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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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Conflict of interest

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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

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

http://www.healthline.com/health/ankylosing-spondylitis/effects-on-body

http://www.healthline.com/health/psoriatic-arthritis/effects-on-body

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



Clinical features




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



Clinical features




• 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



Clinical features




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



Clinical features




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.

strengthening our knowledge in spondylarthritides ... · strengthening our knowledge in...

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