TY - JOUR
T1 - Immunomodulator withdrawal from anti-TNF therapy is not associated with loss of response in inflammatory bowel disease
AU - Mahmoud, Remi
AU - Schultheiss, Hans-Paul
AU - Louwers, Jonas
AU - van der Kaaij, M T
AU - van Hellemondt, B P
AU - Mahmmod, N
AU - van Boeckel, P G
AU - Jharap, B
AU - Fidder, Herma
AU - Oldenburg, Bas
N1 - Funding Information:
Conflicts of interest These authors disclose the following: Remi Mahmoud has received a travel grant from Takeda. B. Oldenburg has received grants from MSD, AbbVie, Takeda, Cablon, Ferring, Falk, and Pfizer. H.H. Fidder has served as a consultant for AbbVie BV, Janssen BV, Ferring BV, and Takeda BV. The remaining authors disclose no conflicts.
Funding Information:
Conflicts of interest These authors disclose the following: Remi Mahmoud has received a travel grant from Takeda. B. Oldenburg has received grants from MSD, AbbVie, Takeda, Cablon, Ferring, Falk, and Pfizer. H.H. Fidder has served as a consultant for AbbVie BV, Janssen BV, Ferring BV, and Takeda BV. The remaining authors disclose no conflicts.
Publisher Copyright:
© 2022 The Authors
PY - 2022/11
Y1 - 2022/11
N2 - BACKGROUND AND AIMS: The benefit of concomitant immunomodulators (thiopurines or methotrexate) in patients with inflammatory bowel disease (IBD) on anti-tumor necrosis factor α (anti-TNF) (infliximab or adalimumab) maintenance therapy is debated. We compared outcomes after immunomodulator withdrawal vs continuation of combination therapy.METHODS: This was a retrospective cohort study in a general hospital and a tertiary referral center. We included adult IBD patients, receiving anti-TNF therapy for ≥4 months, plus an immunomodulator at baseline, between January 1, 2011, and January 1, 2019. The primary endpoints were loss of response (LOR) (ie, anti-TNF discontinuation because of disease activity) and anti-drug antibodies. Adjusted hazard ratios (aHRs) were calculated by mixed-effects Cox regression analysis.RESULTS: We included 614 treatment episodes of combination therapy in 543 individuals, yielding 1664 patient-years of follow-up. The immunomodulator was withdrawn in 296 (48.2%) episodes after 0.9 (interquartile range, 0.6-2.1) years, which was not associated with a higher risk of LOR (aHR, 1.08; 95% confidence interval [CI], 0.72-1.61), although anti-drug antibodies were detected more frequently (aHR, 2.14; 95% CI, 1.17-3.94), compared with continuation. Clinical remission at the time of withdrawal reduced the risk of LOR (aHR, 0.48; 95% CI, 0.25-0.93), while longer duration of combination therapy before withdrawal decreased the risk of anti-drug antibodies (HR per year, 0.56; 95% CI, 0.32-0.91). Higher prewithdrawal infliximab trough levels reduced the subsequent risks of anti-drug antibodies and LOR. Infliximab trough levels were lower after immunomodulator withdrawal (P = .01).CONCLUSIONS: Patients who withdrew the immunomodulator in this retrospective cohort were not at increased risk of LOR within the following 1-2 years, but an increase in anti-drug antibodies was observed. Our findings require prospective validation, preferably in adequately powered randomized controlled trials.
AB - BACKGROUND AND AIMS: The benefit of concomitant immunomodulators (thiopurines or methotrexate) in patients with inflammatory bowel disease (IBD) on anti-tumor necrosis factor α (anti-TNF) (infliximab or adalimumab) maintenance therapy is debated. We compared outcomes after immunomodulator withdrawal vs continuation of combination therapy.METHODS: This was a retrospective cohort study in a general hospital and a tertiary referral center. We included adult IBD patients, receiving anti-TNF therapy for ≥4 months, plus an immunomodulator at baseline, between January 1, 2011, and January 1, 2019. The primary endpoints were loss of response (LOR) (ie, anti-TNF discontinuation because of disease activity) and anti-drug antibodies. Adjusted hazard ratios (aHRs) were calculated by mixed-effects Cox regression analysis.RESULTS: We included 614 treatment episodes of combination therapy in 543 individuals, yielding 1664 patient-years of follow-up. The immunomodulator was withdrawn in 296 (48.2%) episodes after 0.9 (interquartile range, 0.6-2.1) years, which was not associated with a higher risk of LOR (aHR, 1.08; 95% confidence interval [CI], 0.72-1.61), although anti-drug antibodies were detected more frequently (aHR, 2.14; 95% CI, 1.17-3.94), compared with continuation. Clinical remission at the time of withdrawal reduced the risk of LOR (aHR, 0.48; 95% CI, 0.25-0.93), while longer duration of combination therapy before withdrawal decreased the risk of anti-drug antibodies (HR per year, 0.56; 95% CI, 0.32-0.91). Higher prewithdrawal infliximab trough levels reduced the subsequent risks of anti-drug antibodies and LOR. Infliximab trough levels were lower after immunomodulator withdrawal (P = .01).CONCLUSIONS: Patients who withdrew the immunomodulator in this retrospective cohort were not at increased risk of LOR within the following 1-2 years, but an increase in anti-drug antibodies was observed. Our findings require prospective validation, preferably in adequately powered randomized controlled trials.
KW - Azathioprine
KW - Biologicals
KW - De-escalation
KW - Remission
UR - http://www.scopus.com/inward/record.url?scp=85125747698&partnerID=8YFLogxK
U2 - 10.1016/j.cgh.2022.01.019
DO - 10.1016/j.cgh.2022.01.019
M3 - Article
C2 - 35101632
SN - 1542-3565
VL - 20
SP - 2577-2587.e6
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
IS - 11
ER -