Introduction
The combination of two biological agents or a biological agent with novel small molecules, known as advanced combination therapy (ACT), for inflammatory bowel disease (IBD) has shown promising results in phase II studies as well as in real world studies. We describe the real-world experience of 2 Swiss IBD referral centers.
Aims & Methods
A chart review of all IBD patients on ACT from June 2020 to December 2023 was performed in Bern University hospital and the Crohn and Colitis Center Lausanne (Gastro-entérologie Beaulieu SA). Data on disease duration, extension, previous or concomitant treatments as well as efficacy and safety were collected prospectively.
Results
Disease
| Combination of advanced therapy
(number of patients)
| Partial or complete Clinical or biological response
| Adverse effects, Infections
|
Ulcerative colitis (N=11)
| Vedolizumab / Tofacitinib (5)
| 2/5 (40%)
| none
|
| Vedolizumab / Anti-TNFs (3)
| 2/3 (50%)
| none
|
| Vedolizumab /Cyclosporin or Tacrolimus (2) Ustekinumab / Tacrolimus (1)
| 1/2 (50%)
1/1 (100%)
| none
|
Crohn’s disease (N= 17)
| ustekinumab (5)/ Anti-TNFs(infliximab (1), adalimumab (4))
| 5/ 5 (100%)
| Eczema, tumefaction left parotide
|
| ustekinumab (4) / JAK inhibitors Upadacitinib,(3) , Tofacitinib (1)
| 4/4 (100%)
| Lymphoma, mycosis, otitis media, lymphopenia, CMV ileitis
|
| Vedolizumab / Infliximab (1)
Vedolizumab / Tacrolimus
| 0/1 (0%)
1/1 (100%) | none
|
| Vedolizumab / Upadacitinib (3)
| 3/3 (100%)
| Acnea, Headache, nausea
|
| Anti-TNF(adalimumab (2), cimzia (1) / Upadacitinib (3)
| 2/3 (66%)
| Ophthalmic zona
|
| Total |
| 21/28 (75%)
| 11 events (14%)
|
A total of 25 IBD patients (48% women, 10 ulcerative colitis, 15 Crohn’s disease) received 28 ACT. The indications were extended and refractory luminal disease and/or extraintestinal manifestations. The 25 patients were all steroid dependent or refractory and half of them were either refractory or intolerant to at least two anti-TNF alpha agents. These treatments were started after a median disease duration of 5 years (range 1-31). The mean duration of ACT was 10 months (range 1-40). Most frequent ACT combinations were vedolizumab or ustekinumab combined with either JAK inhibitors or TNF- alpha inhibitors. A partial or complete response was observed in 21/28 therapies (75%) with a mean decrease of CRP of 9,4 mg/l (range - 23 to + 59). Among responders, a median decrease of calprotectin by 871 mcg/g (range 0 – 4002; N=8, skewed) was observed. Concerning safety, 3 infections (ophthalmic herpes zoster, otitis media, cutaneous fungal infection) and 1 case of Non-Hodgkin Lymphoma, were reported. 8 minor adverse events (left parotid gland, tumefaction, eczema, 2 patients with lymphopenia, acne nausea and headaches) were reported, with mostly small molecules implicated. One patient had a successful pregnancy and delivery on combined adalimumab and ustekinumab ACT.
Conclusion
Vedolizumab or ustekinumab combined with either JAK or TNF- alpha inhibitors were the most frequent combinations of ACT in this cohort of severe and steroid-dependent/refractory IBD patients. 75% of patients achieved a clinical /biological response. Small molecules appear to be associated with of lymphopenia, and minor infections. There was one case of Non-Hodgkin Lymphoma while receiving ustekinumab and tofacitinib ACT in the context of previous long exposure to adalimumab.
Disclosure
Marianne Vuillèmoz and Maude Martinho Grueber disclose consulting fees from Bristol Myers Squibb. Giulia Santi has nothing to disclose. Pascal Juillerat discloses consulting and speaker fees from AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Ferring Pharmaceuticals, Gilead Sciences, Janssen, Merck Sharp & Dohme, Pfizer, Pierre Fabre, Sandoz, Takeda, Tillotts Pharma AG, and UCB Pharma. Pierre Michetti discloses a grant form Iqone and personal fees from Takeda, Ferring, Hospira, Janssen, Pfizer, UCB Pharma, Vifor Pharma, Nestlé Health Sciences, MSD.
