# Presentation: 742797

## Juvenile Rheumatoid Arthritis Clinical Overview

- Daniel J. Lovell MD, MPH
- Levinson Professor of Pediatrics
- Division of Rheumatology
- Cincinnati Children’s Hospital Medical Center
- Cincinnati, Ohio, USA

## 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 |
| Female:male ratio | 5:1 | 3:1 | 1:1 |
| 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**

## Pain is Commonly Reported  in JRA

**Lovell and Walco. Pediatr Clin North Am 1989; 36:1015-27**

**Self report of pain from 462 children with JRA**** Cincinnati Juvenile Arthritis Database**

## Functional Impact of Pain in Children with JRA

**Parent’s assessment of activities affected by child’s pain**
**22% pauciarticular course**
**48% polyarticular course**
**26% systemic onset**

**Varni/Thompson ****Pediatric Pain Questionnaire**

**Varni et al. Pain 1987; 28:27-38.**

## Articular Erosions in JRA Patients

**Cassidy et al. Arthritis Rheum 1986; 29:274-81.**

**Articular erosions by disease onset subtype from ****132 children with 5 years follow-up **

## 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
- <5 years in 4 studies
- >10 years in 14 studies
- Study sizes varied: 44 – 1082 patients
- 10 studies >200 patients
- Total n = 5342 patients

**Adib N et al. Rheumatology 2005;44:995-1001 **

## Remission Rates and Function in Studies Using ACR JRA Classification Criteria

**Percent of patients in remission**

**Function**

**Adib N et al. Rheumatology 2005;44:995-1001 **

## 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 **

## 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 |

## 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  |

## 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 > 30%.

| Core Set Measures |
| --- |
| Physician’s 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 1997;40(7):1202-1209**

## Meloxicam vs Naproxen in JRA

|  | Meloxicam
0.125 mg/kg/day
N=73 | 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% |
| Parent’s assessment of pain | -50% | -44% | -46% |

**Percent change from Baseline in ACR Pediatric 30 ****Core Measures at 12 Weeks**

**Ruperto N et al. Arthritis Rheum 2005;52 (2): 563-572**

## Meloxicam vs Naproxen in JRA

**ACR Pediatric 30 Response Rate over 12 Months**

**% Responders**

**Ruperto N et al. Arthritis Rheum 2005;52 (2): 563-572**

## 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 2006;33: 985-995**

**Ruperto N et al. Arthritis Rheum 2005;52 (2): 563-572**

**Gedalia A et al.  Arthritis Rheum 2004;50(suppl)S95**

**Foeldvari et al. 2006. Arthritis Rheum 2006;54(suppl)**

## NSAID-induced GI Pain and Injury

**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**

**Dowd et al. Arthritis Rheum 1995; 38:1225-31.**

**Percent of Patients Reporting Abdominal Pain**

**No**
** ****NSAIDs**
**N = 226**

**NSAIDs**
**N = 344**

**Retrospective review of records from 570 patients seen in a pediatric rheumatology clinic over 3-year period**

## Intolerability of NSAIDs in Children with JRA

**Barron KS et al. Journal of Rheumatology 1982; 9:149-55.**

**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**

**101 Patients **
**> 1 NSAID**

**51% Repeat **
**toxicity with NSAID**

**38% Different**
** ****toxicity**

**62% Same **
**toxicity**

**Toxicity = Laboratory abnormality or signs/ symptoms requiring NSAID discontinuation**

**NSAIDs: Aspirin 34%; Tolmetin 21%; Naproxen 12%; Fenoprofen 11%; Ibuprofen 8%, Other 14%**

## 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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