Consequences of living with JIA Troels Herlin

Pediatric Rheumatology Clinic Aarhus University Hospital, Denmark

JIA – Nordic population based study

Incidence: 15:100.000, children < 16 years In Denmark: 120 new patients per year >1000 children with JIA

Incidence of JIA in the Nordic Countries. A Population Based Study with Special Reference to the Validity of the ILAR and EULAR Criteria. Berntson, Anderson, Fasth, Herlin et al. J Rheumatol 2003.

0

5

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40

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

piger n=197 drenge n=118

JIA - categories

Oligo 1-4 joints

Poly >4 joints

RF-neg RF-pos

Systemic

Psoriasis

Enthesitis related

Extended

Undifferentiated

Persistent

11/11/2012

1

Current Practices in Systemic JIA

Management Based on the CARRA

Registry

Yukiko Kimura, MD

Chief, Pediatric Rheumatology

Joseph M. Sanzari Children’s  Hospital

Hackensack, NJ

Disclosures

• Novartis

• Genentech

Evidence Based Medicine

• JE Weiss, EM Dewitt, T Beukelman, LE Schanberg, R Schneider, Y Kimura for the CARRA Investigators Choice of Systemic JIA Treatment among Childhood Arthritis and Rheumatology Research Alliance (CARRA) Rheumatologists. Arthritis Rheum 2012; 74(10S): S492

• EM Dewitt, Y Kimura, T Beukelman, PA Nigrovic, K Onel, et al, Consensus treatment plans for new-onset systemic juvenile idiopathic arthritis. Arthritis Care Res, Arthritis Care Res 2012; 74(7):1001-10

Systemic Juvenile Idiopathic Arthritis:

Clinical Features • Arthritis affecting any number of joints beginning prior to age 16

• Systemic features:

▫ Quotidian fever

▫ Pink evanescent rash

▫ Serositis

▫ Hepatosplenomegaly

▫ Generalized lymphadenopathy

• Morbidity and mortality increased compared to other JIA categories

▫ Macrophage activation syndrome

• Similarities with AOSD

Systemic JIA through the decades

Pre-1940 1950’s-1980’s 1990’s-2000’s

The Biologic Era:

TNF inhibition not as effective in sJIA • Prospective study of etanercept in JIA ▫ Quartier P (Arthritis Rheum 2003) ▫ 61 JIA pts (sJIA=22) treated with etanercept

prospectively

• Retrospective survey study of 82 sJIA patients treated with etanercept ▫ Kimura Y (J Rheum 2005) ▫ Followed for mean of 2 years

• Analysis of etanercept JIA registry data ▫ Southwood TR (Rheumatology 2011) ▫ N=483, 77 had sJIA

JIA – a benign

disease?

Disease activity at follow-up

Follow-up time (years)

0 5 10 15 20 25 30 35

% w

ith a

ctiv

e d

ise

ase

20

30

40

50

60

70

Andersson 1995

Hanson 1977

Flatø 2003

Zak 2000

Packham 2000

Foster 2003

Calabro 1977

Pedersen 1987

Fantini 2003

Levinson 1992

Aim of treatment: To prevent joint destruction

Aim of treatment: To prevent complications

uveitis

TMJ involvement

Time-line of the medical JIA treatment

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70

80

90

Remission off medRemission on medsNot in remission

Prevalence of remission in JIA subtypes > 7 yrs after onset

Pain in a child with JIA?

Pain in JIA

• 56 children with JIA, > 7 yrs

• 3 week pain diary

• ”Faces pain scale” (1-6)

• Mean 1,86 (range 1-5,33)

• 21% had pain all day

• 8% had no pain

Thastum, Herlin, Zachariae. Relationship of pain-coping strategies and pain-specific

beliefs to pain experience in children with JIA. Arthritis Rheum 53: 178-184, 2005.

1 6

Predictors of pain: Disease activity CHAQ Pain coping questionnaire (PCQ) Health beliefs: Survey of pain attitudes (SOPA)

Pain in JIA conclusion of PCQ and SOPA questionnaires

• Psychologic factors have a significant influence on pain experience in children with JIA

• Psychological factors could predict pain experience

(diary) better than – Disease activity – Degree of functional impairment – Disease duration

• Increased pain experience in relation to disease

activity was seen when

– The children perceived themselves as handicapped – If they believe that the pain could do harm to the body – If the children used catastrophizing – If they did not experience control over the pain

Thastum et al. A&R 53:178, 2005

JIA – 2 year follow-up on pain study

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0,5

1

1,5

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2,5

3

Disease activity Pain diary CHAQ

Time 1

Time 2

*

* P < .0005

Pain Intensity Variability in JIA Tupper et al ArthrCareRes 2013

• Within-day patterns of pain intensity differs by JIA subtype and gender

• 65% of youths with JIA have changes in pain intensity >10 units on a 0-100 VAS from one point to another when measuring x 3 daily.

• Magnitude of pain variability has a negative relationship with QoL

112 patients with JIA 8-18 years. Electronic diary x 3 daily for 1 week

Predicted propability of severe pain (>71 on VAS 0-100) by time of day

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0,02

0,04

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0,08

0,1

0,12

0,14

0,16

0,18

0,2

Female Male

Morning

Afternoon

Evening

Tupper et al Arthr Care Res, 2013

Predicted propability of severe pain by time of day for diagnostic categories

0

0,05

0,1

0,15

0,2

0,25

0,3

systemic oligo poly psoriatic+ERA

Morning

Afternoon

Evening

Tupper et al ArthrCareRes 2013

Severe pain: > 71, VAS 0-100

Complications to JIA

• Uveitis

• Growth disturbances

– Especially the temporomandibular joint

• Macrophage activation syndrome

JIA – temporomandibular joint involvement

Micrognathia, retrognathia

”Bird-face” appearance

Prevalence of TMJ arthritis in JIA patients

• Conventional radiographics: 62%

Pedersen et al. 2001

• Contrast-enhanced MRIs: 75-87%

Küseler et al. 1998,2005

Weiss et al. 2008

Cannizaro et al. 2011

JIA – leg length

discrepancy

Other growth distrurbances

Impairment of total

growth in systemic JIA

(Monozygotic twins)

JIA - complications

Uveitis Chronic anterior uveitis

Initially no or only few symptoms Highest risk in oligoarticular type (20-25%) prophylactic split lamp examinations needed.

Uveitis in JIA Saurenman et al, A&R 2007

Time from arthritis diagnosis until diagnosis of uveitis age

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25

30

o-pers

o-ext

poly-R

Fneg

poly-R

Fpos

system

ent. rel.

psor

andre

% af total uveit i % af subtype

Saurenmann et al, A&R 2007

Uveitis – complications Saurenmann et al, A&R 2007

• 53/142 (37,3%) had complications – 33 (23,2%) cataract – 31 (21,8%) synecchies – 22 (15%) glaucoma – 20 (14%) band keratopathy – 7 (4,9%) macular oedema

• Vision – 10/108 Blindness (10 eyes) – 4/108 diminished vision (6 eyes) – 94/108 (87%) normalt vision

Aim of treatment

To relieve pain

To restore normal joint function and movement

To prevent complications

Triamcinolone acetonide (TA) vs. trimacinolon hexacetonide (TH) intraarticular treatment in JIA

Zulian et al, Rheumatol 2004; 43: 1288-91

• 1 mg/kg TH vs. 2 mg/kg TA givet dobbelt-blind i symmetrisk inflammerede led

• 37 patienter (30 piger 7 drenge)

• Follow-up 24 måneder – Først relaps

• 21 (53,8%) injiceret med TA

• 6 (15,4% injiceret med TH

– 3 (7,7%) fik samtidig relaps

– 9 (23%) i remission 0

10

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60

70

80

12 mdr 24 mdr

TH

TA

Enbrel = etanercept Remicade = infliximab Humira = adalimumab Simponi=golimumab Cimzia=certolizumab

TNF-hæmmere

Enbrel – JIA, part 1, open phase Lovell et al, NEJM 2000.

ACR30: 74%

ACR50: 64%

ACR70: 36%

Double Blind Phase: ACR Response Rates by MTX Use at Week 481

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63

32

57

38

63

32

53

27

63

29

47

27

42

18

30

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Placebo Adalimumab Placebo Adalimumab

ACR Pedi 30 ACR Pedi 50 ACR Pedi 70 ACR Pedi 90

33 Company Confidential © 2011 Abbott

% o

f P

atie

nts

n=37 n=38 n=28 n=30

Adalimumab

*P<0.05, †P<0.01 vs placebo. Patients who flared were considered non-responders.

* * † Adalimumab + MTX

1 Lovell DJ et al., N Engl J Med 2008;359:810-20.

Enbrel – extension study Lovell et al, A&R 2003

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måneder

Treatment of Systemic JIA?

Tocilizumab vs.canakinumab

Consequences of medical therapy

Side effects

• NSAIDs: abdominal pain

• MTX: nausea

• Biologics: • infections (e.g.TB)

• Malignancy?

2013?

1953

World trampoline champion Madeleine Johnson (14 yr old) has JIA