2011 Juvenile Arthritis 2011 Juvenile Arthritis ConferenceConference

Bob Colbert MD, PhDSenior Investigator

Chief, Pediatric Translational Research Branch

NIAMS/NIH

Juvenile Spondyloarthritis and

Psoriatic Arthritis

Disclosures:

• No financial relationships to disclose

Objectives:• Provide overview of symptoms,

diagnosis, current treatment options and disease-management for Juvenile Spondyloarthritis and Psoriatic Arthritis

What is Spondyloarthritis?What is Psoriatic

Arthritis?• Spondyloarthritis (SpA)

• Usually involves the back or spine, but does not always cause back pain

• Tender and painful ‘entheses’

• Patients may have eye and bowel inflammation

• Major long-term problem is excessive bone formation and fusion of the spine

• Psoriatic Arthritis (PsA)

• Psoriasis – rash due to inflammation of the skin

• Sausage digits (dactylitis), nail pitting, arthritis

What is Spondyloarthritis?

Sacroiliac Joints

Dactylitis

Psoriatic Skin Rash

Psoriatic Nail Changes

Eye Inflammation(Acute Anterior Uveitis)

• Pain• Redness• One eye or both

eyes• Photophobia• Blurred vision

How are JSpA and JPsA diagnosed ?

• Medical history

• Physical examination

• Laboratory tests of blood

Autoantibodies - Anti-nuclear antibody (ANA); Rheumatoid factor (RF)

Markers of inflammation – erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)

Genetic marker - HLA-B27

• There are several forms of JIA distinguished by number of joints involved, presence of fever, rash, lab tests

JIA Subtypes

Few Joints(less than 5) =Oligoarticular

Many Joints(5 or more) = Polyarticular

Fever/rash= Systemic

SpA (spine)= ERA

WithPsoriasis

= PsA

?

Juvenile Spondyloarthritis(Enthesitis-Related Arthritis)

• Arthritis and Enthesitis OR Arthritis or Enthesitis

• With two or more of following:

• Sacroiliac tenderness or inflammatory lumbosacral pain

• HLA-B27

• Family history of HLA-B27-associated disease

• Acute anterior uveitis

• Male, age >7 years

• Exclusions: psoriasis in patient or family, RF, systemic JIA

Juvenile Psoriatic Arthritis

• Arthritis and Psoriasis OR….

• Arthritis two features:

• Dactylitis

• Nail changes (pitting or onycholysis)

• Psoriasis in first degree relative

• Exclusions: RF, systemic JIA, classification as another form of JIA

Two Subgroups of JPsA

Younger age at onset

• Peak 2-3 years

• More girls, ANA+

• More like early onset oligo/poly JIA

• More small joint and wrist arthritis

Older age at onset

• Peak 10-12 years

• Girls = boys

• More enthesitis and axial involvement

• More like SpA

How common is juvenile arthritis ?

• Occurs in 1 child in every 1,000 each year

• Close to 294,000 children in the US have arthritis or another rheumatic disease

• One of the most common chronic inflammatory diseases of childhood

Lawrence RA, et al., Arth Rheum 1998; 41:778-799Sacks J et al., Arth Rheum 2007; 57:1439-1455

How do we treat JIA ?

Management of JIA

Goals

• Control/eliminate disease activity – pain and inflammation

• Preserve joint function

• Prevent long-term consequences of disease and therapy

Treatment Pyramid

NSAIDS,

PT/OT

NSAIDS,

PT/OT

GLU

CO

CO

RTIC

OID

S

Methotrexate, Corticosteroid

injections

Methotrexate, Corticosteroid

injections

Biologics(anti-TNF,

anti-IL-1, anti-IL-6)

Biologics(anti-TNF,

anti-IL-1, anti-IL-6)

EXPEXP

NSAIDs• Used frequently but no longer mainstay of therapy

• Naproxen, ibuprofen, tolectin, indomethacin, celebrex, oxaprozin approved for use in children

• Generally well tolerated in children, but not effective enough for majority of patients

Methotrexate• Important ‘anchor’ drug known to improve symptoms and

modify underlying course of disease; well tolerated

• Most effective when given as a shot - subcutaneously

Oral steroids• Low doses may help control disease – should not be used long-

term

Joint Injections• Long-lasting benefit in significant proportion (triamcinolone

hexacetamide)

• Multiple joints often done to quickly squelch disease; often done asleep

Management of JIA

Biologics Frequently Used in Juvenile Biologics Frequently Used in Juvenile ArthritisArthritis

Anti-TNF

• Etanercept* (Enbrel)

• Infliximab (Remicade)- also effective for JIA uveitis

• Adalimumab* (Humira) – also effective for JIA uveitis

Anti-IL-1

• Anakinra (Kineret; IL-1RA) (approved for CAPS)

• Rilonacept (Arcalyst, IL-1 TRAP) (approved for CAPS)

• Canakinumab (Ilaris; anti-IL-1) (approved for CAPS)

*FDA approved for poly, extended oligo and systemic JIA with poly course disease.

Biologics Frequently Used in Juvenile Biologics Frequently Used in Juvenile ArthritisArthritis

Anti-IL-6 (blocks soluble IL-6 receptor)

• Tocilizumab (Actemra, RoActemra) (recently approved for sJIA)

CTLA4 Ig (blocks T cell activation)

• Abatacept (Orencia) (approved for poly JIA)

Anti-CD20 (depletes B cells)

• Rituximab (Rituxan) (case reports effective in poly and systemic JIA)

Anti-Others

• Anti-IL-17, anti-IL-23/12, anti-IL-22

Why is it important to do Why is it important to do research in children ?research in children ?

To practice evidence-based To practice evidence-based medicinemedicine

If we don’t do research, every If we don’t do research, every treatment becomes a poorly treatment becomes a poorly controlled experimentcontrolled experiment

Observational Studies

•Retrospective chart review

–Often missing data; potential for bias

–Not rigorous; ?quality of data

•Prospective – “registry” – collect specific information on large numbers of patients

–Can be used to collect information on patients treated a specific way, but not randomized

Translational Studies

•Patient gives one or more samples

–Blood, urine, tissue

–Analysis for biomarkers: RNA, DNA, inflammatory proteins

•Information about the patient is collected at the same time

–Disease characteristics/Medications

•Long-term goal of personalized medicine

Spondyloarthritis

Thank you for your attention!

National Institute of Arthritis and

Musculoskeletal and Skin Diseases