The appropriateness of concomitant immunomodulators with anti-tumor necrosis factor agents for Crohn's disease: one size does not fit all.
OBJECTIVE
There is no consensus on the appropriateness of concomitant immunomodulators with anti-tumor necrosis factor (TNF) therapy for Crohn's disease. Some patients benefit from concomitant immunomodulators, but concerns related to infections and lymphoma risk have dampened enthusiasm for this approach. We applied the RAND/University of California Los Angeles Appropriateness Method toward establishing appropriateness of concomitant immunomodulators and anti-TNF therapies for Crohn's disease.


METHODS
A literature review was conducted regarding efficacy and safety of concomitant immunomodulators in the setting of anti-TNF therapy for Crohn's disease and presented to the Building Research in Inflammatory Bowel Disease Globally group, a globally diverse panel of 13 gastroenterologists clinically experienced in inflammatory bowel disease. A total of 134 scenarios were constructed using several clinical variables. Panelists used a modified Delphi method to rate the appropriateness of concomitant immunomodulators, and met to discuss and re-rate appropriateness. Disagreement was assessed using a validated index.


RESULTS
Concomitant immunomodulators were generally rated appropriate for 63 scenarios, uncertain for 60 scenarios, and inappropriate for 11 scenarios. In general, concomitant immunomodulators were appropriate for those with extensive disease, shorter duration of disease, perianal involvement, prior surgery, females, and older patients (>26 y). Concomitant immunomodulators were generally rated inappropriate for young males, and in some scenarios involving uncomplicated disease. Smoking and the particular anti-TNF medication did not influence ratings. Disagreement was observed in 6 of 134 scenarios.


CONCLUSIONS
The appropriateness of concomitant immunomodulators with anti-TNF therapy for Crohn's disease was determined through a modified Delphi panel approach based on expert interpretation of the available literature. Clinicians should consider multiple factors when considering concomitant immunomodulators with anti-TNF treatment.
Melmed
Gil Y
GY
Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. melmedg@cshs.org
Spiegel
Brennan M
BM
Bressler
Brian
B
Cheifetz
Adam S
AS
Devlin
Shane M
SM
Harrell
Laura E
LE
Irving
Peter M
PM
Jones
Jennifer
J
Kaplan
Gilaad G
GG
Kozuch
Patricia L
PL
Velayos
Fernando S
FS
Baidoo
Leonard
L
Sparrow
Miles P
MP
Siegel
Corey A
CA
D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000068582:Certolizumab Pegol; D003424:Crohn Disease / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000009:adverse effects; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000009:adverse effects*; D007239:Infections / Q000139:chemically induced; D000069285:Infliximab; D008223:Lymphoma / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007140:Immunoglobulin Fab Fragments; D007155:Immunologic Factors; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols; D000069285:Infliximab; D000068879:Adalimumab; D000068582:Certolizumab Pegol