Introduction

Real-world data on the speed of onset of ustekinumab (UST) in patients with ulcerative colitis (UC) are limited. Current information regarding early response in these patients comes from the UNIFI trial.

Aims & Methods

The primary outcome of this study was to evaluate the response to UST in patients with moderate-to-severe UC by assessing PRO2 at 14 days after the first intravenous dose (6mg/kg).
Methods: A multicenter, prospective observational study was designed in patients ≥18 years old with moderate-to-severe UC (partial Mayo score ≥6) who initiated UST 6mg/kg between June 2023 and September 2024. Patients received a diary to record the stool frecuency and rectal bleeding during first 14 days after first dose of induction. The proportion of patients achieving the combined outcome of rectal bleeding score = 0 and stool frequency score ≤ 1 (PRO-2: patient-reported outcome 2 remission) was assessed. FC was measured at baseline and at day 7 and 14. Health-Related Quality of Life was evaluated using the disease-specific shortened Spanish version of the IBDQ (SIBDQ-9) at baseline and at 4 weeks. Patients with previous panproctocolectomy with ileostomy or pouch and those who had received cyclosporine within one month prior to starting UST were excluded. Descriptive statistics are presented as frequencies with percentages for categorical variables.

Results

A total of 54 patients were included across 14 hospitals in Spain. Of these, 29 (53.7%) were men, with a mean age of 54 (± SD 16.1) years. Thirty (55.6%) patients had pancolitis, 20 (37%) had left-sided colitis, and 4 (7.4%) had proctitis. Five (9.3%) patients were bio-naïve, 32 (59.3%) had previously received one biological therapy, 10 (18.5%) had received two, and 7 (13%) had received three biologics prior to starting UST. By day 14, 26% of patients had achieved clinical remission. No significant differences in clinical remission were observed based on disease extent (p = 0.11) or the number of prior biologics (p = 0.39). By day 7, 12/31 (38.7%) patients with baseline bloody stools had achieved a rectal bleeding score = 0. A reduction in FC >50% was observed in 14/48 (29%) patients by day 7 and in 20/47 (43%) patients by day 14. The SIBDQ9 average score was 54.9 (± SD 6.2) at baseline and 61.3 (± SD 7.4) at week 4.

Conclusion

One-quarter of patients with moderate-to-severe UC achieved clinical remission by day 14 following the first induction dose of UST. Nearly 40% of patients achieved a rectal bleeding score = 0 (PRO2) by day 7. A reduction in FC >50% was observed in 43% of patients by day 14.

Disclosure

Manuel Barreiro de Acosta: speaker, consultant and advisory member for or have received research funding from AbbVie, Janssen, Takeda, Pfizer, Lilly, Alphasigma, Sandoz and Oncostellae

Introduction

Tumor necrosis factor-like ligand 1A (TL1A) is a member of the Tumor necrosis factor (TNF) superfamily implicated in the pathogenesis of inflammatory bowel disease (IBD) as a key amplifier of the effector function of several immune cells. TL1A can be expressed by various immune cells, including macrophages, dendritic cells, and some T cell subsets, and exists either as a membrane-bound or as a cleaved soluble trimer. TL1A signals predominantly by activating NF-kB pathway via the only known functional receptor, death receptor 3 (DR3), which has restricted expression mostly on effector T cells and innate lymphoid cells (ILCs). Afimkibart is a fully human anti-TL1A antibody that has shown clinical benefit in Phase 2 clinical studies and specifically blocks the activity of trimeric forms of TL1A. Monomeric TL1A has also been described; however, the relevance of monomeric TL1A in DR3 signaling and disease is unclear. This study aimed to understand the functional characteristics of both monomer and trimer TL1A species in primary cells and cell lines.

Aims & Methods

Immunoassays were used to measure the detection of TL1A species in IBD serum. Recombinant human monomeric and trimeric TL1A proteins were assessed for binding to afimkibart using SPR and in cellular assays using primary immune cells and cell lines for nuclear factor-kappa B (NF-κB) signaling and interferon-gamma (IFNγ) production.

Results

In functional cellular assays with primary immune cells, we demonstrate that trimeric recombinant human TL1A (rhTL1A) protein causes significant NF-κB signaling in human peripheral T lymphocytes, and in the presence of interleukin 12 (IL12) and interleukin 18 (IL18) co-stimulation, a significant increase of IFNγ production by human primary peripheral blood mononuclear cells (PBMCs). In line with the mechanism of action, both the NF-κB signaling and IFNγ production are blocked by afimkibart. In contrast, only high concentrations of monomeric rhTL1A, >100 ng/ml, induced moderate NF-κB signal and demonstrated a minimal increase in IFNγ production above IL12 + IL18 stimulation alone. However, this activity was blocked by afimkibart. Lastly, afimkibart blocks endogenous soluble and membrane-bound TL1A.

Conclusion

Herein, we demonstrate that afimkibart blocks NF-kB signaling and IFNγ production induced by TL1A stimulation. While some signaling activity was observed at high concentrations of monomeric TL1A protein, we hypothesize that any signaling observed with monomeric form is likely due to the formation of trimers, which are efficiently blocked by afimkibart. Overall, any monomeric TL1A present should not be functionally active nor be available as a sink for afimkibart, thus preserving the optimal pharmacokinetic (PK) and pharmacodynamic (PD) properties needed for effective target inhibition.

Disclosure

All the authors are employees of Genentech-Roche.

Introduction

Despite recent advances in the treatment of IBD, patients still suffer from suboptimal efficacy and are eagering for more effective treatment options. Both human TL1A and IL-23 are clinically validated targets in treating IBD. Here we discovered and characterized SIM0709, a half-life extended bi-specific antibody simultaneously tarting both TL1A and IL-23p19, with the aim to further enhance clinical efficacy and improve patient’s compliance.

Aims & Methods

The binding activities to TL1A protein and IL-23 protein were determined by ELISA and BLI. Cell-based blocking functionalities of TL1A to DR3 and IL-23p19 to IL23R were evaluated by using FACS assays, meanwhile the competitive inhibition of TL1A binding to DcR3 and the inhibition of IL-23 binding to IL12R were also determined by ELISA. TL1A induced TF-1 cell apoptosis and interferon γ (IFNγ) secretion from CD4⁺ T cells stimulated by TL1A in combination with IL-12 and IL-18 were used to evaluate the outcomes of functional blockade of TL1A pathway. In addition, mouse IL-17 secretion from mouse splenocytes stimulated by human IL-23 was also assessed to evaluate the functional blockade of IL-23 pathway. The synergistic effect of dual pathway blockade was measured by Th17 differentiation co-stimulated with human IL-23 and TL1A. A cytokine-induced acute gut inflammation model was used to assess the in vivo efficacy of SIM0709 while the extended half-life was revealed in both human FcRn knock-in mice and non-human primate.

Results

SIM0709 simultaneously bound to both TL1A and IL-23 proteins with sub-nanomolar affinity and demonstrated superior functional activities under various functional assays on both TL1A and IL-23 axes compared to that of benchmark anti-TL1A mAb RG6631 and Guselkumab or its combination, respectively. SIM0709 also exhibited superior dual pathway blockade synergy in vitro in inhibiting Th17 differentiation and in vivo in the cytokine-induced acute gut inflammation model. Further analysis on ileum and colon tissues confirmed relived intestinal inflammation after SIM0709 treatment with significantly reduced inflammatory cytokines/chemokine levels and improved histological scores compared to either the anti-TL1A or anti-IL-23p19 monotherapies. SIM0709 also demonstrated an improved serum half-life in human FcRn knock-in mice compared to that of RG6631. Moreover, SIM0709 showed encouraging PK profile with over 15 days half-life, which together with its excellent developability profile, may support extended dosing interval in the clinic with a patient-friendly subcutaneous formulation.

Conclusion

Taken together, these data support the further development of SIM0709 as a potential FIC and BIC therapeutic agent for the treatment of IBD with expected first-in-human study in H1 2026.

Disclosure

The authors are employees of Jiangsu Simcere Pharmaceutical Co., Ltd and State Key Laboratory of Neurology and Oncology Drug Development.

Introduction

Substantial genetic and clinical evidence indicates that TL1A has a key role in the molecular pathology of IBD. Variants in TNFSF15, the gene encoding TL1A, are associated with IBD, rheumatic, and other diseases. Circulating levels of the protein are elevated in patients with CD and UC. Proof-of-concept for TL1A inhibition in IBD is provided by positive Phase 2 trials of monoclonal antibodies targeting and inhibiting the cytokine in patients with UC and CD (1–3).
SPY002 is an investigational fully human IgG1 monoclonal antibody that specifically binds to TL1A at an epitope that is distinct from other TL1A antibodies in development. SPY002 blocks the interaction of TL1A with its receptor, known as death receptor 3 (DR3), and includes a YTE modification in the Fc domain to increase the binding affinity to FcRn and thereby extend the antibody half-life. A Phase 1, first-in-human study in healthy volunteers is being conducted to characterize the safety, tolerability, PK, and PD properties of SPY002.

Aims & Methods

SPY002-101 is a randomized, double-blind, placebo-controlled single ascending dose (SAD) Phase 1 study in healthy volunteers aged 18 to 65. Study participants were randomized to either SPY002 or placebo in a 3:1 ratio as in dose cohorts as follows: 100 mg SC, 300 mg SC, 300 mg IV, 1000 mg IV, or 1500 mg IV. Blood was collected to evaluate safety, PK, PD (serum soluble TL1A levels), and ADA assessments at scheduled study visits. Interim safety and bioanalytical data with up to three months of follow-up from the first SAD cohort were analyzed.

Results

Interim PK data from Cohorts 1-3 demonstrated dose-proportional pharmacokinetics for SPY002. Noncompartmental[BW1] [JF2] [JL3] [BW4] [JL5] analysis and population PK modeling suggested a half-life extension of approximately 3-fold relative to typical monoclonal antibodies. PD analysis demonstrated saturating effects on soluble TL1A levels beginning with the lowest dose tested (100 mg SC) that extend to the latest time points assessed thus far. Blinded safety data from all cohorts thus far demonstrated SPY002 to be well tolerated with no serious or severe adverse events, with most adverse events being mild in severity and unrelated to study agent.

Conclusion

Interim PK analysis following single doses of SPY002 demonstrated half-life extension supporting potential maintenance dosing at a frequency of every 3 to 6 months with a single SC injection. SPY002 resulted in saturating changes in soluble TL1A levels. SPY002 was well tolerated, with all adverse events being non-serious and typical of a Phase 1 study in healthy volunteers. These results support advancement of SPY002 into clinical trials in IBD, rheumatic, and other potential indications as a monotherapy and as a component of combination therapy.

References

1. B. Sands, L. Peyrin-Biroulet, S. Danese, D. T. Rubin, S. Vermeire, O. Laurent, A. Luo, D. Nguyen, J. D. Lu, A. Wiechowska-Kozlowska, J. Leszczyszyn, R. Kempinski, J. Kierkus, C. Ma, T. Ritter, B. G. Feagan, S. Targan, OP40 PRA023 Demonstrated Efficacy and Favorable Safety as Induction Therapy for Moderately to Severely Active UC: Phase 2 ARTEMIS-UC Study Results. J. Crohn’s Colitis 17, i56–i59 (2023).
2. B. G. Feagan, B. E. Sands, C. A. Siegel, M. C. Dubinsky, R. Longman, J. Sabino, O. Laurent, A. Luo, J. D. Lu, D. D. Nguyen, F. Towfic, A. DuVall, M. Woynarowski, H. A. Kharrat, D. McGovern, S1143 The Anti-TL1A Antibody PRA023 Demonstrated Proof-of-Concept in Crohn’s Disease: Phase 2a APOLLO-CD Study Results. Am. J. Gastroenterol. 118, S875–S876 (2023).
3. S. Danese, M. Klopocka, E. J. Scherl, J. Romatowski, J. R. Allegretti, E. Peeva, M. S. Vincent, U. Schoenbeck, Z. Ye, M. Hassan-Zahraee, N. Rath, G. Li, S. Neelakantan, C. Banfield, C. Lepsy, D. E. Chandra, K. E. Hung, Anti-TL1A Antibody PF-06480605 Safety and Efficacy for Ulcerative Colitis: A Phase 2a Single-Arm Study. Clin. Gastroenterol. Hepatol. 19, 2324-2332.e6 (2021).

Disclosure

All authors are employees of and own stock in Spyre Therapeutics.

Introduction

The addition of selective Janus kinase inhibitors (JAKi) ¾tofacitinib (TOFA), upadacitinib (UPA), and filgotinib (FILGO)¾ to the therapeutic arsenal for ulcerative colitis (UC) has provoked the need for comparative studies to establish their positioning in clinical practice. Aim: To compare the durability and the short- and long-term effectiveness of TOFA, UPA, and FILGO in UC, and to evaluate their real-world safety.

Aims & Methods

Adult patients who started JAKi treatment for UC (from April 2021) at least 8 weeks prior to data collection and were part of the prospectively maintained ENEIDA registry of GETECCU, were included. Patients receiving concomitant biologic agents or with a history of colectomy were excluded. Patients were followed from the first JAKi dose until treatment discontinuation or their last visit. Effectiveness analysis was restricted to patients with active disease [Partial Mayo Score (PMS)>2] at JAKi initiation. Clinical effectiveness was measured using PMS, and concomitant steroid use was assessed at each visit. Patients who discontinued JAKi before their last visit were considered not in remission at subsequent time points (negative imputation). The propensity score was calculated using the inverse probability of treatment weighting (IPTW) method to balance confounding factors.

Results

A total of 611 patients were included (74 on FILGO, 369 on TOFA, and 168 on UPA). Baseline characteristics are summarised in Table 1.

Variable	Filgotinib N=74	Tofacitinib N=369	Upadacitinib N=168	p
Exposure time (months), median (IQR)	6.3 (3.9-10)	8.9 (3.5-23)	4.3 (2.7–10)	0.0001
Number of previous biologics, median (IQR)	2 (1-3)	1 (1-2)	2 (1-3)	0.0001
Previous advanced therapies, median (IQR)	2 (1-3)	1 (1-2)	3 (1-4)	0.002
Follow-up time (months), median (IQR)	10 (6.6.-15)	23 (13-35)	5.6 (3.6–14)	0.001
PMS at baseline, median (IQR)	5 (4-6)	6 (4-7)	6 (4-7)	0.001
Extraintestinal manifestations, n (%)	13 (18)	74 (20)	58 (35)	0.001
Previous biologics/JAK inhibitors Tofacitinib, n (%) Filgotinib, n (%) Upadacitinib, n (%) Anti-TNF, n (%) Anti-IL23, n (%) JAKi, n (%) Anti-TNF and vedolizumab, n (%) Anti-TNF, vedolizumab and JAKi, n (%) Anti-TNF, vedolizumab, anti-IL23 and JAKi, n (%)	15 (20) 3 (4) 66 (89) 24 (32) 15 (20) 27 (37) 10 (14) 9 (12)	2 (0.5) 0 (0) 346 (94) 71 (19) 2 (0.5) 139 (38) 1 (0.3) 1 (0.3)	73 (43) 11 (6.5) 153 (91) 89 (53) 80 (48) 84 (50) 63 (38) 52 (31)	<0.001 <0.001 <0.001 0.01 <0.001 <0.001 0.01 <0.001 <0.001
Anemia at baseline, n (%)	11 (16)	114 (33)	45 (28)	0.01
Interquartile range, IQR; Partial Mayo Score, PMS

Discontinuation rates per patient-year were 57% for FILGO, 40% for TOFA, and 27% for UPA (log rank p-value < 0.01). In the multivariate analysis, adjusted by the PMS at baseline and prior exposure to JAKi, the type of JAKi ¾FILGO vs. UPA [Hazard Ratio (HR) = 2.3, 95% confidence interval (CI) = 0.1-0.4] and TOFA vs. UPA (HR = 2.3, 95%CI = 0.1-0.3)¾ was associated with higher risk of treatment discontinuation. Steroid-free clinical remission (SFCR) rates during follow-up were significantly higher with UPA at most time points. At week 8, PMS at baseline [Odds Ratio (OR) = 1.07, 95% confidence internal (CI) = 1.009-1.1], prior JAKi exposure (OR = 0.4, 95%CI = 0.2-0.7), and JAKi type ¾FILGO vs. UPA (OR = 0.2, 95%CI = 0.1-0.4] and TOFA vs. UPA (OR = 0.2, 95%CI = 0.1-0.3) were significantly associated with SFCR. The IPTW method confirmed all these results. Adverse events occurred in 12 (16%) patients with FILGO, 85 (23%) with TOFA, and 45 (27%) with UPA (p=0.2), with a minority leading to discontinuation.

Conclusion

In real-world practice, UPA shows superior effectiveness and drug survival compared to TOFA and FILGO in UC patients, with a comparable safety profile. These findings support the positioning of JAKi treatments in clinical practice and may guide treatment decisions in UC management.

Disclosure

María Chaparro has served as speaker, consultant or research or education funding from MSD, Abbvie, Hospira, Pfizer, Takeda, Janssen, Ferring, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Biogen, Gilead and Lilly.

Raquel Camargo has received funding for different types of training activities from Johnson&Johnson, Avbbie, Pfizer, Ferring, Falk and Galapagos.

MJ Casanova, has received education funding from Pfizer, Takeda, Janssen, MSD, Dr. Falk, Shire, Ferring, Galápagos and Abbvie.

Luisa de Castro has received grants for conference attendance from Abbvie, Johnsson and Johnsson, Takeda, Falk and Pfizer. She has received grants or participated as a speaker for Johnsson and Johnsson, Falk and Tillots.

CJ Gargallo-Puyuelo Conflicts with Abbvie, Takeda, Janssen, Ferring, Lilly.

Lara Arias García scientific advice, research support and/or training activities for Abbvie FAES Pharma, Kern Pharma, Ferring and MSD.

Ruth de Francisco has received support for conference attendance, and research support from AbbVie, Faes Pharma, Ferring, Janssen, Pfizer, Takeda, and Galapagos.

Manuel Barreiro has served as a speaker, consultant and advisory member for or have received research funding from MSD, AbbVie, Janssen, Kern Pharma, Celltrion, Takeda, Gillead, Celgene, Pfizer, Sandoz, Biogen, Fresenius, Ferring, Faes Farma, Dr. Falk Pharma, Chiesi, Gebro Pharma, Adacyte, Vifor Pharma and Oncostellae.

Iago Rodríguez Lago has received financial support for traveling and educational activities from or has served as an advisory board member for Abbvie, Adacyte, Biogen, Celltrion, Chiesi, Faes Farma, Ferring, Fresenius Kabi, Galapagos, Janssen, Lilly, Mirum Pharmaceuticals, MSD, Pfizer, Roche, Takeda, and Tillotts Pharma. Research support from AbbVie. Iago Rodriguez Lago is supported by a research grant from Gobierno Vasco-Eusko Jaurlaritza [Grant No 2020111061].

Marta Calvo Moya has received support for conference attendance, speaker fees, research support, and consultancy fees from AbbVie, MSD, Takeda, Janssen, Pfizer, Lilly, Shire, Chiesi, DrFalk Pharma, Faes Pharma, Ferring, Kern Pharma, and Tillotts Pharma.

R Pajares Villarroya has received financial support for educational activities from Takeda.

Margalida Calafat has served as a speaker or has received research or education funding or advisory fees from Takeda, Janssen, Faes Farma, Falk, Abbvie, Pfizer, Adacyte Therapeutics, Ferring, Gilead, Kern Pharma, and MSD.

B Caballol has received support for congress and conference attendance, speaker fees, research support or consulting fees from Abbvie, Ferring, Janssen, Pfizer, Takeda, Galapagos, Kern Pharma and Lilly.

Mónica Sierra has participated as a speaker and attended courses financed by MSD, Abbvie, Takeda, Pfizer, Lilly, Ferring, Sandoz.

Jesús Castro has served as a speaker or received financial support for travelling or received research funding from Abbvie, Janssen, Takeda, Kern, Lilly, Pfizer, Ferring, Dr.Falk Pharma, Tillots Pharma, and Biogen.

Antonio Giordano has received educational funds and travel grands from Johnson&Johnson, Dr.Falk, Ferring, Galápagos, Casen recordati, Alfasigma, Hospital Hispania.

JM Huguet has served as speaker or has received research funding from MSD, Abbvie, Pfizer, Kern Pharma, Takeda, Janssen, Sandoz, Ferring, Faes Farma and Dr. Falk Pharma.

MA Mejías Manzano has participated as a speaker and I have received funding to attend congresses, meetings and training courses from Abbvie, Pfizer, Takeda, Janssen, Lilly, Falk and Ferring.

Cristina Reygosa Castro has received fees for conferences organised by Intercept, Fresenius, Johnson&Johnson and Tillots Pharma.

E. Iglesias Flores has served as a speaker, consultant and advisory member for or has received research funding from AbbVie, Janssen, Takeda, Gillead, Celgene, Pfizer, Lilly, Ferring, Faes Farma, Dr. Falk Pharma, Chiesi, and Adacyte.

Javier P. Gisbert has served as speaker, consultant, and advisory member for or has received research funding from MSD, Abbvie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos, Lilly, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine and Vifor Pharma.

Introduction

​Biologic therapies play a pivotal role in the management of ulcerative colitis (UC). Anti-TNFα agents are recommended as first-line biologics according to ECCO guidelines; however, JAK inhibitors have recently emerged as a viable alternative (1). Vedolizumab has also demonstrated effectiveness when introduced early in the disease course with a greater 52-week treatment persistence and reduced hospitalisation rates compared to anti-TNFα agents as second-line therapy (2). The AGA guidelines (3) now favour biologics such as anti-IL-23 and JAK inhibitors over Vedolizumab or S1P receptor modulators in patients previously exposed to anti-TNFα agents. Notably, Guselkumab is not yet approved for UC treatment in the UK. The latest ECCO guidelines (1) do not address the role of biologics in third-line or subsequent treatment settings, and there remains a lack of clear clinical guidance.

Aims & Methods

This study aimed to retrospectively evaluate the effectiveness of third-line biologic therapies in adult patients with UC over a 12-month period. Clinical response was assessed using the Simple Clinical Colitis Activity Index (SCCAI), Partial Mayo Score, and Physician Global Assessment, while biochemical and endoscopic responses were measured at 3, 6, and 12 months post-induction. Biochemical markers included faecal calprotectin and CRP levels. Endoscopic response was assessed using the Ulcerative Colitis Endoscopic Index of Severity (UCEIS). Colectomy rates were also recorded. Patients treated at a UK tertiary care centre were included up to March 2025. Statistical analyses were conducted using SPSS.

Results

A total of 24 patients were included in the analysis, with 13 receiving anti-IL-23 therapy and 11 treated with JAK inhibitors. Within the anti-IL-23 group, 5 patients received Mirikizumab and 8 Ustekinumab; Risankizumab was not used in this cohort. In the JAK group, 3 patients were treated with Upadacitinib, 4 with Filgotinib, and 4 with Tofacitinib. A statistically significant reduction in SCCAI scores at 6 months was observed in the JAK groups compared to anti-IL-23 (7.64 ± 3.61 vs 4.90 ± 1.97, p = 0.047). However, biochemical response, assessed by faecal calprotectin reduction, did not reach statistical significance at either 3 or 6 months (p = 1.000 and p = 0.314, respectively). Endoscopic response, measured by changes in UCEIS at 12 months, also showed no significant difference between groups (p = 0.668). Subgroup analysis within the anti-IL-23 cohort revealed no significant difference in SCCAI reduction between Ustekinumab and Mirikizumab at 3 months. Similarly, while Upadacitinib was associated with the greatest SCCAI reduction among the JAK inhibitors at 3 months, the difference among the three agents was not statistically significant (p = 0.106). Subtotal colectomy was performed in one patient in the Mirikizumab group following completion of induction therapy, and in two additional patients within three months of initiating the same agent (Table 1).

Biologic	Patients (N)	Colectomy(N)	Drug persistence
Mirikizumab	5	3	3/5
Ustekinumab	8	1	5/8
Upadacitinib	3	0	3/3
Filgotinib	4	0	3/4
Tofacitinib	4	0	4/4

Table 1. Patients’ characteristics regarding clinical, biochemical and surgical outcomes within 12 months.

Conclusion

JAK inhibitors showed an improvement in SCCAI at 6 months compared to anti-IL-23 agents. No significant differences were found in biochemical or endoscopic response.

References

1. Raine T, Bonovas S, Burisch J, Kucharzik T, Adamina M, Annese V, et al. ECCO Guidelines on Therapeutics in Ulcerative Colitis: Medical Treatment. Journal of Crohn’s and Colitis. 2022 Jan 28;16(1):2–17.
2. Miller C, Kwok H, Harrow P, Vega R, Seward E, Mehta S, et al. Comparative effectiveness of a second-line biologic in patients with ulcerative colitis: vedolizumab followed by an anti-TNF versus anti-TNF followed by vedolizumab. Frontline Gastroenterol. 2022 Sep;13(5):392–401.
3. Singh S, Loftus EV, Limketkai BN, Haydek JP, Agrawal M, Scott FI, et al. AGA Living Clinical Practice Guideline on Pharmacological Management of Moderate-to-Severe Ulcerative Colitis. Gastroenterology. 2024 Dec;167(7):1307–43.