Highlights from our 2024 meeting in Sydney
We were thrilled to welcome over 180 Australian Gastroenterologists and Rheumatologists to our COMPASS meeting, held in Sydney at the end of July. The latest news in clinical immunology was covered by an expert Australian faculty, who were joined by international keynote speakers:
- Dr Tim Raine (IBD team lead, Addenbrooke’s Hospital, Cambridge, UK).
- Prof. Iain McInnes (Muirhead Professor of Medicine and Versus Arthritis Professor of Rheumatology, University of Glasgow, Scotland).
- Prof. Kevin Winthrop (Professor of Public Health and Infectious Diseases, and Ophthalmology, at Oregon Health & Science University, USA).
The overall aim of the COMPASS program is to facilitate collaboration and advance shared care for patients living with chronic inflammatory diseases, and we wanted to share with you some of the key Gastroenterology-focused highlights from the weekend.
How are we using (and abusing) steroids in IBD?
Presented by Dr Tim Raine
Although there may be the perception that corticosteroids (CSs) are used relatively sparingly in modern clinical practice, Dr Tim Raine began his talk on steroid use in inflammatory bowel disease (IBD) by challenging that concept.
Evidence from European IBD cohorts and a US healthcare claims database shows that while, unsurprisingly, CSs are particularly used in the first year after diagnosis, it is a treatment that clinicians continue to go back to throughout the patient journey in both Crohn’s disease (CD) and ulcerative colitis (UC).1–3 In fact, excess use of CSs* were reported in as many as 10–15% of IBD patients in the US database over time.3
The DICE prospective study (>2,600 patients, 7 European countries) showed that patients with the highest risk of excess CS use are those with moderate-to-severe disease and ongoing symptoms – in this risk group, excess use was reported in 37.5% of CD and 53.5% of UC patients.4 Furthermore, a UK multi-centre audit showed that while 30% of patients with IBD (n=1,176) had CS exposure, 14.9% showed excess use; and in 7.1% of the total cohort this was deemed ‘avoidable excess’.5
We know that CS-sparing therapy is possible in IBD. The RINVOQ® clinical trial programmes in UC and CD have both shown that CS-free remission is achievable: in ~1 in 3 patients for the 15 mg dose and ~1 in 2 patients for the 30 mg dose after 52 weeks of maintenance therapy across both indications.6,7 But, Dr Raine asked, are we using the tools that are available?
Evidence does show that steroid prescribing behaviour can change. A follow up study of the UK multi-centre audit showed that overall CS exposure had dropped to 23.8% by 2017 (n=2,385); and excess CS exposure had dropped to 11.5%.8 Dr Raine suggested these data give us hope that behaviour change is possible when it comes to CS prescribing.
Furthermore, the analysis found that participation in a quality improvement programme was an independent predictor of a lower risk of CS excess in both CD (0.72, 95% CI 0.46–0.97) and UC (0.72, 95% CI 0.45-0.95).5,8 In the UK this led to inclusion of recommendations for use and audit of CSs in the National IBD Standards, and provision of educational tools for both patients and General Practitioners.9–11
*Excess according to definitions provided in ECCO guidelines.12,13
Indeed, a recent analysis of temporal trends in corticosteroid use, based on UK primary care data,14 revealed that CS prescriptions in the >1,000 mg/year range have tapered off over time in both CD and UC since the introduction of biologics. However, lower-dose CS exposure has remained fairly persistent in all patients.14
Interestingly, while physician reports of CS adverse effects align with the text-book complaints of osteonecrosis, adrenal insufficiency and cushingoid complications etc,15 patients tend to consider side effects differently. A recent survey of UK IBD patients (>18,000 questionnaires sent, 48.8%, n=9,229 responses) showed that 61.9% of patients using prednisolone and 27.4% of patients using budesonide experienced adverse effects.16 However, the patient steering group for the questionnaire focused on symptoms such as skin or weight changes that affected self-esteem (21.0% and 39.3% respectively with prednisolone), and sleep problems and mood disturbance (32.6% and 39% respectively with prednisolone).16
More soberingly, 4.8% of patients using prednisolone reported experiencing suicidal thoughts or attempts.16 While Dr Raine emphasised that correlation isn’t necessarily causation, he did suggest that this should be food for thought, given that the greatest risk of CS exposure occurs in the first year after diagnosis;1,2 and data from a Scandinavian cohort study indicates that adult IBD patients are at an increased risk of psychiatric morbidity and suicide in that first post-diagnosis year (hazard ratio 1.4, 95% CI, 1.2–1.6, n=69,865, 11 years follow up).17
“The best advocates for patients are the patients themselves. And educating them on what it means to use corticosteroids is vital.”
– Dr T. Raine.
So, what can be done to ensure appropriate CS use in clinical practice? The practical steps suggested by Dr Raine were to:
• educate patients, primary care givers, and healthcare professionals;
• accurately assess patients for response and toxicities;
• regularly audit your practice in terms of steroid use;
• and work towards greater access to, and consideration of, alternatives to CS use.
“Dr. Tim Raine’s presentation made an impact on many participants including myself. It was an important reminder about the necessity of decreasing steroid use for our IBD patients and the need for regular steroid-use audits at our departments. We must remind ourselves that steroids are the most damaging medication in our arsenal and that it is increasingly essential to consider alternative options when possible.”
– Dr Brandon Baraty
Fatigue, sleep and pain in IBD
Presented by A/Prof. Jakob Begun
A/Prof. Jakob Begun (Mater Hospital, Brisbane) described the triumvirate of fatigue, sleep disturbances and pain as a challenging set of symptoms that build on each other; and both impact, and are impacted by, disease activity and mental health. But how are they best tackled in clinical practice?
Underlying inflammation is a key factor in this constellation of symptoms,18,19 and effectively managing inflammation as a first step was a recurring theme. A/Prof. Begun pointed out that RINVOQ® has demonstrated a positive impact on abdominal pain scores and fatigue (measured by FACIT-F) as well as overall quality of life (measured by IBDQ) in CD clinical trials.20–23 Once inflammation is being addressed, tackling each symptom with a personalised approach that combines both pharmacologic and holistic approaches to management was recommended.
Up to 80% of people with IBD report experiencing pain,24,25 and A/Prof. Begun emphasised the importance of assessment based on location, quality, intensity, duration and timing of the pain; as well as assessment of its physical, emotional, and social impacts.24,25 In terms of chronic pain management, combining diet, exercise and psychologic management (e.g. cognitive behavioural therapy [CBT]) was recommended to accompany pharmacological pain relief.26 A/Prof. Begun advocated for a non-opioid approach that may include options such as antispasmodics and tricyclic antidepressants – opioids, he asserted, should not have a place in modern pain management in IBD outside of the peri-operative space.
Sleep disturbance is prevalent in patients with IBD, with studies indicating it may affect at least 1 in 2 patients, and is often associated with increased disease activity.27,28 Recommendations for management included education on sleep hygiene, CBT, and alternative approaches such as acupuncture, as well as a pharmacologic approach (e.g. melatonin, benzodiazapines).
Fatigue is a multifactorial issue, also affecting around 1 in 2 IBD patients, and can be a key driver in associated issues such as disability and absenteeism.29 Instruments to measure fatigue, such as FACIT-F, were suggested to be useful tools, and an emphasis was placed on assessing overall quality of life. In fatigue management, key considerations include assessing for, and addressing, nutritional deficiencies (e.g. iron, vitamin B12, micronutrients) and contributing factors such as sarcopenia, sleep disturbances and mood disorders.29 Holistic approaches such as CBT and encouraging physical activity were again recommended to complement pharmacological therapy (e.g. psychostimulants, microbiota-directed therapy.29
Obesity and IBD
Presented by Dr Lena Thin | Prof. Jerry Greenfield | A/Prof. Saurabh Gupta
Dr Lena Thin (Fiona Stanley Hospital) opened the session by giving an overview of the ever-increasing problem of obesity.30 Being obese can increase the risk of developing IBD, especially in younger patients; and has also been associated with more complex disease, lower rates of response and remission, poorer quality of life, and increased risks of hospitalisation, surgery and postoperative recurrence.31,32
Obesity has also been shown to lead to more rapid drug clearance and increased risk of loss of response in patients treated with anticytokine monoclonal antibodies.33,34 Particularly in patients with a higher visceral fat to muscle ratio.34
The question posed by Dr Thin therefore, was should obese patients who are not doing well on anti-cytokine monoclonal antibodies be switched to small molecule-based therapy? In the U-EXCEL and U-EXCEED induction clinical trials of RINVOQ® 45 mg in CD, patients across all body–mass index (BMI) groups experienced significantly improved rates of CDAI clinical remission vs placebo except for the BMI ≥25 and <30 kg/m2 group.35 However, in the U-ENDURE maintenance trial, all patients with BMI ≥25 kg/m2 in the RINVOQ® 15 mg dose group had a similar response to placebo in terms of CDAI clinical remission. But patients across all BMI subgroups had a significantly better CDAI clinical remission response vs placebo in the RINVOQ® 30 mg maintenance dose group.35
A similar picture emerged from a post-hoc analysis of the OCTAVE tofacitinib clinical study:36 differences in clinical remission vs placebo were not significant in patients with a BMI >25 kg/m2 during the induction phase. But in the maintenance phase, all BMI subgroups had a significantly improved response vs placebo in both dose groups.36 While this data is promising, Dr Thin stated that more real-world studies would be needed to confirm smallmolecule therapy as a preferred treatment choice in obese patients.
Prof. Jerry Greenfield (University of NSW) reviewed the treatment landscape in obesity, summarising that lifestyle interventions are not effective for most people, and metabolic surgery is not sufficiently scalable, leaving GLP1a therapy as a current treatment of choice. However, the TGA recently released a warning that GLP1a therapy can itself cause ileus and bowel obstruction.37 Furthermore, GLP1a-mediated delayed gastric emptying can also be a concern perioperatively, especially in options with longer half-lives.38
A/Prof. Saurabh Gupta (Sydney Adventist Hospital) then gave a summary of the challenges and breakthroughs in endoscopic bariatric therapies, including the use of endoscopic sleeve gastroplasty (ESG) and intragastric balloons. This range of options, he suggested, can be an intermediate step before, or an alternative to, traditional bariatric surgery; but should be undertaken with caution as part of a structured weight-loss program.39
However, a 2018 study showed that bariatric surgery could increase the risk of developing IBD, particularly in females, patients with CD, and those undergoing Roux-en-Y Gastric Bypass and ileo-colonic surgeries.40 On a positive note, a 2020 study found that patients who had bariatric surgery and took weightloss medication had a significantly decreased risk of developing CD and UC.41 Dr Thin suggested there could be a predictive effect after weight loss.
The potential for complications after bariatric surgery must be considered, including dumping syndrome, choleretic diarrhoea, exocrine pancreatic insufficiency, and small intestinal bacterial overgrowth.42 Interestingly, a 2020 meta-analysis of the safety and efficacy of bariatric surgery, found that adverse event profiles were similar for IBD and non-IBD patients. However, adverse event rates were higher in the Roux-en-Y Gastric Bypass group and the greatest need for further medications occurred in the CD group.43 Therefore, Dr Thin advised, if you choose to do bariatric surgery in patients with IBD, opt for sleeve gastrectomy wherever possible, and avoid it entirely in patients with CD, unless they are in remission.
AbbVie would like to extend their gratitude to the Steering Committee for helping us deliver this cross-therapeutic meeting
Dr Brandon Baraty
Head of Gastroenterology, Macquarie University Hospital
A/Prof. Britt Christensen
Head of IBD Unit, the Royal Melbourne Hospital
Dr Emma Flanagan
Head of the IBD and Pregnancy Clinic at St Vincent’s Hospital, Melbourne
Dr Hanish Bagga
Director, Brisbane Rheumatology
Dr Tina Racunica
Director, Southern Rheumatology
Dr Brandon Baraty
Head of Gastroenterology, Macquarie University Hospital
A/Prof. Britt Christensen
Head of IBD Unit, the Royal Melbourne Hospital
Dr Emma Flanagan
Head of the IBD and Pregnancy Clinic at St Vincent’s Hospital, Melbourne
Dr Hanish Bagga
Director, Brisbane Rheumatology
Dr Tina Racunica
Director, Southern Rheumatology
Abbreviations: aMs, adapted Mayo score; BMI, body–mass index; CBT, cognitive behavioural therapy; CD Crohn’s disease; CDAI, CD Activity Index; CI, confidence interval; CS, corticosteroids; ESG, endoscopic sleeve gastroplasty; FACIT-F, Functional Assessment of Chronic Illness Therapy – Fatigue; GLP1a, glucagon-like peptide-1 agonist; IBD, inflammatory bowel disease; IBDQ, IBD questionnaire; PY, patient years; TGA, Therapeutic Goods Association; UC ulcerative colitis.
References: 1. Burisch J et al. Gut 2019;68(3):423–33. 2. Burisch J et al. J Crohn’s Colitis 2018;13(2):198–208. 3. Raine T et al. Trends in corticosteroid (CS) use over time and following diagnosis in patients with Inflammatory Bowel Disease (IBD), using IBM® MarketScan®. Poster P488. Presented at the 17th Congress of the European Crohn’s and Colitis Organization (ECCO 2022), 16–19 February 2022, Vienna, Austria. 4. Wye J et al. Patterns of Corticosteroid Exposure and Excess in Inflammatory Bowel Disease: Results From the Determinants, Incidence, and Consequences of Corticosteroid Excess (DICE) Online Monitoring Tool. Poster MP110. Presented at the United European Gastroenterology Week Annual Meeting 2022. 5. Selinger CP et al. Aliment Pharmacol Ther 2017;46:964–73. 6. Raine T et al. J Crohn’s Colitis 2024;18(5):695–707. 7. Loftus EV Jr et al. N Engl J Med 2023;388(21):1966–80. 8. Selinger CP et al. Aliment Pharmacol Ther 2019;50:1009–18. 9. Royal College of General Practitioners. Inflammatory Bowel Disease Toolkit. Available at: https://www.rcgp.org.uk/ibd. Accessed August 2024. 10. Crohn’s & Colitis UK. Steroids (Corticosteroids) Information Sheet. Available at: https://www.crohnsandcolitis.org.uk/news/new-information-sheet-steroids. Accessed August 2024. 11. IBD UK. Steroid management. Available at: https://ibduk.org/ibd-standards/flare-management/steroid-management. Accessed August 2024. 12. Raine T et al. J Crohn’s Colitis 2022;16(1):2–17. 13. Torres J et al. J Crohn’s Colitis 2020;14(1):4–22. 14. Menzies-Gow AN et al. Prag Obs Research 2024;15:53–64. 15. Raine T et al. J Crohns Colitis 2021:15 (Suppl.1): S9458–9. 16. Al Sulais E et al. Patient-reported burden of corticosteroid use in inflammatory bowel disease in the UK: results from the determinants, incidence and consequences of corticosteroid excess (DICE) impact questionnaire. Oral presentation OP107. Presented at UEG Week 2022; October 8–11, Vienna Austria. 17. Ludvigsson JF et al. J Crohn’s Colitis 2021;15(11):1824–36. 18. Keefer L et al. Gastroenterology 2024;166(6):1182–9. 19. Barnes A et al. Sleep Adv 2022;3(1):zpac025. 20. Colombel JF et al. Upadacitinib therapy reduces Crohn’s disease symptoms within the first week of induction therapy. Digital oral presentation, DOP38. Presented at ECCO, Copenhagen, Denmark, March 1–3, 2023. 21. Loftus EV et al. Improvement in Inflammatory Bowel Disease Questionnaire items: fatigue, depression, anxiety, and bowel urgency in patients with Crohn’s disease treated with upadacitinib in Phase 3 trials. Poster Su1863. Presented at the Digestive Disease Week Annual Meeting, May 18–21, 2024, Washington, DC, USA. 22. Panes J et al. Induction of endoscopic response, remission and ulcer-free endoscopy with upadacitinib is associated with improved clinical outcomes in patients with Crohn’s disease. Poster P786. Presented at the 18th Congress of the European Crohn’s and Colitis Organisation, 1–4 March 2023, Copenhagen, Denmark. 23. Panes J et al. Induction of Endoscopic Response, Remission and Ulcer-Free Endoscopy With Upadacitinib is Associated With Improved Quality of Life in Patients With Crohn’s Disease. Poster P439. Presented at the 18th Congress of the European Crohn’s and Colitis Organisation, 1–4 March 2023, Copenhagen, Denmark. 24. Hardy PY et al. J Crohn’s Colitis 2022;16(9):1363–71. 25. Bakshi N et al. Pain 2021;162(10):2466-71. 26. Baillie S et al. Frontline Gastroenterol 2024;15(2):144–53. 27. Umar N et al. Aliment Pharmacol Ther 2022;56(5):814–22. 28. Barnes A et al. Intest Res 2024;22(1):104–114. 29. Borren NZ et al. Nat Rev Gastroenterol Hepatol 2019;16(4):247–59. 30. Kaazan P et al. Biomedicines 2023;11:3256. 31. Greuter T et al. UEG Journal 2020; 8(10):1196–207. 32. Weissman S et al. J Crohn’s Colitis 2021;15(11):1807–15. 33. Lim Z et al. Clin Transl Gastroenterol 2020;11(9):e00233. 34. Zhi T et al. Clin Transl Gastroenterol 2024;15(7):e00722. 35. Loftus N et al. Engl J Med 2023;388:1966–80. 36. Faraye FA et al. Aliment Pharmacol Ther 2021;54:429–40. 37. Therapeutic Goods Association. Product Information safety updates - June 2024. Available at https://www.tga.gov.au/ news/safety-updates/product-information-safety-updates-june-2024 accessed August 2024. 38. Raven L et al. Med J Aust 2024;220(1):14–6. 39. Abu Dayyeh BK et al. Gastroenterology 2017;152:716–29. 40. Canete F et al Aliment Pharmacol Ther 2018;48:807–16. 41. Kochhar GS et al. Aliment Pharmacol Ther 2020;51:1067–75. 42. Singh A et al. Inflamm Bowel Dis 2020;26(8):1155–65. 43. Garg R et al. Obes Surg 2020;30(10):3872–83.
This newsletter was commissioned and sponsored by AbbVie Pty Ltd. The views and opinions expressed in the presentation highlights are those of the presenters and do not necessarily reflect those of AbbVie Pty Ltd. AbbVie does not endorse the use of unregistered products or products outside of their registered indications. Please consult the full Product Information at www.ebs.tga.au for any medication mentioned in this article.
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AU-ABBV-240193. September 2024