Introduction: Leucine-rich alpha-2 glycoprotein (LRG) is a useful serum biomarker for monitoring disease activity during remission in ulcerative colitis (UC). Because LRG levels differ among patients, it is necessary to assess them after profiling patients, especially in patients with refractory UC undergoing treatment with molecular-targeted drugs. This study aimed to analyze LRG levels that indicate mucosal healing according to clinical characteristics and molecular-targeted drugs. Methods: Among 214 patients with UC treated with biologics or Janus kinase (JAK) inhibitors, this study evaluated 111 patients (174 measurements) who achieved mucosal healing based on colonoscopy performed within 2 months before and after LRG measurement and experienced no changes in disease status or treatment during the same period. We analyzed the relationship of LRG with clinical characteristics (including sex, age, body mass index, and disease type and duration) and molecular-targeted drugs. Results: Compared with men, women had significantly higher LRG levels (9.5 μg/mL vs. 11.3 μg/mL, p < 0.001). In addition, LRG levels were significantly higher in older patients (12.0 μg/mL vs. 9.8 μg/mL, p < 0.01). LRG levels were the highest in patients treated with vedolizumab and lower in patients treated with JAK inhibitors (vedolizumab: 12.7 μg/mL; tofacitinib: 8.9 μg/mL; upadacitinib: 8.5 μg/mL; and filgotinib: 9.1 μg/mL; p < 0.0001). Conclusion: Among the patients who achieved mucosal healing, LRG levels were significantly higher in women and older patients. LRG levels differed according to the molecular-targeted drug used and were higher with vedolizumab and lower with JAK inhibitors.

1.
Shinzaki
S
,
Matsuoka
K
,
Iijima
H
,
Mizuno
S
,
Serada
S
,
Fujimoto
M
, et al
.
Leucine-rich alpha-2 glycoprotein is a serum biomarker of mucosal healing in ulcerative colitis
.
J Crohns Colitis
.
2017
;
11
(
1
):
84
91
.
2.
Shinzaki
S
,
Matsuoka
K
,
Tanaka
H
,
Takeshima
F
,
Kato
S
,
Torisu
T
, et al
.
Leucine-rich alpha-2 glycoprotein is a potential biomarker to monitor disease activity in inflammatory bowel disease receiving adalimumab: PLANET study
.
J Gastroenterol
.
2021
;
56
(
6
):
560
9
.
3.
Matsumoto
S
,
Mashima
H
.
Usefulness of the optimal cutoff value and delta value of leucine-rich alpha 2 glycoprotein in ulcerative colitis
.
Crohns Colitis 360
.
2022
;
4
:
otac039
,
4.
Serada
S
,
Fujimoto
M
,
Terabe
F
,
Iijima
H
,
Shinzaki
S
,
Matsuzaki
S
, et al
.
Serum leucine-rich alpha-2 glycoprotein is a disease activity biomarker in ulcerative colitis
.
Inflamm Bowel Dis
.
2012
;
18
(
11
):
2169
79
.
5.
Lichtiger
S
,
Present
DH
,
Kornbluth
A
,
Gelernt
I
,
Bauer
J
,
Galler
G
, et al
.
Cyclosporine in severe ulcerative colitis refractory to steroid therapy
.
N Engl J Med
.
1994
;
330
(
26
):
1841
5
.
6.
Travis
SP
,
Schnell
D
,
Krzeski
P
,
Abreu
MT
,
Altman
DG
,
Colombel
JF
, et al
.
Reliability and initial validation of the ulcerative colitis endoscopic index of severity
.
Gastroenterology
.
2013
;
145
(
5
):
987
95
.
7.
Kanda
Y
.
Investigation of the freely available easy-to-use software “EZR” for medical statistics
.
Bone Marrow Transplant
.
2013
;
48
(
3
):
452
8
.
8.
Plevris
N
,
Lees
CW
.
Disease monitoring in inflammatory bowel disease: evolving principles and possibilities
.
Gastroenterology
.
2022
;
162
(
5
):
1456
75.e1
.
9.
Furman
D
,
Hejblum
BP
,
Simon
N
,
Jojic
V
,
Dekker
CL
,
Thiébaut
R
, et al
.
Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination
.
Proc Natl Acad Sci USA
.
2014
;
111
(
2
):
869
74
.
10.
Singh
S
,
Picardo
S
,
Seow
CH
.
Management of inflammatory bowel diseases in special populations: obese, old, or obstetric
.
Clin Gastroenterol Hepatol
.
2020
;
18
(
6
):
1367
80
.
11.
Franceschi
C
,
Bonafè
M
,
Valensin
S
,
Olivieri
F
,
De Luca
M
,
Ottaviani
E
, et al
.
Inflamm-aging. an evolutionary perspective on immunosenescence
.
Ann N Y Acad Sci
.
2000
;
908
:
244
54
.
12.
Ferrucci
L
,
Corsi
A
,
Lauretani
F
,
Bandinelli
S
,
Bartali
B
,
Taub
DD
, et al
.
The origins of age-related proinflammatory state
.
Blood
.
2005
;
105
(
6
):
2294
9
.
13.
Paolisso
G
,
Rizzo
MR
,
Mazziotti
G
,
Tagliamonte
MR
,
Gambardella
A
,
Rotondi
M
, et al
.
Advancing age and insulin resistance: role of plasma tumor necrosis factor-alpha
.
Am J Physiol
.
1998
;
275
(
2
):
E294
9
.
14.
Sayed
N
,
Huang
Y
,
Nguyen
K
,
Krejciova-Rajaniemi
Z
,
Grawe
AP
,
Gao
T
, et al
.
An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging
.
Nat Aging
.
2021
;
1
:
598
615
.
15.
Bassi
M
,
Singh
S
.
Impact of obesity on response to biologic therapies in patients with inflammatory bowel diseases
.
BioDrugs
.
2022
;
36
(
2
):
197
203
.
16.
Park
HS
,
Park
JY
,
Yu
R
.
Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-alpha and IL-6
.
Diabetes Res Clin Pract
.
2005
;
69
(
1
):
29
35
.
17.
Tatsumi
Y
,
Kakimoto
K
,
Hara
A
,
Mizuta
N
,
Numa
K
,
Kinoshita
N
, et al
.
Biomarkers for monitoring of changes in disease activity in ulcerative colitis
.
J Clin Med
.
2023
;
12
(
22
):
7165
.
18.
Ullah
N
,
Wu
Y
.
Regulation of conformational changes in C-reactive protein alters its bioactivity
.
Cell Biochem Biophys
.
2022
;
80
(
4
):
595
608
.
19.
Soler
D
,
Chapman
T
,
Yang
LL
,
Wyant
T
,
Egan
R
,
Fedyk
ER
, et al
.
The binding specificity and selective antagonism of vedolizumab, an anti-alpha4beta7 integrin therapeutic antibody in development for inflammatory bowel diseases
.
J Pharmacol Exp Ther
.
2009
;
330
(
3
):
864
75
.
20.
O’Shea
JJ
,
Laurence
A
,
McInnes
IB
.
Back to the future: oral targeted therapy for RA and other autoimmune diseases
.
Nat Rev Rheumatol
.
2013
;
9
(
3
):
173
82
.
21.
Honap
S
,
Danese
S
,
Peyrin-Biroulet
L
.
Are all Janus kinase inhibitors for inflammatory bowel disease the same
.
Gastroenterol Hepatol
.
2023
;
19
(
12
):
727
38
.
22.
Traves
PG
,
Murray
B
,
Campigotto
F
,
Galien
R
,
Meng
A
,
Di Paolo
JA
.
JAK selectivity and the implications for clinical inhibition of pharmacodynamic cytokine signalling by filgotinib, upadacitinib, tofacitinib and baricitinib
.
Ann Rheum Dis
.
2021
;
80
(
7
):
865
75
.
23.
Dal Buono
A
,
Gabbiadini
R
,
Solitano
V
,
Vespa
E
,
Parigi
TL
,
Repici
A
, et al
.
Critical appraisal of filgotinib in the treatment of ulcerative colitis: current evidence and place in therapy
.
Clin Exp Gastroenterol
.
2022
;
15
:
121
8
.
24.
McInnes
IB
,
Byers
NL
,
Higgs
RE
,
Lee
J
,
Macias
WL
,
Na
S
, et al
.
Comparison of baricitinib, upadacitinib, and tofacitinib mediated regulation of cytokine signaling in human leukocyte subpopulations
.
Arthritis Res Ther
.
2019
;
21
(
1
):
183
.
You do not currently have access to this content.