including this one on the right have shown no difference in efficacy or treatment failure rates. This one showed 60% versus 54% treatment failure. Um and there's been no difference in adverse events. So the choice between cyclists born in and took some out for rescue therapy is largely based on provider experience with each drug because inflicts a mob is used more frequently in the outpatient setting. We generally have more familiarity with it. Inflicts a map tends to be preferred in patients with lower albumin levels. And cyclosporin is a lipid bound therapy and so there is a higher likelihood of seizures or other neurologic um Side effects in patients who have low cholesterol or magnesium levels. So the cyclosporin should be avoided or lower doses used and um and the patient's labs monitored carefully if that's chosen. And finally, because data show higher rates of collecting and patients receiving cyclosporin who have failed immuno modulators influx and has historically been chosen um in these this patient population. Um But what about patients, but there might be newer? Some there's some newer data that suggests that other options might be available. And then what about the patient has already been exposed and failed inflicts a mob or another. Anti TNF biologic. Several recent studies have shown that vandalism and may serve as maintenance therapy for these patients when combined with cyclosporin for a more rapid induction of remission. This top table just shows all the studies looking at vandalism and for maintenance of the mission after cyclosporin induction. And the figures on the bottom are from the Rolex study where 71 patients were followed for a median of 25 months and collecting me free survival was 93% at three months and 67% at one year. Fifty% 14 and 43% at week 52 are still in clinical remission and 76% of patients remained in remission on metal is mad at two years. Um There's one case report of two patients successfully treated with you stick in a mob after cyclosporin induction. That's recently been published and then in another case a patient successfully achieved clinical remission with cyclosporin induction and then was transitioned to Tofas IT and 10 mg B. I. D. For maintenance. There has been emerging interest in using Tofas didn't have a small molecule Jak inhibitor and a non protein based therapy to induce response or emission and hospitalized patients with acute severe you see. Um And this is obviously off label but this is a retrospective case control study evaluating the efficacy of tova Sydney for induction of remission in biologic experience patients admitted to the hospital and requiring I. V. Steroids. In this trial 40 patients received took a sitting of 16 patients got 10 mg twice a day and 24 patients got 10 mg three times a day. And the collectively rate was 15% in the tofu group compared to 20% in the control group. And then when you look at the two doses uh separately, the T. I. Dose was the one that was protective while the B. I. D. Dose was not. They also found that albumin number of failed targeted therapies, Kalanick dilation and Mayo score. Uh we're all uh significant cove area predictors of collecting me at 90 days. Um A K. Series of four hospitalized patients with acute severe you see who failed at least two biologics were started on two of the seven of 10 mg twice a day and there was a zero uh collectively rate at both 30 and 90 days. And then finally it's critical that we keep in mind that surgery is really a treatment for acute severe you see and should not should not be considered a failure of treatment or necessarily a last resort. There are absolute indications for collecting me listed here toxic mega colon perforation, uncontrolled bleeding. Multi organ dysfunction. Um but it should be uh considered in patients who have failed to respond to I. v. steroids after 3-5 days. The surgical procedure of choice we talked about is a restorative practice collecting me with a little pouch anal anastomosis. Um That's generally done in a two or a three stage approach. Three stages we talked about earlier is more favored and this minimizes complications and allows for improvement and nutritional status and reduces the potential for infectious complications. So in conclusion patients admitted with acute severe you see should be ruled out for C. Diff and started on DVT profile. Access I. V. Steroids should be started uh patients monitored daily for 3 to 5 days and flicked some avid cyclist for one of the mainstays of rescue therapy and uh inflicts map should be continued of successful for induction as maintenance after cyclosporin, induction maintenance options include five hearings and vandalism. Ab more data at this point is needed for tova signal for induction and acute severe. You see particularly the dose, the appropriate dose and the safety and efficacy. And again surgery should be considered in patients who fail I. V. Steroids and colorectal surgery consulted early. Thank you very much. Published Created by Related Presenters Rebecca Matro, MD GastroenterologistScripps Clinic Rebecca Matro, MD, is a gastroenterologist who specializes in inflammatory bowel disease, including Crohn’s disease and ulcerative colitis. View full profile
