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The goals of therapy for patients with inflammatory bowel disorder  include inducing and maintaining a steroid-free remission, preventing and  treating the complications of the disease, minimizing treatment toxicity,  achieving mucosal healing, and enhancing quality of life.

So what role do antibiotics and corticosteroids play in achieving these  goals?

Here to address that question is Raymond Cross, MD, Associate  Professor of Medicine in the Division of Gastroenterology and Hepatology and  Director of the Inflammatory Bowel Disease Program at the University of  Maryland School of Medicine. Dr Cross recently addressed the use of antibiotics  and corticosteroids in optimizing therapy at the 2012 Advances in Inflammatory  Bowel Diseases, Crohn’s & Colitis Foundation’s Clinical & Research  Conference in Florida.

Dr Moss is Assistant Professor of Medicine at  Harvard Medical School and is a gastroenterologist at Beth Israel Deaconess  Medical Center in Boston, Massachusetts. He discussed diagnosis and  management of extraintestinal manifestations of IBD in his presentation at the  2012 Advances in Inflammatory Bowel Diseases, the Crohn’s & Colitis  Foundation’s Clinical & Research Conference, held December 13-15 in  Hollywood, Florida.

Podcasts

The goals of therapy for patients with inflammatory bowel disorder include inducing and maintaining a steroid-free remission, preventing and treating the complications of the disease, minimizing treatment toxicity, achieving mucosal healing, and enhancing quality of life.

Clinical Tips for Using Antibiotics and Corticosteroids in IBD

Extraintestinal  manifestations (EIMs) of inflammatory bowel disease (IBD) are common in both  ulcerative colitis and Crohn disease. The systems most often involved are the  musculoskeletal and dermatologic systems. Ocular, renal, and pulmonary  manifestations also are seen. For the physician managing these already complex  patients, an additional diagnosis-erythema nodosum, psoriasis, purpura,  arthritis-can be a significant challenge.

In this short podcast, Dr Alan Moss answers several important questions  for primary care physicians that address signs and symptoms to watch for in  your patients with IBD and how first-line therapy impacts both the GI disease  and the extraintestinal presentations.

Dr Moss is Assistant Professor of Medicine at  Harvard Medical School and is a gastroenterologist at Beth Israel Deaconess  Medical Center in Boston. He will be discussing diagnosis and  management of extraintestinal manifestations of IBD in his presentation at the  2012 Advances in Inflammatory Bowel Diseases, the Crohn’s & Colitis  Foundation’s Clinical & Research Conference, to be held December 13-15 in  Hollywood, Florida.


 •Patients with IBD who present with new eye,  skin, joint, or pulmonary symptoms should be evaluated for the possibility of  either an associated inflammatory processes, or adverse effects of their  immunosuppressant medications
 •Extraintestinal symptoms usually correlate with  intestinal disease activity; they typically present when the patient’s IBD is active
 •Corticosteroids and anti-TNF drugs can also improve  inflammatory arthritis or the skin or ocular manifestations of IBD, but  specialist care should be sought in these cases to prevent complications


 Peyrin-Biroulet  L, Loftus EV Jr, Colombel JF, Sandborn WJ. 

Long-term  complications, extraintestinal manifestations, and mortality in adult Crohn's  disease in population-based cohorts.

http://onlinelibrary.wiley.com/doi/10.1002/ibd.21417/pdf

Barrie A, Regueiro M. Biologic therapy in the management of  extraintestinal manifestations of inflammatory bowel disease. 

http://onlinelibrary.wiley.com/doi/10.1002/ibd.20196/pdf.

Extraintestinal manifestations of inflammatory bowel disease affect the musculoskeletal, dermatologic, ocular, renal and pulmonary systems.

Extraintestinal Manifestations of Inflammatory Bowel Disease: Common and Manageable

According to the Centers for Disease Control, more than one-third of US adults are obese. Many are at increased risk for such obesity-related conditions as stroke, heart disease, some types of cancer, and even altered GI motility. The CDC also estimates that as many as 1.4 million Americans suffer from inflammatory bowel disorder. So is there a link?

Joining us today is Dr. Jennifer Seminerio, gastroenterology fellow at  the University of Pittsburgh School of Medicine, to shed some light on this issue. Dr. Seminerio and colleagues received the American College of Gastroenterology Inflammatory Bowel Disease Research Award for their poster on the impact of obesity and IBD; the poster was presented at the American College of Gastroenterology’s 2012 Annual Scientific Meeting held in Las Vegas. 

The Changing Shape of Inflammatory Bowel Disease

(AUDIO) According to the Centers for Disease Control, more than one-third of US adults are obese. The CDC also estimates that as many as 1.4 million Americans suffer from inflammatory bowel disorder. So is there a link?

FDA approves updated indication for upadacitinib in ulcerative colitis and Crohn disease treatment, allowing use after one systemic therapy when TNF blockers are clinically inadvisable. 

FDA Approves Updated Indication Statement for Upadacitinib in Inflammatory Bowel Disease Treatment

Your daily dose of the clinical news you may have missed.

Real-World Study Confirms Upadacitinib’s Efficacy in Crohn Disease Treatment: Daily Dose

Upadacitinib shows promising real-world effectiveness for managing moderate-to-severe Crohn disease, even in patients with prior treatment exposure.

Upadacitinib Found Effective in Achieving Remission in Crohn Disease, Including Biologic-Experienced Patients

Guselkumab (Tremfya) Gains FDA Approval for Crohn Disease: Daily Dose

The IL-23 inhibitor is the only drug in the class available with both subcutaneous and intravenous administration options for treatment induction, according to J&J.  

Guselkumab (Tremfya) Wins Approval for Crohn Disease, Fourth Indication for Immune-Mediated Diseases 

 Looking at some unanswered questions and future directions, Dr Sands, could you tell us about some of the remaining unanswered questions or unmet needs in the treatment of inflammatory bowel disease [IBD]?

 There are so many questions. Patients will often have questions about the role of diet or nontraditional ways of treating IBD. We’re only just starting to embark on reasonably designed dietary trials to try to answer those questions. It’s a sad fact that even though we’ve made a lot of progress in the treatment of Crohn disease and ulcerative colitis over the last few decades, there are still plenty of patients—I’d say a very substantial minority—who aren’t adequately controlled by the medications we have. We have a lot of trouble predicting which patient is going to respond to which drug. Because we have different classes of agents, it gets more complicated understanding which drug we should reach for first, given that the first drug is more likely to be the most effective. We also have questions about how to combine these medications in ways to enhance their efficacy. There’s plenty of work to be done to get a better understanding of how to best treat these patients.

 Thank you. Dr Hanauer, there’s a pretty exciting drug pipeline evolving for the treatment to the inflammatory bowel disease. What are some of the exciting potential treatments that you’ve seen in the upcoming management of inflammatory bowel disease?

 The most likely newer agents that are going to come to market are extensions of the mechanisms that we’ve already discussed and learned about. As far as interleukin-12 and interleukin-23 inhibition, a number of specific interleukin-23 inhibitors are under development for ulcerative colitis and Crohn disease that look very promising based on their effectiveness and relative safety. In addition, while tofacitinib—the Janus kinase inhibitor that Dr Sands described—is effective in ulcerative colitis, another group of more specific JAK1 inhibitors are also being developed and look promising for ulcerative colitis, with several in Crohn disease as well.

Beyond that, the world is wide open. Clinical investigators have dissected the immune cascades and cytokine cascades. A number of evolving agents are looking at specific mechanisms with different cytokines or other anti-inflammatory agents. What we haven’t mentioned is the role of the microbiome. This may be a very promising field, as we learn that both ulcerative colitis and Crohn disease are associated with a lack of diversity within the microbiome. Specific microbiome therapies are being developed that may be used in combination with dietary therapies, as Dr Sands mentioned, until we ultimately identify specific mechanisms for specific individuals. If you ask me what the main unanswered question is, it’s how to personalize medicine and identify biomarkers that are going to predict who’s going to respond to a TNF [tumor necrosis factor] inhibitor vs a JAK inhibitor vs a lymphocyte trafficking agent.

 Thank you for that excellent explanation. Dr Ungaro, I’d like to conclude by asking you, what are some take-home messages regarding the treatment of patients with inflammatory bowel disease?

 Considering this is mostly a primary care audience, No. 1 is that we think if we can get patients into treatment earlier, they’ll do better. This is critical. Identifying and diagnosing patients sooner is paramount. Some of the things we discussed already, like diarrhea and abdominal pain, are very common primary care complaints. It’s important to adopt things like red flags—Dr Hanauer mentioned weight loss, nocturnal symptoms, and blood in the stool—and also check stool for inflammatory markers, like fecal calprotectin, in the work-up of patients with possible symptoms that could be for early signs of IBD, like diarrhea and abdominal pain. That’s the first thing.

The second thing is that the world of IBD has evolved to incorporate a lot of objective metrics in evaluating the disease severity and activity. When a patient with IBD feels well, they may have ongoing active inflammation, so they need to follow up with their gastroenterologists to be evaluated. Lastly—and critically from a primary care standpoint—we mentioned the different adverse-effect profiles, considerations with the medications, health care maintenance exams, vaccinations, skin checks, and DEXA [dual-energy x-ray absorptiometry] scans for patients who have significant steroid exposure. These are things in which the primary care doctor can play a critical role helping—in conjunction with the gastroenterologist—and taking care of patients with IBD. Ultimately, taking care of these patients ends up being a partnership with primary care, multidisciplinary teams with surgeons, and other disciplines.

 Thank you for that very important summary. Thank you to Drs Hanauer, Ungaro, and Sands for joining us in this lively discussion on inflammatory bowel disease treatment brought to you by 

®. And thank you to our viewing audience. We hope you found this interactive discussion to be informative and beneficial to your clinical practice.

Videos

A glance at therapeutic strategies being investigated to improve the treatment and outcomes of patients with ulcerative colitis and Crohn disease.

Optimizing Treatment for Patients With IBD

 Continuing the case, 6 months have passed, and the patient has experienced no significant improvement. The patient underwent repeat imaging and a scope showing ongoing disease activity of moderate severity. Dr Sands, knowing this, how would you treat this patient now?

 Assuming the patient did indeed get combination therapy, as we all endorsed with an anti–TNF [tumor necrosis factor] and thiopurine, this is a serious situation. She hasn’t responded to what may be 1 of our best therapies. The first thing is that you have objective evaluation showing that there’s ongoing disease activity. You’ve shown that. It’s important to not only rely on symptoms of not feeling well. Occasionally patients will respond very well in terms of the inflammation but may still manifest symptoms. But in this case, the inflammation is ongoing, so the process is not under control.

First, make sure the patient has adequate levels of the anti-TNF—in this case, infliximab—to treat the disease. You can send trough levels to understand that. It’s also possible to send levels of the thiopurine, although that may be less helpful here. Assuming the levels are adequate, meaning they’re in a range that we know should be therapeutic for most patients, you may end up switching to a different class of medication, probably a second biologic in this case. Ustekinumab would possibly be your next choice based on network meta-analyses of what works best as second-line biologic therapy.

It’s also possible that the patient has developed antidrug antibodies against the infliximab in that situation, which you can assay for. It’s possible to switch within class to a different anti-TNF. A third option is simply that you test and find the patient doesn’t have antidrug antibodies, but they do have low levels of infliximab below what their trough should be. In that case, it’s possible to dose escalate. That’s how you could think through these options.

 Thank you for that thorough explanation. Dr Hanauer, some patients with Crohn disease can develop perianal disease. How does that change your decision-making with regard to drug management?

 About 20% of patients develop perianal disease, which can include perianal fistula, which are quite troublesome to both men and women. In women, perianal disease can extend into the vagina. It compromises quality of life for the majority of patients. The problem is that we have very limited evidence on the effectiveness of therapies for perianal fistula in the setting of Crohn disease. Dr Sands led a landmark study of infliximab in that setting. This has been our most effective therapy, usually in combination with a thiopurine because of the additional complexity in this individual.

How to best treat a patient with inflammatory bowel disease who demonstrates no disease response to initial biologic treatment, as well as insight surrounding the treatment of patients who develop perianal disease.

Inflammatory Bowel Disease

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