Introduction

Comparative effectiveness of biologics in preventing penetrating disease (PD) complications in Crohn’s disease (CD) is unknown. We compared the risk of developing luminal and perianal PD (LPD and PPD) between biologics used as first-line therapies.

Aims & Methods

We performed a propensity-score adjusted comparative effectiveness study. Adults (≥18 years) with CD (≥3 administrative claims for CD [K50.*]) who initiated their first biologic (anti-tumor necrosis factor [anti-TNF], ustekinumab ([UST]) or vedolizumab [VDZ]) were identified from Merative™ commercial database between 2006 and 2020. LPD was determined by ICD claims and PPD by a validated case definition consisting of ICD claims and procedural codes. We excluded pre-existing PD and prior biologic exposure using a minimum look-back period of one year. Patients were followed until a PD event and censored if a new biologic class was initiated, loss of medical coverage or a study end. Cohorts were balanced by inverse probability of treatment weighting (IPTW) based on age, sex, comorbidities, prior CD surgery, and CD severity. Pairwise comparisons were performed by cox-proportional hazard models, adjusted for immunomodulator exposure, and with biologic exposure treated as a time dependent variable based on a medication possession ratio of 0.8.

Results

Our analysis included 40,693 patients: (93%) anti-TNF, (3%) UST and (4%) VDZ. Our cohort had a median age of 39 years (IQR, 28-50) and 54% were female. Penetrating complications were identified during follow-up in 8567 (21%) patients overall: 2,204 (5%) LPD and 7,474 (18%) PPD. After IPTW all comparisons were well balanced (standardized difference <0.1 for each pairwise comparisons). PPD was more common than LPD overall (Log-rank p<0.0001). Anti-TNF was protective against LPD (HR, 0.66; 95% CI, 0.55–0.78; p<0.0001) and PPD (HR, 0.88; 95% CI, 0.80–0.96; p=0.0045;) compared with VDZ and LPD (HR, 0.37; 95% CI, 0.30–0.46; p<0.0001;) compared with UST (Table 1). There were no significant differences in the risk of LPD and PPD between VDZ and UST. The protective association between anti-TNF therapy and PD was more pronounced when our study period was limited to after 2016 when all three treatments were commercially available.

Conclusion

Anti-TNF therapy was associated with a lower risk of LPD and PPD compared with VDZ and LPD compared with UST. Further studies are needed to validate these findings and to determine potential reasons for these differences.

Disclosure

JM: Consultancy fees and/or Honoraria: Janssen, Abbvie, Takeda, Pfizer. Research funding: BMS, Pfizer and Leo Pharma, Honoraria: Bayer, Pfizer, Sanofi, BMS and Leo Pharma.
PD: has received research support under a sponsored research agreement unrelated to the data in the paper and/or consulting from AbbVie, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Pfizer, Prometheus Biosciences, Takeda Pharmaceuticals, Roche Genentech, Scipher Medicine, Fresenius Kabi, Teva Pharmaceuticals, Landos Pharmaceuticals, Iterative scopes and CorEvitas, LLC.
The other authors have no conflicts

Introduction

Subcutaneous vedolizumab has become available for the treatment of inflammatory bowel diseases in 2021 after intravenous induction. The aim of this multicentre prospective study was to evaluate treatment persistence, efficacy and tolerance after switching from intravenous (IV) to subcutaneous (SC) vedolizumab (VDZ) in stable patients.

Aims & Methods

All consecutive patients with either ulcerative colitis (UC) or Crohn’s disease (CD), in clinical remission for at least 3 months and switching from IV to SC-VDZ, were included in this multicentre cohort study. Inclusion could take place prospectively or within 3 months after switch. Clinical remission was defined by partial Mayo score ≤2 for UC or Harvey Bradshaw index ≤4 for CD; concomitant 5-amonisalycilate or immunosuppressive treatment was allowed at stable doses. Concomitant biologic or JAK-inhibitor treatments were not permitted during the study period, which lasted for 12 months after switch. SC-VDZ was started at 108 mg every other week. Primary endpoint was SC-VDZ treatment persistence at 54 weeks (W54) after switch; need for surgery, prolonged corticosteroid courses (>14 days) and loss of follow-up were considered as treatment failure. This is an analysis based on early 6-months (M6) results, reporting rates of treatment persistence, need for optimisation, switch-back to IV-VDZ and adverse events.

Results

Overall, 337 patients were analysed of 348 included, after removal of 10 patients who had an active disease and one an active infection: 246 patients (73%) had UC, 91 (27%) had CD, with a median disease duration of 9 years [interquartile range: 4-17] in UC and 13 [8-19] years in CD. Patients with UC had been on IV-VDZ for a median time of 1.4 years [0.4-3.3] prior to switch, compared to 3.1 [1.3-6.1] for CD patients, with 205 patients overall (62%) on standard IV-VDZ regimen (300mg 8-weekly).
At M6, the SC-VDZ discontinuation-free survival rate was 93.9% [95% confidence interval: 91.3 - 96.5], with no significant difference between CD and UC (p=0.6). During follow-up, 33 patients (10%) had SC-optimisation, with similar rates in both diseases. Among them, 63% has an optimised IV-VDZ regimen prior to switch. In total, 13 (4%) patients switched-back to IV-VDZ: 3 due to loss of response despite SC-VDZ optimisation, 7 for injection site reaction and 3 for various non severe adverse-events. 181 (54%) patients declared adverse events, the most frequent being injection site reactions (20%) and infections (17%). Only one serious adverse event potentially related to treatment was reported (a digestive infection that led to hospitalisation with negative testing), though it did not lead to treatment discontinuation.

Conclusion

In this multicentre prospective cohort of patients with CD or UC in clinical remission who switched from IV to SC vedolizumab, drug persistence rate at 6 months was over 90%, with good safety results. 12-month results are pending.

Disclosure

Financial support: Takeda

Introduction

Pain is the hallmark and most disabling symptom of chronic calcific pancreatitis (CCP), often severe and significantly impairing patients' quality of life. Its pathophysiology involves increased intraductal pressure, chronic inflammation, and neuropathic changes.

Aims & Methods

This study aimed to assess the prevalence of pain in CCP and to identify factors associated with its occurrence and severity.
This was a retrospective analytical study including patients followed for CCP. We collected data on disease duration, etiology, clinical manifestations, complications, analgesic treatments (AT), and symptom evolution under treatment. Pain intensity and impact on quality of life were assessed using the Izbicki Score (IS), which categorizes pain as mild (0–20), moderate (21–40), severe (41–60), or very severe (>60). Incomplete records that prevented IS calculation were excluded. Data were entered and analyzed using SPSS software, with statistical significance set at p < 0.05.

Results

We included 22 patients (14 men and 8 women), with a mean age of 55.6 years [27–80 years]. The most common symptoms were epigastric pain (n=18), weight loss (n=13), and chronic diarrhea (n=6). The mean delay between symptom onset and diagnosis was 25 months [1–120 months]. Etiologies included hyperparathyroidism (n=6), alcohol use (n=2), pancreas divisum (n=2), autoimmune causes (n=2), and were undetermined in 10 cases. The IS ranged from 0 to 93.75, with a mean of 40.22. Eight patients had an IS >40. Morphine was required in four cases; paracetamol was prescribed for 12 patients, and tramadol for two. Endoscopic treatment was indicated in three cases, while one patient underwent a Wirsungojejunostomy.
In univariate analysis, alcohol consumption was significantly associated with the occurrence of epigastric pain (p=0.01). Smoking and alcohol use were both linked to a higher IS (>50) (p=0.04). Smoking cessation was associated with a better analgesic response (p=0.04). Morphine use was significantly more frequent among alcoholic patients (p=0.01), and their treatment response was often unfavorable (p=0.02).

Conclusion

In our cohort, 80% of patients with CCP experienced pain, which was severe to very severe in nearly half the cases. Pain intensity was significantly associated with tobacco and alcohol consumption, while cessation improved treatment response. These findings underscore the importance of therapeutic education focused on smoking and alcohol cessation, in addition to analgesic management, to slow disease progression and improve pain control.

Introduction

Etrasimod is an oral, once-daily, selective sphingosine 1‑phosphate (S1P)_1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). In patients with moderately to severely active UC, treatment guidelines recommend early use of advanced therapies rather than gradual step up after failure of 5-aminosalicylate (5-ASA).¹

Aims & Methods

This prespecified subgroup analysis assessed the efficacy of etrasimod vs placebo in patients in ELEVATE UC 52 (NCT03945188) with, and without, prior oral 5-ASA failure only (defined as inadequate response, loss of response or intolerance to previous treatment with oral 5-ASA but not to any other previous UC medication). Efficacy endpoints assessed at Weeks 12 and 52 included clinical remission, endoscopic improvement, symptomatic remission and composite histological endpoints.

Results

In total, 45 and 29 patients receiving etrasimod and placebo, respectively, had prior 5-ASA failure only and 244 and 115 patients did not. At Weeks 12 and 52, among those who had failed prior 5-ASA only, significantly more patients receiving etrasimod vs placebo achieved clinical remission (Week 12, % difference [Δ]: 38.3%, p < 0.001; Week 52, Δ: 45.0%, p < 0.001), endoscopic improvement (Week 12, Δ: 54.7%, p < 0.001; Week 52, Δ: 47.8%, p < 0.001), symptomatic remission (Week 12, Δ: 38.6%, p < 0.001; Week 52, Δ: 45.0%, p < 0.001) and endoscopic improvement-histologic remission (Week 12, Δ: 35.6%, p < 0.001; Week 52, Δ: 31.1%, p < 0.001; Table). Significantly more patients receiving etrasimod vs placebo in this subgroup achieved endoscopic normalisation-histologic remission (Week 12, Δ: 19.9%, p = 0.002; Week 52, Δ: 24.3%, p < 0.001) and disease clearance (Week 12, Δ: 15.6%, p = 0.008; Week 52, Δ: 27.8%, p < 0.001). Among those who had failed other therapies, significantly more patients receiving etrasimod vs placebo also achieved all endpoints at Weeks 12 and 52 (p < 0.01).

Conclusion

Etrasimod demonstrated robust efficacy as first-line advanced therapy in patients who had failed oral 5-ASA only, across all evaluated endpoints including stringent composite histological endpoints, consistent with the overall ELEVATE UC population. Etrasimod shows efficacy when used early in the UC treatment algorithm.

References

1. Singh S et al. Gastroenterology 2024; 167: 1307–1343.
Pfizer’s generative artificial intelligence tool MAIA was used to assist production of the abstract first draft. Authors reviewed/edited and take responsibility for the content.

Disclosure

DTR received grant support from Takeda; consultancy fees from AbbVie, Abivax SA, Altrubio, Avalo Therapeutics, Bausch Health, Bristol Myers Squibb, Buhlmann Diagnostics Corp, Celltrion, ClostraBio, Connect BioPharma, Douglas Pharmaceuticals, Eli Lilly & Co., Foresee, Genentech (Roche) Inc., Image Analysis Group, InDex Pharmaceuticals, Iterative Health, Janssen Pharmaceuticals, Odyssey Therapeutics, Pfizer Inc, Sanofi, Takeda Pharmaceuticals, Throne and Vedanta.
CWL received speaker fees from AbbVie, Dr Falk, Ferring, Hospira, Janssen, MSD, Pfizer Inc, Shire, Takeda and Warner-Chilcott; consultancy fees from AbbVie, Dr Falk, Gilead, GSK, Hospira, Iterative Scopes, Janssen, MSD, Oshi Health, Pfizer Inc, Pharmacosmos, Takeda, Topivert, Trellus Health and Vifor Pharma; research funding from AbbVie and Gilead.
FB received research/grant support from AbbVie, Amgen, Eurogenerics, Janssen and Takeda; lecture fees/speaker’s bureau from AbbVie, Arena Pharmaceuticals, Celltrion, Ferring, Galapagos, Janssen, Merck Sharp & Dohme, Pfizer Inc and Takeda; consultancy fees from AbbVie, Abivax, Amgen, Arena Pharmaceuticals, Celgene, Celltrion, Ferring, Fresenius Kabi, Janssen, Merck Sharp & Dohme, Pfizer Inc and Sandoz.
MK is an employee and shareholder of Pfizer Inc.
AB is an employee of Pfizer Healthcare India Private Ltd and shareholder of Pfizer Inc.
KL is an employee of Pfizer AG and shareholder of Pfizer Inc.
MG is an employee of Pfizer AG and shareholder of Pfizer Inc.
AMM is an employee and shareholder of Pfizer Inc.
KW is an employee of Pfizer Canada Inc and shareholder of Pfizer Inc.
JKM is an advisory committee/board member on AbbVie, Alimentiv, Amgen, AstraZeneca, Bausch Health, Bristol Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Janssen, Lilly, Lupin, Organon, Paladin, Pfizer Inc, Pharmascience, Qu Biologics, Roche, Sandoz, SCOPE, Takeda, Teva and Viatris; receives lecture/speaker fees from AbbVie, Amgen, Bausch Health, Ferring, Fresenius Kabi, Janssen, Organon, Pfizer Inc, Pharmascience, Roche, Takeda and Viatris.