Introduction

Following anti-TNF therapy, treatment options include switching between different anti-TNF agents or swapping to therapies with distinct mechanisms of action. It is essential to evaluate these treatment pathways in real-world settings to improve inflammatory bowel diseases (IBD) management.

Aims & Methods

This retrospective study analyzed data from the French National Health Data System and included all adult patients meeting at least one of the following criteria between 2014 and 2023: i) long-term disease related to IBD ii) at least 2 hospitalizations for IBD iii) one hospitalization for IBD coupled with 3 or more IBD treatment deliveries. The study assessed treatment discontinuation (short-term: 1 year; long-term: 5 years), and hospitalizations for IBD, IBD-related surgeries and serious infections among patients initiating a second line treatment (2L) between 2014 and 2022 following a first anti-TNF therapy. All outcomes were evaluated one year post switching between anti-TNF agents (reference) versus swapping to vedolizumab (VDZ) or ustekinumab (UST) using a propensity score (PS)-matched Cox proportional hazards model. Covariates used to estimate PS were age, gender, and medical history (see full list in Table 1). Covariate balance was assessed through standardized mean difference (SMD).

Results

The cohort consisted of 151,999 CD patients and 152,367 UC patients, with 14.5% of CD patients and 9.3% of UC patients undergoing 2L treatment. After PS matching, the profiles of IBD patients who switched to a 2^nd anti-TNF were comparable to those who swapped to UST or VDZ (SMD<0.1 for all covariates). Main outcomes are summarized in Table 1.
CD patients who swapped to VDZ had higher risks of treatment discontinuation compared to those who switched to a 2^nd anti-TNF (short-term: adjusted hazard ratio (aHR)=1.23 95%CI [1.11-1.36]; long-term: aHR=1.14 95%CI [1.06-1.23]). Conversely, patients who swapped to UST showed lower risks of treatment discontinuation (short-term: aHR=0.76 95%CI [0.70-0.81]; long-term: aHR=0.72 95%CI [0.68-0.76]), and experienced fewer hospitalizations due to IBD (aHR=0.77 95%CI [0.71-0.83]) and serious infections (aHR=0.74 95%CI [0.59-0.93]).
UC patients who swapped to VDZ had lower risks of treatment discontinuation (short-term: aHR=0.81 95%CI [0.75-0.87]; long-term: aHR=0.83 95%CI [0.78-0.87]), but a higher risk of IBD-related hospitalizations (aHR=1.11 95%CI [1.02-1.20]) compared to those who switched to another anti-TNF. In contrast, UC patients who swapped to UST showed decreased risks of treatment discontinuation (short term: aHR=0.58 95%CI [0.49-0.69]; long-term: aHR=0.62 95%CI [0.54-0.71]). For all other outcomes, the results were statistically non-significant and are presented in Table 1.

Conclusion

In this large cohort of patients, swapping to UST led to better treatment persistence in both CD and UC while reducing the risks of hospitalizations and serious infections in CD compared to switching between anti-TNF agents. Swapping to VDZ offered better treatment persistence than switching to another anti-TNF agent in UC.

Disclosure

LV received fees from abbvie, amgen, MSD, Ferring, Takeda, Pfizer, Janssen, Lilly, Galapagos, Celltrion, Viatris
LPB received fees from Abbvie, Abivax, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS,
Celltrion, Connect Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK,
Hac Pharma, IAC Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD
Norgine, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeuthics, Pandion Therapeuthics, Par' Immune, Pfizer, Prometheus,
Protagonist, Roche, Roivant, Samsung, Sandoz, Sanofi, Takeda, Theravance, Thermo Fischer, Tigenix, Tillots, Viatris, Vifor, Vectivbio,
Ventyx, Ysopia.
JK received fees from Janssen, Takeda, Lilly, Abbvie, Pfizer, Tillots, Amgen, Celltrion, Roche, Gilead, Galapagos.
SC, VC, HO, LG, KS, LC works for Johnson&Johnson Innovative Medicine.
PR, GB, AH, TN works for IQVIA Operations France.