Clinical characterization of colitis arising from anti-PD-1 based therapy

Daniel Y. Wang, Meghan J. Mooradian, Dae Won Kim, Neil J. Shah, Sarah E. Fenton, Robert M. Conry, Rutika Mehta, Ann Silk, Alice Zhou, Margaret L. Compton, Rami N. Al-Rohil, Sunyoung Lee, Amber L. Voorhees, Lisa Ha, Svetlana McKee, Jacqueline T. Norrell, Janice Mehnert, Igor Puzanov, Jeffrey A. Sosman, Sunandana Chandra & 5 others Geoffrey T. Gibney, Suthee Rapisuwon, Zeynep Eroglu, Ryan Sullivan, Douglas B. Johnson

Research output: Contribution to journalArticle

Abstract

Colitis is a frequent, clinically-significant immune-related adverse event caused by anti-programmed death-1 (PD-1). The clinical features, timing, and management of colitis with anti-PD-1-based regimens are not well-characterized. Patients with advanced melanoma that received either anti-PD-1 monotherapy (“monotherapy”) or combined with ipilimumab (“combination therapy”) were screened from 8 academic medical centers, to identify those with clinically-relevant colitis (colitis requiring systemic steroids). Of 1261 patients who received anti-PD-1-based therapy, 109 experienced colitis. The incidence was 3.2% (30/937) and 24.4% (79/324) in the monotherapy and combination therapy cohorts, respectively. Patients with colitis from combination therapy had significantly earlier symptom onset (7.2 weeks vs 25.4 weeks, p < 0.0001), received higher steroid doses (median prednisone equivalent 1.5 mg/kg vs 1.0 mg/kg, p = 0.0015) and experienced longer steroid tapers (median 6.0 vs 4.0 weeks, p = 0.0065) compared to monotherapy. Infliximab use and steroid-dose escalation occurred more frequently in the combination therapy cohort compared to monotherapy. Nearly all patients had resolution of their symptoms although one patient died from complications. Anti-PD-1 associated colitis has a variable clinical presentation, and is more frequent and severe when associated with combination therapy. This variability in checkpoint-inhibitor associated colitis suggests that further optimization of treatment algorithms is needed.

Original languageEnglish (US)
Article numbere1524695
JournalOncoImmunology
Volume8
Issue number1
DOIs
StatePublished - Jan 2 2019

Fingerprint

Colitis
Steroids
Therapeutics
Prednisone
Melanoma
Incidence

Cite this

Wang, D. Y., Mooradian, M. J., Kim, D. W., Shah, N. J., Fenton, S. E., Conry, R. M., ... Johnson, D. B. (2019). Clinical characterization of colitis arising from anti-PD-1 based therapy. OncoImmunology, 8(1), [e1524695]. https://doi.org/10.1080/2162402X.2018.1524695
Wang, Daniel Y. ; Mooradian, Meghan J. ; Kim, Dae Won ; Shah, Neil J. ; Fenton, Sarah E. ; Conry, Robert M. ; Mehta, Rutika ; Silk, Ann ; Zhou, Alice ; Compton, Margaret L. ; Al-Rohil, Rami N. ; Lee, Sunyoung ; Voorhees, Amber L. ; Ha, Lisa ; McKee, Svetlana ; Norrell, Jacqueline T. ; Mehnert, Janice ; Puzanov, Igor ; Sosman, Jeffrey A. ; Chandra, Sunandana ; Gibney, Geoffrey T. ; Rapisuwon, Suthee ; Eroglu, Zeynep ; Sullivan, Ryan ; Johnson, Douglas B. / Clinical characterization of colitis arising from anti-PD-1 based therapy. In: OncoImmunology. 2019 ; Vol. 8, No. 1.
@article{12e4fc2ddad54aa4aa5ba2ac45342ecc,
title = "Clinical characterization of colitis arising from anti-PD-1 based therapy",
abstract = "Colitis is a frequent, clinically-significant immune-related adverse event caused by anti-programmed death-1 (PD-1). The clinical features, timing, and management of colitis with anti-PD-1-based regimens are not well-characterized. Patients with advanced melanoma that received either anti-PD-1 monotherapy (“monotherapy”) or combined with ipilimumab (“combination therapy”) were screened from 8 academic medical centers, to identify those with clinically-relevant colitis (colitis requiring systemic steroids). Of 1261 patients who received anti-PD-1-based therapy, 109 experienced colitis. The incidence was 3.2{\%} (30/937) and 24.4{\%} (79/324) in the monotherapy and combination therapy cohorts, respectively. Patients with colitis from combination therapy had significantly earlier symptom onset (7.2 weeks vs 25.4 weeks, p < 0.0001), received higher steroid doses (median prednisone equivalent 1.5 mg/kg vs 1.0 mg/kg, p = 0.0015) and experienced longer steroid tapers (median 6.0 vs 4.0 weeks, p = 0.0065) compared to monotherapy. Infliximab use and steroid-dose escalation occurred more frequently in the combination therapy cohort compared to monotherapy. Nearly all patients had resolution of their symptoms although one patient died from complications. Anti-PD-1 associated colitis has a variable clinical presentation, and is more frequent and severe when associated with combination therapy. This variability in checkpoint-inhibitor associated colitis suggests that further optimization of treatment algorithms is needed.",
author = "Wang, {Daniel Y.} and Mooradian, {Meghan J.} and Kim, {Dae Won} and Shah, {Neil J.} and Fenton, {Sarah E.} and Conry, {Robert M.} and Rutika Mehta and Ann Silk and Alice Zhou and Compton, {Margaret L.} and Al-Rohil, {Rami N.} and Sunyoung Lee and Voorhees, {Amber L.} and Lisa Ha and Svetlana McKee and Norrell, {Jacqueline T.} and Janice Mehnert and Igor Puzanov and Sosman, {Jeffrey A.} and Sunandana Chandra and Gibney, {Geoffrey T.} and Suthee Rapisuwon and Zeynep Eroglu and Ryan Sullivan and Johnson, {Douglas B.}",
year = "2019",
month = "1",
day = "2",
doi = "https://doi.org/10.1080/2162402X.2018.1524695",
language = "English (US)",
volume = "8",
journal = "OncoImmunology",
issn = "2162-4011",
publisher = "Landes Bioscience",
number = "1",

}

Wang, DY, Mooradian, MJ, Kim, DW, Shah, NJ, Fenton, SE, Conry, RM, Mehta, R, Silk, A, Zhou, A, Compton, ML, Al-Rohil, RN, Lee, S, Voorhees, AL, Ha, L, McKee, S, Norrell, JT, Mehnert, J, Puzanov, I, Sosman, JA, Chandra, S, Gibney, GT, Rapisuwon, S, Eroglu, Z, Sullivan, R & Johnson, DB 2019, 'Clinical characterization of colitis arising from anti-PD-1 based therapy' OncoImmunology, vol. 8, no. 1, e1524695. https://doi.org/10.1080/2162402X.2018.1524695

Clinical characterization of colitis arising from anti-PD-1 based therapy. / Wang, Daniel Y.; Mooradian, Meghan J.; Kim, Dae Won; Shah, Neil J.; Fenton, Sarah E.; Conry, Robert M.; Mehta, Rutika; Silk, Ann; Zhou, Alice; Compton, Margaret L.; Al-Rohil, Rami N.; Lee, Sunyoung; Voorhees, Amber L.; Ha, Lisa; McKee, Svetlana; Norrell, Jacqueline T.; Mehnert, Janice; Puzanov, Igor; Sosman, Jeffrey A.; Chandra, Sunandana; Gibney, Geoffrey T.; Rapisuwon, Suthee; Eroglu, Zeynep; Sullivan, Ryan; Johnson, Douglas B.

In: OncoImmunology, Vol. 8, No. 1, e1524695, 02.01.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Clinical characterization of colitis arising from anti-PD-1 based therapy

AU - Wang, Daniel Y.

AU - Mooradian, Meghan J.

AU - Kim, Dae Won

AU - Shah, Neil J.

AU - Fenton, Sarah E.

AU - Conry, Robert M.

AU - Mehta, Rutika

AU - Silk, Ann

AU - Zhou, Alice

AU - Compton, Margaret L.

AU - Al-Rohil, Rami N.

AU - Lee, Sunyoung

AU - Voorhees, Amber L.

AU - Ha, Lisa

AU - McKee, Svetlana

AU - Norrell, Jacqueline T.

AU - Mehnert, Janice

AU - Puzanov, Igor

AU - Sosman, Jeffrey A.

AU - Chandra, Sunandana

AU - Gibney, Geoffrey T.

AU - Rapisuwon, Suthee

AU - Eroglu, Zeynep

AU - Sullivan, Ryan

AU - Johnson, Douglas B.

PY - 2019/1/2

Y1 - 2019/1/2

N2 - Colitis is a frequent, clinically-significant immune-related adverse event caused by anti-programmed death-1 (PD-1). The clinical features, timing, and management of colitis with anti-PD-1-based regimens are not well-characterized. Patients with advanced melanoma that received either anti-PD-1 monotherapy (“monotherapy”) or combined with ipilimumab (“combination therapy”) were screened from 8 academic medical centers, to identify those with clinically-relevant colitis (colitis requiring systemic steroids). Of 1261 patients who received anti-PD-1-based therapy, 109 experienced colitis. The incidence was 3.2% (30/937) and 24.4% (79/324) in the monotherapy and combination therapy cohorts, respectively. Patients with colitis from combination therapy had significantly earlier symptom onset (7.2 weeks vs 25.4 weeks, p < 0.0001), received higher steroid doses (median prednisone equivalent 1.5 mg/kg vs 1.0 mg/kg, p = 0.0015) and experienced longer steroid tapers (median 6.0 vs 4.0 weeks, p = 0.0065) compared to monotherapy. Infliximab use and steroid-dose escalation occurred more frequently in the combination therapy cohort compared to monotherapy. Nearly all patients had resolution of their symptoms although one patient died from complications. Anti-PD-1 associated colitis has a variable clinical presentation, and is more frequent and severe when associated with combination therapy. This variability in checkpoint-inhibitor associated colitis suggests that further optimization of treatment algorithms is needed.

AB - Colitis is a frequent, clinically-significant immune-related adverse event caused by anti-programmed death-1 (PD-1). The clinical features, timing, and management of colitis with anti-PD-1-based regimens are not well-characterized. Patients with advanced melanoma that received either anti-PD-1 monotherapy (“monotherapy”) or combined with ipilimumab (“combination therapy”) were screened from 8 academic medical centers, to identify those with clinically-relevant colitis (colitis requiring systemic steroids). Of 1261 patients who received anti-PD-1-based therapy, 109 experienced colitis. The incidence was 3.2% (30/937) and 24.4% (79/324) in the monotherapy and combination therapy cohorts, respectively. Patients with colitis from combination therapy had significantly earlier symptom onset (7.2 weeks vs 25.4 weeks, p < 0.0001), received higher steroid doses (median prednisone equivalent 1.5 mg/kg vs 1.0 mg/kg, p = 0.0015) and experienced longer steroid tapers (median 6.0 vs 4.0 weeks, p = 0.0065) compared to monotherapy. Infliximab use and steroid-dose escalation occurred more frequently in the combination therapy cohort compared to monotherapy. Nearly all patients had resolution of their symptoms although one patient died from complications. Anti-PD-1 associated colitis has a variable clinical presentation, and is more frequent and severe when associated with combination therapy. This variability in checkpoint-inhibitor associated colitis suggests that further optimization of treatment algorithms is needed.

UR - http://www.scopus.com/inward/record.url?scp=85058241647&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85058241647&partnerID=8YFLogxK

U2 - https://doi.org/10.1080/2162402X.2018.1524695

DO - https://doi.org/10.1080/2162402X.2018.1524695

M3 - Article

VL - 8

JO - OncoImmunology

JF - OncoImmunology

SN - 2162-4011

IS - 1

M1 - e1524695

ER -

Wang DY, Mooradian MJ, Kim DW, Shah NJ, Fenton SE, Conry RM et al. Clinical characterization of colitis arising from anti-PD-1 based therapy. OncoImmunology. 2019 Jan 2;8(1). e1524695. https://doi.org/10.1080/2162402X.2018.1524695