Introduction
Anti-tumor necrosis factor (TNF)-α are the first target therapies approved for the treatment of steroid-dependent or -refractory ulcerative colitis (UC). Drugs with different mechanisms of action have recently entered the market, but data on the optimal management of UC after failure of first-line anti-TNF-α are lacking.
Aims & Methods
The PODIUM study is a multicentre, retrospective, observational study that aims to compare the real-life effectiveness and safety of second-line vedolizumab (VDZ), ustekinumab (UST) and tofacitinib (TOF) in patients with UC. Consecutive patients with UC who had failed at least one anti-TNF-α and were never exposed to other target therapies were enrolled from 12 centres across Europe. Sociodemographic data, data on clinical activity and adverse events of interest (AEIs, defined as AE requiring temporary/permanent drug discontinuation or medical intervention) were retrospectively extracted from medical records, from the initiation of second-line therapy until one year of observation/drug discontinuation/last available follow-up. The primary outcome was the cumulative probability of achieving steroid-free clinical remission (SFCR), defined as stool frequency=0-1 and rectal bleeding=0 and no concomitant steroids, over the first year of treatment; inverse probability of treatment weighting (IPTW), calculated as the inverse of the probability of receiving each drug (IPTW=1/Propensity Score), was applied to the primary outcome to account for imbalances in cohorts’ characteristics. We performed an interim analysis including all data collected up to March 15th 2024; data collection is still ongoing at the submission of this Abstract.
Results
Data on 303 patients (172 VDZ, 63 UST, 68 TOF) were included in the analysis. The main baseline characteristics are presented in Table 1. After IPTW, the cumulative probability of achieving SFCR during the first year was 51.0%, 59.1% and 64.1% for VDZ, UST and TOF, respectively; both UST and TOF were superior to VDZ at Log-rank test (p<0.001), with no differences between the two. At weighted logistic regression, female sex (adjusted Odds Ratio, aOR, 0.06, Confidence Interval, CI, 95% 0.41-0.73, p<0.001) and higher Charlosn Comorbidity Index calculated without considering age (aOR 0.73, 95% CI 95% 0.60-0.88, p=0.001) were independently associated with a lower probability of achieving SFCR during the first year. Recorded AEIs were 16 (4 infections) in the VDZ group (9.3% of VDZ-treated patients), 6 (1 infection) in the UST group (9.5% of UST-treated patients), and 15 (5 infections, including 1 Zoster reactivation) in the TOF group (22.1% of TOF-treated patients).
Table 1
| VDZ | UST | TOF | p |
| N | 172 | 63 | 68 |
|
| Sex (F), n (%) | 66 (38.4) | 31 (49.2) | 34 (50.0) | p<0.05 (VDZ vs both) |
| Age, mean (SD) | 45.2 (16.0) | 48.43 (16.5) | 38.7 (12.9) | p<0.05 (TOF vs both) |
| Disease duration, mean (SD) | 8.16 (11.1) | 11.1 (11.8) | 7.4 (7.4) | p<0.05 (UST vs TOF) |
| Extent (E3), n (%) | 107 (62.2) | 35 (60.4) | 38 (55.9) | p=ns |
| CCI without age, mean (SD) | 0.4 (1.0) | 0.8 (1.8) | 0.2 (0.5) | p<0.05 (UST vs both) |
| Baseline steroids, n (%) | 74 (43.0) | 26 (41.2) | 38 (55.8) | p<0.05 (TOF vs both) |
Baseline clinical activity
SF, mean (SD)
RB, mean (SD) |
1.9 (1.0)
1.0 (0.9) |
2.0 (1.0)
0.9 (0.9) |
2.2 (0.8)
1.0 (0.8) |
p=ns
p=ns |
Baseline biochemical activity
CRP (mg/dL), mean (SD)
FCP (ug/g), mean (SD) |
15.4 (29.3)
1611 (2627) |
21.2 (43.1)
1111 (1466) |
15.7 (33.0)
1331 (1684) |
p=ns
p=ns |
Conclusion
This preliminary analysis suggests that both UST and TOF might have superior effectiveness, compared to VDZ, as second-line agents in patients with UC after anti-TNF-α. Confirmatory analysis with a larger sample size will be performed. A slightly higher rate of AEIs was observed in the TOF group.
Disclosure
Giuseppe Privitera received consultancy fees from Alphasigma and Janssen. Cristina Bezzio received lecture fees and served as a consultant for Takeda, MSD, Ferring, Abbvie, Galapagos and Janssen. Edoardo Vincenzo Savarino has served as speaker for Abbvie, Agave, AGPharma, Alfasigma, Aurora Pharma, CaDiGroup, Celltrion, Dr. Falk, EG Stada Group, Fenix Pharma, Fresenius Kabi, Galapagos, Janssen, JB Pharmaceuticals, Innovamedica/Adacyte, Malesci, MayolyBiohealth, Omega Pharma, Pfizer, Reckitt Benckiser, Sandoz, SILA, Sofar, Takeda, Tillots, and Unifarco; has served as a consultant for Abbvie, Agave, Alfasigma, Biogen, Bristol-Myers Squibb, Celltrion, DiademaFarmaceutici, Dr. Falk, Fenix Pharma, Fresenius Kabi, Janssen, JB Pharmaceuticals, Merck & Co, Nestlè, Reckitt Benckiser, Regeneron, Sanofi, SILA, Sofar, Synformulas GmbH, Takeda, and Unifarco; he has received research support from Pfizer, Reckitt Benckiser, SILA, Sofar, Unifarco, Zeta Farmaceutici. Daniela Pugliese received speaker fees and/or advisory board from AbbVie, Galapagos, MSD, Takeda and Janssen, Pfizer. Iago Rodriguez-Lago has received financial support for traveling and educational activities from or has served as an advisory board member for Abbvie, Adacyte, Celltrion, Chiesi, Danone, Ferring, Faes Farma, Janssen, Galapagos, MSD, Pfizer, Roche, Takeda, and Tillotts Pharma. Financial support for research: Tillotts Pharma. Manuel Barreiro-de Acosta has served as a speaker, consultant and advisory member for and has received research funding from MSD, AbbVie, Janssen, Kern Pharma, Celltrion, Takeda, Gilead, Celgene, Pfizer, Sandoz, Biogen, Fresenius, Ferring, Faes Farma, Dr. Falk Pharma, Chiesi, Gebro Pharma, Adacyte and Vifor Pharma. Sara Onali has received speaker fees from AbbVie, Takeda, Janssen, Amgen, Galapagos and Norgine. Massimo Claudio Fantini has received speaker and consultancy fees from AbbVie, Takeda, Janssen-Cilag, Pfizer, Sandoz, Biogen, Galapagos, Bristol-Myers Squibb, and MSD; and research grants from Pfizer and Janssen-Cilag. Karmiris K has served as speaker, consultant, and advisory member for Abbvie, Amgen, Enorasis, Ferring, Galenica, Genesis, Janssen, MSD, Pfizer, Takeda and Vianex. Henit Yanai has received consulting fees Abbvie, Ferring, Janssen, Neopharm Ltd., Pfizer, Takeda; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events Abbvie, Janssen, Pfizer, Takeda, Neopharm Ltd.; Participation on a Data Safety Monitoring Board or Advisory Board Abbvie, Neopharm Ltd., Pfizer, Takeda. Ana Gutierrez has served as speaker, consultant and advisory member for or has received research funding from MSD, Abbvie, Pfizer, Kern Pharma, Takeda, Janssen, Ferring, Faes Farma, Shire Pharmaceuticals, Tillotts Pharma, Chiesi and Otsuka Pharmaceutical. Luca Pastorelli has received consultant and/or speaker fees from Giuliani, Ferring, Janssen, Takeda. María Chaparro has served as a speaker and consultant for and has received research or education funding from MSD, AbbVie, Hospira, Pfizer, Takeda, Janssen, Ferring, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Biogen, Gilead and Lilly. Yamile Zabana has received speaker and/or consultant fees from AbbVie, Adacyte, Almirall, Amgen, Dr Falk Pharma, FAES Pharma, Ferring, Janssen, MSD, Otsuka, Pfizer, Shire, Takeda, Galapagos, Boehringer Ingelheim and Tillots. Alessandro Armuzzi: consulting and/or advisory board fees from AbbVie, Amgen, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mylan, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, Takeda; lecture and/or speaker bureau fees from AbbVie, Amgen, Arena, Biogen, Bristol-Myers Squibb, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mitsubishi-Tanabe, Novartis, Pfizer, Roche, Sandoz, Samsung Bioepis, Takeda; and research grants from MSD, Pfizer, Takeda and Biogen. The remaining authors declare no competing interests. The remaining Authors declare no competing interests.
