Rheumatoid Arthritis: Wallace CA

Wallace CA. · No affiliation provided · J Rheumatol. · Pubmed #10955320 No free full text.

This publication has no abstract.

Ringold S, Wallace CA. · Department of Rheumatology, Children's Hospital and Regional Medical Center/University of Washington, Seattle, Washington, USA. · Curr Opin Rheumatol. · Pubmed #17762613 No free full text.

Abstract: PURPOSE OF REVIEW: The increasing availability of new medications for the treatment of juvenile idiopathic arthritis has made the accurate assessment of treatment outcomes critically important. The purpose of this review is to describe recent investigations focused on the development of new outcome measures in the domains of disease activity and joint damage, and to summarize recently published data within the area of health-related quality of life. RECENT FINDINGS: Since the development of the preliminary definition of disease improvement in 1997, the American College of Rheumatology pediatric response criteria have become the primary outcome measures in therapeutic trials in juvenile idiopathic arthritis. Additional definitions, including preliminary definitions of flare and remission have subsequently been added. Investigations have also sought to determine whether measures currently in use in adult rheumatoid arthritis might have utility in juvenile idiopathic arthritis. As the pathogenesis of juvenile idiopathic arthritis becomes better understood, biomarkers have significant potential as outcome measures. Lastly, recent reports regarding the health-related quality of life in large cohorts of children with juvenile idiopathic arthritis are important in guiding investigators towards areas most in need of improved treatment. SUMMARY: Significant progress has been made in the measurement of outcomes in juvenile idiopathic arthritis. Outcome measures will continue to be designed and tested to keep pace with the development of new therapies and the improved understanding of the disease pathogenesis.

Wallace CA. · Division of Immunology, Rheumatology and Infectious Diseases, Children's Hospital and Regional Medical Center, University of Washington School of Medicine, 4800 Sandpoint Way NE MS-B-6583, Seattle, WA 98105, USA. · Best Pract Res Clin Rheumatol. · Pubmed #16546057 No free full text.

Abstract: The goal of juvenile idiopathic arthritis (JIA) treatment is to achieve remission of disease. The absence of a full understanding of the disease pathogenesis for JIA hinders the development of truly effective treatment approaches. Further, the lack of clear knowledge regarding the mechanisms of action of rheumatologic medications and the existence of few randomized controlled trials leaves clinicians with very little evidence upon which to base decisions regarding the best timing, dosages or combinations of medications to be used for fully effective treatment of JIA. There is now a shift in treatment focus from that of chasing failure (gradual add-on approach to the use of medications) to one of early aggressive combination treatment. This chapter will discuss the current approaches to medical management of JIA and the medications currently available for use. JIA treatment is a vast, rich area in need of research.

Sreedharan A, Bowyer S, Wallace CA, Robertson MJ, Schmidt K, Woolfrey AE, Nelson RP. · Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA. · Bone Marrow Transplant. · Pubmed #16501594 No free full text.

Abstract: Autologous hematopoietic cell transplantation (HCT) is being used to treat autoimmune diseases refractory to conventional therapy, including rheumatoid arthritis. Macrophage activation syndrome (MAS) is a descriptive term for a systemic inflammatory disorder that has been described in patients with juvenile rheumatoid arthritis (JRA). This case report describes a young adult with systemic JRA (sJRA) who developed MAS on day # 12 post-autologous transplantation. The patient developed high fever, laboratory evidence of disseminated intravascular coagulation (DIC), hepatocellular injury, pancytopenia and hyper-ferritinemia. All viral, bacterial and fungal studies were negative and the patient improved with high-dose glucocorticosteroid and cyclosporine therapy. Extreme elevation of serum ferritin was documented and helpful in monitoring response to therapy. A number of systemic inflammatory syndromes have been described in association with HCT. These include DIC, 'engraftment syndrome,' infection-associated hemophagocytic syndrome and familial hemophagocytic lymphohistiocytosis. Macrophage activation syndrome presents with features of DIC and is closely related or identical to infection-associated hemophagocytic syndrome. The diagnosis needs to be established in a timely fashion because early and appropriate treatment may improve outcome.

Wallace CA. · Department of Pediatrics, University of Washington and Children's Hospital and Regional Medical Center, Seattle 98105-0371, USA. · Clin Exp Rheumatol. · Pubmed #10464566 No free full text.

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Ruperto N, Lovell DJ, Quartier P, Paz E, Rubio-Pérez N, Silva CA, Abud-Mendoza C, Burgos-Vargas R, Gerloni V, Melo-Gomes JA, Saad-Magalhães C, Sztajnbok F, Goldenstein-Schainberg C, Scheinberg M, Penades IC, Fischbach M, Orozco J, Hashkes PJ, Hom C, Jung L, Lepore L, Oliveira S, Wallace CA, Sigal LH, Block AJ, Covucci A, Martini A, Giannini EH, Anonymous00184, Anonymous00185. · IRCCS G Gaslini, PRINTO, Genoa, Italy. · Lancet. · Pubmed #18632147 No free full text.

Abstract: BACKGROUND: Some children with juvenile idiopathic arthritis either do not respond, or are intolerant to, treatment with disease-modifying antirheumatic drugs, including anti-tumour necrosis factor (TNF) drugs. We aimed to assess the safety and efficacy of abatacept, a selective T-cell costimulation modulator, in children with juvenile idiopathic arthritis who had failed previous treatments. METHODS: We did a double-blind, randomised controlled withdrawal trial between February, 2004, and June, 2006. We enrolled 190 patients aged 6-17 years, from 45 centres, who had a history of active juvenile idiopathic arthritis; at least five active joints; and an inadequate response to, or intolerance to, at least one disease-modifying antirheumatic drug. All 190 patients were given 10 mg/kg of abatacept intravenously in the open-label period of 4 months. Of the 170 patients who completed this lead-in course, 47 did not respond to the treatment according to predefined American College of Rheumatology (ACR) paediatric criteria and were excluded. Of the patients who did respond to abatacept, 60 were randomly assigned to receive 10 mg/kg of abatacept at 28-day intervals for 6 months, or until a flare of the arthritis, and 62 were randomly assigned to receive placebo at the same dose and timing. The primary endpoint was time to flare of arthritis. Flare was defined as worsening of 30% or more in at least three of six core variables, with at least 30% improvement in no more than one variable. We analysed all patients who were treated as per protocol. This trial is registered, number NCT00095173. FINDINGS: Flares of arthritis occurred in 33 of 62 (53%) patients who were given placebo and 12 of 60 (20%) abatacept patients during the double-blind treatment (p=0.0003). Median time to flare of arthritis was 6 months for patients given placebo (insufficient events to calculate IQR); insufficient events had occurred in the abatacept group for median time to flare to be assessed (p=0.0002). The risk of flare in patients who continued abatacept was less than a third of that for controls during that double-blind period (hazard ratio 0.31, 95% CI 0.16-0.95). During the double-blind period, the frequency of adverse events did not differ in the two treatment groups. Adverse events were recorded in 37 abatacept recipients (62%) and 34 (55%) placebo recipients (p=0.47); only two serious adverse events were reported, both in controls (p=0.50). INTERPRETATION: Selective modulation of T-cell costimulation with abatacept is a rational alternative treatment for children with juvenile idiopathic arthritis. FUNDING: Bristol-Myers Squibb.

Lovell DJ, Giannini EH, Reiff A, Jones OY, Schneider R, Olson JC, Stein LD, Gedalia A, Ilowite NT, Wallace CA, Lange M, Finck BK, Burge DJ, Anonymous00012. · Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA. · Arthritis Rheum. · Pubmed #12528122 links to  free full text

Abstract: OBJECTIVE: To evaluate the long-term efficacy and safety of etanercept in children with juvenile rheumatoid arthritis (JRA) participating in an ongoing multicenter, open-label, extended-treatment trial. All patients had been participants in an initial randomized efficacy and safety trial of etanercept. METHODS: Etanercept was administered at a dosage of 0.4 mg/kg (maximum 25 mg) subcutaneously twice each week. Safety and efficacy evaluations were performed every 3-4 months. The JRA 30% definition of improvement (DOI) was defined as improvement of > or =30% in at least 3 of 6 response variables used to assess disease activity, with no more than 1 variable worsening by more than 30%. RESULTS: At the time of analysis, 48 of the 58 patients (83%) were still enrolled in the study; 43 of them (74%) had completed 2 years of treatment. Of these 43 patients, 81% met the JRA 30% DOI, 79% met the JRA 50% DOI, and 67% met the JRA 70% DOI. Ten children started low-dose methotrexate after year 1. Of the 32 children taking prednisone, the dosage was decreased to <5 mg/day in 26 (81%). Two children had serious infections (varicella with aseptic meningitis in one and complicated sepsis in the other). In general, adverse events were of the types seen in a general pediatric patient population. CONCLUSION: Children with severe, longstanding, methotrexate-resistant polyarticular JRA demonstrated sustained clinical improvement with >2 years of continuous etanercept treatment. Etanercept was generally well-tolerated. There were no increases in the rates of adverse events over time. However, children taking etanercept should be monitored closely for infections.

Lovell DJ, Giannini EH, Reiff A, Cawkwell GD, Silverman ED, Nocton JJ, Stein LD, Gedalia A, Ilowite NT, Wallace CA, Whitmore J, Finck BK. · Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA. · N Engl J Med. · Pubmed #10717011 links to  free full text

Abstract: BACKGROUND: We evaluated the safety and efficacy of etanercept, a soluble tumor necrosis factor receptor (p75):Fc fusion protein, in children with polyarticular juvenile rheumatoid arthritis who did not tolerate or had an inadequate response to methotrexate. METHODS: Patients 4 to 17 years old received 0.4 mg of etanercept per kilogram of body weight subcutaneously twice weekly for up to three months in the initial, open-label part of a multicenter trial. Those who responded to treatment then entered a double-blind study and were randomly assigned to receive either placebo or etanercept for four months or until a flare of the disease occurred. A response was defined as an improvement of 30 percent or more in at least three of six indicators of disease activity, with no more than one indicator worsening by more than 30 percent. RESULTS: At the end of the open-label study, 51 of the 69 patients (74 percent) had had responses to etanercept treatment. In the double-blind study, 21 of the 26 patients who received placebo (81 percent) withdrew because of disease flare, as compared with 7 of the 25 patients who received etanercept (28 percent) (P=0.003). The median time to disease flare with placebo was 28 days, as compared with more than 116 days with etanercept (P<0.001). In the double-blind study, there were no significant differences between the two treatment groups in the frequency of adverse events. CONCLUSIONS: Treatment with etanercept leads to significant improvement in patients with active polyarticular juvenile rheumatoid arthritis. Etanercept is well tolerated by pediatric patients.

Jarvis JN, Jiang K, Frank MB, Knowlton N, Aggarwal A, Wallace CA, McKee R, Chaser B, Tung C, Smith LB, McGhee JL, Chen Y, Osban J, O'Neil KM, Centola M. · Pediatric Rheumatology Research, College of Medicine, Children's Hospital of Oklahoma, University of Oklahoma, Oklahoma City, OK 73013, USA. · Arthritis Rheum. · Pubmed #19404961 No free full text.

Abstract: OBJECTIVE: We have previously reported a defect in neutrophil activation in children with polyarticular juvenile idiopathic arthritis (JIA). The current study was undertaken to determine whether gene expression abnormalities persist in JIA in remission and to use systems biology analysis to elucidate pathologic pathways in polyarticular JIA. METHODS: We performed gene expression profiling on neutrophils from children with polyarticular JIA. Children were grouped according to disease status. We studied 14 children with active disease who were taking medication, 8 children with clinical remission of disease who were taking medication (CRM status), and 6 children with clinical remission of disease who were not taking medication (CR status). We also studied 13 healthy children whose age ranges overlapped those of the patients. RESULTS: Neutrophil abnormalities persisted in children with polyarticular JIA even after disease remission was achieved. Children with active disease and those with CRM status showed no differences in expression of specific genes, although they could be separated on cluster analysis. A comparison of children with CR status and healthy control children revealed networks of pro- and antiinflammatory genes that suggested that remission is a state of homeostasis and balance rather than a return to normal immune function. Furthermore, gene overexpression in patients with CR status supports the hypothesis that neutrophils play a role in regulating adaptive immunity in this disease. CONCLUSION: Neutrophil gene profiling in polyarticular JIA suggests important roles for neutrophils in disease pathogenesis. These findings suggest the presence of complex interactions between innate and adaptive immunity, that are not easily modeled in conventional, linear, reductionist systems.

Lovell DJ, Reiff A, Ilowite NT, Wallace CA, Chon Y, Lin SL, Baumgartner SW, Giannini EH, Anonymous00023. · Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. · Arthritis Rheum. · Pubmed #18438876 links to  free full text

Abstract: OBJECTIVE: To evaluate the safety and efficacy of up to 8 years of etanercept treatment in patients with polyarticular-course juvenile rheumatoid arthritis (JRA). METHODS: Patients with JRA who previously participated in a randomized controlled trial (RCT) of etanercept were eligible to receive etanercept in a long-term open-label extension (OLE) trial. Safety end points included the incidences of serious adverse events (SAEs), medically important infections (MIIs), and death. Efficacy end points included the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30), Pedi 50, Pedi 70, Pedi 90, and Pedi 100 criteria for improvement. RESULTS: Of the 69 patients originally enrolled in the RCT, 58 (84%) participated in the OLE, for a total of 318 patient-years of etanercept exposure. A total of 42 of the 58 patients (72%) entered the fourth year of continuous etanercept treatment, and 26 patients (45%) entered the eighth year. Sixteen patients (23% of those entering the RCT) reported 39 SAEs. The overall rate of SAEs (0.12 per patient-year) did not increase with long-term exposure to etanercept. The rate of MIIs (0.03 per patient-year) remained low; 1 new MII was reported in patients with > or =5 years of etanercept exposure. No cases of tuberculosis, opportunistic infections, malignancies, lymphomas, lupus, demyelinating disorders, or deaths were reported. An ACR Pedi 70 response or higher was achieved by 100% of patients with 8 years of data (11 of 11) and by 61% of patients according to the last observation carried forward data (28 of 46). CONCLUSION: These data suggest that the acceptable safety profile of etanercept therapy is maintained for up to 8 years in this population of JRA patients. Improvements in the signs and symptoms of JRA were also maintained for up to 8 years.

Ringold S, Torgerson TR, Egbert MA, Wallace CA. · Children's Hospital and Regional Medical Center, Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington 98105, USA. · J Rheumatol. · Pubmed #18398938 No free full text.

Abstract: OBJECTIVE: To describe the clinical and radiographic outcomes in a series of patients with juvenile idiopathic arthritis (JIA) who underwent one or more intraarticular corticosteroid (IAS) injections of the temporomandibular joint (TMJ) performed without imaging guidance. METHODS: Retrospective chart review was performed for all patients with JIA diagnosed and treated at our institution between January 1, 2000, and January 1, 2006, who underwent one or more IAS injections of their TMJ. IAS injections were performed by the same oral and maxillofacial surgeon without imaging guidance, using either triamcinolone acetonide or triamcinolone hexacetonide. The primary outcomes assessed were maximal incisal opening (MIO) measurements, patient-reported symptoms, physical examination findings, and imaging results. RESULTS: Twenty-five patients were identified. Twenty-one (84%) had radiographic evidence of TMJ disease when TMJ disease was first suspected by their physician. The 25 patients underwent 74 IAS injections on 47 separate occasions. When baseline MIO measurements were compared to the last MIO measurements of the study period, there was a mean increase in MIO of 6.9 mm (p = 0.002; 95% CI 3, 10.7). There was a mean increase in MIO of 3.8 mm following each IAS injection (p = 0.003; 95% CI 1.4, 6.2). Patients who underwent multiple IAS injections had a mean increase in MIO after first injection of 6.6 mm (p < 0.001; 95% CI 4.1, 9.1); however, the mean increase in MIO after subsequent injections was 0.4 mm (p = 0.8; 95% CI -3.5, 4.4). One patient developed subcutaneous atrophy at the injection site. Two patients developed small, asymptomatic intraarticular calcifications. No additional adverse events were reported. CONCLUSIONS: In this patient population, there was an overall increase in MIO measurements following initial IAS injection and during the study period. Patients tended to have minimal response to subsequent injections. IAS injections performed without imaging guidance by an experienced oral and maxillofacial surgeon were well tolerated with only rare adverse events. The presence of radiographic changes when the physician first suspected TMJ disease in 84% of patients emphasizes the need for better screening and early intervention for synovitis in this joint.

Ward TM, Brandt P, Archbold K, Lentz M, Ringold S, Wallace CA, Landis CA. · Biobehavioral Nursing and Health Systems, University of Washington, Seattle, WA, 98195-7266, USA. · J Pediatr Psychol. · Pubmed #18073234 No free full text.

Abstract: OBJECTIVE: To compare polysomnography (PSG) and self-reported sleep, symptoms (pain and fatigue), and anxiety between children with active and inactive juvenile rheumatoid arthritis (JRA) and examine relations among sleep, symptoms, and anxiety. METHODS: Two consecutive nights of PSG, self-reported sleep, and symptoms were obtained in 70 children 6-11 years of age with active (n = 35) or inactive (n = 35) JRA. RESULTS: On the second (study) night, PSG and self-reported sleep variables were not different, but pain and fatigue were significantly higher (both p <.02) in children with active compared to inactive disease. In a stepwise regression, age, medications, disease status, anxiety, evening pain, total sleep time, and arousals explained 36% of the variance in fatigue and age, disease status, and evening pain were significant (all p <.04) predictors of fatigue. All children showed longer sleep latency and reduced sleep efficiency on the first night in the laboratory. CONCLUSIONS: Sleep was not altered in children with active JRA, however, the "first night effect" suggests that valid laboratory sleep assessments require an adaptation night.

Lovell DJ, Reiff A, Jones OY, Schneider R, Nocton J, Stein LD, Gedalia A, Ilowite NT, Wallace CA, Whitmore JB, White B, Giannini EH, Anonymous00068. · Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. · Arthritis Rheum. · Pubmed #16732547 links to  free full text

Abstract: OBJECTIVE: Previous studies showed that etanercept treatment in patients with polyarticular-course juvenile rheumatoid arthritis (JRA) provided rapid clinical improvement that was sustained for up to 2 years. The goal of our study was to provide data on safety and efficacy after 4 years of etanercept treatment in patients with JRA. METHODS: Patients with active polyarticular-course JRA who participated in an efficacy study continued etanercept treatment in an open-label extension. Safety was assessed by measuring rates of serious adverse events (SAEs) and serious infections. Efficacy was assessed using the American College of Rheumatology (ACR) Pediatric 30 criteria for improvement and standard measures of disease activity. (The ACR Pediatric 30 criteria are defined as improvement of > or = 30% in at least 3 of 6 core response variables used to assess disease activity, with no more than 1 variable worsening by > or = 30%.) RESULTS: Of the 69 patients who enrolled in the original efficacy study, 58 patients (84%) enrolled in the extension, 34 patients received etanercept treatment for > or = 4 years, and 32 of these received complete efficacy assessments. The rate of SAEs was 0.13 per patient-year, and the rate of serious infections was 0.04 per patient-year, in a total etanercept exposure of 225 patient-years. Eighty-two percent of patients who received corticosteroids at any time during the extension were able to decrease their dosage to < or = 5 mg/day prednisone equivalent. Of the 32 patients with complete efficacy data who received etanercept for > or = 4 years, 94% achieved an ACR Pediatric 30 response and 78% achieved an ACR Pediatric 70 response at the last study visit. CONCLUSION: Etanercept offers an acceptable safety profile in children with polyarticular-course JRA and provides significant improvement in disease manifestations that are sustained for > or = 4 years.

Wallace CA, Ravelli A, Huang B, Giannini EH. · Division of Immunology, Rheumatology, and Infectious Disease, Children's Hospital and Regional Medical Center, Seattle, Washington 98105, USA. · J Rheumatol. · Pubmed #16482643 No free full text.

Abstract: OBJECTIVE: To begin the validation process of the preliminary criteria for inactive disease (ID), clinical remission on medication (CRM), and clinical remission off medication (CR) in children with select forms of juvenile idiopathic arthritis (JIA). METHODS: We used the OMERACT filter paradigm to estimate the validity of the criteria within each of the filter's 3 components: truth, discrimination, and feasibility, in 5 categories of JIA: systemic arthritis, persistent and extended oligoarthritis, and rheumatoid factor-positive and negative polyarthritis. Data sources for determining validity estimates included a Delphi questionnaire survey sent to 246 pediatric rheumatologists in 34 countries, a consensus conference attended by 20 senior pediatric rheumatologists representing 9 countries, a retrospective chart review of 437 patients with JIA from 3 tertiary care clinics who had been followed between 4 and 22 years, and the literature. RESULTS: Truth component: face and content validity. These aspects of validity were largely established via the Delphi questionnaire exercise and the consensus conference. Using an 80% consensus level, participants felt that a set of non-redundant variables could effectively differentiate the clinical states of ID, CRM, and CR. Criterion validity could not be irrefutably established because no gold standard for inactive disease exists for JIA. As an alternative, published investigations of remission in JIA were used to estimate concurrent and convergent validity, as surrogates for criterion validity and as indicators of overall construct validity. Correlational analyses revealed the new criteria to have good construct validity. Discrimination component: the criteria demonstrated moderate to high levels of classification, prognosis, and responsiveness (sensitivity to change) using data from the chart review. Patients who were able to attain CR remained disease-free for substantially longer periods than did those who attained only ID or CRM. Responsiveness was evidenced by the ability of the criteria to allow movement of most patients between the disease states, consistent with what is known of the course of the disease. Feasibility component: Results of the Delphi and consensus conference produced a set of criteria that are easily, quickly, and inexpensively completed in the physician's office, and present minimal or no risk to the patient. CONCLUSION: The preliminary criteria demonstrated moderate to excellent validity characteristics in some, but not all components of the OMERACT filter. Prospective validation studies are under way.

Wallace CA, Huang B, Bandeira M, Ravelli A, Giannini EH. · Children's Hospital and Regional Medical Center, and University of Washington School of Medicine, 4800 Sand Point Way NE, Seattle, WA 98105, USA. · Arthritis Rheum. · Pubmed #16255044 links to  free full text

Abstract: OBJECTIVE: To characterize disease activity patterns in a large cohort of children with juvenile idiopathic arthritis (JIA), by applying newly developed preliminary definitions of inactive disease, clinical remission on medication, and clinical remission off medication. METHODS: Children with persistent or extended oligoarthritis, polyarthritis (either rheumatoid factor [RF] positive or RF negative), or systemic JIA who had been followed up for a period of at least 4 years were evaluated for episodes of inactive disease, clinical remission on medication, and clinical remission off medication. Descriptive statistics, correlation analyses, and survival analyses were performed. RESULTS: Four hundred thirty-seven children met the criteria for review. Three hundred ninety-one patients (89%) experienced a total of 878 episodes of inactive disease, with a median episode length of 12.7 months. Two hundred twenty-eight episodes of inactive disease (26%) resulted in clinical remission off medication; it was equally as likely that episodes of inactive disease would or would not follow a period of clinical remission on medication. Thirty-six percent of episodes of clinical remission off medication persisted for at least 2 years, and only 6% of such episodes persisted for 5 years. RF-positive patients were the least likely to achieve clinical remission off medication (5%), and patients with persistent oligoarticular JIA were the most likely (68%). Among patients with persistent oligoarticular JIA, most of the disease course was characterized by inactive disease; in most other patients the majority of the disease course involved active disease. CONCLUSION: Using newly developed preliminary criteria for inactive disease, clinical remission on medication, and clinical remission off medication, we observed that only one-fourth of 878 episodes of inactive disease resulted in clinical remission off medication during followup of at least 4 years. Only a small proportion of episodes of clinical remission off medication were sustained for >5 years. These results highlight the critical need for therapies that have the ability to induce sustained remission of JIA.

Wallace CA, Ruperto N, Giannini E, Anonymous00326, Anonymous00327, Anonymous00328. · Children's Hospital and Regional Medical Center, Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington 98105, USA. · J Rheumatol. · Pubmed #15517647 No free full text.

Abstract: OBJECTIVE: To develop preliminary criteria for inactive disease and clinical remission for select categories of juvenile idiopathic arthritis (JIA), and to decide what such clinical states should predict in terms of probability of disease recurrence. METHODS: A Delphi serial questionnaire consensus-formation approach was used initially to gather criteria in use by pediatric rheumatologists (PR) for defining clinical remission in oligoarticular (persistent and extended), rheumatoid factor (RF) positive and negative polyarticular, and systemic JIA. Results from sequential questionnaires provided an agenda for a nominal group technique (NGT) conference to reach consensus on unresolved questions. RESULTS: One hundred and thirty PR from 34 countries responded to the questionnaires and 20 PR from 9 countries attended the conference. Draft criteria for inactive disease include the following: no active arthritis; no fever, rash, serositis, splenomegaly, or generalized lymphadenopathy attributable to JIA; no active uveitis; normal erythrocyte sedimentation rate or C-reactive protein; and a physician's global assessment of disease activity rated at the best score possible for the instrument used. According to consensus vote, 6 continuous months of inactive disease on medication defines clinical remission on medication, while 12 months of inactive disease off all anti-arthritis (and anti-uveitis) medications defines clinical remission off medication. The finalized criteria for remission off medication ideally should predict that a patient has </= 20% probability of disease recurrence within the next 5 years. CONCLUSION: Using consensus formation techniques, we formulated preliminary criteria for inactive disease and clinical remission on and off medication for use in select categories of JIA. Retrospective validation is in progress; prospective validation will follow. Future efforts will include other categories of JIA.