Novel method to collect medication adverse events in juvenile arthritis: results from the childhood arthritis and rheumatology research alliance enhanced drug safety surveillance project.

OBJECTIVE: Few data are available regarding the rates of serious adverse events (SAEs) and important medical events (IMEs) outside of product-based registries and clinical trials for juvenile idiopathic arthritis (JIA). The Enhanced Drug Safety Surveillance Project (EDSSP) was developed to pilot a novel system to collect SAEs/IMEs in children with JIA. This analysis reports the results from this 4-year (2008-2012) EDSSP. METHODS: Participating physicians were surveyed monthly to ascertain whether their JIA patients experienced an SAE or IME. Sites were surveyed every 6 months to determine the number of unique JIA patients seen at each site during that 6-month period. Reporting rates were calculated per 100 person-years and 95% confidence intervals (95% CIs) were calculated based on a Poisson distribution. RESULTS: Thirty-seven Childhood Arthritis and Rheumatology Research Alliance sites with 115 physicians participated. The mean response rate to the monthly surveys was 65%. There were 147 total SAEs and 145 total IMEs. The largest proportion of SAEs and IMEs occurred in children with polyarticular JIA (39% and 37%, respectively). The majority of SAEs and IMEs were reported for patients receiving therapy with biologic agents (76% and 69%, respectively). The total event rate for SAEs and IMEs combined was 1.07 events per 100 person-years (95% CI 0.95-1.19). The rates for SAEs and IMEs were 0.54 per 100 person-years (95% CI 0.45-0.63) and 0.53 per 100 person-years (95% CI 0.49-0.62), respectively. CONCLUSION: The EDSSP provided a simple tool for SAE/IME reporting within an established research network and resulted in a similar range of reported events as captured by a traditional product-based registry.

Consensus treatment plans for induction therapy of newly diagnosed proliferative lupus nephritis in juvenile systemic lupus erythematosus.

OBJECTIVE: To formulate consensus treatment plans (CTPs) for induction therapy of newly diagnosed proliferative lupus nephritis (LN) in juvenile systemic lupus erythematosus (SLE). METHODS: A structured consensus formation process was employed by the members of the Childhood Arthritis and Rheumatology Research Alliance after considering the existing medical evidence and current treatment approaches. RESULTS: After an initial Delphi survey (response rate = 70%), a 2-day consensus conference, and 2 followup Delphi surveys (response rates = 63-79%), consensus was achieved for a limited set of CTPs addressing the induction therapy of proliferative LN. These CTPs were developed for prototypical patients defined by eligibility characteristics, and included immunosuppressive therapy with either mycophenolic acid orally twice per day, or intravenous cyclophosphamide once per month at standardized dosages for 6 months. Additionally, the CTPs describe 3 options for standardized use of glucocorticoids, including a primarily oral, a mixed oral/intravenous, and a primarily intravenous regimen. There was consensus on measures of effectiveness and safety of the CTPs. The CTPs were well accepted by the pediatric rheumatology providers treating children with LN, and up to 300 children per year in North America are expected to be candidates for the treatment with the CTPs. CONCLUSION: CTPs for induction therapy of proliferative LN in juvenile SLE based on the available scientific evidence and pediatric rheumatology group experience have been developed. Consistent use of the CTPs may improve the prognosis of proliferative LN, and support the conduct of comparative effectiveness studies aimed at optimizing therapeutic strategies for proliferative LN in juvenile SLE.

Multilevel airway involvement in children with Wegener's granulomatosis: clinical course and the utility of a multidisciplinary approach.

OBJECTIVE: To examine the prevalence of airway involvement in children with Wegener's granulomatosis (WG) at our institution and to evaluate the utility of a treatment paradigm involving a multidisciplinary team. DESIGN: Retrospective medical chart review. SETTING: Tertiary children's hospital. PATIENTS: Pediatric subjects with WG treated at a tertiary children's hospital over the past 15 years. MAIN OUTCOME MEASURES: The medical records of all subjects with airway lesions were reviewed for clinical characteristics of airway involvement and for the medical and surgical treatment regimens. RESULTS: Seven of 28 pediatric patients with WG were identified to have airway lesions (25%), including vocal fold granuloma, subglottic stenosis, and multilevel stenoses. Three of these patients had isolated and limited lesions. The 4 remaining patients are the focus of this study. One patient underwent a cricotracheal resection. All patients underwent repeated surgical treatment from combined services (otolaryngology and pulmonology) with flexible and rigid endoscopy, dilatation, and corticosteroid injection to manage subglottic, tracheal, and bronchial stenoses. Operative findings were communicated to the rheumatology service for manipulation of medical therapy. The 3 most recent patients received the anti-CD20 chemotherapeutic agent rituximab. This treatment approach led to temporary remission in some of the patients. CONCLUSIONS: Airway involvement in pediatric patients with WG is known to occur, but multilevel airway involvement is rare and clinically challenging. We advocate a combined surgical approach involving otolaryngology, pulmonology, and rheumatology in managing aggressive cases of multilevel airway involvement in WG.

Anakinra for systemic juvenile arthritis: the Rocky Mountain experience.

BACKGROUND: Poor outcomes in systemic juvenile arthritis have been associated with persistent thrombocytosis, increased sedimentation rates, anemia, polyarthritis, and prolonged steroid use. Off-label treatment with recombinant interleukin-1 receptor antagonist therapy (anakinra) has become more common since reports of its association with reduced systemic symptoms and arthritis scores, improved laboratory parameters of inflammation, and decreased corticosteroid requirements. OBJECTIVE: To examine the efficacy and safety of anakinra in a regional cohort of systemic juvenile arthritis patients. METHODS: We performed a retrospective case series of systemic juvenile arthritis patients (n = 33) treated with anakinra at 3 Pediatric Rheumatology centers. The effect of anakinra on corticosteroid dose, sedimentation rate, platelet count, albumin, hemoglobin, arthritis joint counts, and height Z score was determined using the paired t test. We evaluated differences in change in these variables between patient groups within the sample determined by: age of onset, anakinra dose, and duration from diagnosis until anakinra treatment. RESULTS: Treatment was associated with decreases in corticosteroid dosage and sedimentation rate and increases in hemoglobin and albumin (P < 0.02). There were decreases in large joint arthritis counts (P < 0.04) but not small joint counts after 3 to 4 months. There were greater decreases in sedimentation rates from pre to post (1-2 months) in patients on high versus low dose anakinra (P < 0.001). Fever and rash, present in 7 cases before treatment, was resolved. Eight patients had periods of arthritis, 1 developed macrophage activation syndrome, and another Epstein Barr virus. Over half of patients reported localized pain or swelling at their injection site. CONCLUSIONS: Treatment with anakinra was associated with short-term improvements in large joint counts and laboratory parameters of active disease. Higher anakinra doses may be more efficacious in treating the systemic inflammatory response in systemic onset juvenile idiopathic arthritis patients. A subset of patients had periods of arthritis during treatment, and local side-effects were frequent. Our experience supports the continued use of interleukin-1 inhibition in systemic juvenile arthritis and the search for more effective and more tolerable forms of interleukin-1 inhibition.

Case report: severe microscopic polyangiitis successfully treated with extracorporeal membrane oxygenation and immunosuppression in a pediatric patient.

Severe microscopic polyangiitis can result in acute respiratory failure and renal failure and is commonly treated with mechanical cardiopulmonary support, along with immunosuppression. We report the use of continuous renal replacement therapy and rituximab in a 13-year-old boy with P-antineutrophil cytoplasmic antibody-positive microscopic polyangiitis, resulting in pulmonary hemorrhage and acute renal failure. The patient was treated with high-frequency oscillatory ventilation, extracorporeal membrane oxygenation, and continuous renal replacement therapy, in addition to plasmapheresis, corticosteroids, cyclophosphamide, and rituximab.