Introduction: The aim of the study was to systematically assess the efficacy and safety of tumor necrosis factor inhibitors (TNFi), interleukin-17 inhibitors (IL-17i), and Janus kinase inhibitors (JAKi) in patients with non-radiographic axial spondyloarthritis (nr-axSpA). Methods: A systematic literature search was conducted in PubMed, Embase, Web of Science, the Cochrane Register of Clinical Trials, and Scopus to find randomized controlled trials in patients with nr-axSpA published until June 2023. Stata 17.0 software and Review Manager 5.4 software were used for data analysis. The results for binary and continuous variables were expressed as the values of odds ratio and mean difference and their 95% confidence interval, respectively. Results: For Assessment of SpondyloArthritis International Society Response Criteria for 40% improvement (ASAS40), the efficacy of the 12 interventions ranked as follows: certolizumab pegol (CZP) 200 mg every 2 weeks (Q2W) > CZP 400 mg Q4W > golimumab (GOL) > bimekizumab (BKZ) > adalimumab (ADA) > upadacitinib (UPA) > etanercept (ETN) > brodalumab (BRO) > ixekizumab (IXE) > secukinumab (SEC) 150 mg no loading (NL) > SEC 150 mg loading dose (LD) > placebo (PBO). For assessment of ASAS20, the NMA results were ranked as follows: GOL > CZP 400 mg Q4W> BKZ> ADA > UPA > CZP 200 mg Q2W > ETN > BRO > SEC 150 mg NL > SEC 150 mg LD > PBO, and GOL > ADA > PBO > UPA > SEC 150 mg NL > BKZ > IXE > SEC 150 mg LD > ETN > CZP 200 mg Q2W for adverse events. Conclusions: Most TNFi may be more effective than JAKi and IL-17i. They were all well tolerated. However, the efficacy and safety of TNFi/IL-17i/JAKi remain to be further analyzed in studies with larger sample sizes and longer follow-up times.

1.
Truong
SL
,
McEwan
T
,
Bird
P
,
Lim
I
,
Saad
NF
,
Schachna
L
, et al
.
Australian consensus statements for the assessment and management of non-radiographic axial spondyloarthritis
.
Rheumatol Ther
.
2022
;
9
(
1
):
1
24
.
2.
Navarro-Compán
V
,
Sepriano
A
,
El-Zorkany
B
,
van der Heijde
D
.
Axial spondyloarthritis
.
Ann Rheum Dis
.
2021
;
80
(
12
):
1511
21
.
3.
Rudwaleit
M
,
Sieper
J
.
Referral strategies for early diagnosis of axial spondyloarthritis
.
Nat Rev Rheumatol
.
2012
;
8
(
5
):
262
8
.
4.
Poddubnyy
D
,
Brandt
H
,
Vahldiek
J
,
Spiller
I
,
Song
IH
,
Rudwaleit
M
, et al
.
The frequency of non-radiographic axial spondyloarthritis in relation to symptom duration in patients referred because of chronic back pain: results from the Berlin early spondyloarthritis clinic
.
Ann Rheum Dis
.
2012
;
71
(
12
):
1998
2001
.
5.
Strand
V
,
Rao
SA
,
Shillington
AC
,
Cifaldi
MA
,
McGuire
M
,
Ruderman
EM
.
Prevalence of axial spondyloarthritis in United States rheumatology practices: assessment of SpondyloArthritis International Society criteria versus rheumatology expert clinical diagnosis
.
Arthritis Care Res Hob
.
2013
;
65
(
8
):
1299
306
.
6.
Ramiro
S
,
Nikiphorou
E
,
Sepriano
A
,
Ortolan
A
,
Webers
C
,
Baraliakos
X
, et al
.
ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update
.
Ann Rheum Dis
.
2023
;
82
(
1
):
19
34
.
7.
Callhoff
J
,
Sieper
J
,
Weiß
A
,
Zink
A
,
Listing
J
.
Efficacy of TNFα blockers in patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis: a meta-analysis
.
Ann Rheum Dis
.
2015
;
74
(
6
):
1241
8
.
8.
Corbett
M
,
Soares
M
,
Jhuti
G
,
Rice
S
,
Spackman
E
,
Sideris
E
, et al
.
Tumour necrosis factor-α inhibitors for ankylosing spondylitis and non-radiographic axial spondyloarthritis: a systematic review and economic evaluation
.
Health Technol Assess
.
2016
;
20
(
9
):
1
334
. v-vi.
9.
Wang
S
,
He
Q
,
Shuai
Z
.
Risk of serious infections in biological treatment of patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis: a meta-analysis
.
Clin Rheumatol
.
2018
;
37
(
2
):
439
50
.
10.
Hutton
B
,
Salanti
G
,
Caldwell
DM
,
Chaimani
A
,
Schmid
CH
,
Cameron
C
, et al
.
The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations
.
Ann Intern Med
.
2015
;
162
(
11
):
777
84
.
11.
Higgins
J
,
Green
S
.
Cochrane handbook for systematic reviews of interventions version 5.1.0
.
The Cochrane Collaboration
;
2013
.
12.
Salanti
G
.
Indirect and mixed-treatment comparison, network, or multiple-treatments meta-analysis: many names, many benefits, many concerns for the next generation evidence synthesis tool
.
Res Synth Methods
.
2012
;
3
(
2
):
80
97
.
13.
Salanti
G
,
Ades
AE
,
Ioannidis
JP
.
Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial
.
J Clin Epidemiol
.
2011
;
64
(
2
):
163
71
.
14.
Sieper
J
,
van der Heijde
D
,
Dougados
M
,
Mease
PJ
,
Maksymowych
WP
,
Brown
MA
, et al
.
Efficacy and safety of adalimumab in patients with non-radiographic axial spondyloarthritis: results of a randomised placebo-controlled trial (ABILITY-1)
.
Ann Rheum Dis
.
2013
;
72
(
6
):
815
22
.
15.
Landewé
R
,
Braun
J
,
Deodhar
A
,
Dougados
M
,
Maksymowych
WP
,
Mease
PJ
, et al
.
Efficacy of certolizumab pegol on signs and symptoms of axial spondyloarthritis including ankylosing spondylitis: 24-week results of a double-blind randomised placebo-controlled Phase 3 study
.
Ann Rheum Dis
.
2014
;
73
(
1
):
39
47
.
16.
Deodhar
A
,
Gensler
LS
,
Kay
J
,
Maksymowych
WP
,
Haroon
N
,
Landewé
R
, et al
.
A fifty-two-week, randomized, placebo-controlled trial of certolizumab pegol in nonradiographic axial spondyloarthritis
.
Arthritis Rheumatol
.
2019
;
71
(
7
):
1101
11
.
17.
Dougados
M
,
van der Heijde
D
,
Sieper
J
,
Braun
J
,
Maksymowych
WP
,
Citera
G
, et al
.
Symptomatic efficacy of etanercept and its effects on objective signs of inflammation in early nonradiographic axial spondyloarthritis: a multicenter, randomized, double-blind, placebo-controlled trial
.
Arthritis Rheumatol
.
2014
;
66
(
8
):
2091
102
.
18.
Sieper
J
,
van der Heijde
D
,
Dougados
M
,
Maksymowych
WP
,
Scott
BB
,
Boice
JA
, et al
.
A randomized, double-blind, placebo-controlled, sixteen-week study of subcutaneous golimumab in patients with active nonradiographic axial spondyloarthritis
.
Arthritis Rheumatol
.
2015
;
67
(
10
):
2702
12
.
19.
Deodhar
A
,
van der Heijde
D
,
Gensler
LS
,
Kim
TH
,
Maksymowych
WP
,
Østergaard
M
, et al
.
Ixekizumab for patients with non-radiographic axial spondyloarthritis (COAST-X): a randomised, placebo-controlled trial
.
Lancet
.
2020
;
395
(
10217
):
53
64
.
20.
Deodhar
A
,
Blanco
R
,
Dokoupilová
E
,
Hall
S
,
Kameda
H
,
Kivitz
AJ
, et al
.
Improvement of signs and symptoms of nonradiographic axial spondyloarthritis in patients treated with secukinumab: primary results of a randomized, placebo-controlled phase III study
.
Arthritis Rheumatol
.
2021
;
73
(
1
):
110
20
.
21.
Wei
JC
,
Kim
TH
,
Kishimoto
M
,
Ogusu
N
,
Jeong
H
,
Kobayashi
S
, et al
.
Efficacy and safety of brodalumab, an anti-IL17RA monoclonal antibody, in patients with axial spondyloarthritis: 16-week results from a randomised, placebo-controlled, phase 3 trial
.
Ann Rheum Dis
.
2021
;
80
(
8
):
1014
21
.
22.
Deodhar
A
,
Van den Bosch
F
,
Poddubnyy
D
,
Maksymowych
WP
,
van der Heijde
D
,
Kim
TH
, et al
.
Upadacitinib for the treatment of active non-radiographic axial spondyloarthritis (SELECT-AXIS 2): a randomised, double-blind, placebo-controlled, phase 3 trial
.
Lancet
.
2022
;
400
(
10349
):
369
79
.
23.
van der Heijde
D
,
Deodhar
A
,
Baraliakos
X
,
Brown
MA
,
Dobashi
H
,
Dougados
M
, et al
.
Efficacy and safety of bimekizumab in axial spondyloarthritis: results of two parallel phase 3 randomised controlled trials
.
Ann Rheum Dis
.
2023
;
82
(
4
):
515
26
.
24.
Akkoç
N
,
Arteaga
CH
,
Auteri
SE
,
Betts
M
,
Fahrbach
K
,
Kim
M
, et al
.
Comparative efficacy of biologic disease-modifying anti-rheumatic drugs for non-radiographic axial spondyloarthritis: a systematic literature review and bucher indirect comparisons
.
Rheumatol Ther
.
2023
;
10
(
2
):
307
27
.
25.
Robinson
PC
,
van der Linden
S
,
Khan
MA
,
Taylor
WJ
.
Axial spondyloarthritis: concept, construct, classification and implications for therapy
.
Nat Rev Rheumatol
.
2021
;
17
(
2
):
109
18
.
26.
Taams
LS
,
Steel
KJA
,
Srenathan
U
,
Burns
LA
,
Kirkham
BW
.
IL-17 in the immunopathogenesis of spondyloarthritis
.
Nat Rev Rheumatol
.
2018
;
14
(
8
):
453
66
.
27.
Deodhar
A
,
Machado
PM
,
Mørup
M
,
Taieb
V
,
Willems
D
,
Orme
M
, et al
.
Comparative efficacy and safety of bimekizumab in axial spondyloarthritis: a systematic literature review and network meta-analysis
.
Rheumatol
.
2024
;
63
(
5
):
1195
205
. kead598.
28.
Tam
HKJ
,
Nash
P
,
Robinson
PC
.
The effect of etanercept in nonradiographic axial spondyloarthritis by stratified C-reactive protein levels
.
ACR Open Rheumatol
.
2021
;
3
(
10
):
699
706
.
29.
Braun
J
,
Blanco
R
,
Marzo-Ortega
H
,
Gensler
LS
,
van den Bosch
F
,
Hall
S
, et al
.
Secukinumab in non-radiographic axial spondyloarthritis: subgroup analysis based on key baseline characteristics from a randomized phase III study, PREVENT
.
Arthritis Res Ther
.
2021
;
23
(
1
):
231
.
30.
van der Horst-Bruinsma
IE
,
de Vlam
K
,
Walsh
JA
,
Bolce
R
,
Hunter
T
,
Sandoval
D
, et al
.
Baseline characteristics and treatment response to ixekizumab categorised by sex in radiographic and non-radiographic axial spondylarthritis through 52 Weeks: data from three phase III randomised controlled trials
.
Adv Ther
.
2022
;
39
(
6
):
2806
19
.
31.
Robinson
PC
,
Maksymowych
WP
,
Gensler
LS
,
Hall
S
,
Rudwaleit
M
,
Hoepken
B
, et al
.
Certolizumab pegol efficacy in patients with non-radiographic axial spondyloarthritis stratified by baseline MRI and C-reactive protein status: an analysis from the C-axSpAnd study
.
ACR Open Rheumatol
.
2022
;
4
(
9
):
794
801
.
32.
Macaluso
FS
,
Rodríguez-Lago
I
.
JAK inhibition as a therapeutic strategy for inflammatory bowel disease
.
Curr Drug Metab
.
2020
;
21
(
4
):
247
55
.
33.
van der Heijde
D
,
Sieper
J
,
Maksymowych
WP
,
Lambert
RG
,
Chen
S
,
Hojnik
M
, et al
.
Clinical and MRI remission in patients with nonradiographic axial spondyloarthritis who received long-term open-label adalimumab treatment: 3-year results of the ABILITY-1 trial
.
Arthritis Res Ther
.
2018
;
20
(
1
):
61
.
34.
van der Heijde
D
,
Dougados
M
,
Landewé
R
,
Sieper
J
,
Maksymowych
WP
,
Rudwaleit
M
, et al
.
Sustained efficacy, safety and patient-reported outcomes of certolizumab pegol in axial spondyloarthritis: 4-year outcomes from RAPID-axSpA
.
Rheumatol
.
2017
;
56
(
9
):
1498
509
.
35.
van der Heijde
D
,
Gensler
LS
,
Maksymowych
WP
,
Landewé
R
,
Rudwaleit
M
,
Bauer
L
, et al
.
Long-term safety and clinical outcomes of certolizumab pegol treatment in patients with active non-radiographic axial spondyloarthritis: 3-year results from the phase 3 C-axSpAnd study
.
RMD Open
.
2022
;
8
(
1
):
e002138
.
36.
Maksymowych
WP
,
Dougados
M
,
van der Heijde
D
,
Sieper
J
,
Braun
J
,
Citera
G
, et al
.
Clinical and MRI responses to etanercept in early non-radiographic axial spondyloarthritis: 48-week results from the EMBARK study
.
Ann Rheum Dis
.
2016
;
75
(
7
):
1328
35
.
37.
van der Heijde
D
,
Dougados
M
,
Maksymowych
WP
,
Bergman
G
,
Curtis
SP
,
Tzontcheva
A
, et al
.
Long-term tolerability and efficacy of golimumab in active non-radiographic axial spondyloarthritis: results from open-label extension
.
Rheumatol
.
2022
;
61
(
2
):
617
27
.
38.
Kim
TH
,
Kishimoto
M
,
Wei
JC
,
Jeong
H
,
Nozaki
A
,
Kobayashi
S
.
Brodalumab, an anti-interleukin-17 receptor A monoclonal antibody, in axial spondyloarthritis: 68-week results from a phase 3 study
.
Rheumatol
.
2023
;
62
(
5
):
1851
9
.
39.
Baraliakos
X
,
Deodhar
A
,
van der Heijde
D
,
Magrey
M
,
Maksymowych
WP
,
Tomita
T
, et al
.
Bimekizumab treatment in patients with active axial spondyloarthritis: 52-week efficacy and safety from the randomised parallel phase 3 BE MOBILE 1 and BE MOBILE 2 studies
.
Ann Rheum Dis
.
2024
;
83
:
199
213
.
40.
Gracey
E
,
Yao
Y
,
Green
B
,
Qaiyum
Z
,
Baglaenko
Y
,
Lin
A
, et al
.
Sexual dimorphism in the Th17 signature of ankylosing spondylitis
.
Arthritis Rheumatol
.
2016
;
68
(
3
):
679
89
.
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