TY - JOUR
T1 - No benefit of continuing vs stopping 5-aminosalicylates in patients with ulcerative colitis escalated to anti-metabolite therapy
AU - Singh, Siddharth
AU - Kim, Jihoon
AU - Zhu, Wenhong
AU - Dulai, Parambir S.
AU - Sandborn, William J.
AU - Jairath, Vipul
N1 - Funding Information:
This project was funded through a research credit from OptumLabs in partnership with the University of California, to Siddharth Singh. Siddharth Singh is supported by the American College of Gastroenterology Junior Faculty Development Award #144271, Crohn's and Colitis Foundation Career Development Award #404614, the National Institute of Diabetes and Digestive and Kidney Diseases K23DK117058. William Sandborn was supported in part by NIDDK‐funded San Diego Digestive Diseases Research Centre (P30 DK120515). The project is also partially supported by the National Institutes of Health, Grant UL1TR001442. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. ®
Funding Information:
: Siddharth Singh: has received research support from AbbVie and Janssen. Parambir Dulai: has received research support from Takeda, Pfizer, Abbvie, Janssen, Polymedco, ALPCO, Buhlmann, Prometheus, and consulting fees from Takeda, Pfizer, Abbvie and Janssen. William Sandborn: has received research grants from Atlantic Healthcare Limited, Amgen, Genentech, Gilead Sciences, Abbvie, Janssen, Takeda, Lilly, Celgene/Receptos,Pfizer, Prometheus Laboratories (now Prometheus Biosciences); consulting fees from Abbvie, Allergan, Amgen, Arena Pharmaceuticals, Avexegen Therapeutics, BeiGene, Boehringer Ingelheim, Celgene, Celltrion, Conatus, Cosmo, Escalier Biosciences, Ferring, Forbion, Genentech, Gilead Sciences, Gossamer Bio, Incyte, Janssen, Kyowa Kirin Pharmaceutical Research, Landos Biopharma, Lilly, Oppilan Pharma, Otsuka, Pfizer, Progenity, Prometheus Biosciences (merger of Precision IBD and Prometheus Laboratories), Reistone, Ritter Pharmaceuticals, Robarts Clinical Trials (owned by Health Academic Research Trust, HART), Series Therapeutics, Shire, Sienna Biopharmaceuticals, Sigmoid Biotechnologies, Sterna Biologicals, Sublimity Therapeutics, Takeda, Theravance Biopharma, Tigenix, Tillotts Pharma, UCB Pharma, Ventyx Biosciences, Vimalan Biosciences, Vivelix Pharmaceuticals; and stock or stock options from BeiGene, Escalier Biosciences, Gossamer Bio, Oppilan Pharma, Prometheus Biosciences (merger of Precision IBD and Prometheus Laboratories), Progenity, Ritter Pharmaceuticals, Ventyx Biosciences, Vimalan Biosciences. Spouse: Opthotech—consultant, stock options; Progenity—consultant, stock; Oppilan Pharma—employee, stock options; Escalier Biosciences—employee, stock options; Prometheus Biosciences (merger of Precision IBD and Prometheus Laboratories)—employee, stock options; Ventyx Biosciences—employee, stock options; Vimalan Biosciences—employee, stock options. Vipul Jairath: has received consulting fees from AbbVie, Eli Lilly, GlaxoSmithKline, Arena pharmaceuticals, Genetech, Pendopharm, Sandoz, Merck, Takeda, Janssen, Robarts Clinical Trials, Topivert, Celltrion; and speaker's fees from Takeda, Janssen, Shire, Ferring, Abbvie, and Pfizer. All other authors declare no conflicts of interest. Declaration of personal interest
Funding Information:
This project was funded through a research credit from OptumLabs? in partnership with the University of California, to Siddharth Singh. Siddharth Singh is supported by the American College of Gastroenterology Junior Faculty Development Award #144271, Crohn's and Colitis Foundation Career Development Award #404614, the National Institute of Diabetes and Digestive and Kidney Diseases K23DK117058. William Sandborn was supported in part by NIDDK-funded San Diego Digestive Diseases Research Centre (P30 DK120515). The project is also partially supported by the National Institutes of Health, Grant UL1TR001442.
Publisher Copyright:
© 2020 John Wiley & Sons Ltd
PY - 2020/8/1
Y1 - 2020/8/1
N2 - Background: Whilst continuation of 5-aminosalicylates (5-ASA) after escalation to biologic therapy is considered ineffective in patients with ulcerative colitis (UC), their role in patients escalated to anti-metabolites is unclear. Aim: To compared patterns and outcomes of continuing vs stopping 5-ASA in patients with UC who escalated to anti-metabolite monotherapy, using a de-identified administrative claims database. Methods: We identified patients with UC who were new users of anti-metabolite monotherapy who were receiving 5-ASA, and were followed for at least 12 months after starting anti-metabolite therapy. We evaluated patterns of 5-ASA use (stopped 5-ASA, short-term 5-ASA use for <6 months after starting anti-metabolites, persistent 5-ASA use for >6 months after starting anti-metabolites). We compared outcomes (risk of UC-related hospitalisation and/or surgery, need for corticosteroids, treatment escalation to biologic therapy) by pattern of 5-ASA use, using Cox proportional hazard analysis adjusting for age, sex, race, comorbidity burden, and hospitalisation or emergency department visit, abdominal surgery and corticosteroid use in the previous 12 months (as measures of disease severity), with a 12-month immortal time period. Results: Of 4068 patients with UC who were new-users of anti-metabolite monotherapy, 578 (14.2%), 782 (19.2%) and 2708 (66.6%) stopped 5-ASA, used 5-ASA transiently or persistently, respectively. Compared to patients who stopped 5-ASA after starting anti-metabolites, persistent 5-ASA use was associated with a higher risk of UC-related hospitalisation (HR, 1.40 [1.07-1.83]) and corticosteroid use (HR, 1.48 [1.28-1.70]), without an increase in risk of UC-related surgery (HR, 1.32 [0.86-2.00]) or treatment escalation (HR, 0.80 [0.53-1.20]). Sensitivity analyses using a 3 months window after initiation of anti-metabolites to classify patients as continuing vs stopping 5-ASA showed similar results. Residual confounding by disease severity could not be excluded. Conclusion: 5-ASA are usually continued long-term even after escalating to anti-metabolite therapy in patients with UC without clinical benefit.
AB - Background: Whilst continuation of 5-aminosalicylates (5-ASA) after escalation to biologic therapy is considered ineffective in patients with ulcerative colitis (UC), their role in patients escalated to anti-metabolites is unclear. Aim: To compared patterns and outcomes of continuing vs stopping 5-ASA in patients with UC who escalated to anti-metabolite monotherapy, using a de-identified administrative claims database. Methods: We identified patients with UC who were new users of anti-metabolite monotherapy who were receiving 5-ASA, and were followed for at least 12 months after starting anti-metabolite therapy. We evaluated patterns of 5-ASA use (stopped 5-ASA, short-term 5-ASA use for <6 months after starting anti-metabolites, persistent 5-ASA use for >6 months after starting anti-metabolites). We compared outcomes (risk of UC-related hospitalisation and/or surgery, need for corticosteroids, treatment escalation to biologic therapy) by pattern of 5-ASA use, using Cox proportional hazard analysis adjusting for age, sex, race, comorbidity burden, and hospitalisation or emergency department visit, abdominal surgery and corticosteroid use in the previous 12 months (as measures of disease severity), with a 12-month immortal time period. Results: Of 4068 patients with UC who were new-users of anti-metabolite monotherapy, 578 (14.2%), 782 (19.2%) and 2708 (66.6%) stopped 5-ASA, used 5-ASA transiently or persistently, respectively. Compared to patients who stopped 5-ASA after starting anti-metabolites, persistent 5-ASA use was associated with a higher risk of UC-related hospitalisation (HR, 1.40 [1.07-1.83]) and corticosteroid use (HR, 1.48 [1.28-1.70]), without an increase in risk of UC-related surgery (HR, 1.32 [0.86-2.00]) or treatment escalation (HR, 0.80 [0.53-1.20]). Sensitivity analyses using a 3 months window after initiation of anti-metabolites to classify patients as continuing vs stopping 5-ASA showed similar results. Residual confounding by disease severity could not be excluded. Conclusion: 5-ASA are usually continued long-term even after escalating to anti-metabolite therapy in patients with UC without clinical benefit.
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U2 - 10.1111/apt.15876
DO - 10.1111/apt.15876
M3 - Article
C2 - 32573825
AN - SCOPUS:85087163424
VL - 52
SP - 481
EP - 491
JO - Alimentary Pharmacology and Therapeutics
JF - Alimentary Pharmacology and Therapeutics
SN - 0269-2813
IS - 3
ER -