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Strengthening our knowledge in Spondylarthritides:Focusing on Ankylosing Spondylitis and Psoriatic Arthritis
Department of PathophysiologyMetical School National and Kapodestrian University of Athens
Panayiotis G. Vlachoyiannopoulos MDProfessor of Medicine-Immunology
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2
Conflict of interest
3
The speaker was paid by Novartis for this presentation
through the Special Research Account of National and Kapodistrian University of
Athens
Outline Spondyloarthritis: definition and prevalence
Ankylosing spondylitis and psoriatic arthritis
Clinical features
Pathophysiology of SpA
Diagnosis and treatment
Comorbidities and disease load
McAllister K, et al., BMJ 2017;356:j839
Identifying and referring Spondyloarthritis
5
Spondyloarthritis (SpA) can have diverse symptoms and be difficult to identify
Πλάγια ακτινογραφία οσφυϊκής
μοίρας σπονδυλικής στήλης σε
ασθενή με σοβαρή AS δείχνει
γέφυρες συνδεσμόφυτων (ακίδες) σε
πολλαπλά επίπεδα.5
Spondyloarthritis
van Tubergen, A. Nat. Rev. Rheumatol. 11, 110–118 (2015).Khan, M. A. Ann. Intern. Med. 136, 896–907 (2002).Rudwaleit, M. Curr. Opin. Rheumatol. 22, 375–380 (2010).
• Spondyloarthritis (SpA) is a group of inflammatory rheumatic diseases comprising ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, undifferentiated SpA and SpA associated with inflammatory bowel disease
• These interrelated disorders share clinical features, run in families and are associated with HLA-B27
• SpA can also be characterized as axial or peripheral according to predominant articular features at clinical presentation
• Axial SpA involves spondylitis and sacroiliitis, whereas the main features of peripheral SpA are peripheral arthritis, enthesitis and dactylitis
Οι οροαρνητικές αρθρίτιδες χαρακτηρίζονται από διαβρώσεις και οστεοπαραγωγή
Ρευματοειδής αρθρίτιδαΔιαβρώσεις μεταταρσοφαλαγγικών
Ψωριασική αρθρίτιδαΔιαβρώσεις αλλά και εξωαρθρικήπεριοστίτιδα
Features of the Spondyloarthritis
10van Tubergen, A. Nat. Rev. Rheumatol. 11, 110–118 (2015);
ASAS classification criteria for axial and peripheral SpA
11van Tubergen, A. Nat. Rev. Rheumatol. 11, 110–118 (2015);
Diseases That Make Up the SpA Syndrome Share Common Features
Disorders share distinctive clinical, radiographic, and genetic features:
Rheumatic diseases characterized by sacroiliitis, spondylitis, enthesitis, dactylitis and synovitis
Extra-articular manifestations (uvea, gut, skin)
Strong association with HLA B27
Positive family history of SpA
Images taken from: ASAS Assessment of SpondyloArthritis International Society. http://www.asas-group.org/mission-statement.php. Accessed 5 August 2015.
Uveitis
Sacroiliitis (Grade II) Synovitis of SI joint
Spondylitis anterior
and posterior
Enthesitis
Gut lesions in
Crohn’s disease
Psoriasis
Diffuse idiopathic skeletal hyperostosis vs sPA
Diffuse idiopathic skeletal hyperostosis vs sPA
AS Has a Multitude of Effects on the Body
AS, ankylosing spondylitis; CV, cardiovascular.
http://www.healthline.com/health/ankylosing-spondylitis/effects-on-body (accessed 14 July 2015)
AS in
knees
Respiratory
effects
CV/circulatory
effects
Stooped
shoulders
Neck pain Impaired vision
Stiff
spine
Weak
hip
Scaly
skin
Foot
function
PsA, psoriatic arthritis
http://www.healthline.com/health/psoriatic-arthritis/effects-on-body#Skeletal-System (accessed 6 July 2015)
Weakness
in knees
PsA in
hands
Elbow
pain
Shoulder
swelling
Flaky scalp Emotional health
Spine and
neck pain
Weak
muscles
Scaly
skin
Foot
problems
PsA Impacts Both Physical and Emotional Well-being
Prevalence of SpA
Stolwijk et al., Arthritis Care & ResearchVol. 68, No. 9, September 2016, pp 1320–1331
✓ The prevalence of SpA ranged from 0.20% (95% CI 0.00–0.66) in South-East Asia to 1.61% (95% CI 1.27–2.00) in Northern Arctic communities
✓ The following characteristics were significantly associated with variation in prevalence of SpA:
- proportion of females- mean age of the sample- geographic area and setting- year of data collection- case finding and case ascertainment (methodologic
characteristics)
✓ The prevalence of SpA has been reported higher in more recent studies (year of data collection from 2000 onwards)
Prevalence of AS
Shapira et al., Nature Reviews Rheumatology volume 6, pages 468–476 (2010) doi:10.1038/nrrheum.2010.86
Exarchou et al. Arthritis Research & Therapy (2015) 17:118
✓ The prevalence of AS ranges ~ 0,5-1,9% globally
✓ Additionally there is some gender disparity within AS, with reported gender ratios of around 2:1 male to female
✓ There were also differences between the sexes regarding some AS-related clinical manifestations. I.e. anterior uveitis was more common in men, and peripheral arthritis and psoriasis were more common in women
✓ AS usually initially presents during the second and third decade of life, and rarely after the age of 45 years
✓ There is a considerable delay (8 to 15 years) in obtaining a definitive diagnosis from a specialist
✓ AS prevalence correlates with the prevalence of HLA-B27
Prevalence of AS in Greece
Christophers E et al. J Eur Acad Dermatol Venereol. 2010 May;24(5):548-54
25
20
15
10
5
0
Pa
tie
nts
wit
h p
so
ria
sis
wh
o
de
ve
lop
PsA
(%)
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30
Duration of psoriasis (years)
% of patients with psoriasis who develop PsA per annum
Cumulative% of patients with psoriasis who develop PsA
0
10
20
30
40
50
60
70
80
<1% 1%–2% 3%–10% >10%
Bodysurfacearea(BSA)involvement
PsAprevalenceinpsoriasispa
ents
Gelfand JM et al. J Am Acad Dermatol. 2005;53:573-577
The prevalence of psoriatic arthritis among patients with psoriasis increased significantly on the basis of the body surface area involved with psoriasis
Prevalence of PsA
The development of PsA appears to occur at a constant rate during each year following psoriasis diagnosis, resulting in a steady increase in PsA prevalence
Outline Spondyloarthritis: definition and prevalence
Ankylosing spondylitis and psoriatic arthritis
Clinical features
Pathophysiology of SpA
Diagnosis and treatment
Comorbidities and disease load
Ankylosing spondylitis (AS)
Taureg et al., 2016. N Engl J Med 374;26
Σκελετός με αλλοιώσεις ΑΣ που περιγράφηκε από τον Bernard Connor το 1695
AS classification
▪ AS is axial SpA with significant X-ray changes manifested through sacroiliitis, meeting the modified New York
criteria (1984) for AS 1,2
ASAS, Assessment of SpondyloArthritis international Society
1. Sieper J et al. Ann Rheum Dis. 2009;68(Suppl II):ii1-ii44; 2. Rudwaleit M et al. Arthritis Rheum. 2005;52:1000-1008.
Clinical features of AS
Clinical features
• Long-term disease that causes inflammation of joints between spinal bones and the joints between the spine and pelvis1
• Eventually causes affected spinal bones to fuse together1
• Clinical features include inflammation, structural damage,and repair2
• Negative impact on QoL and psychological well-being3
• Likely related to genetic and environmental factors4
• It is majorly diagnosed in young men
1. Spondylitis Association of America. Ankylosing Spondylitis. Available at: http://www.spondylitis.org/about/as.aspx. Accessed on 8 November 2011;2. Maksymowych W. Nat Rev Rheumatol. 2010;6:75-81; 3. Sieper J et al. Ann Rheum Dis. 2002;61:iii8-iii18; 4. El-Gabalawy H et al. J Rheumatol. 2010;37(Suppl 85):2-10; 5. Jang JH et al. Radiology. 2011;258:192-198.
Laboratory features
• No laboratory test is diagnostic of AS1
• HLA-B27- Presence of the gene HLA-B27 is a strong predictor of axial SpA1,2
- Approximately 80-95% of patients with AS are HLA-B27 positive1,3,4
• C-reactive protein (CRP)3
- Levels of CRP increase in response to inflammation and may be associated with structural changes in the spine associated with axial SpA
• Erythrocyte sedimentation rate (ESR)1
- A measure of inflammation- Commonly used in the assessment of RA and other inflammatory disorders
HLA, human leukocyte antigen; RA, rheumatoid arthritis1. Sieper J et al. Ann Rheum Dis. 2002;61(Suppl III):iii8–iii18; 2. Rudwaleit M et al. Ann Rheum Dis 2009;68:777–83; 3. Rudwaleit M et al. Arthritis Rheum. 2009;60:717–727; 4. Chung HY et al. Ann Rheum Dis. 2011;70:1930–1936.
Inflammatory vs mechanical back pain
Mechanical back pain:
• is much more frequent
• refers to pain that arises from an injury to a specific structure within the spine
• has usually a full recovery within the first few weeks
• has morning stiffness <30 min
• is improved with rest
Taurog et al., 2016. N Engl J Med 374;26
New bone formation progressively leads to ankylosis
Little H et al. Am J Med. 1976;60:279-85
Clinical features of PsA
Ritchlin et al., 2017. N Engl J Med 376;10
Psoriasis
Nail psoriasis
Polyarthritis(RA-like)
25% → 65%
Oligoarthritis
65% → 25%
Erosions of
Distal phalanx
(OA-like)
10-20%
Erosive arthritis
<1%
Axial
involvement
(40%)
Dactylitis
35%
Enthesitis
35%
Peripheral involvement
(60-90%)
Arthritis
Clinical manifestations of PsA
Clinical features
Peripheral arthritis
Achilles enethesitis PsoriasisCrohn’s disease
Anterior UveitisDactylitis
Outline Spondyloarthritis: definition and prevalence
Ankylosing spondylitis and psoriatic arthritis
Clinical features
Pathophysiology of SpA
Diagnosis and treatment
Comorbidities and disease load
• Mechanical stress can induce an inflammatory response at the enthesis in genetically susceptible individuals and/or those under microbial stress1–4
Mechanicalstress
Impaired barrierfunction (e.g., microbial stress)
Genetics(e.g., HLA-B27)
Enthesitis
Plus and or
1. Haroon M, et al. Ann Rheum Dis. 2016;75:155–62; 2. Kehl AS, et al. Arthritis Rheumatol. 2016;68:312–22;3. Sieper J, Poddubnyy D. Lancet. 2017;90:73–84; 4. McGonagle D, Benjamin M. Topical Reviews. 2009;4:1–6.
Mechanical stress is a key trigger for enthesitis in AS and PsA
Schett, G. et al. (2017) Enthesitis: from pathophysiology to treatment
Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2017.188
Enthesitis differentiates AS and PsA from rheumatoid arthritis
• Primary synovial membrane disease vs. entheseal disease with secondary synovial membrane involvement
• Aids differential diagnosis of AS / PsA vs. rheumatoid arthritis
Pathophysiology of enthesitis
IL-17A is an amplifier of enthesitis, leading to irreversible structural damage
Mechanosensation & immune activation
Innate inflammatory response
Mesenchymal proliferation
New bone formation
Triggers• Mechanical
stress• Disturbed
barrier function• Infections
Vasodilation
Bone
Enthesis
Muscle
Tendon
PGE2
IL-23
Activation
gdTcells
ILC3
gdTcells
ILC3
IL-17
TNF
Neutrophils
gdTcells
ILC3
IL-17
IL-22MSCs
MSCs
• Hedgehog• PTHrP
• Wnts• BMPs
Osteoblast Hypertrophicchondrocyte
Bone
BMP, bone morphogenic proteins; IL-22, interleukin 22; PTHrP, parathyroid hormone related-peptide; MSC, mesenchymal stem cellAdapted from Schett G, et al. Nat Rev Rheumatol. 2017;13:731–41.
ILC= innate lymphoid cellsILC1IFN-γILC2IL-5,IL-6, IL-13ILC3IL-17, IL-22
IL-17 stimulates osteoblast to express RANKL which stimulates Osteoclast to destroy the bone
Taureg et al., 2016. N Engl J Med 374;26
Pathogenic Mechanisms in Axial Spondyloarthritis
Προσαρμογή από Paine A et al. Curr Opin Rheumatol 2016;28:66-75Uluckan O, et al. Transl Med 2016;8:330ra37; Shaw AT, et al. Arthritis Res Ther 2016;18:104
Pathogenic Pathways in Ankylosing Spondylitis
Outline Spondyloarthritis: definition and prevalence
Ankylosing spondylitis and psoriatic arthritis
Clinical features
Pathophysiology of SpA
Diagnosis and treatment
Comorbidities and disease load
Feldtkeller E et al. Rheumatol Int 2003;23:61–66Sengupta R & Stone MA. Nat Clin Pract Rheumatol 2007;3:496-503
First diagnosis
Age in years
Men (n=920)
Women (n=476)
00 10 20 30 4
050
60
70
20
40
80
60
100
Per
cen
tage
of
Pat
ien
ts (
%)
Mean delay in diagnosis: 8.8 yearsB27(+) 8.5 vs B27(-) 11.4
The delay in diagnosis and the worsening of AS symptoms leads to physical, emotional and disease-related work disability
40
Delay in diagnosis in AS
Currently, there is a long delay, from 5 to 10 years, between the first occurrence of AS symptoms and a diagnosis of AS.
Two major reasons can be named for such a delay: (a) There is certainly a low awareness of AS among
non-rheumatologists and it can be seen as a major challenge for any physician in primary care to think of and to identify patients with inflammatory spine disease among the large group of patients with chronic back pain, most often of another origin.
(b) Radiographic sacroiliitis grade 2 bilaterally or grade 3 or 4 unilaterally is usually a requirement for making the diagnosis of AS according to the modified New York criteria.
Delay in diagnosis of AS
Alamanos Y. Rheumatology 2004;43:615–618
Diagnosis of AS: Indexes that are commonly used in clinical trials
Axial skeletonPeripheral skeleton
EnthesitisRadiographic
findingsFunctionality/ Quality of life
Mobility
BASDAI ✓ ✓ ✓
BASMI ✓
BASFI ✓
MEI/MASES/ SPARCC/LEI
✓
ASAS 20/40 ✓ ✓
ASAS 5/6 ✓ ✓ ✓
ASDAS ✓ ✓
HAQ ✓
SF-36 ✓
mSASSS ✓
Pain DactylitisInflammation
indexes
Gladman DD et al. Ann Rheum Dis. 2005 Mar;64 Suppl 2:ii14-7
Progression of psoriatic arthritis
Psoriasis onset
10 20 30
Έτη
12
At least 1 erosion
47%
Erosion of at least 5 joints
55%
Increased mortality due to CVDDis
eas
e s
ever
ity
Severe pain and disability
(30% of pts will be diagnosed with PsA)
20%: Severe/Erosive disease
4.25
2.2
1.47
0.42
0
1
2
3
4
5
Erosions Functionaldisability
(HAQ)
No. of DMARDs/TNFi failures
DMARD/TNFi free
Od
ds
Rat
io (
OR
)
Delay in diagnosis > 6 months
30
53
71
0
20
40
60
80
< 6 months < 1 year < 2 years
Rheumatologist’s diagnosis
%
Haroon M et al. Ann Rheum Dis. 2015 Jun;74(6):1045-50
Diagnostic delay of more than 6 months contributes to poor radiographic and functional outcome in psoriatic arthritis after a mean of 10 years of follow-up
Clinical features recorded as percent, unless otherwise statedCI, confidence interval; DMARD, disease-modifying anti-rheumatic drug; OR, odds ratio Haroon M, et al. Ann Rheum Dis. 2015;74:1045–50.
4.6 (2.5–8.2)
1.1 (1.0–1.1)
2.3 (1.2–4.4)
10.6 (1.4–80.6)
2.2 (1.3–3.6)
0.4 (0.2–0.9)
Odds r
atio (
95%
CI)
5
8
9
10
11
0
7
6
4
3
2
1
Erosions Number of
deformed
joints (score)
Sacroiliitis Arthritis
mutilansFunctional
disability
(HAQ score)
DMARD/
anti-TNF free
Smolen JS et al. Ann Rheum Dis. 2017 Jul 6.
Treatment
Ann Rheum Dis 2011;70:905–908
Spondyloarthritis– Current treatments
• NSAIDs
• DMARDs :
• Methotrexate
• Sulfasalazine
• Cyclosporine (?)
• Leflunomide
• TNF-a inhibitors
• Ustekinumab (anti-p14, IL-12/IL-23)
• Apremilast (ts DMARD)
• Secukinumab (anti-IL-17A)
Olivieri, I. et al. Nat. Rev. Rheumatol. 10, 531–542 (2014)
van Mens et al. Curr Opin Rheumatol 2018, 30:79–86
New compounds in spondyloarthritis
Efficacy of biologics and other novel drugs in SpA and other chronic inflammatory diseases
Sieper and Poddubnyy, Nat Rev Rheumatol. 2016 May;12(5):282-95.doi:10.1038/nrrheum.2016.42
Efficacy of biologics and other novel drugs in SpA and other chronic inflammatory diseases
Sieper and Poddubnyy, Nat Rev Rheumatol. 2016 May;12(5):282-95.doi:10.1038/nrrheum.2016.42
Outline Spondyloarthritis: definition and prevalence
Ankylosing spondylitis and psoriatic arthritis
Clinical features
Pathophysiology of SpA
Diagnosis and treatment
Comorbidities and disease load
Prevalence of evaluated comorbidities in the 3984 patients with spondyloarthritis
Anna Moltó et al. Ann Rheum Dis 2016;75:1016-1023
Withdrawal from work due to disease-related disability in patients with AS in the period before biologic treatments
Ann Rheum Dis 2001;60:1033–1039
Efficacy and Safety of secukinumab (anti-IL-17A)up to 4 years of treatment
MEASURE 1 is a 2-year study with 3-year extension study; MEASURE 2 is a 5-year study; MEASURE 3 is a 3-year study; MEASURE 4 is a 2-year study. The primary endpoint for all studies is at Week 16. i.v., intravenous; s.c., subcutaneous.
Clinicaltrials.gov: NCT01358175 (MEASURE 1);NCT01649275 (MEASURE 2);NCT02008916 (MEASURE 3);NCT02159053 (MEASURE 4).
2013 2014 2015 2016 2017
Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q1 Q2 Q3 Q4 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4
MEASURE 2 – N = 219s.c. loading (75 or 150 mg) → s.c. maintenance dosing (75 or 150 mg)Pre-filled syringe
Extension Study MEASURE 1 – N = 371i.v. loading (10 mg/kg) → s.c. maintenance dosing (75 or 150 mg)
MEASURE 3 – N = 226i.v. loading (10 mg/kg) → s.c. maintenance dosing (150 or 300 mg)
MEASURE 4 – N = 350s.c. 150 mg with or withouts.c. loading (Pre-filled syringe)
The MEASURE Clinical Trial Program: Assessment of Secukinumab in AS
0
25
50
75
100
0 16 32 48 64 80 96 112 128 144 160 176 192 208
% R
esp
on
der
s
ASAS, Assessment of Spondyloarthritis International Society; n, number of pts evaluated in the treatment group; N, total number of pts in the extension trial; Obs, observed data. Solid lines represent observed data through Week 208. Dashed lines represent multiple imputation data through Week 208
76.4%79.7%
0
25
50
75
100
0 16 32 48 64 80 96 112 128 144 160 176 192 208
% R
esp
on
der
sASAS20
ASAS40
60.8%
58.0%
weeks
weeks
Secukinumab 10 mg/kg i.v. → 150 mg s.c.
Observed data Imputed data (N = 87)
8084 86 7986Obs n = 8752
52
104
104
156
156
Core study Extension study
57
Secukinumab 150 mg Provided Sustained ASAS20/ASAS40 Responses Through 4 Years
-3.3 -3.3 -3.4 -3.4
-4.0
-3.5
-3.0
-2.5
-2.0
-1.5
-1.0
-0.5
0.0
52 104 156 208
BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BASFI, Bath Ankylosing Spondylitis Functional Index; BASMI, Bath Ankylosing Spondylitis Metrology Index; n, number of pts evaluated in the treatment group; Obs, observed data. Observed data through Week 208
-0.6 -0.6-0.7
-0.5
-1.5
-1.3
-1.1
-0.9
-0.7
-0.5
-0.3
-0.1
52 104 156 208M
ea
n C
ha
nge
fro
m B
ase
line
-2.7-2.9 -2.9 -2.9
-4.0
-3.5
-3.0
-2.5
-2.0
-1.5
-1.0
-0.5
0.0
52 104 156 208WeekObs n = 84 80 86 80 84 80 86 80 79 76 81 76
Secukinumab 10 mg/kg i.v. → 150 mg s.c.
Core study Extension Core study Extension Core study Extension
BASDAI BASFI BASMI
Secukinumab 150 mg Provided Sustained Improvement in BASDAI, BASFI and BASMI Through 4 Years
2013 2014 2015 2016 2017
Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4
Extension study FUTURE 1 – N = 606i.v. loading (10 mg/kg) s.c. maintenance dosing (75 and 150 mg)
FUTURE 2 – N = 397s.c. loading (75, 150, and 300 mg) s.c. maintenance dosing (75, 150, and 300 mg)Pre-filled syringe
FUTURE 3 – N = 414s.c. loading (150 and 300 mg) s.c. maintenance dosing (150 and 300 mg)Autoinjector
FUTURE 4 – N = 341s.c 150 mg with or without s.c. loadingPre-filled syringe
FUTURE 5 – N = 996s.c 150 mg and 300 mg with or without s.c. loading (Pre-filled syringe)
FUTURE 1 is a 2-year study (primary endpoint at Week 24) with 3 year extension study; FUTURE 2 is a 5 year study (primary endpoint at Week 24); FUTURE 3 is a 3 year study (primary endpoint at Week 24); FUTURE 4 is a 2 year study (primary endpoint at Week 16); FUTURE 5 is a 2 year study (primary endpoint at Week 24). i.v., intravenous; s.c., subcutaneous
Clinicaltrials.gov: NCT01392326 (FUTURE 1);NCT01752634 (FUTURE 2);NCT01989468 (FUTURE 3);NCT02294227 (FUTURE 4); NCT02404350 (FUTURE 5).
The FUTURE Clinical Trial Program: Assessment of Secukinumab in PsA
61.5
35.9
17.9
0
20
40
60
80
100
ACR20 ACR50 ACR70
n=39 n=39 n=39
81.0
62.9
38.8
0
20
40
60
80
100
ACR20 ACR50 ACR70
n=116 n=116 n=116
Mease PJ, et al. Arthritis Rheumatol. 2016;68 (suppl 10): abstract 961.
Overall(Multiple Imputation)
Anti–TNF-naive(Observed Data)
Anti–TNF-IR(Observed Data)
76.8
54.9
32.9
0
20
40
60
80
100
ACR20 ACR50 ACR70
n=161 n=161 n=161
Per
cen
tage
of
sub
ject
s
Secukinumab IV→150 mg
Sustained Improvement in ACR20/50/70 Responses Through 3 years (Overall Population)
Αποδρομή Δακτυλίτιδας και Ενθεσίτιδας σε ασθενείς με αυτά τα συμπτώματα κατά την έναρξη
82.086.5 88.1
84.488.6 86.8
0
20
40
60
80
100
Per
cen
tage
of
pat
ien
ts 74.8 74.5 76.775.6
80.374.8
0
20
40
60
80
100
Per
cen
tage
of
pat
ien
ts
Resolution of Dactylitis Resolution of Enthesitis
Week 52 Week 104
Secukinumab 10 mg/kg i.v. 150 mg s.c.(Daktylitis: N = 83)(enthesitis: N = 99 )
Secukinumab 10 mg/kg i.v. 75 mg s.c.(Daktylitis: N = 77)(enthesitis: N = 91 )
Week 156 Week 52 Week 104 Week 156
Secukinumab Provided Sustained Resolution of Dactylitis and Enthesitis Through 3 years (Overall Population)
Mease PJ, et al. Arthritis Rheumatol. 2017;76 (suppl 2): abstract SAT0470.
53.6 53.6
15.4
10.4
54.5
47.744.7
20.0
Secukinumab 300 mg s.c. Secukinumab 75 mg s.c. Placebo
60
Perc
enta
ge o
f R
esp
on
der
s
40
30
0
60
Perc
enta
ge o
f R
esp
on
der
s
40
30
0
Co-treatment With MTX No MTX Treatment
20
10
20
10
Secukinumab 150 mg s.c.
50 50‡
§
†**
n = 44 n = 44 n = 47 n = 56 n = 56 n = 52n = 50 n = 48
*P < 0.0001; †P < 0.001; §P < 0.01; ‡P < 0.05 vs. placeboMissing values were imputed as nonresponse (nonresponder imputation) up to Week 52 McInnes IB, et al. Lancet. 2015 Jun 26. pii: S0140-6736(15)61134-5
Sustained Improvement in ACR20 Responses with or without co-treatment with methotrexate
*P < 0.0001; †P < 0.001; §P < 0.01 vs. placebo
P-values at Week 24 adjusted for multiplicity of testing
Data from subjects with psoriasis ≥ 3% body surface area at baseline.
McInnes IB, et al. Lancet. 2015;386:1137–46;
McInnes IB, et al. Poster presentation at the American College of Rheumatology
(ACR) 2016 Annual Scientific Meeting, Washington DC, USA. Abstract no. 2757.
63.4
79.7 79.5
48.3
60.1
73.3
16.3
*
Pe
rcen
tage o
f R
esp
on
ders
0
60
40
80
20
Week 24 Week 104
n=41
100
Week 52
PASI 75
(NRI data at Week 24; MI data at Week 52
and Week 104)
§
n=58 n=43 n=41 n=58 n=56 n=53
48.8
61.2
69.6
32.8
45.4
52.5
9.3
Pe
rcen
tage o
f R
esp
on
ders
0
60
40
80
20
Week 24 Week 104
n=41
100
Week 52
§
n=58 n=43 n=41 n=58 n=56 n=53
PASI 90
(NRI data at Week 24; MI data at Week 52
and Week 104)
†
Secukinumab 300 mg Secukinumab 150 mg Placebo
Secukinumab 300 and 150 mg provided Significant and Sustained Improvements in PASI 75 and PASI 90 Through Week 104 (Overall Population)
a Skin involvement while on etanercept. b Marked improvement on week 4 of secukinumab administration. c Significant improvement on week 36 of secukinumab administration
Pelechas et al., Rheumatol Ther (2017) 4:509–513
Conclusions
• spAs are diseases which increase morbidity and mortality
• sPAs decrease drastically the quality of life
• Early detection and referral the patients to the specialist is important in decreasing disease progression
• Criteria for early identification of sPA cases are available
• Criteria for measuring disease activity are available and helpful in evaluating the efficacy of drugs used for treatment of spAs
• Anti-TNF agents, moAbs to P40 subunit of IL-12 and IL-23
and moAbs to IL-17 are important therapeutic agents in our era.