Tofacitinib in juvenile idiopathic arthritis: a double-blind, placebo-controlled, withdrawal phase 3 randomised trial.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor. This trial assessed the efficacy and safety of tofacitinib versus placebo in patients with polyarticular course juvenile idiopathic arthritis (JIA). METHODS: This double-blind, withdrawal phase 3 trial enrolled patients with polyarticular course JIA (extended oligoarthritis, rheumatoid factor-positive or rheumatoid factor-negative polyarthritis, or systemic JIA without active systemic features) aged 2 years to younger than 18 years, and was done at 64 centres of the Paediatric Rheumatology International Trials Organisation and Pediatric Rheumatology Collaborative Study Group networks in 14 countries. Patients with psoriatic arthritis or enthesitis-related arthritis were enrolled for exploratory endpoints. During part 1 of the study, patients received oral open-label tofacitinib (weight-based doses; 5 mg twice daily or lower) for 18 weeks. Patients achieving at least JIA/American College of Rheumatology 30 response were randomly assigned (1:1) using an Interactive Response Technology system to continue tofacitinib or switch to placebo in part 2 of the study for 26 weeks. The primary endpoint was JIA flare rate by week 44 in part 2 in patients with polyarticular course JIA; the intention-to-treat principle was applied. Safety was evaluated throughout part 1 and part 2 of the study in all patients who received one dose or more of study medication. This trial is registered with ClinicalTrials.gov, NCT02592434. FINDINGS: Between June 10, 2016, and May 16, 2019, of 225 patients enrolled, 184 (82%) patients had polyarticular course JIA, 20 (9%) had psoriatic arthritis, and 21 (9%) had enthesitis-related arthritis. 147 (65%) of 225 patients received concomitant methotrexate. In part 2, 142 patients with polyarticular course JIA were assigned to tofacitinib (n=72) or placebo (n=70). Flare rate by week 44 was significantly lower with tofacitinib (21 [29%] of 72 patients) than with placebo (37 [53%] of 70 patients; hazard ratio 0·46, 95% CI 0·27-0·79; p=0·0031). In part 2 of the study, adverse events occurred in 68 (77%) of 88 patients receiving tofacitinib and 63 (74%) of 85 in the placebo group. Serious adverse events occurred in one (1%) and two (2%), respectively. In the entire tofacitinib exposure period, 107 (48%) of 225 patients had infections or infestations. There were no deaths during this study. INTERPRETATION: The results of this pivotal trial show that tofacitinib is an effective treatment in patients with polyarticular course JIA. New oral therapies are particularly relevant for children and adolescents, who might prefer to avoid injections. FUNDING: Pfizer.

Tapering Canakinumab Monotherapy in Patients With Systemic Juvenile Idiopathic Arthritis in Clinical Remission: Results From a Phase IIIb/IV Open-Label, Randomized Study.

OBJECTIVE: To evaluate the efficacy and safety of 2 canakinumab monotherapy tapering regimens in order to maintain complete clinical remission in children with systemic juvenile idiopathic arthritis (JIA). METHODS: The study was designed as a 2-part phase IIIb/IV open-label, randomized trial. In the first part, patients received 4 mg/kg of canakinumab subcutaneously every 4 weeks and discontinued glucocorticoids and/or methotrexate as appropriate. Patients in whom clinical remission was achieved (inactive disease for at least 24 weeks) with canakinumab monotherapy were entered into the second part of the trial, in which they were randomized 1:1 into 1 of 2 treatment arms. In arm 1, the dose of canakinumab was reduced from 4 mg/kg to 2 mg/kg and then to 1 mg/kg, followed by discontinuation. In arm 2, the 4 mg/kg dose interval was prolonged from every 4 weeks, to every 8 weeks, and then to every 12 weeks, followed by discontinuation. In both arms, canakinumab exposure could be reduced provided systemic JIA remained in clinical remission for 24 weeks with each step. The primary objective was to assess whether >40% of randomized patients in either arm maintained clinical remission of systemic JIA for 24 weeks in the first part of the study. RESULTS: In part 1 of the study, 182 patients were enrolled, with 75 of those patients randomized before entering part 2 of the trial. Among the 75 randomized patients, clinical remission was maintained for 24 weeks in 27 (71%) of 38 patients in arm 1 (2 mg/kg every 4 weeks) and 31 (84%) of 37 patients in arm 2 (4 mg/kg every 8 weeks) (P ≤ 0.0001 for arm 1 versus arm 2 among those meeting the 40% threshold). Overall, 25 (33%) of 75 patients discontinued canakinumab, and clinical remission was maintained for at least 24 weeks in all 25 of these patients. No new safety signals were identified. CONCLUSION: Reduction of canakinumab exposure may be feasible in patients who have achieved clinical remission of systemic JIA, but consistent interleukin-1 inhibition appears necessary to maintain this response.

Burden of illness in hereditary periodic fevers: a multinational observational patient diary study.

OBJECTIVES: This study aimed to characterise the burden of illness of patients with inadequately controlled hereditary periodic fevers (HPFs), during and outside of flares. It was focused on the burden to the patients and also considered the wider impact on their caregivers and families. METHODS: The target population was patients or caregivers of patients with clinically/genetically confirmed colchicine resistant FMF (crFMF), mevalonate kinase deficiency/hyperimmunoglobinaemia D with periodic fever syndrome (MKD/HIDS) or TRAPS, who were expected to flare at least once in a 6-month period based on patient history. Disease burden was captured during and between flares using an electronic diary (e-diary) with questions on patient functioning, emotional/social well-being and pain, using validated instruments. RESULTS: HPF-related symptoms such as fever, joint, muscle or bone pain and tiredness and fatigue were reported by patients both during and outside of a flare. The SF-10 Health Survey (SF-10v2) (paediatric patients) and SF-12 Health Survey (SF-12v2) (adult patients) showed that flares negatively impacted patients' psychosocial and physical health. Negative effect of on-flare status on health utility index score assessed by the Short-Form Six-Dimension (SF-6D) was significant only for crFMF patients. Furthermore, the Sheehan Disability Score (SDSv3) showing the on-flare status resulted in significant functional impairment in all 3 disease cohorts through assessment of impact on work/school, social and family life. CONCLUSIONS: crFMF, MKD/HIDS and TRAPS negatively affected the quality of life (QoL) of adult and paediatric patients, including their physical, mental, psychosocial health, and social functioning. There remains, however, a high number of unmet needs for these patients to reduce their disease burden.

Efficacy and Safety of Canakinumab in Patients With Systemic Juvenile Idiopathic Arthritis With and Without Fever at Baseline: Results From an Open-Label, Active-Treatment Extension Study.

OBJECTIVE: To evaluate the long-term efficacy and safety of canakinumab and explore prediction of response in patients with systemic juvenile idiopathic arthritis (JIA) with or without fever at treatment initiation. METHODS: At enrollment, patients with active systemic JIA (ages 2 to <20 years) started open-label canakinumab (4 mg/kg every 4 weeks subcutaneously). Efficacy measures included the adapted American College of Rheumatology (ACR) Pediatric 50/70/90 criteria, the Juvenile Arthritis Disease Activity Score (JADAS), and clinically inactive disease and clinical remission on medication, evaluated by either the JADAS or ACR criteria. RESULTS: Of the 123 patients (70 with fever and 52 without fever [fever status was not reported for 1 patient]), 84 (68.3%) completed the study (median duration 1.8 years). Comparable efficacy (adapted ACR Pediatric 50/70/90/100) was observed by day 15 in both subgroups (60.0%/48.6%/37.1%/24.3% in those with fever and 67.3%/48.1%/34.6%/19.2% in those without fever), and further increased thereafter. By month 6, clinical remission according to the JADAS or the ACR criteria was achieved in 17 (24.3%) and 26 (37.1%), respectively, of patients with fever and 9 (17.3%) and 12 (23.1%), respectively, of patients without fever. Median time to onset of clinical remission according to the JADAS or ACR criteria was 57 and 30 days, respectively, in those with fever, and 58 and 142 days, respectively, in those without fever. An adapted ACR Pediatric 50 response by day 15 was the strongest predictor of achieving clinical remission according to the JADAS (odds ratio [OR] 13 [95% confidence interval (95% CI) 4, 42]; P < 0.0001) or glucocorticoid discontinuation (OR 19 [95% CI 3, 114]; P = 0.002). Of the 71 of 123 patients (57.7%) who received glucocorticoids at study entry, 27 (38.0%) discontinued glucocorticoids and 21 (29.6%) reached a dose of <0.2 mg/kg/day, with no difference between those with and those without fever; 13 patients (10.6%) tolerated a sustained canakinumab dose reduction to 2 mg/kg every 4 weeks. No new safety findings were observed. CONCLUSION: Canakinumab provided rapid and sustained improvement of active systemic JIA irrespective of the presence of fever at treatment initiation.

Long-term efficacy and safety of canakinumab in patients with colchicine-resistant familial Mediterranean fever: results from the randomised phase III CLUSTER trial.

OBJECTIVES: To evaluate the long-term efficacy and safety of canakinumab to treat patients with colchicine-resistant familial Mediterranean fever (crFMF) during Epoch 4 (weeks 41 to 113) of the CLUSTER study. METHODS: Patients received open-label canakinumab 150 or 300 mg, every 4 or 8 weeks during a 72-week period. We evaluated disease activity every 8 weeks using the physician global assessment (PGA) of disease activity, counting the number of flares, and measuring concentrations of C reactive protein (CRP) and serum amyloid A (SAA). Safety was studied by determination and classification of observed adverse events (AEs). We analysed safety and efficacy separately in two subgroups of patients receiving a cumulative dose of less than 2700 mg, or equal or more than 2700 mg. RESULTS: Of the 61 patients that started the CLUSTER study, 60 entered Epoch 4 and 57 completed it. During the 72-week period, 35/60 (58.3%) patients experienced no flares, and 23/60 (38.3%) had one flare, as compared with a median of 17.5 flares per year reported at baseline. PGA scores indicated no disease activity for the majority of patients throughout the study. Median CRP concentrations were always lower than 10 mg/L, while median SAA concentrations remained over the limit of normal (10 mg/L) but under the 30 mg/L threshold. No new or unexpected AEs were reported. CONCLUSION: crFMF patients treated with canakinumab during 72 weeks experienced a minimal incidence of flares and good control of clinical disease activity, with no new safety concerns reported.

Safety and Effectiveness of Adalimumab in Patients With Polyarticular Course of Juvenile Idiopathic Arthritis: STRIVE Registry Seven-Year Interim Results.

OBJECTIVE: To evaluate safety and effectiveness of adalimumab (ADA) in polyarticular-course juvenile idiopathic arthritis (JIA) in the STRIVE registry. METHODS: STRIVE enrolled patients with polyarticular-course JIA into 2 arms based on treatment with methotrexate (MTX) alone or ADA with/without MTX (ADA ± MTX). Adverse events (AEs) per 100 patient-years of observation time were analyzed by registry arm. Patients who entered the registry within 4 weeks of starting MTX or ADA ± MTX, defined as new users, were evaluated for change in disease activity assessed by the 27-joint Juvenile Arthritis Disease Activity Score with the C-reactive protein level (JADAS-27CRP ). RESULTS: At the 7-year cutoff date (June 1, 2016), data from 838 patients were available (MTX arm n = 301, ADA ± MTX arm n = 537). The most common AEs were nausea (10.3%), sinusitis (4.7%), and vomiting (4.3%) in the MTX arm and arthritis (3.9%), upper respiratory tract infection (3.5%), sinusitis, tonsillitis, and injection site pain (3.0% each) in the ADA ± MTX arm. Rates of serious infection were 1.5 events/100 patient-years in the MTX arm and 2.0 events/100 patient-years in the ADA ± MTX arm. AE and serious AE rates were similar in patients receiving ADA with versus without MTX. No deaths or malignancies were reported. New users in the ADA ± MTX arm showed a trend toward lower mean JADAS-27CRP compared with new users in the MTX arm in the first year of STRIVE. CONCLUSION: The STRIVE registry 7-year interim results support the idea that ADA ± MTX is well tolerated by most children. Registry median ADA exposure was 2.47 (interquartile range 1.0-3.6) years, with 42% of patients continuing ADA at the 7-year cutoff date.

Recurrent Kawasaki Disease: A Case Report of Three Separate Episodes at >4-Year Intervals.

Kawasaki disease (KD) is a self-limited systemic vasculitis, most often occurring in children 1⁻5 years old. It has a 2% recurrence rate and is associated with coronary aneurysms (CA), which can develop within two weeks of onset. A 25% increased risk is noted in patients who are recalcitrant to treatment. We describe a patient with recurrence of KD three times, approximately four years apart. A 10-year-old female with two previous episodes of KD, at 11 months and five years of age), in which she met five out of five criteria for KD and had no coronary involvement, presented with 15 days of fever, conjunctivitis and mucocutaneous changes. Infectious work-up was negative, and she was diagnosed with incomplete KD meeting three out of five criteria. An echocardiogram (ECHO) on day 12 revealed dilation of the right coronary artery (RCA) and left coronary artery (LCA). Treatment with intravenous immunoglobulin (IVIG) and high-dose aspirin was started at an outside hospital. After transfer, serial ECHOs showed evolving coronary aneurysms, left anterior descending (LAD) z-score + 8.2 and RCA z-score + 4.0. She received 10 mg/kg infliximab (day 18) and began clopidogrel. A cardiac MRI (day 20) demonstrated progression of the LAD aneurysm, with a z-score + 13, and warfarin was started. To our knowledge, this is the first report of recurrent KD occurring three times at ~5 year intervals.

Do pedometers with or without education on exercise increase functional walking capacity and physical activity level in adolescents with juvenile idiopathic arthritis?

To evaluate the impact of pedometer use on the physical activity (PA) and functional walking capacity (FWC) of adolescents with juvenile idiopathic arthritis (JIA) and lower extremity (LE) involvement. Twenty-seven adolescents, aged 11-19 years with JIA and LE involvement, participated in the three-phase pedometer study that introduced the use of a pedometer and an education seminar at 6 weeks. Measurements were taken at the baseline first visit and at weeks 6, 12, and 20. The primary outcome measure was the 6-minute walk test (6MWT). Thirteen completed the study. Six-minute walk distance (6MWD) significantly increased from baseline (458.0 ± 70.8 m) to the end of phase 1 (501.4 ± 59.8 m) (p = 0.035), prior to receiving the pedometer; and from baseline to the end of study (p = 0.0037). No significant changes in 6MWD were found between weeks 6 and 12 (intervention) (p = 0.77) or between weeks 12 and 20 (follow through phase) (p = 0.27). In adolescents with LE JIA, consistent guidance and support by rheumatology professionals appears to positively influence PA and measures of FWC as seen through improved 6MWD. There was insufficient evidence to show that pedometers further increased FWC or PA.

Benign pneumatosis intestinalis in a pediatric patient with multiple risk factors including granulomatosis with polyangiitis: a case report and review of the literature.

OBJECTIVE: To describe the first reported case of pneumatosis intestinalis (PI) in a pediatric patient with granulomatosis with polyangiitis (GPA) and multiple other risk factors and review the literature for PI in adult and pediatric rheumatologic conditions. METHODS: A PubMed search was completed using the search phrase "pneumatosis intestinalis." Searches were limited to humans and the English language, and remaining articles involving patients with rheumatologic diagnoses were identified and included in our discussion. RESULTS: This is the first reported of case of PI in a patient with underlying GPA or antineutrophil cytoplasmic antibody-associated vasculitides. Out of 90 previously reported cases of PI in patients with rheumatologic conditions, 79 cases were in adults and 11 in children. There were 30 patients with systemic sclerosis, 18 with MCTD/overlap syndrome, 18 with dermatomyositis or polymyositis, 16 with SLE, and 8 with other diagnoses. Overall, 81% of the patients were on corticosteroids or other immunosuppressants prior to development of PI. The most common presenting symptom was abdominal pain, and 51% of patients had associated pneumoperitoneum. CONCLUSIONS: PI can be associated with a broad spectrum of rheumatic diseases, including GPA, and should be included in the differential diagnosis of patients with rheumatologic conditions and nonspecific gastrointestinal symptoms.

Treatment of Pediatric Takayasu arteritis with infliximab and cyclophosphamide: experience from an American-Brazilian cohort study.

BACKGROUND: Pediatric Takayasu arteritis (pTA) is difficult to treat and can lead to significant morbidity and mortality. OBJECTIVES: The objective of this study was to describe clinical characteristics for pTA and determine the safety and efficacy of cyclophosphamide (CYC) and infliximab (IFX) in pTA. METHODS: This was a retrospective analysis of 23 pTA patients seen at Children's Hospital Los Angeles and Universidade Federal de São Paulo-Brazil from 1990 to 2011. All patients fulfilled the 1990 American College of Rheumatology criteria for Takayasu arteritis. Disease activity was assessed using a modified National Institutes of Health score. RESULTS: Twenty-three patients (14 female and 9 male patients), mean age of 15.7 ± 6.0 years, were included. Cyclophosphamide was used before IFX treatment in 17 of 23 and IFX before CYC in 2 of 23 patients. The average time from disease onset to treatment initiation was 2.6 ± 2.4 years for CYC and 4.1 ± 2.4 years for IFX. Nine (60%) of 15 patients failed CYC, and of these 6 were changed to IFX with subsequent clinical stabilization in 5 (83%) of 6. Two patients initially treated with IFX were switched to CYC because of lack of appropriate response: 1 patient later worsened, and the other was lost to follow-up. Five opportunistic infections requiring hospitalization occurred in the CYC group, whereas none were observed in the IFX group. Patients in the IFX group were more likely to decrease or stop their corticosteroids when compared with the CYC patients. CONCLUSIONS: Cyclophosphamide is often used as initial treatment but has many adverse effects. In this retrospective case series, IFX was equivalent to CYC with fewer adverse effects, making IFX an alternative therapeutic option for pTA.

Diagnosis and management of infectious complications of childhood rheumatic diseases.

Progress in the diagnosis and management of pediatric rheumatic disease has improved complications from underlying disease and the survival of children. However, as a consequence, infection has now become one of the leading causes of morbidity and mortality. Differentiating between infections and disease flares in children with rheumatic conditions can often pose diagnostic quandaries. Children with rheumatic diseases are at risk of infection, not only because of the use of immune-modulating medications but also because of underlying immune dysfunction associated with their disease. Although bacterial infections are the most common, any organism can potentially be a causative agent and, at times, more invasive measures of diagnosis, for example bronchoscopy and tissue biopsies may be necessary. Maintaining a high index of suspicion of infection with prompt diagnosis and treatment are important to further improve patient outcomes.

Early juvenile idiopathic arthritis.

Early juvenile idiopathic arthritis (JIA) is important to recognize as timely diagnosis and treatment improves prognosis. It is a misconception that complications of JIA arise only from long-standing disease and that children will outgrow it. Early aggressive treatment is the paradigm as early disease activity has long-term consequences. There are predictors of persistent disease and joint erosions that may identify patients at higher risk. Control of disease activity within the first 6 months of onset confers improved clinical course and outcomes. The treatment perspective is thus one of early aggressive treatment for induction of disease control and ultimately remission.

Pediatric rheumatic disease in the intensive care unit: lessons learned from 15 years of experience in a tertiary care pediatric hospital.

OBJECTIVE: This study describes the 15-yr experience of a large urban tertiary care children's hospital in treating critically ill patients with pediatric rheumatic diseases. DESIGN: Retrospective case series. SETTING: Children's Hospital Los Angeles, a large urban tertiary care children's hospital. PATIENTS: All patients with pediatric rheumatic diseases admitted to the Children's Hospital Los Angeles pediatric intensive care unit from January 1995 to July 2009. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: An internal database and medical records were reviewed for demographics, diagnoses, treatments, organ dysfunction, interventions, infections, and outcomes. Standardized mortality ratio was calculated based on Pediatric Risk of Mortality III estimated mortality. Factors associated with mortality were identified by univariate analyses.Ninety patients with 122 total admissions were identified. The majority of patients were Hispanic (63%), female (73%), and had systemic lupus erythematosus (62%). Pediatric rheumatic disease-related complications (50%) were the most common reason for admission; 32% of admissions involved multiorgan dysfunction. Eighteen admissions (15%) resulted in mortality. Deaths were most commonly attributed to combined infection and active rheumatic disease (50%), infection only (22%), rheumatic disease only (11%), or other causes (17%). In 30 (25%) admissions, a new rheumatologic diagnosis was established. Standardized mortality ratio was 0.72 (95% confidence interval 0.38-1.25) for pediatric rheumatic disease patients compared to 0.87 (95% confidence interval 0.79-0.96) for all pediatric intensive care unit patients. Factors associated with mortality included use of mechanical ventilation, vasopressors, and renal replacement (continuous venovenous hemodialysis) (all p < .05). CONCLUSIONS: Pediatric rheumatic disease-related complications were the principal cause of pediatric intensive care unit admission. Deaths occurred most often from severe infections in patients with active rheumatic disease. Pediatric rheumatology patients admitted to the pediatric intensive care unit had outcomes similar to the global pediatric intensive care unit population when adjusted for severity of illness.

Acanthamoeba meningoencephalitis presenting as neuropsychiatric lupus in a pediatric patient.

We present the case of a 16-year-old patient with systemic lupus erythematosus who presented with altered mental status and regressive behaviour. She was worked up and empirically treated for common and opportunistic infectious agents. All work-up was negative and after an extensive course of antibiotics she was treated for neuropsychiatric lupus with cytoxan. She initially responded, but this was short-lived and she eventually became comatose and passed away. On brain biopsy she was found to have numerous trophozoites with round nucleus, prominent nucleolus and thin nuclear membrane. Methenamine silver stain showed encysted amoeba, corresponding with a diagnosis of acanthamoeba meningoencephalitis. Making the diagnosis of acanthamoeba meningoencephalitis requires a high degree of suspicion. Specific serum antibodies may not be a reliable measure in immunocompromised patients and trophozoites in CSF can be confused with monocytes. Brain biopsy may be required to make a definitive diagnosis. It is important for clinicians treating immunocompromised patients to keep this agent in mind in an immunocompromised patient with neurological manifestations. Acanthamoeba infections have only been reported in a small handful of patients and, to our knowledge, this is the first reported case in the United States.

High dose infliximab in the treatment of refractory uveitis: does dose matter?

Background. Infliximab (INF) has been shown to be beneficial in treating refractory uveitis, however, no data exist on optimal dosing and the efficacy of higher dosing. Objectives. To compare the efficacy of low-dose (LD) (<10 mg/kg), moderate-dose (MD) (≥10-15 mg/kg), and high-dose (HD) INF (≥15-20 mg/kg) in the treatment of uveitis. Methods. Retrospective chart review children with uveitis diagnosed at Childrens Hospital Los Angeles and Millers Children's Hospital, CA, USA. Results. Of the 34 INF-treated children, 6 patients received LD, 19 received MD, and 9 received HD. Average disease duration prior to therapy was 10.6, 24.6, and 37.1 months each group, respectively. Topical steroids were discontinued after an average of 3 months, 9.5 months, and 10.2 months in the LD, MD, and HD groups, respectively. We found that 66% of patients receiving LD, 42% of MD, and 66% receiving HD INF failed therapy and required either dose escalation or alternate medication for disease control. Conclusions. INF is beneficial in the treatment of uveitis, and dose escalation up to 4 times above the approved dose is often necessary to achieve disease control in patients with uveitis. Doses < 10 mg/kg every 4 weeks may not be sufficient to control disease.

Role of adalimumab in the management of children and adolescents with juvenile idiopathic arthritis and other rheumatic conditions.

Treatment of children and adolescents with juvenile idiopathic arthritis and other pediatric rheumatic diseases has evolved. Where once there was only a limited arsenal of medications, with significant side effects and inadequate efficacy, today, with an increased understanding of the pathogenesis of these diseases, there is a wider variety of more targeted and effective treatments. TNF-α is a cytokine involved in a number of inflammatory pathways in pediatric rheumatic diseases. The emergence of biologic modifiers that target TNF-α has been pivotal in providing the ability to deliver early and aggressive treatment. Adalimumab, a recombinant monoclonal antibody to TNF-α, is an important therapeutic option, which affords children and adolescents with chronic illnesses an improved quality of life.

A child with x-linked agammaglobulinemia and enthesitis-related arthritis.

X-linked agammaglobulinemia (XLA) is a primary immune deficiency characterized by recurrent bacterial infections and profoundly depressed serum immunoglobulin levels and circulating mature B cells. We describe a 12-year-old boy with XLA and enthesitis-related arthritis (ERA). To date, there has been a paucity of reports of noninfectious inflammatory arthritis in children with XLA. This case illustrates that functional B cells and/or immunoglobulin are not required for ERA pathogenesis. In addition, this case suggests a possible link between immune deficiency, immune dysregulation, and rheumatic illness.

B lymphocyte stimulator expression in pediatric systemic lupus erythematosus and juvenile idiopathic arthritis patients.

OBJECTIVE: To assess the expression of B lymphocyte stimulator (BLyS) in patients with pediatric systemic lupus erythematosus (SLE) or juvenile idiopathic arthritis (JIA). METHODS: Blood samples collected from patients with pediatric SLE (n = 56) and patients with JIA (n = 54) at the beginning and end of a 6-month interval were analyzed for plasma BLyS protein levels by enzyme-linked immunosorbent assay and for blood leukocyte full-length BLyS and DeltaBLyS messenger RNA (mRNA) levels by quantitative real-time polymerase chain reaction (normalized to 18S expression). Healthy siblings (n = 34) of these patients served as controls. RESULTS: In pediatric SLE, plasma BLyS protein and blood leukocyte BLyS mRNA levels were each significantly elevated, and plasma BLyS protein levels, but not blood leukocyte BLyS mRNA levels, were correlated with disease activity. In contrast, plasma BLyS protein levels were normal in JIA despite blood leukocyte BLyS mRNA levels being elevated to degrees similar to those in pediatric SLE. Among JIA patients, neither BLyS parameter was correlated with disease activity. In both pediatric SLE and JIA, the BLyS expression profiles remained stable at 6 months. CONCLUSION: Our findings indicate that, as previously noted in adult SLE, plasma BLyS protein and blood leukocyte BLyS mRNA levels are elevated in pediatric SLE. The correlation of plasma BLyS protein levels with disease activity points to BLyS as a candidate therapeutic target in pediatric SLE. Contrary to previous observations in adults with rheumatoid arthritis, plasma BLyS protein levels are normal in JIA despite elevated blood leukocyte BLyS mRNA levels. The absence of correlation between either of the BLyS parameters and disease activity in JIA calls for circumspection prior to assigning BLyS as a candidate therapeutic target in this disorder.

Adalimumab in juvenile rheumatoid arthritis/juvenile idiopathic arthritis.

Chronic arthritis in childhood is the most common pediatric rheumatic disease and can lead to significant short- and long-term disability. TNF-a is a cytokine involved in joint inflammation and destruction. It has been suggested that early and aggressive treatment leads to improved outcomes by ameliorating clinical signs and symptoms, inhibiting joint destruction and improving functional disability. The early and aggressive use of disease-modifying antirheumatic drugs and biologic response modifiers are key to achieving this goal. Anti-TNF agents are effective biologic modifiers that have had a major impact on the clinical course of arthritis. Adalimumab, a recombinant monoclonal antibody to TNF-alpha, is emerging as a valuable new therapy for juvenile arthritis.