The meanwhile 11th Swiss IBD Roadshow (10. – 12. June 2024) took place this year under the title “ADVANCED THERAPIES IN IBD – TOWARDS A NEW SEQUENCE”. Between his lectures in seven Swiss centers, Prof. Laurent Peyrin-Biroulet from Nancy University Hospital, France, shared his experiences and thoughts on advanced therapies and treatment procedures in inflammatory bowel disease (IBD). He highlighted the effectiveness of recent additions to the treatment landscape and called for a closer analysis of the risk-benefit profile of available therapies.
Roadshow interview with Prof. Laurent Peyrin-Biroulet, Gastroenterology, Nancy University Hospital, Vandoeuvre-les-Nancy, France
How have the treatment algorithms for IBD evolved in recent years, especially after the introduction of the STRIDE II guidelines?1
The STRIDE I guidelines already taught us to treat patients beyond the symptoms, i.e. to also treat the inflammation in the gut.2 An important addition from the STRIDE II guidelines is the use of biomarkers such as calprotectin, which is now part of everyday practice thanks to growing evidence. In addition, we now work with short-, medium- and long-term treatment goals. In the short term, we want to alleviate symptoms, in the medium term we want to achieve remission with regard to biomarkers and in the long term we aim for endoscopic healing and a return to normal life for patients.
What do the guidelines recommend when choosing an IBD treatment, and how should these be weighed up against the wishes of patients and the medical profession?
It is easy to justify a change in treatment if a patient continues to show symptoms. With the treat-to-target concept, we sometimes have to optimize treatment even though patients are in clinical remission and feel well. This is often a long process that requires explanation and additional motivation, because patients ask: “Why treat the bowel if I’m fine?”. Finding the right medication for the right patient remains an important task, which has not yet been successful enough.
How has the landscape of IBD treatment changed with the recent approval of JAK and IL-23 inhibitors in Switzerland? What key data should physicians pay attention to?
The data on upadacitinib* (RINVOQ®, UPA) are extremely interesting in both ulcerative colitis (UC) and Crohn’s disease (CD). In both indications, the drug appears to be well suited for very severe and complicated cases. If we look at the indications separately, UPA shows very good induction and high efficacy in UC in direct comparisons and meta-analyses.3, 4 The induction with UPA is probably the strongest I have seen with an advanced therapy so far.5, 6 UPA is also effective in severe cases of CD, with promising data on perianal disease and extraintestinal manifestations despite the low level of evidence.7, 8 Risankizumab** (SKYRIZI®, RISA) is also a very potent drug with a fantastic benefit-risk profile.9
Given the current treatment options, is it realistic to achieve the treatment goals set for IBD, or are there still considerable unmet needs?
Only around 20 % of UC and CD patients achieve a deep remission, so we are still a long way from an IBD cure. In everyday clinical practice, it is a treatment success if we can reduce inflammation by 50 % and improve quality of life (QoL). Every patient should be able to achieve the realistic minimal therapy goals, i.e. a good QoL and no or only mild endoscopic lesions. Deep remission with an endoscopic cure would be ideal, but this is currently only achievable for a small number of patients.
Can you explain the importance of mucosal healing in the treatment of IBD and how therapies such as IL-23 or JAK inhibitors help to achieve this goal?
Mucosa healing is our major goal in the treatment of IBD. There is growing evidence that achieving mucosa healing reduces the number of operations and hospitalizations and can improve the lives of patients in the long term. However, data from a large randomized clinical trial on this topic is still lacking. With JAK inhibitors, we see high rates of mucosal healing in UC.10 IL-23 inhibition is also of interest in CD patients, both bio-naïve and bio-refractory, due to high mucosal healing rates.9
What are the best methods for monitoring IBD patients?
It is important to monitor all patients as well as possible with the tools available. These include ultrasound, magnetic resonance imaging (MRI), C-reactive protein (CRP), calprotectin and endoscopy. We use a selection of these methods, depending on the localization of the inflammation and the therapeutic goal.
Can you explain the importance of the risk-benefit profile when choosing advanced treatment options? In your experience, what are the most important factors when deciding on IBD treatment?
The risk-benefit profile is very important for all drugs and I think there is still a lot of work to be done in this regard for IBD therapies. We have a range of treatments to choose from and so the risk-benefit profile is a crucial factor, but one that is difficult to discuss with patients. We need better illustrations and figures here, as well as a robust evaluation of the findings.
How do you think the course of treatment will develop with advanced therapies?
For me, there are clearly two types of patients. Patients with mild disease should not be overtreated and benefit from steroids or, in the case of UC, 5-aminosalicylic acid. For moderate to severe disease, a new type of therapy must be started early in most cases.
What was the most important message from your IBD roadshow presentation that you would like participants to take away with them?
We need to be more ambitious with our treatment goals, but remain realistic. We need realistic goals, early disease control, close monitoring and good consultation with patients.
What is your most important goal or wish for the future of IBD therapy?
An IBD cure would be more of a dream than a wish, as we are still a long way from it. My wish is that we continuously improve the risk-benefit profile of the available drugs.
* RINVOQ® has been approved since June 7, 2024 for the treatment of moderate to severe active UC and moderate to severe active CD in adult patients who have had an inadequate response to, no longer respond to or are intolerant to at least one biologic or for whom such therapy is contraindicated.11
** SKYRIZI® is indicated for the treatment of adult patients with moderate to severe active Crohn’s disease who have responded inadequately to, are no longer responding to or have failed to tolerate conventional therapy or biologic(s).12
Brief technical information SKYRIZI® and RINVOQ®
Literature
1 Turner D et al. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology, 2021. 160(5): p. 1570-1583.
2 Peyrin-Biroulet L et al. Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): Determining Therapeutic Goals for Treat-to-Target. Am J Gastroenterol, 2015. 110(9): p. 1324-38.
3 Lasa JS et al. Efficacy and safety of biologics and small molecule drugs for patients with moderate-to-severe ulcerative colitis: a systematic review and network meta-analysis. Lancet Gastroenterol Hepatol, 2022. 7(2): p. 161-170.
4 Panaccione R et al. Efficacy and Safety of Advanced Therapies for Moderately to Severely Active Ulcerative Colitis at Induction and Maintenance: An Indirect Treatment Comparison Using Bayesian Network Meta-analysis. Crohn’s Colitis 360, 2023. 5(2): p. otad009.
5 Colombel JF et al. Upadacitinib Reduces Crohn’s Disease Symptoms Within the First Week of Induction Therapy. Clin Gastroenterol Hepatol, 2024.
6 Loftus EV, Jr. et al. Upadacitinib Therapy Reduces Ulcerative Colitis Symptoms as Early as Day 1 of Induction Treatment. Clin Gastroenterol Hepatol, 2023. 21(9): p. 2347-2358 e6.
7 Colombel JF, et al: Efficacy and Safety of Upadacitinib for the Treatment of Fistulas and Fissures in Patients With Crohn’s Disease. Presented at ECCO, Copenhagen, Mar 2023.
8 Colombel JF, et al: Effect of Upadacitinib on Extraintestinal Manifestations in Patients With Moderately to Severely Active Crohn’s Disease. Presented at UEGW, Copenhagen, Oct 2023.
9 Ferrante M et al. Risankizumab as maintenance therapy for moderately to severely active Crohn’s disease: results from the multicentre, randomized, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial. Lancet, 2022. 399(10340): p. 2031-2046.
10 Vermeire S et al. Efficacy and safety of upadacitinib maintenance therapy for moderately to severely active ulcerative colitis in patients responding to 8 week induction therapy (U-ACHIEVE Maintenance): overall results from the randomized, placebo-controlled, double-blind, phase 3 maintenance study. Lancet Gastroenterol Hepatol, 2023. 8(11): p. 976-989. Incl. Suppl.
11. current technical information for RINVOQ® (upadacitinib) at www.swissmedicinfo.ch.
12. current expert information on SKYRIZI® (risankizumab) Crohn’s disease at www.swissmedicinfo.ch.
The references can be requested by specialists at medinfo.ch@abbvie.com.
Interview: Dr. sc. nat. Stefanie Jovanovic and Dr. sc. nat. Katja Becker
This article was produced with the financial support of AbbVie AG, Alte Steinhauserstrasse 14, 6330 Cham.
CH-ABBV-240086 08/2024
This article has been released in German.
