Introduction
Drug positioning in ulcerative colitis (UC) patients refractory to anti-tumor necrosis factor (TNF) is still debated. We aimed to compare the real-life effectiveness and safety of tofacitinib and vedolizumab as second-line therapy in anti-TNFs experienced UC patients.
Aims & Methods
In this Italian multicenter cohort study, we retrospectively included consecutive UC adult patients exposed to ≥ 1 anti-TNF agent starting tofacitinib or vedolizumab. Clinical remission (defined as partial Mayo score (PMS) <3 and no subscore >1) and corticosteroid-free clinical remission (CFREM) were assessed at week 26. Patients who discontinued treatment due to a primary or secondary non-response, adverse events, or intolerance were considered as treatment failure and classified as non-responders. The primary outcome was to compare clinical remission in tofacitinib- and vedolizumab-treated patients at week 26. Propensity score with inverse probability of treatment weighting (IPTW) was used to adjust for confounding, including sex, age at drug initiation, age at diagnosis, smoking habit, disease extension, use of immunosuppressant and steroids at baseline, disease activity at baseline by PMS, reason for anti-TNF discontinuation. Multiple imputation was used for missing data. Venous thromboembolism event, herpes zoster reactivation, major cardiovascular adverse event, severe lymphopenia, initiation or escalation of cholesterol-lowering drugs, hospitalization, surgery, dysplasia or colorectal carcinoma, and death were assessed for the safety profile.
Results
Overall, 99 tofacitinib- and 230 vedolizumab-treated patients were included. Baseline characteristics are summarized in Table 1. The groups were comparable except that tofacitinib-treated patients were younger and of pediatric onset, with lower comorbidities and cardiovascular risk factors. Of note, 22 patients were excluded due to a lack of sufficient follow-up. After IPTW analysis, no difference between tofacitinib- and vedolizumab-treated patients in terms of clinical remission 1.23 (0.68 – 2.23) and CFREM 1.27 (0.71 – 2.29) was observed at week 26. Similar results in terms of clinical remission 1.13 (0.60 – 2.14) and CFCR 1.16 (0.62 – 2.20) were obtained when analyzing patients with a baseline PMS ≥ 2 (Figure 1). Safety wasconsistent with known tofacitinib and vedolizumab profiles in ulcerative colitis.
| | Tofacitinib
(n=99) | Vedolizumab
(n=230) | p |
| Age at baseline, y | 36 (28.5 – 46) | 46 (33 –57.8 ) | <0.001 |
| Concomitant steroids | 40 (40%) | 106 (46%) | 0.31 |
| Partial Mayo Score | 3 (3 – 6.5) | 5 (3 – 6) | 0.74 |
| Mayo Endoscopic Subscore | | | 0.56 |
| 1 | 1 | |
| 6 (8.3%) | 8 (5.6%) | |
| 24 (33%) | 58 (41%) | |
| 41 (57%) | 76 (53%) | |
| Cardiovascular risk factor | 13 (13%) | 62 (28%) | <0.01 |
Conclusion
Our preliminary results suggest no difference in terms of clinical remission and CFREM oftofacitinib and vedolizumab as second-line therapy in anti-TNFs experienced UC patients atthe 26th week. Safety was consistent with known tofacitinib and vedolizumab profiles inulcerative colitis.
Disclosure
DN received research grant from Pfizer, consulting fees from Dr. Falk, lecturer fees from Ferring. AO served as an advisory board member for AbbVie, Galapagos, MSD, Janssen, Pfizer, Takeda Pharmaceuticals, and received lecture grants from AbbVie, MSD, Sofar, Chiesi, Janssen, Pfizer, and Takeda Pharmaceuticals. SO has received speaker fees from AbbVie, Takeda, Janssen, Amgen, Galapagos and Norgin MCF received consultancy fees from Roche, Takeda, Jannsen-Cilag, Pfizer, Sandoz, Biogen, Galapagos and research economic support from Abbvie. ES has served as speaker for AbbVie, AGPharma, Alfasigma, EG Stada Group, Fresenius Kabi, Grifols, Janssen, Innovamedica, Malesci, Medtronic, Novartis, Pfizer, Reckitt Benckiser, Sandoz, SILA, Sofar, Takeda and Unifarco; has served as consultant for Alfasigma, Amgen, Biogen, Bristol Myers Squibb, Celltrion, Diadema Farmaceutici, Falk, Fresenius Kabi, Janssen, Merck & Co., Reckitt Benckiser, Regeneron, Sanofi, Shire, SILA, Sofar, Synformulas GmbH, Takeda and Unifarco; and has received research support from Reckitt Benckiser, SILA, Sofar and Unifarco. Grants or contracts from any entity AbbVie, Janssen, Kern, Takeda, Galapagos, Pfizer Consulting fees: Janssen. Payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events, AbbVie, Janssen, Takeda, Pfizer. Support for attending meetings and/or travel from Ferring and Janssen. Educational activities research projects scientific meetings or advisory boards sponsored by MSD, Ferring and Abbvie. MV served as a consultant for Abbvie, MSD, Takeda, Janssen-Cilag, and Celgene. He received lecturer fees from Abbvie, Ferring, Takeda, MSD, Janssen-Cilag, and Zambon. FC served as consultant to Abbvie, MSD, Takeda, Janssen, Roche, Celgene, Bristol-Meyers Squipp, Galapagos, Gllead, Pfizer, Mundipharma, Galapagos, Biogen, received lecture fees from Abbvie, Ferring, Takeda, Allergy Therapeutics, Janssen, Pfizer, Biogen, and unrestricted research grants from Giuliani, Sofar, MSD, Takeda, Abbvie.