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SpA non-radiografica: fase precoce di spondilite anchilosante o altro?
Ignazio Olivieri
Rheumatology Department of Lucania, S. Carlo Hospital of Potenza and Madonna delle Grazie Hospital of Matera
Disclosures
Consulting fees, research or institutional support and educational grants from: Abbott, Bristol Meyer Squibb, Merck Sharp & Dohme, Novartis, Pfizer, Roche
Juvenile SpA
Reactive arthritis
Arthritis associated with
Ulcerative colitis and Crohn’s disease
Psoriatic Arthritis
Undifferentiated SpA
Acute anterior uveitis
Ankylosing Spondylitis
The spondyloarthritis complex
Historical Look at Classification Criteria for Axial SpA
Modified New York Criteria for AS1
1984
Sacroiliitis (x-ray) (required) Plus 1 below: IBP/stiffness >3 months Limitation of Lumbar spine motion Limitation of chest expansion
1 van der Linden et al. Arthritis Rheum. 1984 Apr;27(4):361-8.
Juvenile SpA
Reactive arthritis
Arthritis associated with
Ulcerative colitis and Crohn’s disease
Psoriatic Arthritis
Undifferentiated SpA
Acute anterior uveitis
Ankylosing Spondylitis
The spondyloarthritis complex
Historical Look at Classification Criteria for Axial SpA
Modified New York Criteria for AS1
1984
Amor Classification Criteria for Spondyloarthritis2
1990
1 van der Linden et al. Arthritis Rheum. 1984 Apr;27(4):361-8. 2Amor et al. Rev Rhum Mal Osteoartic.1990 Feb;57(2):85-9.
Sacroiliitis (x-ray) (required) Plus 1 below: Inflammatory LBP/stiffness >3 months Limitation of Lumbar spine motion Limitation of chest expansion
Scoring ≥6/23 points Examples: Good response to NSAIDs Expanded pain description Articular & Extra-articular manifestations Genetic Background (HLA-B27, family hx) Sacroiliitis (x-ray)
Historical Look at Classification Criteria for Axial SpA
Modified New York Criteria for AS1
1984
Amor Classification Criteria for Spondyloarthritis2
European Spondyloarthropathy Study Group (ESSG) Criteria3
1991 1990
1van der Linden et al. Arthritis Rheum. 1984 Apr;27(4):361-8. 2Amor et al. Rev Rhum Mal Osteoartic.1990 Feb;57(2):85-9. 3Dougados et al, Arthritis Rheum. 1991 Oct;34(10):1218-27.
IBP or Synovitis (required) Plus 1 below: Enthesitis Family hx Psoriasis, CD, or UC Preceding infection Buttock pain Sacroiliitis (x-ray) No HLA-B27
Sacroiliitis (x-ray) (required) Plus 1 below: Inflammatory LBP/stiffness >3 months Limitation of Lumbar spine motion Limitation of chest expansion
Scoring ≥6/23 points Examples: Good response to NSAIDs Expanded pain description Articular & Extra-articular manifestations Genetic Background (HLA-B27, family hx) Sacroiliitis (x-ray)
Historical Look at Classification Criteria for Axial SpA
Modified New York Criteria for AS1
1984
Amor Classification Criteria for Spondyloarthritis2
European Spondyloarthropathy Study Group (ESSG) Criteria3
1991 1990
van der Linden et al. Arthritis Rheum. 1984 Apr;27(4):361-8. Amor et al. Rev Rhum Mal Osteoartic.1990 Feb;57(2):85-9. Dougados et al, Arthritis Rheum. 1991 Oct;34(10):1218-27. Rudwaleit M et al. Ann Rheum Dis 2009;68 777-83
Sacroiliitis (x-ray) (required) Plus 1 below: Inflammatory LBP/stiffness >3 months Limitation of Lumbar spine motion Limitation of chest expansion
Scoring ≥6/23 points Examples: Good response to NSAIDs Expanded pain description Articular & Extra-articular manifestations Genetic Background (HLA-B27, family hx) Sacroiliitis (x-ray)
IBP or Synovitis (required) Plus 1 below: Enthesitis Family hx Psoriasis, CD, or UC Preceding infection Buttock pain Sacroiliitis (x-ray) No HLA-B27
Assessment of SpondyloArthritis (ASAS) Criteria for Axial Spondyloarthritis4
2009
Sacroiliitis (X-ray or MRI) Plus ≥1 SpA feature or HLA-B27 Plus ≥2 SpA features
Duration of symptoms (years)
Back pain Back pain Radiographic
sacroiliitis
Back pain
Syndesmophytes
Non-radiographic stage (axial undifferentiated
SpA)
Radiographic stage
Modified New York Criteria 1984
Rudwaleit M, et al. Arthritis Rheum. 2005;52:1000-8.
MRI sacroiliitis
Ankylosing Spondylitis
13
Definition of Positive MRI-SI Joint
ASAS handbook, Ann Rheum Dis 2009;68 (Suppl II) (with permission) 13
14
Age at First Symptoms and at First Diagnosis in Ankylosing Spondylitis Patients
1Feldtkeller et al. Current Opinion in Rheum 2000;12:239-247 (with permission).
Duration of symptoms (years)
Back pain Back pain Radiographic
sacroiliitis
Back pain
Syndesmophytes
Non-radiographic stage (axial undifferentiated
SpA)
Radiographic stage
Modified New York Criteria 1984
Rudwaleit M, et al. Arthritis Rheum. 2005;52:1000-8.
MRI sacroiliitis
Ankylosing Spondylitis
Duration of symptoms (years)
Back pain Back pain Radiographic
sacroiliitis
Back pain
Syndesmophytes
Non-radiographic stage (axial undifferentiated
SpA)
Radiographic stage
Modified New York Criteria 1984
Rudwaleit M, et al. Arthritis Rheum. 2005;52:1000-8.
MRI sacroiliitis
Axial spondyloarthritis
Predominantly Axial SpA
Ankylosing Spondylitis
Non-radiographic axial SpA
Predominantly Peripheral SpA
Reactive arthritis
Psoriatic Arthritis
Arthritis with inflammatory bowel disease
Undifferentiated SpA
Concept of Spondyloarthritides (SpA)
Disease course of axial spondyloarthritis
New Nomenclature (1)
Spondyloarthritis
Axial Peripheral
SIJ structural damage (plain pelvic X-Rays)
Yes No
Ankylosing Spondylitis Axial non radiographic spondyloarthritis
Axial radiographic Spondyloarthritis (1) Claudepierre P.et al. Joint Bone Spine 2012,79:534-5
Disease course of axial spondyloarthritis
Labelling of biologics in axial SpA
• 2004 → 2012: Ankylosing Spondylitis • 2012 → ongoing:
[ Ankylosing Spondylitis] OR Axial non-radiographic spondyloarthritis
and - SIJ inflammation at MRI OR Abnormal CRP axial spondyloarthritis with at least one of the following: - Presence of SIJ structural damage at pelvic X-Rays - Presence of SIJ inflammation at MRI or Abnormal CRP
57,1 54 54,6
68,2
47,6
0102030405060708090
100
GESPIC* Haibel ABILITY-I Kiltz ASASValidation
%
Percent Female in Non-Radiographic Axial SpA Cohorts
Rudwaleit. Arthritis Rheum. 2009:60(3)717–727. Haibel et al. Arthritis Rheum 2008;58(7):1981-91. Sieper et al. ACR 2011. Tues2486A. 4Kiltz et al. EULAR 2011 FRI 0529. Rudwaleit et al.Ann Rheum Dis 2009;68:777-783.
Female sex generally >50% of nr-axSpA cohort
*GESPIC combines patients with primarily axial and primarily peripheral symptoms
2 3 4
5
1
Disease course of axial spondyloarthritis
Structural damage in axial Spondyloarthritis
* Dougados M. et al. Joint Bone Spine 2011;78:598-603
Disease course of axial spondyloarthritis
Cross sectional analysis of familial SpA*
40%
70%
86%
<10n = 99
10-19n = 110
≥20 n = 120
Rad
iogr
aphi
c
Sacr
oilii
tis (%
)
Disease duration (years)
*Saïd-Nahal R, … Amor B, Dougados M, Breban M. Arthritis Rheum 2000;43:1356-1365
Disease course of axial spondyloarthritis
Baseline radiographic sacroiliitis
Yes no
112 11 3 84
11.6%
The GESPIC cohort
yes
no
2 ye
ar
Rad
iogr
aphi
c sa
croi
liitis
(115) (95) 2.6%
Disease course of axial spondyloarthritis
Baseline radiographic sacroiliitis
Yes no
116 16 7 310
yes
no
2 ye
ar
Rad
iogr
aphi
c sa
croi
liitis
(123) (326) 5.7%
4.9%
0-2 years1-2 2-9 years1,3-7 ≥10 years1,5
% progression 8-12% 20-45% 36-59%
Progression from non-radiographic axial SpA to AS: Longitudinal Studies
1Sampaio-Barros et al, J Rheumatol 2010; 37:1195-9. 2Poddubnyy et al, Ann Rheum Dis 2011; 70: 1369-74. 3Schattenkirchner et al, Clin Rheumnatol 1987; 6 (Suppl 2): 83-6. 4Sany et al. Arthritis Rheum 1980;23(2):258-9. 5Mau et al. J Rheumatol. 1988;15:1109–14. 6Oostveen et
al, J Rheumatol 1999; 26:1953-8. 7Bennett et al. Arthritis Rheum 2008; 58(11):3413-18.
Includes² only patients age ≥17
• Variable methodology and disease definitions were used in the studies reported • Most studies included report mixed axial and peripheral disease at baseline
• No study used ASAS criteria for axial SpA • Reported range represents data from different sources, study N range 23-119
32
Hypothetical Development of Radiographic Sacroiliitis in Patients With Axial SpA
0
20
40
60
80
100
2 5 10 20
Axi
al S
pA (%
)
Time (years)
Radiographic Non-radiographic
Chronic back pain
Disease course of axial spondyloarthritis
Natural history of the disease
Clinical features of Spa
CDER, FDA 2013. Regulatory considerations for the potential novel indication axial spondyloarthritis. Available at: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ArthritisAdvisoryCommittee/UCM366488.pdf. Accessed 20 February 2014.
Disease course of axial spondyloarthritis
Clinical features of Spa
Sacroiliitis on imaging
Natural history of the disease
CDER, FDA 2013. Regulatory considerations for the potential novel indication axial spondyloarthritis. Available at: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ArthritisAdvisoryCommittee/UCM366488.pdf. Accessed 20 February 2014.
Disease course of axial spondyloarthritis
Clinical features of Spa MRI
sacroiliitis
Radiographic sacroiliitis
Natural history of the disease
CDER, FDA 2013. Regulatory considerations for the potential novel indication axial spondyloarthritis. Available at: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ArthritisAdvisoryCommittee/UCM366488.pdf. Accessed 20 February 2014.
Disease course of axial spondyloarthritis
Clinical features of Spa
PROGRESSION
RESOLUTION
RESOLUTION
STABILITY
Natural history of the disease
Radiographic sacroiliitis
CDER, FDA 2013. Regulatory considerations for the potential novel indication axial spondyloarthritis. Available at: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ArthritisAdvisoryCommittee/UCM366488.pdf. Accessed 20 February 2014.
Disease course of axial spondyloarthritis
27,5 31,7 29,4
43,8
27,4
X-RAY +MRI +
n = 132
X-RAY +MRI -n = 55
X-RAY -MRI +n = 99
X-RAY -MRI -CRP +n = 33
X-RAY -MRI -CRP -
n = 154
BAS
FI (m
ean)
Imaging clinical
*Molto A…Dougados M. Ann Rheum Dis 2014, jan, Epub ahead of print
Validity of the ASAS criteria
Burden of the disease: BASFI*
Burden of disease in pre-radiographic axial SpA and established AS is similar
Rudwaleit M, et al. Arthritis Rheum. 2004;50:S211.
0
1
2
3
4
5
6
BASDAI Pain BASFI BASMI
AS 5-10 yrs. (n=120)AS <5 yrs. (n=105)Pre-radiogr. AS <5 yrs. (n=196)
ADALIMUMAB IN RHEUMATIC DISEASES
Sieper J, et al. Ann Rheum Dis 2013; 72:815-822
18 11
27
55
0
20
40
60
80
% p
atie
nts
baseline CRP * treatment
p=.03
Abnormal Normal 10/57 17/62 4/37 16/29
Baseline CRP
n/N:
% p
atie
nts
14 16
38 35
0
20
40
60
80 baseline sacroiliitis by MRI * treatment
p=.65
Positive Negative
7/51 17/45 7/45 16/46
Sacroiliitis on Baseline MRI
n/N:
Whole population * treatment
15
36
0
20
40
60
80
Placebo (n=94) Adalimumab (n=91)
% p
atie
nts
*
p<.001
Whole population
Efficacy (% ASAS40 response) Adalimumab in non-radiographic axial spondyloarthritis
Placebo
Adalimumab
111 65 46
0
15,2 20
28,6 33,3
41,4
44
0 3,8 14,8
15,7 14,8
38,5
51,9
0
10
20
30
40
50
60
0 2 4 6 8 10 12 14 16 18 20 22 24
Patie
nts (
%)
Weeks
ETN/ETN
PBO/ETN
Pfizer 1031 study – proportion of patients achieving ASAS40 response at week 12 and 24
*p<0.05; †p<0.01 vs placebo. ASAS, Assessment of SpondyloArthritis international Society; ETN, etanercept; LOCF, last observation carried forward; mITT, modified intention to treat; nr-axSpA, non-radiographic axial spondyloarthritis; NSAID, non-steroidal anti-inflammatory drug; PBO, placebo.
• In this population of patients with early, active nr-axSpA who had an inadequate response to ≥2 NSAIDs, ETN was more effective than PBO in decreasing disease activity
ASAS40 response at week 12 and 24 (mITT, LOCF)
Double blind Open label
*
* †
(n = 105)
(n = 108)
Dougados M, et al. Arth Rheum 2014;66:2091–2102.
15,4 15,4
44,9 43,5
49,3 54,3
0
20
40
60
80
Week 14 Week 24
Res
pons
e R
ate
(% P
atie
nts)
ASAS40 at Weeks 14 and 24
■ PBO ■ GLM 50 mg ■ GLM 100 mg
GO-RAISE Study In Ankylosing Spondylitis
50 mg golimumab every four weeks vs 100
mg golimumab every four weeks vs placebo
n= 78 138 140 Inman R et al. A&R 2008; 58:3402-12
* p<0.001 *
* *
*
GO-AHEAD Study
In non-radiographic axial spondyloarthritis
50 mg golimumab every four weeks vs placebo
Abstracts with data from GO-AHEAD are presented during the scientific sessions Posters THU0218 & THU0238 Abstract AB0757
Treatment of AS and nr-axSpA with Golimumab
CHMP positive opinion for
nr-axSpA indication received May 2015
Take home messages
CONCLUSIONS
Non-radiographic/Non-imaging axial
spondyloarthritis DOES EXIST The natural history of axial spondyloarthritis requires
further investigations Non-radiographic/Non-imaging axial
spondyloarthritis deserves to have access to all the therapies available for radiographic axial spondyloarthritis
Grazie per l’attenzione