TY - JOUR
T1 - Stopping 5-aminosalicylates in patients with ulcerative colitis starting biologic therapy does not increase the risk of adverse clinical outcomes
T2 - analysis of two nationwide population-based cohorts
AU - Ungaro, Ryan C
AU - Limketkai, Berkeley N
AU - Jensen, Camilla Bjørn
AU - Allin, Kristine Højgaard
AU - Agrawal, Manasi
AU - Ullman, Thomas
AU - Colombel, Jean-Frederic
AU - Jess, Tine
N1 - © Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2019/6
Y1 - 2019/6
N2 - OBJECTIVE: The benefit of continuing 5-aminosalicylate (5-ASA) in patients with ulcerative colitis (UC) who initiate anti-tumour necrosis factor-alpha (anti-TNF) biologics is unknown. We aimed to compare clinical outcomes in patients with UC already on 5-ASA who started anti-TNF and then either stopped or continued 5-ASA.DESIGN: Our primary outcome was any adverse clinical event defined as a composite of new corticosteroid use, UC-related hospitalisation or surgery. We used two national databases: the United States (US) Truven MarketScan health claims database and the Danish health registers. Patients with UC who started anti-TNF after having been on oral 5-ASA for at least 90 days were included. Patients were classified as stopping 5-ASA if therapy was discontinued within 90 days of starting anti-TNF. We performed multivariable Cox regression models controlling for demographics, clinical factors and healthcare utilisation. Adjusted HRs (aHR) with 95% CI are reported comparing stopping 5-ASA with continuing 5-ASA.RESULTS: A total of 3589 patients with UC were included (2890 US and 699 Denmark). Stopping 5-ASA after initiating anti-TNF was not associated with an increased risk of adverse clinical events in the U.S. cohort (aHR 1.04; 95% CI 0.90 to 1.21, p=0.57) nor in the Danish cohort (aHR 1.09; 95% CI 0.80 to 1.49, p=0.60). Results were similar in sensitivity analyses investigating concomitant immunomodulator use and duration of 5-ASA treatment before initiating anti-TNF.CONCLUSION: In two national databases, stopping 5-ASA in patients with UC starting anti-TNF therapy did not increase the risk of adverse clinical events. These results should be validated in a prospective clinical trial.
AB - OBJECTIVE: The benefit of continuing 5-aminosalicylate (5-ASA) in patients with ulcerative colitis (UC) who initiate anti-tumour necrosis factor-alpha (anti-TNF) biologics is unknown. We aimed to compare clinical outcomes in patients with UC already on 5-ASA who started anti-TNF and then either stopped or continued 5-ASA.DESIGN: Our primary outcome was any adverse clinical event defined as a composite of new corticosteroid use, UC-related hospitalisation or surgery. We used two national databases: the United States (US) Truven MarketScan health claims database and the Danish health registers. Patients with UC who started anti-TNF after having been on oral 5-ASA for at least 90 days were included. Patients were classified as stopping 5-ASA if therapy was discontinued within 90 days of starting anti-TNF. We performed multivariable Cox regression models controlling for demographics, clinical factors and healthcare utilisation. Adjusted HRs (aHR) with 95% CI are reported comparing stopping 5-ASA with continuing 5-ASA.RESULTS: A total of 3589 patients with UC were included (2890 US and 699 Denmark). Stopping 5-ASA after initiating anti-TNF was not associated with an increased risk of adverse clinical events in the U.S. cohort (aHR 1.04; 95% CI 0.90 to 1.21, p=0.57) nor in the Danish cohort (aHR 1.09; 95% CI 0.80 to 1.49, p=0.60). Results were similar in sensitivity analyses investigating concomitant immunomodulator use and duration of 5-ASA treatment before initiating anti-TNF.CONCLUSION: In two national databases, stopping 5-ASA in patients with UC starting anti-TNF therapy did not increase the risk of adverse clinical events. These results should be validated in a prospective clinical trial.
KW - Adult
KW - Anti-Inflammatory Agents, Non-Steroidal/adverse effects
KW - Biological Therapy/adverse effects
KW - Cohort Studies
KW - Colitis, Ulcerative/drug therapy
KW - Databases, Factual
KW - Denmark
KW - Dose-Response Relationship, Drug
KW - Drug Administration Schedule
KW - Female
KW - Humans
KW - Kaplan-Meier Estimate
KW - Male
KW - Mesalamine/adverse effects
KW - Proportional Hazards Models
KW - Retrospective Studies
KW - Risk Assessment
KW - Severity of Illness Index
KW - Statistics, Nonparametric
KW - Treatment Outcome
KW - United States
KW - Withholding Treatment
UR - http://www.scopus.com/inward/record.url?scp=85056848656&partnerID=8YFLogxK
U2 - 10.1136/gutjnl-2018-317021
DO - 10.1136/gutjnl-2018-317021
M3 - Journal article
C2 - 30420398
SN - 0017-5749
VL - 68
SP - 977
EP - 984
JO - Gut
JF - Gut
IS - 6
ER -