Juvenile Rheumatoid Arthritis Clinical Overview

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Juvenile Rheumatoid Arthritis Clinical Overview

• Daniel J. Lovell MD, MPH
• Levinson Professor of Pediatrics
• Division of Rheumatology
• Cincinnati Childrens Hospital Medical Center
• Cincinnati, Ohio, USA

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American College of Rheumatology Characteristics
of JRA
Pauciarticular Course Polyarticular Course Systemic Disease
Frequency of cases 60 30 10
Number of joints involved ?4 ?5 Variable
Age at onset Early childhood peak at 1-3 yrs Throughout childhood peak at 6-7 yrs and 8-11 yrs Throughout childhood no peak
Femalemale ratio 51 31 11
Systemic involvement Not present Moderate involvement Prominent
Treatment paradigm Primarily NSAIDs or intra-articular corticosteroids DMARDs or biologics with adjunctive NSAIDs DMARDs or biologics NSAIDs for fever and pain corticosteroids for systemic features
Cassidy and Petty. Textbook of Pediatric
Rheumatology, 2005
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Pain is Commonly Reported in JRA
Self report of pain from 462 children with JRA
Cincinnati Juvenile Arthritis Database
Lovell and Walco. Pediatr Clin North Am 1989
361015-27
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Functional Impact of Pain in Children with JRA
Varni/Thompson Pediatric Pain Questionnaire

• Parents assessment of activities affected by
  childs pain
• 22 pauciarticular course
• 48 polyarticular course
• 26 systemic onset

Varni et al. Pain 1987 2827-38.
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Articular Erosions in JRA Patients
Articular erosions by disease onset subtype from
132 children with 5 years follow-up
Cassidy et al. Arthritis Rheum 1986 29274-81.
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Outcome Following Onset of JRA

• Systematic review of published outcome data in
  JIA, JCA, JRA
• 21 studies published over 10-year period
• 19 retrospective studies 2 prospective
• Follow up varied
• lt5 years in 4 studies
• gt10 years in 14 studies
• Study sizes varied 44 1082 patients
• 10 studies gt200 patients
• Total n 5342 patients

Adib N et al. Rheumatology 200544995-1001
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Remission Rates and Function in Studies Using ACR
JRA Classification Criteria
Function
Percent of patients in remission
Adib N et al. Rheumatology 200544995-1001
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CV Thrombotic Adverse Events CARRA Survey

• Childhood Arthritis and Rheumatology Research
  Alliance (CARRA)
• 98 pediatric rheumatologists in North America
• Survey (sponsored by CARRA)
• Conducted post Vioxx withdrawal
• Distributed to 130 pediatric rheumatologists
• Request for information regarding frequency of
  vascular complications in JRA patients
• In association with NSAIDs and COX-2 inhibitors
• Request for number of years of practice
• Results
• 73 responded (95/130)
• 1546 years of practice in pediatric rheumatology
• 0 vascular events in JRA population
• 1 pulmonary embolism event reported for possible
  psoriatic arthritis patient

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NSAID Trials in JRA Predating 1998 Approval of
Celecoxib for Adults
Treatments Number of Patients Study Design Source
Tolmetin Aspirin 107 12-week double-blind, parallel group Levinson et al. 1977
Naproxen Aspirin 18 12-week, randomized, double-blind, crossover Makela 1977
Naproxen Aspirin 23 8-week randomized, double-blind, crossover (two 4-week periods) 12-month open-label Moran et al. 1979
Naproxen Aspirin 80 24-week randomized, parallel group, double-blind Kvien et al. 1984
Ibuprofen Aspirin 92 12-week, randomized, double-blind, parallel-group Giannini et al. 1990
Ibuprofen 86 24-week, open-label, multidose Giannini et al. 1990
Oxaprozin 59 12-week open-label with 9 month extension Bass et al. 1985
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NSAID Trials in JRA Subsequent to 1998 Approval
of Celecoxib for Adults
Treatments Number of Patients Study Design Source
Rofecoxib Naproxen 310 12-week, randomized, double-blind 52-week open-label active comparator-controlled extension Reiff et al. 2006
Meloxicam Naproxen 225 12-week randomized, double-blind, with a 40-week double-blind extension Ruperto et al. 2005
Meloxicam Naproxen 207 12-week randomized, double-blind, active-controlled 12-week open-label extension Gedalia et al. 2004
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American College of Rheumatology (ACR) Pediatric
30 Response

• ACR Pediatric 30 Response Criterion 30
  improvement in any 3 of 6 core set measures with
  no more than 1 of the remaining measures
  worsening by gt 30.

Core Set Measures
Physicians Global Assessment of Disease Activity
Patient/Parent Global Assessment of Overall Well Being
Assessment of Physical Function
Number of joints with active arthritis
Number of joints with limited range of motion
Laboratory measure of inflammation
Giannini E et al. Arthritis Rheum
199740(7)1202-1209
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Meloxicam vs Naproxen in JRA
Percent change from Baseline in ACR Pediatric 30
Core Measures at 12 Weeks
Meloxicam 0.125 mg/kg/day N73 Meloxicam 0.25 mg/kg/day N 74 Naproxen 10 mg/kg/day N 78
Patient/ parent overall assessment of well being -43 -39 -41
MD global assessment of disease activity -48 -46 -44
CHAQ index -33 -37 -37
No. of joints with active arthritis -52 -46 -43
No. of joints with limited range of motion -44 -29 -37
ESR 2 -20 -5
Parents assessment of pain -50 -44 -46
Ruperto N et al. Arthritis Rheum 200552 (2)
563-572
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Meloxicam vs Naproxen in JRA
ACR Pediatric 30 Response Rate over 12 Months
Responders
Ruperto N et al. Arthritis Rheum 200552 (2)
563-572
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Comparison of ACR Pediatric 30 Response Rates
with Naproxen
Study Number of Patients Dose mg/kg/day ACR Pediatric 30 Response Week 12
Reiff 2006 101 15 55
Ruperto 2005 78 10 64
Gedalia 2004 75 10-15 68
Foeldvari 2006 83 15 67
Reiff A et al. J Rheum 200633 985-995
Ruperto N et al. Arthritis Rheum 200552 (2)
563-572
Gedalia A et al. Arthritis Rheum
200450(suppl)S95
Foeldvari et al. 2006. Arthritis Rheum
200654(suppl)
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NSAID-induced GI Pain and Injury
Retrospective review of records from 570 patients
seen in a pediatric rheumatology clinic over
3-year period
Percent of Patients Reporting Abdominal Pain

• Among patients with abdominal pain who underwent
  GI evaluation, gastroduodenal injury was reported
  in
• 34 of patients taking NSAIDs
• 7.1 of patients not taking NSAIDs
• No complicated events

No NSAIDs N 226
NSAIDs N 344
Dowd et al. Arthritis Rheum 1995 381225-31.
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Intolerability of NSAIDs in Children with JRA
101 Patients gt 1 NSAID
Mean age onset 6.7 years 21 Systemic Onset 23
Polyarticular Course 57 Pauciarticular Course
22 No toxicity
78 Discontinued NSAID due to toxicity
49 No Toxicity
51 Repeat toxicity with NSAID
38 Different toxicity
62 Same toxicity
NSAIDs Aspirin 34 Tolmetin 21 Naproxen 12
Fenoprofen 11 Ibuprofen 8, Other 14
Toxicity Laboratory abnormality or signs/
symptoms requiring NSAID discontinuation
Barron KS et al. Journal of Rheumatology 1982
9149-55.
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Conclusion JRA and Current Treatments

• JRA comprises a group of heterogeneous yet
  related disorders in children
• Chronic inflammatory arthritis with significant
  impact on function and health-related quality of
  life
• Treatment effects include disease modification
  and symptom control
• NSAIDs are used by most patients at some point in
  their disease
• NSAIDs are generally well tolerated
• GI adverse symptoms commonly reported
• Serious GI complications uncommon

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