Comparative effectiveness of a second TNF inhibitor versus a non-TNF biologic in the treatment of polyarticular course juvenile idiopathic arthritis.

OBJECTIVE: The objective of this study was to compare the effectiveness of a second tumor necrosis factor inhibitor (TNFi) versus a non-TNFi biologic following discontinuation of a TNFi for patients with polyarticular-course juvenile idiopathic arthritis (pJIA). METHODS: Using the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry, patients with pJIA who started a second biologic following a first TNFi were identified. Patients were required to have no active uveitis on index date and a visit 6 months after the index date. Outcome measures included clinical juvenile arthritis disease activity score 10 (cJADAS10), cJADAS10 inactive disease (ID<2.5) and cJADAS10 minimal disease activity (MiDA<5). Multiple imputation was used to account for missing data. Adjusted odds ratios (aOR) were calculated using propensity score quintiles to compare outcomes at 6 months following second biologic initiation. RESULTS: There were 216 patients included, 84% initially received etanercept and most patients stopped it for ineffectiveness (74%). 183 (85%) started a second TNFi and 33 (15%) started a non-TNFi. Adalimumab was the most common second biologic (71% overall, 84% of second TNFi) and tocilizumab was the most common non-TNFi second biologic (9% overall, 58% of non-TNFi). There was no difference between TNFi and non-TNFi in cJADAS ID (29% versus 25%; aOR 1.23 [0.47-3.20]) or at least MiDA (43% versus 39%; aOR 1.11 [0.47-2.62]) at 6 months. CONCLUSION: Most patients with polyarticular course JIA started TNFi rather than non-TNFi as their second biologic, and there were no differences in disease activity at 6 months.

Using Electronic Health Records and Linked Claims Data to Assess New Medication Use and Primary Nonadherence in Rheumatology Patients.

OBJECTIVE: The objective of this study was to determine the proportion of new medication prescriptions observed in electronic health records (EHR) that represent true incident medication use, accounting for undocumented previous prescriptions (prevalent medication use) and failure to initiate treatment (primary nonadherence) with linked administrative claims data as the reference standard. METHODS: Using single-specialty rheumatology EHR data from more than 700 community practices in the United States linked to administrative claims data, we identified first (index) EHR prescriptions and assessed the positive predictive value (PPV) of different EHR-derived new user definitions to identify true incident use (no prior claims). We then assessed how often index EHR prescriptions that met a definition of new use resulted in primary nonadherence (no subsequent claims). RESULTS: Overall, 12,405 index EHR prescriptions were identified with PPVs of 0.59 to 0.67 for true incident use. PPVs increased to 0.76 to 0.85 by excluding medications listed during the EHR medication reconciliation process and further increased to 0.87 to 0.93 by requiring ≥12 elapsed months since the first rheumatology office visit. Primary nonadherence at three months was observed in 33% to 38% overall and varied substantially by medication class, ranging from 15% to 23% for conventional synthetic disease-modifying antirheumatic drugs (DMARDs) to 54% to 64% for targeted synthetic DMARDs. CONCLUSION: New DMARD use was accurately distinguished from prevalent use with EHR prescriptions and simple new user definitions that include current medications collected during medication reconciliation. Primary nonadherence was frequent and varied by DMARD class. This has important implications for epidemiologic studies using EHR data and for optimal delivery of clinical care.

Prediction of Survival by IL-6 in a Randomized Placebo-Controlled Trial of Anakinra in COVID-19 Cytokine Storm.

(1) Background: Some severe COVID-19 patients develop hyperinflammatory cytokine storm syndrome (CSS). We assessed the efficacy of anakinra added to standard of care (SoC) in hospitalized COVID-19 CSS patients. (2) Methods: In this single-center, randomized, double-blind, placebo-controlled trial (NCT04362111), we recruited adult hospitalized patients with SARS-CoV-2 infection, evidence of pneumonia, new/increasing oxygen requirement, ferritin ≥ 700 ng/mL, and at least three of the following indicators: D-dimer ≥ 500 ng/mL, platelet count < 130,000/mm3, WBC < 3500/mm3 or lymphocyte count < 1000/mm3, AST or ALT > 2X the upper limit of normal (ULN), LDH > 2X ULN, C-reactive protein > 100 mg/L. Patients were randomized (1:1) to SoC plus anakinra (100 mg subcutaneously every 6 h for 10 days) or placebo. All received dexamethasone. The primary outcome was survival and hospital discharge without need for intubation/mechanical ventilation. The data were analyzed according to the modified intention-to-treat approach. (3) Results: Between August 2020 and January 2021, 32 patients were recruited, of which 15 were assigned to the anakinra group, and 17 to the placebo group. Two patients receiving the placebo withdrew within 48 h and were excluded. The mean age was 63 years (SD 10.3), 20 (67%) patients were men, and 20 (67%) were White. At Day 10, one (7%) patient receiving anakinra and two (13%) patients receiving the placebo had died (p = 1.0). At hospital discharge, four (27%) patients receiving anakinra and four (27%) patients receiving the placebo had died. The IL-6 level at enrollment was predictive of death (p < 0.01); anakinra use was associated with decreases in CXCL9 levels. (4) Conclusions: Anakinra added to dexamethasone did not significantly impact the survival of COVID-19 pneumonia patients with CSS. Additional studies are needed to assess patient selection and the efficacy, timing, and duration of anakinra treatment for COVID-19 CSS.

Identifying inpatient mortality in MarketScan claims data using machine learning.

PURPOSE: Inpatient mortality is an important variable in epidemiology studies using claims data. In 2016, MarketScan data began obscuring specific hospital discharge status types for patient privacy, including inpatient deaths, by setting the values to missing. We used a machine learning approach to correctly identify hospitalizations that resulted in inpatient death using data prior to 2016. METHODS: All hospitalizations from 2011 to 2015 with discharge status of missing, died, or one of the other subsequently obscured values were identified and divided into a training set and two test sets. Predictor variables included age, sex, elapsed time from hospital discharge until last observed claim and until healthcare plan disenrollment, and absence of any discharge diagnoses. Four machine learning methods were used to train statistical models and assess sensitivity and positive predictive value (PPV) for inpatient mortality. RESULTS: Overall 1 307 917 hospitalizations were included. All four machine learning approaches performed well in all datasets. Random forest performed best with 88% PPV and 93% sensitivity for the training set and both test sets. The two factors with the highest relative importance for identifying inpatient mortality were having no observed claims for the patient on days 2-91 following hospital discharge and patient disenrollment from the healthcare plan within 60 days following hospital discharge. CONCLUSION: We successfully developed machine learning algorithms to identify inpatient mortality. This approach can be applied to obscured data to accurately identify inpatient mortality among hospitalizations with missing discharge status.

Assessment of Real-World Patient-Reported Outcomes in Patients Initiating Biologic Agents for the Treatment of Autoimmune Diseases: An Observational Study in Four Patient-Powered Research Networks.

Background: The most reliable and meaningful approach for inclusion of patient-reported outcomes (PROs) in the evaluation of real-world clinical effectiveness of biologics in the treatment of autoimmune diseases is u ncertain. This study aimed to assess and compare the proportions of patients who had abnormalities in PROs measuring important general health domains at the initiation of treatment with biologics, as well as the effects of baseline abnormalities on subsequent improvement. Methods: PROs were collected for patient participants with inflammatory arthritis, inflammatory bowel disease, and vasculitis using Patient-Reported Outcomes Measurement Information System instruments. Scores were reported as T-scores normalized to the general population in the United States. Baseline PROs scores were collected near the time of biologic initiation, and follow-up scores were collected 3 to 8 months later. In addition to summary statistics, the proportion of patients with PROs abnormalities (scores ≥5 units worse than the population norm) was determined. Baseline and follow-up scores were compared, and an improvement of ≥5 units was considered significant. Results: There was wide variation across autoimmune diseases in baseline PROs scores for all domains. For example, the proportion of participants with abnormal baseline pain interference scores ranged from 52% to 93%. When restricted to participants with baseline PROs abnormalities, the proportion of participants experiencing an improvement of ≥5 units was substantially higher. Conclusion: As expected, many patients experienced improvement in PROs following initiation of treatment with biologics for autoimmune diseases. Nevertheless, a substantial proportion of participants did not exhibit abnormalities in all PROs domains at baseline, and these participants appear less likely to experience improvement. For PROs to be reliably and meaningfully included in the evaluation of real-world medication effectiveness, more knowledge and careful consideration are needed to select the most appropriate patient populations and subgroups for inclusion and evaluation in studies measuring change in PROs.

Occurrence of adverse events and change in disease activity after initiation of etanercept in paediatric patients with juvenile psoriatic arthritis in the CARRA Registry.

OBJECTIVE: Etanercept is commonly used to treat juvenile idiopathic arthritis, including juvenile psoriatic arthritis (JPsA); however, information on etanercept's safety and effectiveness in clinical practice is limited. We used data from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry to evaluate etanercept's safety and effectiveness in JPsA in clinical practice. METHODS: We analysed safety and effectiveness data for paediatric patients enrolled in the CARRA Registry who had a JPsA diagnosis and had used etanercept. Safety was assessed by calculating rates of prespecified adverse events of special interest (AESIs) and serious adverse events (SAEs). Effectiveness was assessed by a variety of disease activity measures. RESULTS: Overall, 226 patients had JPsA and received etanercept; 191 met criteria for safety analysis and 43 met criteria for effectiveness analysis. AESI and SAE incidence rates were low. There were five events: three uveitis, one new-onset neuropathy and one malignancy. Incidence rates were 0.55 (95% CI: 0.18, 1.69), 0.18 (95% CI: 0.03, 1.29) and 0.13 (95% CI: 0.02, 0.09) per 100 patient-years for uveitis, neuropathy and malignancy, respectively. Etanercept showed effectiveness for JPsA treatment; 7 of 15 (46.7%) had an American College of Rheumatology-Pediatric Response 90, 9 of 25 (36.0%) had a clinical Juvenile Arthritis Disease Activity Score 10-joint ≤1.1 and 14 of 27 (51.9%) had clinically inactive disease at the 6-month follow-up. CONCLUSION: Data in the CARRA Registry showed that etanercept treatment was safe in treating children with JPsA, with low AESIs and SAEs. Etanercept was also effective, even when assessed in a small sample size.

Using pooled electronic health records data to conduct pharmacoepidemiology safety studies: Challenges and lessons learned.

PURPOSE: We assessed the suitability of pooled electronic health record (EHR) data from clinical research networks (CRNs) of the patient-centered outcomes research network to conduct studies of the association between tumor necrosis factor inhibitors (TNFi) and infections. METHODS: EHR data from patients with one of seven autoimmune diseases were obtained from three CRNs and pooled. Person-level linkage of CRN data and Centers for Medicare and Medicaid Services (CMS) fee-for-service claims data was performed where possible. Using filled prescriptions from CMS claims data as the gold standard, we assessed the misclassification of EHR-based new (incident) user definitions. Among new users of TNFi, we assessed subsequent rates of hospitalized infection in EHR and CMS data. RESULTS: The study included 45 483 new users of TNFi, of whom 1416 were successfully linked to their CMS claims. Overall, 44% of new EHR TNFi prescriptions were not associated with medication claims. Our most specific new user definition had a misclassification rate of 3.5%-16.4% for prevalent use, depending on the medication. Greater than 80% of CRN prescriptions had either zero refills or missing refill data. Compared to using EHR data alone, there was a 2- to 8-fold increase in hospitalized infection rates when CMS claims data were added to the analysis. CONCLUSIONS: EHR data substantially misclassified TNFi exposure and underestimated the incidence of hospitalized infections compared to claims data. EHR-based new user definitions were reasonably accurate. Overall, using CRN data for pharmacoepidemiology studies is challenging, especially for biologics, and would benefit from supplementation by other sources.

Attack phenotypes and disease course in pediatric MOGAD.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an autoimmune demyelinating condition that affects children differently than adults. We performed a literature review to assess the presentation and clinical course of pediatric MOGAD. The most common initial phenotype is acute disseminated encephalomyelitis, especially among children younger than five years, followed by optic neuritis (ON) and/or transverse myelitis. Approximately one-quarter of children with MOGAD have at least one relapse that typically occurs within three years of disease onset and often includes ON, even if ON was not present at onset. Clinical risk factors for a relapsing course have not been elucidated.

Incidence of Antiphospholipid Syndrome: Is Estimation Currently Possible?

Antiphospholipid syndrome is a systemic autoimmune disorder characterized by vascular thrombosis and/or obstetric events in association with persistently elevated antiphospholipid antibodies. Antiphospholipid syndrome is typically considered a rare disease, but the true incidence is uncertain owing to the diverse antiphospholipid antibody-related clinical manifestations, inconsistent definitions of antiphospholipid antibody positivity, under-recognition of the disease, and limited population-based studies. Published estimates of the incidence of antiphospholipid syndrome range from approximately 2 to 80 per 100 000 person-years. A targeted literature review and applied methodology were performed to derive a best available estimate. Significant limitations of the published literature were observed, some of which have been previously reported. The incidence of antiphospholipid syndrome in the United States was estimated to be approximately 7.1 to 13.7 per 100 000 person-years in the general population. Although this estimate is likely more accurate than previously reported estimates, large, contemporary, population-based studies that reasonably adhere to the antiphospholipid syndrome classification criteria are needed to further refine estimates of the incidence of antiphospholipid syndrome.

Childhood-Onset Lupus Nephritis in the Childhood Arthritis and Rheumatology Research Alliance Registry: Short-Term Kidney Status and Variation in Care.

OBJECTIVE: The goal was to characterize short-term kidney status and describe variation in early care utilization in a multicenter cohort of patients with childhood-onset systemic lupus erythematosus (cSLE) and nephritis. METHODS: We analyzed previously collected prospective data from North American patients with cSLE with kidney biopsy-proven nephritis enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry from March 2017 through December 2019. We determined the proportion of patients with abnormal kidney status at the most recent registry visit and applied generalized linear mixed models to identify associated factors. We also calculated frequency of medication use, both during induction and ever recorded. RESULTS: We identified 222 patients with kidney biopsy-proven nephritis, with 64% class III/IV nephritis on initial biopsy. At the most recent registry visit at median (interquartile range) of 17 (8-29) months from initial kidney biopsy, 58 of 106 patients (55%) with available data had abnormal kidney status. This finding was associated with male sex (odds ratio [OR] 3.88, 95% confidence interval [95% CI] 1.21-12.46) and age at cSLE diagnosis (OR 1.23, 95% CI 1.01-1.49). Patients with class IV nephritis were more likely than class III to receive cyclophosphamide and rituximab during induction. There was substantial variation in mycophenolate, cyclophosphamide, and rituximab ever use patterns across rheumatology centers. CONCLUSION: In this cohort with predominately class III/IV nephritis, male sex and older age at cSLE diagnosis were associated with abnormal short-term kidney status. We also observed substantial variation in contemporary medication use for pediatric lupus nephritis between pediatric rheumatology centers. Additional studies are needed to better understand the impact of this variation on long-term kidney outcomes.

Dosing Variation at Initiation of Adalimumab and Etanercept and Clinical Outcomes in Juvenile Idiopathic Arthritis: A Childhood Arthritis and Rheumatology Research Alliance Registry Study.

OBJECTIVE: To determine the dose-response relationship of tumor necrosis factor (TNF) inhibition in the treatment of juvenile idiopathic arthritis (JIA). METHODS: Participants of the Childhood Arthritis and Rheumatology Research Alliance Registry were eligible for inclusion in the analyses if they started TNF inhibition treatment for JIA. The primary treatment response was determined 3 to 7 months after the start of treatment, based on the JIA American College of Rheumatology Pediatric criteria for improvement, clinical Juvenile Arthritis Disease Activity Score, and persistence of treatment after 6 months. Subsequently, pooled logistic regression models were performed to include long-term follow-up data. The models were adjusted for risk factors associated with poor treatment response. Dosing was expressed by body weight, body surface area, ideal body weight, fat free mass, and lean body mass. RESULTS: Participants treated with adalimumab (n = 328) and etanercept (n = 437) were included in the analyses (median dose 0.82 mg/kg body weight [interquartile range (IQR) 0.66-1.04] and 0.83 mg/kg body weight [IQR 0.75-0.95], respectively). The majority of analyses did not show a relationship between dose and outcome. Where associations were found, results were conflicting. Alternative dosing characteristics based on ideal body weight, fat free mass, and lean body mass did not result in stronger or more consistent associations. CONCLUSION: This study was not able to confirm our hypothesis that increased dosing of TNF inhibitors results in improved treatment outcomes. Although adjustment was performed for risk factors of impaired treatment response, residual confounding by indication likely explains the negative associations found in this study.

Trajectories of disease activity in patients with JIA in the Childhood Arthritis and Rheumatology Research Alliance Registry.

OBJECTIVE: To describe 2-year trajectories of the clinical Juvenile Arthritis Disease Activity Score, 10 joints (cJADAS10) and associated baseline characteristics in patients with JIA. METHODS: JIA patients in the Childhood Arthritis and Rheumatology Research Alliance Registry enrolled within 3 months of diagnosis from 15 June 2015 to 6 December 2017 with at least two cJADAS10 scores and 24 months of follow-up were included. Latent growth curve models of cJADAS10 were analysed; a combination of Bayesian information criterion, posterior probabilities and clinical judgement was used to select model of best fit. RESULTS: Five trajectories were identified among the 746 included patients: High, Rapidly Decreasing (HRD) (n = 199, 26.7%); High, Slowly Decreasing (HSD) (n = 154, 20.6%); High, Increasing (HI) (n = 39, 5.2%); Moderate, Persistent (MP) (n = 218, 29.2%); and Moderate, Decreasing (MD) (n = 136, 18.2%). Most patients spent a significant portion of time at moderate to high disease activity levels. At baseline, HSD patients were more likely to be older, have a lower physician global assessment, normal inflammatory markers, longer time to first biologic, and have taken systemic steroids compared with HRD. Those with a HI trajectory were more likely to be ANA negative, have a longer time to first biologic, and less likely to be taking a conventional synthetic DMARD compared with HRD. MP patients were more likely to be older with lower household income, longer time to diagnosis, and markers of higher disease activity than those with a MD trajectory. CONCLUSIONS: Five trajectories of JIA disease activity, and associated baseline variables, were identified.

Disease Recapture Rates After Medication Discontinuation and Flare in Juvenile Idiopathic Arthritis: An Observational Study Within the Childhood Arthritis and Rheumatology Research Alliance Registry.

OBJECTIVE: Children with well-controlled juvenile idiopathic arthritis (JIA) frequently experience flares after medication discontinuation, but the outcomes of these flares have not been well described. The objective of this study was to characterize the rates and predictors of disease recapture among children with JIA who restarted medication to treat disease flare. METHODS: Children with JIA who discontinued conventional synthetic or biologic disease-modifying antirheumatic drugs for well-controlled disease but subsequently experienced a flare and restarted medication were identified from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry. The primary outcome was inactive disease (ID) (physician global assessment <1 and active joint count = 0) 6 months after flare. RESULTS: A total of 333 patients had complete data for ID at 6 months after flare. The recapture rate for the cohort was 55%, ranging from 47% (persistent oligoarthritis) to 69% (systemic arthritis) (P = 0.4). Approximately 67% of children achieved ID by 12 months. In the multivariable model, history and reinitiation of biologic drugs were associated with increased odds of successful recapture (odds ratio [OR] 4.79 [95% confidence interval (95% CI) 1.22-18.78] and OR 2.74 [95% CI 1.62-4.63], respectively). Number of joints with limited range of motion was associated with decreased odds (OR 0.83 per 1 joint increase [95% CI 0.72-0.95]). CONCLUSION: Approximately half of JIA flares post-discontinuation were recaptured within 6 months, but rates of recapture varied across JIA categories. These findings inform shared decision-making for patients, families, and clinicians regarding the risks and benefits of medication discontinuation. Better understanding of biologic predictors of successful recapture in JIA are needed.

First-line options for systemic juvenile idiopathic arthritis treatment: an observational study of Childhood Arthritis and Rheumatology Research Alliance Consensus Treatment Plans.

BACKGROUND: The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed consensus treatment plans (CTPs) to compare treatment initiation strategies for systemic juvenile idiopathic arthritis (sJIA). First-line options for sJIA treatment (FROST) was a prospective observational study to assess CTP outcomes using the CARRA Registry. METHODS: Patients with new-onset sJIA were enrolled if they received initial treatment according to the biologic CTPs (IL-1 or IL-6 inhibitor) or non-biologic CTPs (glucocorticoid (GC) monotherapy or methotrexate). CTPs could be used with or without systemic GC. Primary outcome was achievement of clinical inactive disease (CID) at 9 months without current use of GC. Due to the small numbers of patients in the non-biologic CTPs, no statistical comparisons were made between the CTPs. RESULTS: Seventy-three patients were enrolled: 63 (86%) in the biologic CTPs and 10 (14%) in the non-biologic CTPs. CTP choice appeared to be strongly influenced by physician preference. During the first month of follow-up, oral GC use was observed in 54% of biologic CTP patients and 90% of non-biologic CTPs patients. Five (50%) non-biologic CTP patients subsequently received biologics within 4 months of follow-up. Overall, 30/53 (57%) of patients achieved CID at 9 months without current GC use. CONCLUSION: Nearly all patients received treatment with biologics during the study period, and 46% of biologic CTP patients did not receive oral GC within the first month of treatment. The majority of patients had favorable short-term clinical outcomes. Increased use of biologics and decreased use of GC may lead to improved outcomes in sJIA.

Intraarticular steroids as DMARD-sparing agents for juvenile idiopathic arthritis flares: Analysis of the Childhood Arthritis and Rheumatology Research Alliance Registry

BACKGROUND: Children with juvenile idiopathic arthritis (JIA) who achieve a drug free remission often experience a flare of their disease requiring either intraarticular steroids (IAS) or systemic treatment with disease modifying anti-rheumatic drugs (DMARDs). IAS offer an opportunity to recapture disease control and avoid exposure to side effects from systemic immunosuppression. We examined a cohort of patients treated with IAS after drug free remission and report the probability of restarting systemic treatment within 12 months. METHODS: We analyzed a cohort of patients from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry who received IAS for a flare after a period of drug free remission. Historical factors and clinical characteristics and of the patients including data obtained at the time of treatment were analyzed. RESULTS: We identified 46 patients who met the inclusion criteria. Of those with follow up data available 49% had restarted systemic treatment 6 months after IAS injection and 70% had restarted systemic treatment at 12 months. The proportion of patients with prior use of a biologic DMARD was the only factor that differed between patients who restarted systemic treatment those who did not, both at 6 months (79% vs 35%, p < 0.01) and 12 months (81% vs 33%, p < 0.05). CONCLUSION: While IAS are an option for all patients who flare after drug free remission, it may not prevent the need to restart systemic treatment. Prior use of a biologic DMARD may predict lack of success for IAS. Those who previously received methotrexate only, on the other hand, are excellent candidates for IAS.

Investigation of Inactive Disease States Among Patients With Juvenile Idiopathic Arthritis in the Childhood Arthritis and Rheumatology Research Alliance Registry.

OBJECTIVE: Inactive disease is the treatment goal for juvenile idiopathic arthritis (JIA), but there are multiple measures for disease activity. The objective was to compare individuals with JIA who meet different definitions for inactive disease. METHODS: Disease activity measures were determined at the 1-year follow-up visit for all patients with JIA enrolled in a North American multicenter registry from 2015 to 2019, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Patient and disease characteristics between those who met only one composite definition of inactive disease were compared by χ2 for categorical variables and Wilcoxon rank sum for continuous variables. The Spearman correlation coefficient was calculated for simple disease measures. RESULTS: Among all 2904 patients with JIA enrolled in the CARRA Registry with 1-year visit data, 1984 (68%) had no active joints, 1485 (51%) had a physician global score of 0, 1366 (47%) had a patient/parent global score of 0, 1293 (45%) met the American College of Rheumatology provisional criteria for clinical inactive disease (ACR CID), and 1325 (46%) had a clinical Juvenile Arthritis Disease Activity Score (cJADAS10) of 1 or less. Almost half (47%) did not meet either composite definition of inactive disease, and 38% met both ACR CID and cJADAS10 of 1 or less. CONCLUSION: In a multicenter cohort of patients with JIA in North America, a large proportion of patients had inactive disease by single or composite measures after 1 year of observation in the Registry. There was significant overlap between patients who met ACR CID criteria and those who had a cJADAS10 of 1 or less. Additional studies are needed to evaluate the reasons for discordance in inactive disease measures.

Psoriasis rate is increased by the exposure to TNF inhibition in children with JIA.

OBJECTIVE: We aimed to investigate the relationship between tumour necrosis factor inhibitors (TNFi) therapy and the onset of new psoriasis in children with juvenile idiopathic arthritis (JIA) using Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry data. METHODS: De-identified data were obtained from the CARRA Registry. Patients with inflammatory bowel disease or psoriasis documented on or prior to JIA diagnosis date or with incomplete data were excluded. Exposure to TNFi was categorised as: (1) ever use; (2) current use or (3) first use only. Adjusted HRs (aHRs) were calculated between exposed and unexposed groups adjusted for methotrexate exposure, sex, race, family history of psoriasis and initial JIA category. RESULTS: A total of 8225 patients were included with a median follow-up of 3.9 years. Over half of the patients were prescribed TNFi (n=4437, 54%). The aHR of new onset of psoriasis after ever exposure to TNFi was 2.93 (2.15 to 3.98). The incidence rate of psoriasis was the highest in children ever receiving and actively receiving adalimumab. Ever concurrent methotrexate use (HR 0.45, 0.29 to 0.69) was associated with lower risk. CONCLUSION: In a large prospective JIA patient registry, we observed a nearly threefold increased risk of psoriasis after TNFi exposureCite Now.

Effectiveness and Safety of High-Dose Biologics in Juvenile Idiopathic Arthritis in the Childhood Arthritis and Rheumatology Research Alliance.

OBJECTIVE: To describe high-dose biologic use when treating juvenile idiopathic arthritis (JIA). METHODS: Patients with JIA enrolled in the Childhood Arthritis and Rheumatology Research Alliance Registry and treated with a biologic after enrollment were eligible. We described the frequency of high-dose biologic use and characteristics of patients receiving high-dose biologics. We used regression modeling to compare 6-month outcomes (using disease activity measures) between those who increased their biologic from standard to high dose (high-dose group) to those who initiated and remained on standard dosing (no-change group), and to those who switched biologic agents (biologic-switch group). We also compared serious adverse events (SAEs) between groups. RESULTS: A total of 5,352 patients with JIA were treated with biologics following enrollment; 1,080 (20%) had ever received a high-dose biologic. There were no significant differences in outcomes between the high-dose group and the biologic-switch group; both improved disease activity measures, including the clinical Juvenile Arthritis Disease Activity Score 10 (-3.53 and -3.95, respectively; P = 0.68). Although the SAE rates in the high-dose group and the biologic-switch group were numerically higher than the no-change group, the event rates were similar, and neither rate was significantly higher than in the no-change group (unadjusted incident rate ratio 2.5 [95% confidence interval (95% CI) 0.7-8.5] and 1.8 [95% CI 0.7-4.6], respectively). CONCLUSION: Dosing escalation appears to be a reasonable choice to improve disease control, but large, prospective, randomized studies evaluating specific biologic agents are needed.

Pharmacosurveillance in Juvenile Idiopathic Arthritis.

The advent of biologic disease-modifying antirheumatic drugs targeting specific cytokines or cell-cell interactions has dramatically changed the outlook of patients with juvenile idiopathic arthritis. However, safety concerns remain around the use of therapeutic agents for children with juvenile idiopathic arthritis. Foremost among these are the risks of serious infections and malignancy. This article provides an overview of methodologies for pharmacosurveillance in juvenile idiopathic arthritis, including spontaneous reporting systems and the use of diverse data sources, such as electronic health records, administrative claims, and clinical registries. The risks of infections and malignancies are then briefly reviewed.