Introduction

Real-world data are needed to confirm clinical trial results and determine treatment effects in a more diverse population. The NIS COLIBRI (NCT05382715) assesses the use, effectiveness, and safety of ozanimod (OZA) and quality of life in patients (pts) with moderate-to-severe (MOD/SEV) active ulcerative colitis (UC) in routine clinical practice in Germany. This interim analysis (IA) reports baseline (BL) characteristics, safety information, and effectiveness of OZA until Week (W) 10.

Aims & Methods

Up to 380 adults with UC eligible for OZA treatment will be enrolled and observed over 52 or 104 weeks with visits and diagnostic and therapeutic measures corresponding to routine practices of the respective sites. In this IA, the partial Mayo score (pMS; sum of stool frequency subscore [SFS], rectal bleeding subscore [RBS], and Physician Global Assessment subscore [PGA]), RBS, SFS, and clinical response (defined as reduction by ≥ 2 points in pMS + a reduction of ≥ 35% in pMS & RBS reduction of ≥ 1 point or an absolute RBS of ≤1 or pMS of ≤1 + RBS=0) were assessed at W4 and W10. Data are collected by electronic case report forms and the study-specific interface of the MyTARGET app (Kiel, Germany) for pt-reported outcomes, which are evaluated throughout the study.

Results

Of 109 pts included in the IA, the median (interquartile range) age of pts was 41 (29.0–53.0) years, 55 (50.5%) were female, 51.4% had prior exposure to ≥3 advanced therapies (ATs). Additional BL pt and clinical characteristics are shown in the Table. 104 pts had pMS data at BL, 79 pts at W4 and 54 pts at W10. Mean [SD] pMS decreased from BL (5.2 [2.1]) to 4.0 [2.5] at W4 (mean change from BL (CBL): -1.31 [2.2]) and to 3.48 [2.2] at W10 (CBL: -1.69 [2.3]). All mean [SD] disease activity subscores showed a numerical improvement from BL to W4 and W10: SFS at BL (2.0 [1.0]), W4 (1.6 [1.2; CBL: -0.48 [1.2]), and W10 (1.45 [1.1]; CBL: -0.51 [1.0]); RBS at BL (1.1 [1.1]), W4 (0.74 [1.0]; CBL: -0.38 [0.9]), and W10 (0.58 [0.9]; -0.55 [1.0]). Clinical response was achieved in 36.3% (29/80) of pts at W4 and 42.9% (24/56) at W10. The most common reasons for dropping out were adverse events (AEs) (n=14; 13.2%), insufficient effectiveness (n=10; 9.4%) and patient request (n=4; 3.8%). The most frequently reported AEs (non-UC associated; ≥1.5%, n, %) were lymphopenia (n=2, 1.8%), headache (n=2, 1.8%), and rash (n=3, 2.8%).

Table. BL demographics, clinical characteristics, and disease activity of pts enrolled in COLIBRI as of 4 January 2024
​

Conclusion

This first IA of the German COLIBRI study showed that highly refractory pts with MOD/SEV UC on OZA achieved clinical response and improvement in disease activity subscores at W4 and W10, indicating that OZA is effective in real-world clinical practice.

Disclosure

SZ: consulted for AbbVie Deutschland GmbH, Amgen GmbH, Biogen GmbH, Bristol Myers Squibb GmbH, Celgene GmbH, Celltrion, Ferring Arzneimittel GmbH, Galapagos Biopharma Germany GmbH, Hogg Robinson GmbH, Janssen Pharmaceutica NV, Janssen Cilag GmbH, MICE Service GmbH, Mylan, Pfizer Pharma GmbH, and Takeda Pharma GmbH; speaker for AbbVie Deutschland GmbH, Amgen GmbH, Biogen GmbH, Bristol Myers Squibb GmbH, CED Service GmbH, Falk Foundation, Ferring Arzneimittel GmbH, FORGA Solutions GmbH, GWT-TUD GmbH, Janssen Cilag GmbH, Janssen Pharmaceutica NV, Merck Sharp & Dohme, Pfizer Pharma GmbH, Pharma-Zentrale GmbH, Roche, Takeda Pharma GmbH, and WebMD Global.
JSt: received consultancy fees from AbbVie, Fresenius Kabi, GI Dynamics, Immundiagnostik, MSD, Pharmacosmos, Takeda, and Vifor; received payment for lectures from AbbVie, Falk Foundation, Ferring, GI Dynamics, Immundiagnostik, MSD, Pharmacosmos, Takeda, ThermoFisher, and Vifor; received payment for manuscript preparation from AbbVie, Falk Foundation, and MSD.
PE: consulted for AbbVie, Galapagos, and Janssen.
UH: received lecture and/or consulting fees from AbbVie, Amgen, Biogen, Bristol Myers Squibb, Celltrion, Eli Lilly, Falk Foundation, Ferring, Janssen, MSD, Mundipharma, Mylan Pharma, Pfizer, Sandoz, Shield Therapeutics, Takeda, and Vifor.
TH: consulted for and received speaker fees from Bristol Myers Squibb GmbH and Galapagos Biopharma Germany GmbH, and Pfizer Pharma GmbH.
EJ: conducted research studies for, served as an advisor for, or received travel grants from AbbVie, Arena, AstraZeneca, Bausch Health, Galapagos, Janssen, Pfizer, SymBio Pharma, and Takeda.
JRM: nothing to declare.
JMZ: Received lecture and/or consulting fees or speaker from Abbvie, Bristol Myers Squibb GmbH, Ferring Arzneimittel GmbH, Galapagos Biopharma Germany GmbH, Jannssen Cilag GmbH, Mylan, Pfizer Pharma GmbH, Takeda Pharma Gmbh, and Falk Foundation.
AMP, MM, and GE: employees and/or shareholders of Bristol Myers Squibb.
SS: consulted for AbbVie Deutschland GmbH, Bristol Myers Squibb GmbH, Celltrion, Galapagos Biopharma Germany GmbH, Janssen Pharmaceutica NV, Pfizer Pharma GmbH, and Takeda Pharma GmbH; speaker for AbbVie Deutschland GmbH, Amgen GmbH, Bristol Myers Squibb GmbH, CED Service GmbH, Falk Foundation, Galapagos Biopharma Germany GmbH, Janssen Cilag GmbH, Lilly Pharma Germany, Pfizer Pharma GmbH, and Takeda Pharma GmbH.

Introduction

GLPG3970, a potent and selective salt-inducible kinase (SIK) 2/3 inhibitor, exerts a dual mechanism combining anti-inflammatory and immunoregulatory activity.¹ In chronic inflammatory diseases, such as inflammatory bowel disease (IBD), GLPG3970 has the potential to restore immune balance and homeostasis.^2,3 In a 6-week signal-detection phase 2a study in patients with ulcerative colitis (UC),⁴ GLPG3970 showed positive effects in histology, endoscopy and faecal calprotectin versus placebo, despite no differentiation from placebo on change from baseline on total Mayo Clinic Score at week 6.^4,5

Aims & Methods

We investigated the dual mechanism of GLPG3970 in severely inflamed ex vivo treated IBD tissue biopsies. Inflamed intestinal biopsies (most affected segment; n = 9 per patient) were obtained from patients with UC (n = 10) and Crohn’s disease (CD; n = 10) with active endoscopic disease (UC: Mayo endoscopic subscore ≥ 2; CD: SES-CD of ≥ 4). Patients were biologic-naive (UC: n = 5; CD: n = 5) or biologic-experienced (UC: n = 5; CD: n = 5). Three individual biopsies per condition were exposed ex vivo for 24 hours to vehicle control (DMSO), tofacitinib (10 µM, positive control) or GLPG3970 (60 µM). Protein secretion in supernatant was analysed by V-PLEX Human Biomarker 54-Plex (two-way ANOVA, Dunnett’s multiple comparison). RNA sequencing of biopsies was performed on Illumina NovaSeq 6000. Gene expression was quantified using Salmon (v1.5.2) and differential expression analysis was performed with DESeq2 (v1.28.0; criteria: |log2FC|> 0.58, FDR < 0.05, baseMean > 32).

Results

High levels of inflammatory cytokines and chemokines were observed in the supernatant after ex vivo culturing. Exposure to GLPG3970 resulted in a significant decrease of pro-inflammatory cytokines (e.g. TNFα, GM-CSF, IFN-γ, IL-2) and chemokines (e.g. MCP-1, MIP1α, MIP1β) in both UC and CD biopsies, relative to vehicle control. GLPG3970 activity was statistically stronger than tofacitinib for most evaluated proteins (p value), except for IL-1RA, IL-3, IL-9, IL-22, IL-23, among others. RNAseq analysis showed a clear signature of differentially expressed genes (DEGs) for GLPG3970 versus vehicle control (UC: 549 DEGs, with 288 downregulated, including pro-inflammatory genes CSF2, MMP9 and CCL4; CD: 673 DEGs, with 238 downregulated, including CSF​2, CXCL10 and CXCL11). Tofacitinib versus vehicle resulted in 582 (UC) and 681 (CD) DEGs including JAK/STAT dependent genes, such as MX1, SOCS3 and IFITM1. Direct comparison of GLPG3970 versus tofacitinib highlighted the impact of GLPG3970 on pathways involved in ‘TGF-β signalling’, indicative of enhancing immunoregulatory mechanisms, ‘TNFα signalling via NF-κB’ and ‘glycolysis’, whereas tofacitinib mainly affected ‘IFN-α response’ and ‘IFN-γ response’ in both UC and CD biopsies. In addition, GLPG3970 exposure to ex vivo biopsies resulted in a partial reversion of UC and CD transcriptome signatures (Spearman correlation: -0.25 [UC], -0.22 [CD]).⁶

Conclusion

Acute exposure of GLPG3970 to ex vivo inflamed tissue biopsies from patients with UC and CD showed a strong reduction in the release of pro-inflammatory mediators. Transcriptomic analysis further confirmed GLPG3970’s robust activity in reducing inflammatory NF-κB-mediated pathways while modulating TGF-β-related immunoregulatory pathways versus tofacitinib. Our findings support the dual mechanism of GLPG3970 in relevant pathogenic pathways in IBD and confirm the therapeutic potential of SIK2/SIK3 inhibition in treating patients with either UC or CD.

References

1. Peixoto C et al. J Med Chem 2024;67:5233–58.
2. Pereira-Fernandes A et al. [abstract] United European Gastroenterol J 2021;9:S8.
3. Lavazais S et al. [abstract] United European Gastroenterol J 2021;9:S8.
4. ClinicalTrials.gov. A Study Evaluating the Effects of GLPG3970 Given as an Oral Treatment for 6 Weeks in Adults With Ulcerative Colitis (SEA TURTLE). 2020. Available from: https://clinicaltrials.gov/study/NCT04577794 (Accessed 8 April 2024).
5. Galapagos. Galapagos demonstrates early clinical activity with SIK2/3 inhibition in inflammation. 2021. Available from: https://www.glpg.com/press-releases/galapagos-demonstrates-early-clinical-activity-with-sik2-3-inhibition-in-inflammation/ (Accessed 8 April 2024).
6. Massimo L et al. Nat Comput Sci 2021;1:511–15.

Disclosure

This study was funded by Galapagos NV (Mechelen, Belgium).
Editorial and publications management support was provided by PharmaGenesis London, London, UK, and was funded by Galapagos NV.
LG and KA are joint first authors.
LG, KA and EV report no disclosures.
MC and SDV are employees of Galapagos.
BV reports research support from AbbVie, Biora Therapeutics (formerly Progenity), Landos Biopharma, Pfizer, Sosei Heptares and Takeda; speaker fees from Abbvie, Biogen, Bristol Myers Squibb, Celltrion, Chiesi, Falk, Ferring Pharmaceuticals, Galapagos, Janssen Pharmaceuticals, Lily, MSD, Pfizer, R-Biopharm, Sandoz, Takeda, Tillots Pharma, Truvion Healthcare and Viatris; consultancy fees from Abbvie, Alfasigma, Alimentiv, Applied Strategic, AstraZeneca, Atheneum, BenevolentAI, Biora Therapeutics (formerly Progenity), Boxer Capital, Bristol Myers Squibb, Galapagos, Guidepont, Landos, Lily, Mylan, Inotrem, Ipsos, Janssen Pharmaceuticals, Pfizer, Sandoz, Sanofi, Santa Ana Bio, Sapphire Therapeutics, Sosei Heptares, Takeda, Tillots Pharma and Viatris; and stock options from Vagustim.
SV reports speaker and/or consultancy fees from AbbVie, Abivax, AbolerIS Pharma, AgomAb Therapeutics, Alimentiv, Arena Pharmaceuticals, AstraZeneca, Biora Therapeutics (formerly Progenity), Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cytoki Pharma, Dr Falk Pharma, Ferring Pharmaceuticals, Galapagos, Genentech/Roche, Gilead Sciences, GSK, Hospira, IMIDomics, Janssen Pharmaceuticals, Johnson & Johnson, Lilly, Materia Prima, Mestag Therapeutics, MiroBio, Morphic Therapeutic, MRM Health, MSD, Mundipharma, Pfizer, ProDigest, Prometheus Biosciences, Robarts Clinical Trials, Surrozen, Takeda, Theravance Biopharma, Tillotts Pharma, VectivBio, Ventyx Biosciences and Zealand Pharma; grants from AbbVie, Galapagos, Johnson & Johnson, Pfizer and Takeda; and participation on a data safety monitoring board for Sanofi.

Introduction

Ozanimod (OZA) is approved for the treatment of moderately to severely active ulcerative colitis (UC). Approximately 30% of patients (pts) were clinical nonresponders after 10 wk of OZA treatment in the phase 3 True North (TN) study (NCT02435992), but ~50% of these OZA nonresponders achieved symptomatic response after 5–10 wk of additional OZA treatment during the open-label extension (OLE) study (NCT02531126).

Aims & Methods

This analysis evaluated the impact of TN baseline (BL) endoscopic disease activity on the durability of OZA response in Week (W) 10 OZA clinical nonresponders after extended induction during the OLE up to 4 years (OLE W190). Pts were categorized by BL Mayo endoscopy subscore (MES) as moderate (MES=2) or severe (MES=3). Symptomatic, clinical, and mucosal efficacy were assessed through OLE W190 using observed case (OC) and nonresponder imputation (NRI) analyses.

Results

Of the 226 W10 OZA clinical nonresponders who entered the OLE, 67 had moderate and 159 had severe endoscopic disease at BL. Pt characteristics were generally similar between groups, but more pts with severe vs moderate endoscopic activity had prior immunomodulator (52.8% vs 34.3%), anti–tumor necrosis factor (TNF; 45.9% vs 25.4%), or non–anti-TNF biologic (36.5% vs 19.4%) exposure. Some symptomatic response was observed in OZA W10 clinical nonresponders from BL to W10/OLE entry, which was greater in pts with moderate disease and further improved with extended OZA exposure by OLE W5 (moderate: 36.9% at W10 and 66.2% by OLE W5; severe: 23.8% at W10 and 47.9% by OLE W5). Similar patterns were observed with symptomatic remission but overall rates were lower (moderate: 6.2% at W10 and 26.2% by OLE W5; severe: 1.3% at W10 and 13.0% by OLE W5). Symptomatic response and remission rates after OLE W5 were generally similar in moderate and severe endoscopic activity groups, and rates were maintained throughout the OLE. Likewise, clinical and mucosal efficacy were durable and rates were generally similar between subgroups through OLE W190 (Table). Notably, higher endoscopic improvement rates were achieved through OLE W190 in pts with BL moderate endoscopic activity despite ~50% of these pts progressing to severe by TN W10. Similar data trends were observed in the NRI analysis.

Conclusion

Delayed response to OZA was observed in pts who did not achieve clinical response after 10 wk of OZA therapy, regardless of BL endoscopic activity. W10 nonresponders with moderate endoscopic activity responded faster with additional OZA exposure, whereas those with severe endoscopic activity needed longer exposure to OZA to achieve similar efficacy rates that were durable with continuous OZA exposure. These results suggest that some pts may require a longer induction on OZA but ultimately maintain durable OZA response.

Disclosure

Acknowledgment: This study was sponsored by Bristol Myers Squibb. Professional medical writing assistance was provided by Traci Stuve, MA, and Julie Ko, PharmD, of Peloton Advantage, LLC, an OPEN Health company, and funded by Bristol Myers Squibb.
PI: received lecture fees from AbbVie, Bristol Myers Squibb, Celgene, Celltrion, Dr. Falk Pharma, Ferring, Galapagos, Gilead, Janssen, MSD, Pfizer, Sandoz, Sapphire Medical, Shire, Takeda, Tillotts, and Warner Chilcott; received financial support for research from Celltrion, MSD, Pfizer, and Takeda; received advisory fees from AbbVie, Arena, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Eli Lilly, Genentech, Gilead, Hospira, Janssen, MSD, Pfizer, Pharmacosmos, Prometheus Biosciences, Roche, Samsung Bioepis, Sandoz, Takeda, TopiVert, VH2, Vifor, and Warner Chilcott.
RKC: consulted for AbbVie, Bristol Myers Squibb, Fresenius Kabi, Fzata, Janssen, Magellan Health, Option Care, Pfizer, Pharmacosmos, Samsung Bioepis, Sandoz, Sebela, and Takeda; scientific co-director of the CorEvitas Registry and executive committee member of the IBD Education Group; received financial support for research from Janssen.
TR: served on advisory boards for AbbVie, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Genentech, Intercept Health, Janssen, Merck, Pfizer, and Takeda; speaker for AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Pfizer, and Takeda.
AS: declares no competing financial or nonfinancial interests.
PH: consultant and speaker for Boston Scientific, FujiFilm, MedWork, and Viatris.
SC: consultant for AbbVie, Bristol Myers Squibb, Janssen, and Pfizer.
ST, HW, MTO, and AJ: employees and/or shareholders of Bristol Myers Squibb.
DCW: received research funding from AbbVie, Amgen, Arena/Pfizer, Celgene/Bristol Myers Squibb, Genentech, and Janssen; lectured for AbbVie, Bristol Myers Squibb, Janssen, and Takeda; consulted for AbbVie, Arena/Pfizer, Celgene/Bristol Myers Squibb, Eli Lilly, Janssen, and Takeda.

Introduction

Abdominal pain is a common but often overlooked symptom in patients with ulcerative colitis (UC). The causes of pain during deep remission remain incompletely known, although factors in the brain-gut axis may play a role.

Aims & Methods

The aim of this study was to determine factors associated with abdominal pain in UC patients. Three existing study cohorts of adults with UC were used. Cohort I included 133 patients (49 active), cohort II 287 patients (155 active) and cohort III 92 patients (20 active). The abdominal pain domain of the Gastrointestinal Symptom Rating Scale was used to assess the severity of pain, identifying subjects with at least mild severity of abdominal pain. The Hospital Anxiety and Depression Scale was used to identify subjects with anxiety and or depression (scores ≥8) Patients also completed questionnaires to assess severity of fatigue (Fatigue Impact Scale (FIS, cohort I)), and quality of life (QoL, the IBD questionnaire (IBDQ, cohort II)).

Results

In the three cohorts 39%, 24% and 20% of the patients with active disease and 20%, 7% and 15% of the patients in remission reported at least mild severity of abdominal pain. A higher proportion of UC patients with at least mild abdominal pain had anxiety (83%, 44%, and 40% vs 42%, 18% and 7%; p<0.01) and depression (40%, 33% and 40% vs 13%, 9% and 13% p<0.05). Disease-specific QoL was lower in patients with at least mild abdominal pain, both in patients with active disease (median [IQR] IBDQ score 182 [150-198] vs 144 [115-160], p<0.001) and in remission (IBDQ score 203 [190-213] vs 171 [141-181], p<0.001). In UC patients in remission, having at least mild abdominal pain was associated with more severe impact of fatigue on daily life, (FIS 81 [67-100] versus 29 [14-58], p<0.001).

Conclusion

Abdominal pain is relatively common in patients with UC with active disease as well as in remission. This is associated with anxiety, depression and more severe fatigue and a lower QoL. Hence, paying attention to abdominal pain and associated factors seems important to optimize clinical management of these patients.

Disclosure

Tom van Gils: None
Hans Törnblom: Consultant/Advisory Board member: Cinclus Pharma, Dr Falk Pharma Gmbh, VIPUN Medical.
Speakers’ bureau: Tillotts, Takeda, Galapagos
Börje Jonefjäll: Consultant/advisory board member: Tillots. Speaker for MSD, AbbVie, Tillotts, MEDA, and Takeda.
Hans Strid: Consultant/Advisory Board member: Tillotts, Takeda, Abbvie, Pharmacosmos, BMS
Magnus Simrén: Unrestricted research grants: Glycom/DSM, Genetic Analysis AS
Consultant/Advisory Board member: Danone Nutricia Research, Ironwood, Biocodex, Genetic Analysis AS, Tillotts, Takeda, Arena, Kyowa Kirin, Abbvie, BioGaia, Cinclus Pharma and Pharmanovia.
Speakers’ bureau: Tillotts, Kyowa Kirin, Takeda, Biocodex, Sanofi, Janssen Immunology, Pfizer, Ferrer, BioGaia and Falk Foundation.

Introduction

Ileus, a slowing or halting of intestinal motility, develops in trauma, critically ill, and surgical patients, resulting in prolonged hospital and ICU stays, increased infectious complications, and more hospital readmissions. Inflammatory insult to the gastrointestinal smooth muscle is frequently brought on by direct manipulation of the intestines during surgery, but can also be caused by systemic inflammation, which activates mast cells and macrophages and increases the production of inflammatory cytokines. We have demonstrated that the chemokine (C-X-C motif) ligand 1 (CXCL1), which inhibits intestinal motility, is enhanced in rodent ileus models and in the blood of trauma patients who develop ileus. P21-activated kinase (PAK) 1, which is elevated in response to mechanical stretch, has also been connected to the emergence of ileus.

Aims & Methods

In this study, we focused on the relationship between mechanotransduction, CXCL1, and PAK1. We utilized both an organ bath system and cyclical stretch of cell models via a Flex cell apparatus to study the role of mechanotransduction. Both human intestinal smooth muscle cells (hiSMCs) and macrophages were subjected to physiological (control cyclical stretch, CCS) and pathological (edema cyclical stretch, ECS, as experienced during edema development or ileus) stretch. The role of NF-kB, which has been shown to regulate CXCL1 expression, was investigated. Intestinal tissue samples from wildtype and PAK1 knockout mice were also stretched in the presence or absence of IPA-3, a PAK1 inhibitor, and IMD-5304, an NF-kB inhibitor. The expression and secretion of CXCL-1 in intestinal smooth muscle cells and macrophages were determined by ELISA and RT-qPCR.

Results

In response to the induction of ileus (via gut manipulation), CXCL1 expression was increased in wild-type mice but not PAK1 knockout mice. PAK1 inhibition did not attenuate the inhibitory effects of CXCL1 on intestinal motility; however, the inhibitory effects of CXCL1 were partially inhibited in PAK1 knockout mice. Mechanical stretch increased CXCL1 in the media of macrophages and human intestinal smooth muscle cells. PAK1 inhibition did not prevent the increased CXCL1 secretion in human intestinal smooth muscle cells. NF-kB activation was increased in response to increased stretch, and NF-kB inhibition prevented stretch-induced increase in CXCL1 secretion.

Conclusion

We conclude that during the development of edema and/or ileus, pathological strain can stimulate CXCL1 release from both intestinal smooth muscle cells and macrophages. However, inhibition of NF-kB, but not PAK1, prevents stretch-induced CXCL1 secretion.

References

Asgeirsson, T., El-Badawi, K. I., Mahmood, A., Barletta, J., Luchtefeld, M., & Senagore, A. J. (2010). Postoperative Ileus: It Costs More Than You Expect. Journal of the American College of Surgeons, 210(2), 228–231. https://doi.org/10.1016/j.jamcollsurg.2009.09.028
Chu, J., Pham, N. T., Olate, N., Kislitsyna, K., Day, M. C., LeTourneau, P. A., Kotss, A., Stewart, R. H., Laine, G. A., Cox, C. S., & Uray, K. (2013). Biphasic regulation of myosin light chain phosphorylation by p21-activated kinase modulates intestinal smooth muscle contractility. Journal of Biological Chemistry, 288(2), 1200–1213. https://doi.org/10.1074/JBC.M112.370718
Docsa, T., Bhattarai, D., Sipos, A., Wade, C. E., Cox, C. S., & Uray, K. (2020). CXCL1 is upregulated during the development of ileus resulting in decreased intestinal contractile activity. Neurogastroenterology & Motility, 32(3), e13757. https://doi.org/10.1111/NMO.13757
Joshi, V., Strege, P. R., Farrugia, G., & Beyder, A. (2021). Mechanotransduction in gastrointestinal smooth muscle cells: Role of mechanosensitive ion channels. American Journal of Physiology - Gastrointestinal and Liver Physiology, 320(5), G897–G906. https://doi.org/10.1152/AJPGI.00481.2020/ASSET/IMAGES/MEDIUM/GI-00481-2020R01.PNG
Rychter, J., & Clavé, P. (2013). Intestinal inflammation in postoperative ileus: pathogenesis and therapeutic targets. Gut, 62(11), 1534–1535. https://doi.org/10.1136/gutjnl-2012-304176

Introduction

Recent research finds 25%-30% of IBD patients experience chronic post-traumatic stress due to their disease (IBD-PTS) and IBD-PTS is associated with poorer outcomes. Post-traumatic growth (PTG) is defined as “positive psychological changes that occur as a result of one’s struggle to cope with trauma or a major life crisis.” PTG can reduce the negative impacts of IBD-PTS, which may be moderated by disease activity in IBD.

Aims & Methods

We aim to examine the relationship between remission status, patient expectations regarding if they can achieve and sustain remission, and PTG among patients with IBD. Adults (18+) with IBD were recruited via social media IBD support groups, and flyers posted in gastroenterology clinics and community bathrooms with additional snowball sampling methods. Surveys were completed online via Qualtrics and included demographics, Patient Simple Clinical Colitis Activity Index (P-SCCAI), Post-Traumatic Growth Inventory (PTGI), and PTSD Checklist for DSM-5 (PCL-5). Participants reported if they were in remission or experiencing a flare of symptoms, and their expectations of experiencing a flare in the next 2 months on a 4-Point Likert scale.

Results

313 adults with IBD: UC (n=140, 44.7%), CD (n=173, 55.3%). Age 18-70 years (M=33, SD=11), 75.1% female. Scores for PTGI, P-SCCAI, and PCL-5 are in Table 1. Participants tended to have active disease and high levels of IBD-PTS. No significant correlation existed between P-SCCAI score and PTG (r= -.09 p=.127). Those in a current IBD flare (n=133,42.4%) reported lower confidence in the longevity of their remission over the next 2 months compared to participants who were in remission (Χ2=114.01,p<.001), with no difference in PTG levels between groups (p=.310). However, participants who demonstrated optimism about sustained remission had higher levels of PTG (F(3,309)=4.688,p=.003). Participants who endorsed “I am positive I will experience a flare up in the next two months” had much lower levels of PTG (M=65.91,SD=25.33) than participants who endorsed “I am positive I will not experience another flare up in the next two months” (M=81.52,SD=25.58;p=.004). Those who endorsed “I am at least 50% positive I will experience another flare up” had lower rates of PTG (M=69.99, SD=22.95) than those who endorsed “I am positive I will not experience another flare up in the next 2 months” (M=65.91,SD=25.33;p=.026). A linear regression found the extent of the differences in the levels of confidence in maintaining remission influenced levels of PTG (F(3,309)=4.688 p=.003). Participants who were the least confident in their remission scored 15.61 points lower for PTG than for participants who were the most confident. Participants who were at least 50% sure they would experience another flare in the next two months scored 11.53 points lower for PTG than participants who were the most confident in their remission.

Conclusion

Our findings suggest IBD patients who expect to achieve disease remission are more likely to have higher levels of PTG than those who are more pessimistic about their disease course, independent of current symptom activity. However, those in an IBD flare are less likely to believe they can attain remission. Due to the unpredictable nature of IBD, patients are chronically exposed to risks for medically traumatic experiences. Patients with confidence in their remission longevity may conceptualize remission as an “end” to the threat of IBD-PTS, thus allowing PTG to occur. Conversely, if remission is seen as a temporary reprieve before the next inevitable flare, it may limit patients’ abilities to cultivate PTG. Providers can help patients move towards a PTG mindset by assessing patients’ expectations of remission, modeling optimism in a patient’s prognosis, and providing evidence for ongoing hope.

References

Fuss, A., & Lease, S. (2023). Moderating the Relationship Between Ulcerative Colitis and Crohn’s Disease and Symptoms of PTSD: The Role of Remission. Journal of Clinical Gastroenterology, 57(8), 816-823.

Purc-Stephenson, R. J. (2014). The posttraumatic growth inventory: Factor structure andinvariance among persons with chronic diseases. Rehabilitation Psychology, 59, 10–18.https://doi.org/10.1037/a0035353

Disclosure

The authors have no disclosures