Musculoskeletal Health in Europe Juvenile Idiopathic Arthritis

Juvenile idiopathic arthritis (JIA) Definition: Juvenile idiopathic arthritis = arthritis of unknown etiology that begins before the 16th birthday and persists for at least 6 weeks. Other known conditions are excluded.

Practitioner- or register-based study Incidence per 100,000 Savolainen, Finland, Pruunsild, Estonia, Berntson, Norway, Finland, Sweden, Denmark, Iceland, Riise, Norway, Hanova, Czech Republic, Modesto, Spain, Danner, France, JIA - Incidence

JIA – Age at Disease Onset % 5% 10% 15% 20% 25% 30% 35% Systemic arthritis Psoriatic arthritis Enthesitis-related arthritis Rheumatoid factor negative polyarthritis Age at onset in years Oligoarthritis Rheumatoid factor positive polyarthritis

Practitioner- or register-based study Prevalence per 100,000 Pruunsild, Estonia, Hanova, Czech Republic, Modesto, Spain, Danner, France, Solau-Gervais, France, JIA - Prevalence

JIA - Categories Oligoarthritis Rheumatoid factor negative polyarthritis Enthesitis-related arthritis Psoriatic arthritis Systemic arthritis (Still´s disease) Rheumatoid factor positive polyarthritis 52% 16% 15% 5% 4% Patients with recent onset JIA

JIA-categoryHLA-alleles conferring susceptibility Protective alleles Systemic arthritisDRB1*04, DRB1*11, DQA1*05- Oligoarthritis A2, DRB1*01, DRB1*08, DRB1*11, DRB1*13, DPB1*02, DQA1*04, DQB1*04 DRB1*04, DRB1*07, DQA1*03 Seronegative PolyarthritisA2, DRB1*08, DQA1*04, DPB1*03- Seropositive PolyarthritisDRB1*04, DQA1*03, DQB1*03DQA1*02 Psoriatic arthritisDRB1*01, DQA1*0101 DRB1*04, DQA1*03 Enthesitis-related arthritisB27, DRB1*01, DQA1*0101, DQB1*05- JIA - HLA associations

Definition: Arthritis affecting one to 4 joints during the first 6 months of disease. Two subcategories are recognized: 1. Persistent oligoarthritis: affecting not more than 4 joints throughout the disease course 2. Extended oligoarthritis: affecting a total of more than 4 joints after the first 6 months of disease JIA - Oligoarthritis

 Joints:1 joint with arthritis 1 joint with limited range of motion  Function:CHAQ-score 0.63 (median)  Eyes:4% uveitis  Lab:ESR 17 mm/h, CrP 7 mg/l (mean) 60-70% ANA, 0% RF Phenotype at onset: JIA - Oligoarthritis

Course and outcome: After 5 yearsPersistent OAExtended OA Percentage of patients2/31/3 (up to 50%) After 15 years Patients in remission, % Functional limitations (HAQ>0), % 2247 Frequency of erosions, % 533

JIA - Rheumatoid factor negative polyarthritis Definition: Polyarthritis (Rheumatoid Factor [RF] Negative) Arthritis affecting 5 or more joints during the first 6 months of disease A test for RF is negative ICD10-Code: M08.3

JIA - RF negative polyarthritis Phenotype at onset:  Joints:9 active joints and 6 with LOM  Function:CHAQ 1.25 (median)  Eyes:3% uveitis  Lab:ESR 22 mm/h, CrP 14 mg/l (median) 40-70% ANA, 0% RF

JIA - RF negative polyarthritis

Course and outcome: Follow-up > 10 years Patients in remission, %15-30 Patients with functional limitations (HAQ>0), % 47 Prevalence of erosions, % 40-75

JIA - Enthesitis related arthritis Definition: Arthritis and enthesitis, or arthritis or enthesitis with at least 2 of the following: 1. The presence of or a history of sacroiliac joint tenderness and/or inflammatory lumbosacral pain 2. The presence of HLA-B27 antigen 3. Onset of arthritis in a male over 6 years of age 4. Acute (symptomatic) anterior uveitis 5. History of ankylosing spondylitis, enthesitis related arthritis, sacroiliitis with inflammatory bowel disease, Reiter’s syndrome, or acute anterior uveitis in a first- degree relative

JIA - Enthesitis related arthritis Phenotype at onset:  Joints:2 active joints and 2 with LOM  Function:CHAQ 0.56 (median)  Eyes:9% uveitis  Lab:ESR 10 mm/h, CrP 3 mg/l (median) 20% ANA, 0% RF

JIA - Enthesitis related arthritis Course and outcome: Follow-up > 10 years Patients in remission, %17-44 Patients with functional limitations (HAQ>0), % 47 Prevalence of sacroiliits, % 35

JIA - Psoriatic arthritis Definition: Arthritis and psoriasis, or arthritis and at least 2 of the following: 1. Dactylitis 2. Nail pitting or onycholysis 3. Psoriasis in a first-degree relative ICD10-Code: M09.0*, L40.5 †

JIA - Psoriatic arthritis Phenotype at onset:  Joints:3 active joints and 2 with LOM  Function:CHAQ 0.56 (median)  Eyes:3% uveitis  Lab:ESR 26 mm/h, CrP 7 mg/l 45% ANA, 0% RF

JIA - Psoriatic arthritis Course and outcome: 68% oligoarticular onset  65% polyarticular course Outcome after > 15 years Patients in remission off medication (> 1 year), %55 Patients with functional limitations (HAQ>0), % 45 Prevalence of erosions, % 23

JIA - Systemic arthritis Definition: Arthritis in one or more joints with or preceded by fever of at least 2 weeks’ duration that is documented to be daily (“quotidian”) for at least 3 days, and accompanied by one or more of the following: 1. Evanescent (non-fixed) erythematosus rash 2. Generalized lymph node enlargement 3. Hepatomegaly and/or splenomegaly 4. Serositis

JIA - Systemic arthritis Phenotype at onset:  Joints:2 active joints and 0 with LOM  Function:CHAQ 1.0 (median)  Eyes:0% uveitis  Lab:ESR 93 mm/h, CrP 98 mg/l (median) 15% ANA, 0% RF

JIA - Systemic arthritis Complications: Macrophage activation syndrome % Growth failure20-41% Osteopenia/osteoporosis 0-7.5% Amyloidosis 1.4-9%

JIA - Systemic arthritis Course: 42% monocyclic  remission within 2-4 years 7% relapsing  flares of systemic features and mild arthritis 51% persistent  chronic progressive polyarthritis

JIA - Systemic arthritis Follow-up > 10 years Patients in remission, %20-76 Patients with functional limitations (HAQ>0), % 47 Prevalence of erosions, % Course and outcome:

JIA - Rheumatoid factor (RF) positive polyarthritis Definition: Polyarthritis (RF positive) Arthritis affecting 5 or more joints during the first 6 months of disease 2 or more tests for RF at least 3 months apart during the first 6 months of disease are positive ICD10-Code: M08.0

JIA - RF positive polyarthritis Phenotype at onset:  Joints:9 active joints and 7 with LOM  Function:CHAQ 1.0 (median)  Eyes:0% uveitis  Lab:ESR 15 mm/h, CrP 12 mg/l (median) 55% ANA, 100% RF

JIA - RF positive polyarthritis Course and outcome: Follow-up > 10 years Patients in remission, %0-46 Patients with functional limitations (HAQ>0), % 46 Prevalence of erosions, % 39-77

JIA - Estimated annual health care cost per patient (in Euro) Study Patients (n) Biologic drugs Health care cost (in €)Cost components Minden et al. Germany, 1999 JIA (215) 0%1,800 (mean) Medication: 15% Inpatient care: 55% Haapasaari et al. Finland, 2000 JIA (31) 100% 27,700 (median) converted from 2000 US$ Medication: 56% Inpatient care: n.r. Minden et al, Germany, 2003 JIA (369) 6%4,200 (mean) Medication: 47% Inpatient care: 39% Thornton et al. U.K., 2005 JIA (297) n.r.2,400 (mean) Medication: 11% Inpatient care: 0%

JIA - Estimated annual total cost per patient (in Euro) 02,0004,0006,0008,000 cost (€) Functional limitation (CHAQ) Disease activity (NRS) Pain intensity (NRS) moderate/severe mild none p = p < p = 0.020

JIA - mortality in children entire JIA group (90/2,076) 4% systemic JIA (84/611) 14% 1990 entire JIA group (33/11,287) 0.29% systemic JIA 3% 2010entire JIA group (19/9,604) 0.2%

JIA - mortality SMR 5.1 women (95% CI ) 3.4 men (95% CI )  4-fold increase in mortality in JIA compared to the general population in adults

JIA - malignancy Malignancy n Standardized rate (per 100,000 p-ys) SIR (95% CI) Simard et al., 2010, Sweden JIA: 13 cases/5,296 Controls: 30/26,480n.r.* 2.3 ( ) Beukelman et al. 2010, U.S. JIA: < 11 cases/7, ADHS: 63/308,45423 Asthma: 183/23,66327 Bernatsky et al., 2011, Canada JIA: 1 case/1,843 General population (0-0.7)

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