AIBD 2020: Beyond Anti-TNF Therapy

My last session I was able to attend for AIBD 2020 focused on therapies for IBD that are beyond Anti-TNF medications. The specific sessions I attended were led by Anita Afzali, MD, MPH, FACG and Raymond Cross, MD, MS, AGAF, FACG. I wanted to attend this session because I have always found immunology fascinating and absolutely loved the classes I took on it. Kind of ironic that I was later diagnosed with IBD, right? Anyway, hearing discussions about newer biologic therapies and what is in the pipeline is encouraging as an IBD patient and a medical provider. I know many of you are on immunomodulator therapy or biologics, and there are risks and benefits to consider when starting and continuing these medications. 

First, let’s do a basic intro to one way that inflammation plays a role in IBD, specifically through TNF-alpha. I love this video from Animated IBD Patient if you are more of an auditory/visual learner. TNF-alpha is only one mediator of inflammation, and that’s why we are looking at other inflammatory targets, such as interleukins (IL-), JAK pathways, leukocyte (white blood cell) trafficking and preventing adhesion of these inflammatory molecules to name a few. (I also promise this will make more sense down below :) ). It’s pretty amazing that we know some pathways to target specifically to reduce inflammation, paving the way for medicines like Remicade (infliximab), Humira (adalimumab), Stelara (ustekinumab), Entyvio (vedolizumab), Xeljanz (Tofacitinib) and others. This decreases our reliance on medicines like prednisone, which lower inflammation in a broad way and typically have more unwanted side effects.

We have to consider the limitations of our current therapies when looking at new targets - 30-40% of us will fail to have an initial response to anti-TNF therapy and up to 50% of us may lose our positive response to biologics in the first year of therapy. There is also the cost, route of administration (like if you need to go to an infusion center) and treatment related adverse events (i.e. immunosuppression, allergic reactions, etc.) that are very important to consider when looking at our current therapies and targets for the future. We do know from recent studies that patients who have never been on anti-TNF therapies do better on medications that target other specifics in the inflammatory pathway, such as Entyvio, Stelara and Xeljanz. And, as with any medication you take, from Tylenol to biologic medications, there are always risks to consider. These are the safety concerns highlighted from the talk below: 

IL-12 and IL-23 inhibitors - what are our safety concerns? 

Data from the PSOLAR registry showed no increased risk of: 

• Serious infections

• Malignancy (except non-melanoma skin cancers)

• Major adverse cardiac events 

• All-cause mortality (death)

JAK inhibitors - what are our safety concerns? 

• Infection - herpes zoster (shingles)

• Thromboembolism/VTE - aka blood clots; this was seen in Rheumatoid Arthritis (RA) literature 

• All-cause mortality (death) - also seen in RA literature

• Increased total cholesterol, HDL and LDL cholesterols

• Cardiovascular events - this could mean heart attacks, strokes, etc. 

Anti-trafficking agents, specifically S1P Receptor Modulators which prevent lymphocytes from contributing to tissue inflammation - what are our safety concerns? 

• Serious infection - herpes zoster (shingles), PML (progressive multifocal leukoencephalopathy)

• Bradyarrhythmia and AV conduction delays - heart issues 

• Macular edema - visual problems

A good thing I noticed when I was looking at the study results on newer medications in the pipeline is that they all look at both clinical and endoscopic remission. This is a step in the right direction for us as IBD patients since things may look great on endoscopy or colonoscopy, but we may not feel well clinically. I hope that the clinical remission criteria look at patient-centered endpoints as well.

Portion from Positioning IBD Therapies 

Going off of our information above, Dr. Cross reviewed some important goals of therapy when considering newer IBD therapies and how they affect the patient based on low- and high-risk disease, among other things. Our goals of therapy are to induce clinical remission (no IBD symptoms), avoid short- and long-term toxicity of therapy, maintain steroid-free remission, enhance quality of life, achieve mucosal healing in the gut (aka deep remission), prevent/treat complications of IBD and to decrease unnecessary health care expenditures such as ER visits and hospitalizations. 

There have also been studies, such as the CALM study, that look at a “treat to target” approach for patients. This includes targets such as absence of ulceration via endoscopy/colonoscopy or other imaging modalities, and does not just rely on resolution of symptoms alone as the only target. The CALM study, which involved Crohn’s patients, found that the treat to target approach led to higher rates of mucosal healing than typical clinical management. Have specific targets to meet, including clinical remission for patients and imaged-guided remission could help streamline treatment and increase the involvement of the patient in their care.

Dr. Cross also discussed how to approach highly-effective treatments in IBD patients. This decision is based on the severity of symptoms, the inflammatory burder, risk factors for severe disease or a disabling disease course and the presence/absence of complicated Crohn’s disease. Once the decision has been made by you and your provider to initiate highly effective therapy, there are even MORE factors to consider! These include: 

• Is there evidence that one agent is more efficacious than another? 

• How severe are the patient’s symptoms? 

• What safety considerations are present? This could include an elderly patient, having comorbid conditions or being risk-averse. 

• Does the patient have a preference regarding mode of delivery? This can mean taking a medication by mouth, injection, IV infusion, etc. 

• What type of insurance does the patient have? I’m so glad they’re taking this into consideration! As much as providers wish they didn’t have to consider this when prescribing the therapy for patients, this is so important to keep in mind. 

• Does the patient have extra-intestinal manifestations of disease? This can mean things like arthritis, uveitis (eye inflammation), skin changes and others. 

• Are patients with a uterus/ovaries of childbearing age? 

Without boring you further by reviewing studies and their data, IBD researchers are doing great work at comparing older and newer biologic therapies and how they affect patients who have never been on biologics, have failed biologics, IBD patients with extra-intestinal manifestations and how they compare in IBD patients with moderate to severe disease. 

Based on studies comparing these various aspects of treatment and how newer therapies that target more specific aspects of inflammation in IBD, the decision to start highly effective therapy is one that should be made with you in mind, but with your GI provider taking your entire clinical picture and risk factors into account. The goals of treatment will be clinical remission and endoscopic improvement. Based on current data, it is recommended that IBD patients who are older, have less severe symptoms/inflammatory burden and those with comorbid conditions take a “safety first” approach - utilize ustekinumab (Stelara) or vedolizumab (Entyvio) as their data shows improvement and has the least amount of serious side effects. 

For IBD patients with more severe symptoms, it is recommended to start with infliximab (Remicade) or tofacitinib (Xeljanz); however, Xeljanz should be avoided in patients with a uterus/ovaries who are of childbearing age. In IBD patients with prominent extra-intestinal manifestations, they recommend anti-TNFs, tofacitinib or ustekinumab. I know this all sounds like a lot, but know there are inflammatory-specific treatments being studied in the pipeline and that IBD researchers are comparing current treatment modalities and how they can best serve their patients with evidence-based data for treatment in conjunction with your clinical picture. As always, if you have questions about a particular treatment or side effects (anything really), always ask your GI provider. They went to school for years to be able to care for you, and they should be happy to answer any questions you have about treatment. All questions are good questions, and I hope this article was interesting and inspiring for you as you continue on your IBD journey. 

AIBD 2020: Highlights of the 1st Fellows Session on Translating the Language of IBD to the Patient

As part of the Advances in Inflammatory Bowel Diseases (AIBD) conference, I joined the Fellows Session I: Translating the Language of IBD to the Patient. The session was co-chaired by Christina Ha and Lisa Malter and was targeted at Fellows. For those who aren’t familiar with the medical training system in the United States, a Fellow is a doctor who has completed their residency (specialist training programme), and elects to complete further training in a speciality, such as gastroenterology.

There were a number of distinguished healthcare professionals from the IBD community involved in moderating and facilitating different aspects of this session, covering: different frameworks for effective partnering between IBD providers and people with IBD; how doctors can help to inform and empower people with IBD; choosing the optimal IBD therapy as a shared decision-making process; and the goals of caring for people with IBD. Attendees were split into different breakout groups for discussion at several time points during the session, with groups consisting of up to 10 Fellows and one member of the conference session faculty.

Dr. Regueiro discussed a framework for choosing the optimal IBD therapy, highlighting the concept of ‘treat-to-target’. ‘Treat-to-target’ is based on finding and defining appropriate treatment targets, using available evidence. For certain conditions, like high blood pressure, there are very clear targets which should be met, such as having a systolic blood pressure (top blood pressure number) less than 140 mmHg; since otherwise, you are at a higher risk of a stroke or heart attack. ‘Treat-to-target’ in conditions like IBD are a little more challenging, because the ‘target’ is less clear or straightforward. For example, some doctors say that it should be the normalisation of biomarkers (e.g., fecal calprotectin in range), whereas others argue for mucosal healing (disease activity is not seen during an endoscopy procedure), and histological healing (complete recovery of the digestive tract, with absence of inflammation or structural changes under the microscope).

Dr. Regueiro then went on to summarise the current IBD therapy landscape, prompting for the choice of biologic or small molecule to be personalised for every individual person with IBD. He recognised the need to start biologic/small molecule therapy earlier, particularly for those at high risk for rapid progression. He outlined four key groups of treatment falling under the biologic/small molecule categories as we enter 2021: 

• Anti-TNFs (e.g., adalimumab, certolizumab, golimumab, infliximab);

• Anti-IL-12/-23 (e.g., Ustekinumab);

• Anti-α₄β₇ integrin (e.g., Vedolizumab);

• JAK inhibitors (e.g., Tofacitinib).

An important part of the conversation around the most suitable treatment for people with IBD relates to treatment safety. Dr. Regueiro highlighted the importance of open and honest conversations between doctors and people with IBD, and the need for transparency in evidence. During his presentation, he presented a new safety pyramid of different treatment options based upon available evidence, including conventional treatments such as steroids and thiopurines. Regueiro stated that this safety pyramid was most relevant at the time of AIBD 2020. The safest treatments were vedolizumab and ustekinumab. These were followed by single treatment with anti-TNFs (e.g., adalimumab, certolizumab, golimumab, infliximab) and tofacitinib. Thiopurines (e.g., azathioprine, 6-mercaptopurine, thioguanine) and combined thiopurine/anti-TNF treatment then followed, respectively. Steroids were seen as the least safe treatment for people with IBD.

Laura Raffals spoke about the goals of caring for people with IBD, emphasising the privileged position of healthcare professionals to be able to support people with IBD. She also highlighted the importance of a multi-disciplinary approach to care, recognising that the doctor alone is inadequate. As part of the team, you ideally need nurse practitioners/specialists, physician assistants, medical assistants, pharmacists, dieticians, advanced practice providers, and social workers, to ensure that care is holistic and meets the needs of every individual person. This also needs to include those outside of gastroenterology, including the likes of other specialists (e.g., rheumatology), surgical teams, primary care providers, radiology, pathology, behavioural health specialists, and support service providers, to name but a few. 

Discussion continued about the need to think about preventative care, such as immunisations, bone health and cancer, and how this should be optimally achieved with other healthcare professionals and people with IBD. Ideally, healthcare maintenance should be co-managed between specialists and primary care providers; however, this is not always the case, leaving people with IBD feeling ‘lost’. Specialists in those circumstances recommend checklists to help ensure preventative measures are considered from the outset.

Access to care also needs to be fit for purpose, combining in-person care, telephone care, urgent care, support services, electronic access to information, data, and services, and education. In terms of looking forward, we have already seen a glimpse of what the future of healthcare will look like as a result of the COVID-19 pandemic. The likes of remote monitoring, telehealth and self-scheduling are likely to increase, and should be used in the right situations, dependent on the specific needs and wishes of people with IBD. Laura finished by saying, “patients are expecting care on their terms”, which is indeed a fitting way to summarise the changing healthcare provider-patient relationship as we move in 2021 and beyond. 

AIBD 2020: A Lens on COVID-19 and IBD

I enjoyed attending the session “A Lens of COVID-19 and IBD”, specifically those chaired by Dr. Maria Abreu, Dr. Michael Kappelman and Dr. Brennan Spiegel. We reviewed some basics of COVID-19 pathophysiology, updates from data gathered from the Secure-IBD Registry, European updates and the role of digital health in IBD in the era of COVID-19. 

If you want a little background or review of the virus before we dive in, COVID-19 is a single-stranded RNA virus that is spread primarily by respiratory droplets (coughing, sneezing, etc.). We know that disease severity of COVID-19 varies greatly, from some people being completely asymptomatic to those who are so ill they need care in the ICU. They can include, but are not limited to, fever, cough, shortness of breath, nausea, vomiting and diarrhea. Studies have shown that patients can have prominent GI symptoms, especially in patients who are hospitalized. 

Good news that we have found out through studies are: 

• IBD patients are not more susceptible to COVID-19 than others - there is not evidence supporting this so far. 

• COVID-19 is present in stool and can infect cells grown in a culture in a lab, but there are no known cases from contaminated stool. 

• Biologic medications, such as anti-TNFs (think Humira), JAK-inhibitors (think Xeljanz) or anti-interleukins (think Stelara) seem to be potentially beneficial in COVID-19 infection. Some of these therapies are being looked at further as potential COVID-19 treatments.

Some information that we know could potentially make COVID-19 worse in IBD patients: 

• COVID-19 causes dysbiosis in the microbiome, and we know that there is a relationship between dysbiosis and disease severity.

• A study from the Veterans Affairs (VA) system showed that COVID-19 severity was more dependent on comorbid conditions than being on thiopurine medication. This means that the more chronic conditions you have, the more likely a course of COVID-19 is to be severe. 

• Broad immunosuppression appears to lead to worse outcomes. So, taking a medication like prednisone that broadly suppresses all arms of your immune system is not ideal. However, if you are in a situation where your body needs prednisone, then your GI provider may weigh the risks/benefits of these medications. 

• There is some data that suggests that mesalamine and sulfasalazine medications could lead to slightly worse COVID-19 infections. 

The next segment of this discussion focused on updates from the Secure-IBD registry, a voluntary reporting system for COVID-19 occurring in IBD patients that started in mid-March. This system has been utilized by IBD providers in 62 countries and 47 US states as of late November. The mean age reported in 40 years old, and 57% of patients have Crohn’s disease. From the data we have, it is difficult to say if there is true increased mortality risk in IBD patients since we need more data and we are still learning about this novel virus. Here are some highlights from the other statistically significant data from the registry: 

• Pediatric IBD patients appear to do quite well, which is in line with findings from the rest of the pediatric population. 

• There is a strong trend with increasing age by decade and need for hospitalization and even death, but this also matches data on non-IBD patients. 

• IBD patients with COVID-19 do have more GI symptoms, with abdominal pain and diarrhea being hallmark. 

• Anti-TNF biologics seem to have a protective effect against COVID-19, and this matches data coming from the rheumatoid arthritis (RA) community as well. 

• Combination therapy with immunomodulatory medications seems to lead to more requirements for ICU admission or severity, but this will continue to be closely monitored as more data is gathered. 

Lastly, we looked at the role of digital health in IBD; Dr. Brennan Spiegel has been doing research with virtual reality (VR) headsets with his IBD patients, specifically as a way to target intractable abdominal pain and other forms of chronic pain that IBD patients deal with in the hospital setting. VR has long been used in studies about pain and perception, and was found to reduce anxiety and self-administered Propofol (that nice sleepy drug we all get!) during routine colonoscopies back in the 1990s. For many of us watching, we are so excited to see a non-pharmacological treatment utilized for IBD patients. We hope this can become widely available and affordable for all patients and that we can find ways to use it in outpatient settings. If you are interested, Dr. Spiegel suggested visiting virtualmedicine.org and clicking under the “Clinical Tools” link to learn more and explore products. Do you think using VR as a way to treat pain could be a long-term addition to a comprehensive team approach to treatment? 

It was great to hear from multiple experts about COVID-19 and IBD. I think that, all in all, the data so far shows that we are not as high risk compared to the general population as we originally thought. I find it hopeful that some of the biologic medications many of us take are considered to be protective. Yet, the most important things we can do now is to continue to be careful, social distance, wash hands, and wear your masks religiously. I hope to see digital tools continue to be utilized not only with telemedicine appointments, but with ways to innovate and find treatment options such as VR that complement medical treatments for IBD.

AIBD 2020: Advances in Pediatric IBD

On the final day of AIBD, the session I chose to focus on for this article was “Advances in Pediatric IBD”, which included presentations from Dr. Anne Griffiths, MD, FRCPC, Dr. Joel Rosh, MD, FACG, and Dr. Carlo Di Lorenzo, MD.

Dr. Griffiths opened with a review of the advancements in pediatric IBD throughout the year. In her presentation, she noted that early use of anti-TNF therapies are associated with remission and a decreased risk of disease progression later on in life. This led into Dr. Rosh’s presentation on when to begin treatment with anti-TNF therapies. Dr. Rosh noted that while 40% of pediatric Ulcerative Colitis (UC) patients can maintain steroid-free remission with mesalamine, the remaining 60% of pediatric UC patients are likely to need immune-modifying therapy.

When determining which biologic to use on pediatric IBD patients, Dr. Rosh listed that some of the factors include:

• Time of disease onset

• Biomarkers (the patient’s test results)

• Safety and efficacy of the treatment

• Psychosocial aspects and the opinion of the pediatric patient themself

The presentation on pediatric IBD included what was, in my opinion, a well-rounded approach to holistic care. The doctors spoke to the importance of mental health care, and other lifestyle factors that may have a role in a patient’s symptoms. The majority of this information came from Dr. Lorenzo’s presentation on “Therapeutic Approaches to Functional Bowel Disorders in Children with IBD”. In other words, his presentation covered the segment of the pediatric IBD population that also suffers from Irritable Bowel Syndrome (IBS). Dr. Lorenzo explained in his presentation that approximately 35% of IBD patients fit the criteria for IBS as well, and it is especially common in patients with Crohn’s disease. Even I myself have been diagnosed with having IBS and IBD.

This combination of IBD and IBS in patients can affect multiple aspects of a person’s quality of life, including but not limited to increased fatigue, anxiety and depression. In order to combat this negative impact on mental health and quality of life, Dr. Lorenzo outlined steps that a patient and their care team can make, which I have listed below:

• Involve mental health providers earlier on in the patient’s care. In some clinics they even have providers who specialize in mental health for IBD patients.

• 30 minutes of daily exercise is associated with decreased symptoms. This does not necessarily mean vigorous exercise (as that can be challenging for many of us with chronic illness) - but even a walk around the neighborhood can improve a patient’s well being.

• Providers are encouraged to teach parents to respond to their children with reassurance. This was associated with a decrease in pain among the children.

• Symptoms may worsen with less sleep. Healthy sleeping habits can increase a patient’s quality of life.

As someone who was diagnosed at a young age, and was introduced to the world of IBD as a pediatric patient, I enjoyed this talk and seeing the advancements that are being made for the pediatric community. After attending AIBD this past week, I look forward to the future of IBD treatment and advancements with confidence and positivity.

AIBD 2020: Optimal Management of Clostridium Difficile Infection (CDI) and CDI Recurrence in Patients With IBD

C. difficile is a naturally occurring gut bacteria which is harmless, until the gut bacteria balance gets altered by antibiotics, allowing C. difficile to multiply. This is when it becomes an infection, leading to diarrhea and potentially causing serious bowel issues. Many cases of C. difficile infections occur in a healthcare setting because of their links to antibiotic therapy.

As mentioned in my previous article, a C. difficile infection (CDI) can be incredibly destabilising for IBD patients and can cause flare-ups even in patients who had previously been in deep remission. Hence, to know more about CDI and IBD, I attended the AIBD 2020 CME Symposium on ‘Optimal Management of Clostridium Difficile Infection (CDI) and CDI Recurrence in Patients With IBD’. 

The first talk in the symposium was given by Dr Sahil Khanna on the epidemiology, risk factors, and diagnosis of C. difficile infections in IBD patients, and here are the key takeaways from his presentation - 

• The number of patients with C. diff infections is rising every year, and so is the proportion of patients with both IBD and C. diff.

• The risk of recurrent C. diff infections is higher for patients with IBD compared to patients that do not have IBD.

• Risk factors for CDI in IBD - antibiotic use, prior CDI, colonic disease, active/uncontrolled IBD, active immunosuppression (biologics), chemotherapy, long-term hospitalisation, surgery

• Patients with IBD and CDI are more likely to not respond to IBD therapy, undergo surgery, have more frequent ER visits/hospitalizations, greater recurrence and mortality rates, and incur higher healthcare costs compared to IBD patients with no CDI.   

• All IBD patients with a flare should be tested for CDI because of overlapping symptoms.

• A PCR test is insufficient for testing CDI. A 2-step algorithm comprising of GDH and EIA is desirable.

The second talk in the symposium was given by Dr Ari Grinspan on the treatment of CDI, and the important points of his presentation, from a patient perspective, are listed below - 

• IBD patients are at a very high risk of CDI recurrence.

• FMT is a safe and effective option for treating recurrent CDI. It has a cure rate of 80-90% among IBD patients with recurrent CDI and the probability of a post-FMT IBD flare is very low. It also improves the microbiome diversity. 

• FMT should be done earlier, perhaps after a 1st recurrence of CDI, for better long-term results.

• Escalation of IBD therapy after a C. diff infection is safe.

• COVID hasn’t increased CDI rates, but patients with diarrhoea should be checked for CDI.

• OpenBiome (stool bank) is on a temporary clinical hold because of COVID, hence, FMT for recurrent CDI is on hold at many centres. 

The symposium concluded with case discussions and a Q/A session, of which an important point to note was

• Probiotics have no role in the treatment of CDI among patients with IBD. Recent research has shown that probiotics may not only be ineffective at preventing recurrence but may even cause harm. 

The symposium, although directed at clinicians, was enlightening to me as a patient. Chronic illness takes over almost every aspect of our lives, and as a patient, the more knowledge and information we have about what we are dealing with, potential scenarios, control measures, the more we feel at ease and are able to move forward with life without having a constant fear of the unknown. This information is even more valuable to patients living in regions with substandard healthcare facilities and/or are financially strained. I’ve thoroughly enjoyed AIBD 2020 so far, and even though many sessions have been technical, it has really increased my understanding of my condition, and also made me aware of my own lapses in self-care. I hope this article helps you in similar and other ways. 

Thank you! Stay safe :)

AIBD 2020: Talking Nutrition with Your IBD Patients

On the first day of AIBD 2020, one of the breakout sessions I attended was “Talking Nutrition with Your IBD Patients.” Led by Dr. Maria Abreau from the University of Miami Miller School of Medicine, she was joined by Ashwin Ananthakrishnanan, MD, MPH (Massachusetts General Hospital and Harvard Medical School); Kelly Issokson, MS,RD, CNSC (Cedars-Sinai); Andrew Grossman, MD (Children’s Hospital of Philadelphia); and Mark Mattar, MD, FACG (MedStar Georgetown University Hospital). 

I want to start out by saying that this session and what was discussed made me extremely hopeful for the future of patient care when it comes to incorporating and implementing complementary therapies. The word complimentary was used to highlight the fact that dietary therapies are not necessarily alternative therapies, but can play a role in and be an integral part of treating mild to moderate IBD. 

As Dr. Abreau mentioned, too often patients are told by doctors that food doesn’t matter, and that they’ll come to her and say, “My last doctor said it doesn’t matter what I eat.” 

Having personally experienced this exact situation firsthand, when a doctor once told me that no food will affect me except for popcorn and Chinese food, to hear an expert in the field finally say that, “You lose the patient’s trust when you tell that diet doesn’t have anything to do with it,” is in itself a step in the right direction. Her hope is that those who joined this session, which was specifically centered around approaching and having discussions about nutrition with patients, will have at least learned not to say that it doesn’t matter what you eat. I share that same hope. And no, this does not mean that food causes IBD, and it certainly doesn’t mean that food can cure IBD - this just means that food, something that is a part of our everyday lives, does play a role when it comes to your body. It means that both the progression and management of the disease, as well as the process of bringing one closer to remission, need to be seen with a multi-faceted lense. 

The presentation consisted of addressing a variety of patient scenarios, from the management of stricturing of Crohn’s disease to a teenager with growth stunting. By going through each case and discussing their individual situations and needs, this inherently showcases how incredibly individualized both IBD and nutrition are. 

When discussing the presence of strictures in patients, as seen in one of the patient cases discussed, the panel brought up an important point. While this is a scenario where low fiber needs to and should be emphasized, low fiber is brought up much more often than it should be. It ends up being the default suggestion to everyone, which is not beneficial, and can actually be harmful. Instead, patient individuality needs to be at the forefront. 

There were a few distinct common threads that were woven through each of the cases that I want to especially highlight below. 

1: The importance of Mental Health/Mindset Surrounding Food

• As a patient, it gives me hope that doctors and dieticians are working together and having discussions about helping patients with the very real food avoidance/ food fear that can come with IBD by focusing on not only mindset reframing, but also their own verbiage. It is critical to help patients establish a better relationship with food as part of their healing, and this is something that requires support, which I’ll dive into soon when addressing the importance of working with a dietitian who is well-versed in IBD. 

• Too often, it creates great duress in patients when they are presented solely with a seemingly-never ending list of foods that are off limits to them; the thought of food elimination alone can be triggering on top of an already overwhelming situation. Instead of solely focusing on, “What do I need to avoid?” it’s imperative to help shift it to “What CAN I eat?” (like proven anti-inflammatory foods). In doing so, it’s also important that more doctors begin to make it clear to patients that in a setting of active inflammation, food intolerances may be different than they are in remission. 

• The fact that these conversations are being had and these changes are being made on a professional level is going to be of immense benefit to both the physical and mental health of IBD patients. 

2: The Importance of Nutritional Status 

• Assessing and addressing nutritional status in IBD patients is a must, both in general and in those on dietary therapies when any kind of elimination is involved. This includes vitamin b12, d, iron, etc.  

• As I learned in another session, “Infectious Complications in IBD and How to Manage the Patient with Ongoing Infection,” malnutrition increases the risk of infections in IBD patients. Intervening early and being vigilant in respect to nutritional status is imperative to mitigating additional repercussions. 

3: The Importance of Working with a GI-trained Dietitian 

• To sum it all up, one of the most prominent threads woven throughout this session was the need for quality, accessible dietitian support. All of the above points come back to this one; because there is wide variability in which foods can trigger symptoms in an individual, because food fear is a very real thing, and because malnutrition can lead to even more complications, all experts on the panel recommend seeing a GI/IBD focused dietician. 

• It’s imperative to know that nutritionists are NOT registered dieticians. Yet, as patients, it can often be difficult and challenging to identify and find true GI or IBD focused dietitians. To help with this, as Kelly Issokon suggested, these following sites have searchable databases to locate one:  

  • https://iffgd.org

  • https://www.eatright.org

I hope that with resources and insights like the ones above, and with conversions like these, access to dietary therapies, information about dietary therapies, and the ability to succeed with dietary therapies (again, as complementary therapies, not necessarily alternative therapies), will become more attainable and feasible for all IBD patients. 

AIBD 2020: Highlights of IBD Publications in 2020

As part of the Advances in Inflammatory Bowel Diseases (AIBD) conference, I joined Session V: 2020 Editor’s Focus, introduced by Miguel Regueiro and moderated by David Rubin. In the session, David, alongside Gary Lichtenstein, Jean-Frederic Colombel, and Raymond Cross showcased some notable pieces of research that had been published in various gastroenterology journals throughout 2020. These were followed by the best clinical abstract research presentation by Shintaro Akiyama, and a summary of the pregnancy and IBD study called ‘PIANO’ by Uma Mahadevan.

Notable papers from four different gastroenterology journals were discussed. The journals included Gastroenterology https://www.gastrojournal.org, the American Journal of Gastroenterology https://journals.lww.com/ajg/pages/default.aspx, Clinical Gastroenterology and Hepatology https://www.cghjournal.org, and Inflammatory Bowel Diseases® https://academic.oup.com/ibdjournal.

Managing IBD during the COVID-19 pandemic

David Rubin and colleagues published an article about managing IBD during the COVID-19 pandemic (https://www.gastrojournal.org/article/S0016-5085(20)30482-0/fulltext). The key take home messages from this article were that:

1. people with IBD do not appear to be at a high risk for infection with SARS-CoV-2, the coronavirus which causes COVID-19;

2. People with IBD who aren’t infected with SARS-CoV-2 should not stop their IBD treatment;

3. People with IBD who are infected with SARS-CoV-2 but have not developed symptoms of COVID-19 should temporarily stop methotrexate, thiopurines (e.g. azathioprine, 6-mercaptopurine, thioguanine), and tofacitinib, while delaying biologics for two weeks while monitoring for symptoms of COVID-19;

4. People with IBD who develop COVID-19 should temporarily stop methotrexate, thiopurines, and tofacitinib, and biologics, until their symptoms have gone, or if available, when a follow-up test comes back negative;

5. The severity of COVID-19 and IBD should result in a careful risk-benefit decision regarding COVID-19 treatment and IBD treatment.

One study by Erica Brenner and colleagues (https://www.gastrojournal.org/article/S0016-5085(20)30655-7/pdf) found that steroids, but not anti-TNF biologics (e.g., adalimumab, certolizumab, golimumab, infliximab), are associated with worst COVID-19 outcomes in people with inflammatory bowel diseases (IBD), providing some reassurance for those on anti-TNFs.

Identifying people with Crohn’s disease who are more likely to fail on certain biologics

Aleksejs Sazonovs and colleagues in the UK published a paper (https://www.gastrojournal.org/article/S0016-5085(19)41414-5/abstract) which looked at a new way of potentially predicting those people with Crohn’s disease who may develop anti-drug antibodies to infliximab and adalimumab. When people develop anti-drug antibodies to biologics, they can become ineffective, resulting in a change in treatment. This study found that a particular variation of a gene, called HLA-DQA1*05, was linked with an increased chance of developing anti-drug antibodies to infliximab and adalimumab in people with Crohn’s disease. Although further research is needed, if this finding is proven, it could mean that people with this type of gene could be identified before starting treatment, so that they could be placed on different treatments or combinations of treatments to help prevent the development of anti-drug antibodies.

Low FODMAP diet does not influence microbiome

Cox and colleagues performed a study in people with inactive IBD looking at the FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diet. They looked for an effect on symptoms, the fecal microbiome, and markers of inflammation. Although a low FODMAP diet appeared to improve irritable bowel symptoms, the researchers did not find any difference in the composition of the microbiome and markers of inflammation. They concluded that they don’t really know whether a low FODMAP diet has anti-inflammatory effects for those with IBD.

Safety of newer medicines called JAK inhibitors

Olivera and colleagues looked at the safety of a newer type of medicine used to treat IBD (and other immune-related conditions) called JAK inhibitors (short for Janus Kinase inhibitors). The only JAK inhibitor medicine approved in Ulcerative Colitis is called Tofacitinib, although there are others available and licensed in rheumatology. The researchers looked for the risk of serious infections and infection with the varicella-zoster virus (herpes zoster infection). Compared to other treatments, serious infection risk with JAK inhibitors were no different than other treatments used. However, there was an increased risk of herpes zoster with JAK inhibitors. Therefore, people starting these treatments should receive a vaccination against herpes zoster.

Differences in IBD gut microbiota

Pittayanon and colleagues looked for differences in gut microbiota in people with and without IBD. Although some differences between Crohn’s disease and ulcerative colitis were seen, the researchers concluded that while there were some differences between people with and without IBD, these findings were not consistent. 

Promising results from a new biologic called Mirikizumab

Sandborn and colleagues presented findings from a Phase 2 clinical study on a new biologic called mirikizumab in people with ulcerative colitis. Mirikizumab is known as an anti-IL-23 biologic, since it attaches to IL-23, an inflammatory molecule in the body involved in IBD.  The study looked at clinical remission, clinical response and improves on endoscope at 12 weeks. The results were positive and showed that the 200 mg dose seemed to be more effective than 600 mg. As a result, mirikizumab would move into a larger phase 3 clinical study in a larger group of people.

Subcutaneous injection of vedolizumab in ulcerative colitis

Sandborn and colleagues also looked at the effects and safety of vedolizumab as a subcutaneous (under the skin) injection, compared to intravenous vedolizumab, which is how it is currently given. In people with ulcerative colitis, the subcutaneous injection had the same effects and safety as the intravenous version. The researchers now wait for the subcutaneous injection to be approved by the medicine regulators. They then expect doctors to begin moving some people with ulcerative colitis over to the subcutaneous injection, which may provide some more convenience for people to fit treatment around their daily lives.

New oral medicine called Etrasimod appears to be effective in ulcerative colitis

Sandborn and colleagues found that a new medicine called Etrasimod at a dose of 2 mg was more effective than placebo, and the study would be progressing from a Phase 2 to Phase 3 study in ulcerative colitis. Etrasimod is a next-generation, once-daily, oral treatment which changes signals within cells involved in inflammation.

Another new oral medicine called Mongersen does not appear to be effective in Crohn’s disease

Sands and colleagues published the findings of a phase 3 study of Mongersen, an oral medicine that targets inflammatory signals in gut cells, in people with Crohn’s disease. Although the phase 2 study showed promising results, the phase 3 study was disappointing, showing that clinical remission was no more likely with mongersen than with placebo. The researchers said that reflections on the negative results led to another piece of research to help them learn why the results of this study were negative. These reflections showed how it is important to ensure that the study design is well thought out. They noted that the phase 2 study was performed in a small number of hospitals in Italy, and pointed out that collecting study data from a single centre can risk the future results of studies.

Other research highlights published in IBD journals throughout 2020

• Antibiotic-resistant intestinal microbiome can persist in people with pouchitis.

• A number of different biomarkers (biological clues) were found to be present years before an IBD diagnosis. This understanding may lead to the development of future trials to prevent IBD for people who are at higher risk, or at least to help ensure people are diagnosed earlier on.

• Home infliximab infusions cost more than office and hospital infusions. Home infusion-based patients were also seen to be more likely to not adhere to their treatment, compared to office and hospital-based infusions. 

• Further studies are required to understand whether further treatment is needed after people have been in hospital with IBD to prevent acute venous thromboembolism (blood clot) within 60 days of being in hospital.

• Imaging of the anus using Magnetic resonance (MR) enterography can reveal unsuspected perianal fistulas in people with Crohn’s disease. 

• IBD-attributable hospital costs declined modestly over time for people with Crohn’s disease, but did not change for people with ulcerative colitis.

• Anxiety and mood disorders increased the risk of stopping anti-TNF biologics, especially during the first year following treatment initiation in over 1000 patients.

• Curcumin was shown to not be effective in preventing post-operative recurrence of Crohn’s disease.

• A Mediterranean diet can improve body composition, liver steatosis and disease activity in IBD. 

• High levels of certain while blood cells called eosinophils is more common in paediatric-onset IBD and is associated with a more severe disease course.

• Primary sclerosing cholangitis-ulcerative colitis (PSC-UC) is a milder form of ulcerative colitis and should be regarded as a unique form of UC. People with PSC-tend to be younger at diagnosis and have milder disease severity, despite being more likely to have inflammation of the entire colon. Response to treatment similar to people with ulcerative colitis.

• Daily aspirin use is not associated with worsening IBD. 

• Infliximab is not associated with excess weight gain in women with IBD.

• Cumulative histologic disease activity is associated with neoplasia in chronic colitis. 

• Anti-TNF biologic use is associated with lower rates of colon cancer, as shown by analysis of the Explores EMR database between 1999 and 2020. Anti-TNF biologics on their own or given with other treatment reduced the rate of colon cancer.

• The prevalence of anxiety, depression, and post-traumatic stress disorder (PTSD) over a 15-year time period in veterans with IBD was shown to be increasing. 

• High dose flu vaccinations are associated with better response to vaccine in people receiving anti-TNF biologics. 

• A Canadian based study in 2016 estimated the cost of IBD, at $ 498 bn for Crohn’s disease, and $ 377 bn for ulcerative colitis. Pharmacy costs were shown to have the largest incremental cost. 

• Direct healthcare costs attributable to IBD have more than doubled over 10 years between 2005 and 2015, driven mostly by increasing expenditures on biologic medicine. 

• The Crohn’s and Colitis Foundation’s Cost of IBD Care Initiative also reported the cost of IBD care to be high. From a study with over 50,000 people with IBD, the average direct costs per year were $ 22,987 per person. Costs per year increased significantly from 2013, driven by the cost of biologics, opioids, steroids, and emergency department use, among other factors.

• High deductible health plans do not decrease costs and are associated with delays in essential care.

Best clinical abstract research presentation - winner of the best clinical abstract

Shintaro Akiyama looked at contributing factors for fistula development in people with IBD treated with proctocolectomy (surgical removal of the colon and rectum), with ileal pouch-anal anastomosis (J-pouch surgery). He found that pouchitis (inflammation of the lining of a pouch created during surgery) can develop in up to 70% of people with IBD after J-pouch surgery. He also highlighted that not all instances of pouchitis are the same, which has led to the development of the Chicago Classification of Pouchitis. He concluded that deep inflammation of the resected colon is a specific predictor for fistula formation in J Pouch, and so people with this may require closer monitoring by their healthcare teams.

Pregnancy and IBD - The PIANO study

Uma Mahadevan talked about the 12-year PIANO study, which included over 1700 pregnant women with IBD in the US. The study is still ongoing and still recruiting those on biologics or small molecules. Of 1490 women with a pregnancy outcome, the average maternal age at delivery was approximately 32 years, with a total pregnancies averaging 2.1. The womens’ disease duration was around 8.3 years, with 62% having Crohn’s disease, 36% having ulcerative colitis, 2% having undifferentiated IBD. Most of them were on infliximab, followed by adalimumab, certolizumab, golimumab, natalizumab, vedolizumab, and ustekinumab. 51 women had multiple biologic exposure (mostly with other anti-TNF biologics).

She concluded that exposure to biologic, thiopurine or combinations of treatment during pregnancy was not associated with increased negative maternal or fetal outcomes at birth or within the 1st year of life. Disease activity of the mothers is an independent risk factor for spontaneous abortion, and preterm birth increased the risk of infant infections.

Healthcare professionals should continue biologic and/or thiopurine therapy throughout pregnancy and lactation, given no evidence of increase in harm from drug exposure and the clear association of active disease with side effects.

AIBD 2020: The Role of FMT in IBD

I attended the Clinical Breakout Session titled ‘Role of FMT in IBD’ chaired by Dr Jessica Allegretti. On the panel were Dr David Binion, Dr Alan Moss, and Dr Monika Fisher.  

Fecal Microbiota Transplant, or FMT, is one of the emerging treatment options for IBD. It is considered as an effective treatment option for C.Difficile infections. As around the world, several clinical trials are underway in India as well. It can be an attractive option for patients in a country like India, where biological therapy is expensive and not covered by insurance. As a result, patient interest in FMT has increased considerably in recent times. 

Although the session was not aimed at a patient audience, I absorbed a significant amount of information that can be useful for patients. Some of the key points to note as a patient were:

• A C.Difficile infection (CDI) is very destabilising for someone with Inflammatory Bowel Disease (IBD). Even patients who have been in deep remission for years can suddenly experience flare-ups post a C.Difficile infection. Hence, it is of utmost important to treat the infection as early as possible in patients with IBD.

• Patients with IBD have a 50% chance of recurrence of C. Difficile infection post-treatment with a 10-day Vancomycin course. 

• COVID has impacted the availability of FMT as a treatment. 

• IBD therapy may need to be ramped up post a CDI, but high-dose steroids should be avoided. 

• Diet can be considered in some regards as a prebiotic and influences the microbiome, which can have significant effects on the clinical course of a patient.

• Patients with mild disease (ulcerative colitis specifically) benefit the most from FMT.

• There is very little data to support the usage of FMT for the treatment of patients with Acute Severe ulcerative colitis. 

• For some patients with mild-to-moderate Crohn’s/colitis, FMT may be beneficial.

• FMT is not yet FDA approved for the treatment of IBD in the absence of CDI. It has to be done in a clinical trial setting.

• FMT can be done for patients with internal pouches as well. The success rate is almost the same as for IBD patients without a pouch.

• Colonoscopic delivery of FMT seems to be more effective and provides the best results.

• Retention of donor material can be an issue for patients. The therapy still works even if some material comes out.

• Sometimes, patients can be sedated to take a small nap post the procedure to avoid loss of material.

AIBD 2020: Clarifying Complications of Therapy

One of the sessions I delved deeply into on the first day of AIBD was “Clarifying Complications of Therapy”, which began with a presentation by Dr. Laurent Peyrin-Biroulet, MD from Nancy University Hospital, on malignancy (cancer) in IBD patients. Following Dr. Peyrin-Biroulet, was a presentation on infectious complications in IBD, by Dr. Edward V. Loftus Jr., MD from the Mayo Clinic.

Before delving into the details of risks and complications associated with immunosuppressive therapy, let us first outline which factors play into how immunosuppressed an individual is. First and foremost, not every patient with IBD is inherently immunosuppressed, rather only those who are on immunosuppressive medications fall into this category. Even amongst patients on the same drug, the following factors alter the amount of immunosuppression an individual may experience:

• Increased age

• Malnutrition

• Comorbidities

• Medications

• Hospitalization

In other words, if two patients are both on the same immunosuppressive drug, but patient A is 20 years old with no comorbidities, and patient B is 60 years old and has COPD, patient B may be at a higher risk.

During the presentation on cancers in IBD patients, Dr. Peyrin-Biroulet noted that the focus was on anti-TNF drugs specifically, and that no robust data was available for other immunosuppressants. I want to make note of that, because this data does not speak for all IBD treatments, or all IBD patients.

Three of the cancers that were discussed in this presentation were skin cancers, lymphoma, and cervical cancer, all of which are associated with heightened risk in IBD patients who are immunosuppressed. That being said, Dr. Peyrin-Biroulet noted certain measures physicians can take to mitigate these risks as much as possible. I’ve created a simplified outline below for each of the cancers discussed:

Skin Cancer

1. Risk: there is an increased risk of non-melanoma skin cancer in IBD patients.

2. Prevention: use of sun protection and skin surveillance.

Lymphoma

1. Risk: there is a risk of lymphomas in IBD patients who are immunosuppressed.

2. Prevention: avoid more than 2 years of combination therapy in young males, and for older males who have tested positive for Epstein-Barr in their past, restrict the use of thiopurine drugs such as 6-Mercaptopurine (6MP), and azathioprine, as they may pose a greater risk of lymphoma in the patient.

Cervical Cancer

1. Risk: there is an increased risk of cervical dysplasia and cervical cancer in IBD patients.

2. Prevention: HPV vaccine is recommended to protect against HPV, which may lead to cancer.

In addition to Dr. Peyrin-Biroulet’s presentation on cancers associated with IBD and immunosuppression, Dr. Loftus spoke to the increased risk of other types of infections among immunosuppressed IBD patients. This included an increased risk of fungal infections, an increased risk for herpes zoster, and the importance of testing (and if necessary, treating) tuberculosis prior to starting anti-TNF therapy. 

In the presentation, Dr. Loftus included a table that I found interesting and informative on determining whether or not to pause immunosuppressant treatment for IBD during an infection, in addition to treating the infection. I’ve simplified the table below, and added examples to the different drug classifications. Please note to consult with your doctor before making any changes to your actual drug treatment plan.

For Thiopurine (Including azathioprine and 6-mercaptopurine [6MP]):

1. Viral: you may need to stop immunosuppressants

2. Bacterial: stop, then individualize plan

3. Fungal: stop, then restart when cleared

4. C.Diff: continue

For Anti-TNF (Including but not limited to infliximab and adalimumab):

1. Viral: probably OK to continue (exception of Hepatitis B)

2. Bacterial: stop, then individualize plan

3. Fungal: stop, then restart when cleared

4. C.Diff: continue

Anti-Integrins (Including but not limited to vedolizumab):

1. Viral: continue

2. Bacterial: continue

3. Fungal: continue

4. C.Diff: continue