Long-term efficacy and safety of subcutaneous tocilizumab in clinical trials of polyarticular or systemic juvenile idiopathic arthritis.

OBJECTIVE: To investigate the safety and efficacy of subcutaneous tocilizumab (SC-TCZ) treatment in a long-term extension (LTE) of clinical trials in polyarticular or systemic juvenile idiopathic arthritis (pJIA or sJIA). METHODS: Patients with pJIA or sJIA from two open-label, 52-week phase 1b core trials of SC-TCZ who had adequate response per investigator assessment entered the LTE and continued SC-TCZ treatment according to body weight-based dosing regimens until commercial availability or up to 5 years. Pharmacokinetics, pharmacodynamics, and efficacy were assessed for up to 3 years, and safety for up to 5 years in the LTE. RESULTS: Forty-four patients with pJIA and 38 patients with sJIA entered the LTE. Tocilizumab trough concentrations were maintained within the range expected to provide clinical benefit (mean values: pJIA, ∼10 µg/ml; sJIA, ∼75 µg/ml over 3 years). Pharmacodynamic parameters (interleukin-6, soluble interleukin-6 receptor, erythrocyte sedimentation rate, C-reactive protein) were maintained throughout the LTE at levels achieved in the core trials. Inactive disease per American College of Rheumatology provisional criteria was reported for 90% (17/19) and 53% (8/15) of patients with pJIA and 91% (10/11) and 92% (12/13) of patients with sJIA in the <30 and ≥30 kg body weight groups, respectively. Serious adverse events in the LTE were reported in six patients with pJIA (13.6%; five serious infections) and five patients with sJIA (13.2%; one serious infection). CONCLUSION: Patients with pJIA or sJIA experienced long-term disease control with SC-TCZ treatment. Long-term safety was consistent with the known tocilizumab safety profile. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, NCT02165345.

Childhood Sjögren syndrome: features of an international cohort and application of the 2016 ACR/EULAR classification criteria.

OBJECTIVE: Sjögren syndrome in children is a poorly understood autoimmune disease. We aimed to describe the clinical and diagnostic features of children diagnosed with Sjögren syndrome and explore how the 2016 ACR/EULAR classification criteria apply to this population. METHODS: An international workgroup retrospectively collected cases of Sjögren syndrome diagnosed under 18 years of age from 23 centres across eight nations. We analysed patterns of symptoms, diagnostic workup, and applied the 2016 ACR/EULAR classification criteria. RESULTS: We identified 300 children with Sjögren syndrome. The majority of patients n = 232 (77%) did not meet 2016 ACR/EULAR classification criteria, but n = 110 (37%) did not have sufficient testing done to even possibly achieve the score necessary to meet criteria. Even among those children with all criteria items tested, only 36% met criteria. The most common non-sicca symptoms were arthralgia [n = 161 (54%)] and parotitis [n = 140 (47%)] with parotitis inversely correlating with age. CONCLUSION: Sjögren syndrome in children can present at any age. Recurrent or persistent parotitis and arthralgias are common symptoms that should prompt clinicians to consider the possibility of Sjögren syndrome. The majority of children diagnosed with Sjögren syndromes did not meet 2016 ACR/EULAR classification criteria. Comprehensive diagnostic testing from the 2016 ACR/EULAR criteria are not universally performed. This may lead to under-recognition and emphasizes a need for further research including creation of paediatric-specific classification criteria.

Outcomes from a Multidisciplinary Otolaryngology and Rheumatology Clinic for the Management of Chronic Sialadenitis.

OBJECTIVE: Determine the outcomes in children with recurrent sialadenitis after establishment of a multidisciplinary pediatric otolaryngology and rheumatology clinic. STUDY DESIGN: Retrospective review. SETTING: Single-center tertiary medical center. METHODS: We reviewed all children presenting to a multidisciplinary pediatric otolaryngology/rheumatology clinic with recurrent parotitis between December 2019 and April 2023. RESULTS: Thirty-three children presented with recurrent parotitis to a multidisciplinary clinic. Seventy-seven percent of those with childhood Sjögren's disease (cSjD) had xerophthalmia, and 67% had xerostomia. The cSjD group was more likely to have both abnormal parotid and submandibular findings when compared to the non-cSjD group (P < .001). Sixteen percent of the cSjD group had a positive SSA/SSB autoantibody and 47% were antinuclear antibody positive. Fifty percent of the cSjD cohort had a focus score of ≥1 from a minor salivary gland biopsy. There were no significant differences from sialendoscopy outcome between the 2 groups. Seventy percent with juvenile recurrent parotitis showed partial response (PR) or complete response (CR) to sialendoscopy. In the cSjD cohort 3 (27%) reported a CR and 5 (45%) reported a PR. In the non csSjD cohort 5 (42%) reported a CR and 3 (25%) reported a PR. Ten of the 12 cSjD patients on hydroxychloroquine have shown symptom improvement. CONCLUSION: The establishment of a multidisciplinary otolaryngology and rheumatology clinic can provide a more comprehensive evaluation and treatment of the child with recurrent or persistent parotitis than from a regular ENT clinic.

Feasibility of Conducting Comparative Effectiveness Research and Validation of a Clinical Disease Activity Score for Chronic Nonbacterial Osteomyelitis.

OBJECTIVE: Prospective comparative effectiveness research (CER) in chronic nonbacterial osteomyelitis (CNO) is lacking. Our objectives were to (1) determine the use and safety of each consensus treatment plan (CTP) regimen for CNO, (2) assess the feasibility of using the Chronic Nonbacterial Osteomyelitis International Registry (CHOIR) data for CER, and (3) develop and validate a CNO clinical disease activity score (CDAS) using CHOIR. METHODS: Consenting children or young adults with CNO were enrolled into CHOIR. Demographic, clinical, and imaging data were prospectively collected. The CNO CDAS was developed through a Delphi survey and nominal group technique. External validation surveys were administered to CHOIR participants. RESULTS: One hundred forty (78.2%) CHOIR participants enrolled between August 2018 and September 2020 received at least 1 CTP regimen. Baseline characteristics from different CTP groups were well matched. Patient pain, patient global assessment, and clinical CNO lesion count were key variables included in the CNO CDAS. The CDAS showed a strong correlation with patient/parent report of difficulty using a limb, back, or jaw and patient/parent report of disease severity, but a weak correlation with patient/parent report of fatigue, sadness, and worry. The change in CDAS was significant in patients reporting disease worsening or improvement (P < 0.001). The CDAS significantly decreased after initiating second-line treatments from median 12.0 (IQR 8.0-15.5) to 5.0 (IQR 3.0-12.0; P = 0.002). Although second-line treatments were well tolerated, psoriasis was the most common adverse event. CONCLUSION: The CNO CDAS was developed and validated for disease monitoring and assessment of treatment effectiveness. CHOIR provided a comprehensive framework for future CER.

Pediatric rheumatologists' perspectives on diagnosis, treatment, and outcomes of Sjögren disease in children and adolescents.

BACKGROUND: Sjögren disease in children and adolescents (pedSD) presents differently than adult disease. Diagnosis and classification are controversial, optimal treatment is unknown and outcomes are poorly understood. Here, we describe the current perspectives of pediatric rheumatologists on diagnosis, treatment, and outcomes of pedSD. METHODS: A voluntary, 17-question survey was distributed to providers in the Childhood Arthritis and Rheumatology Research Alliance and/or the American College of Rheumatology Childhood Sjögren's Study Group at the 2020 Convergence Virtual Conference. Findings are reported using descriptive statistics and chi-square testing. RESULTS: Of 465 eligible providers, 157 (34%) responded with 135 (29%) completing the survey. The majority (85%) saw five or fewer patients with pedSD in the past year. Parotitis, dry eye and/or dry mouth, and constitutional symptoms were among the most specific and common clinical features. Most providers (77%) used clinical judgment guided by adult criteria for diagnosis. The vast majority (86-99%) of survey participants indicated routine use of serologic testing, while salivary gland ultrasound, minor salivary gland biopsy and other diagnostic tests were less often used. The most commonly prescribed systemic immunomodulators were hydroxychloroquine, corticosteroids, methotrexate, rituximab, and mycophenolate. Seven providers reported malignancy in a patient with pedSD, including one death. CONCLUSIONS: Pediatric rheumatologists diagnose and treat pedSD; however, most only see a few patients per year and rely on clinical judgment and laboratory testing for diagnosis. Treatment frequently includes systemic immunomodulators and malignancies are reported. More studies are needed to better understand natural history, risk factors, and the impact of interventions on outcomes.

Sjögren's syndrome in children with recurrent parotitis.

OBJECTIVE: Optimize the diagnosis of pediatric Sjögren's syndrome in children who present with parotitis. METHODS: Twenty children presented to a pediatric otolaryngology or rheumatology clinic with recurrent parotitis. Presenting symptoms, serologies, sialendoscopy findings, and minor salivary gland biopsy pathology results were reviewed. RESULTS: Twenty patients aged 3-17 years presented with recurrent parotitis. Ten percent of this cohort met the American-European Consensus Group adult diagnostic criteria for Sjögren's syndrome. Forty percent of this cohort met diagnosis of Sjögren's syndrome when utilizing Bartunkova's proposed pediatric criteria for diagnosis of Sjögren's syndrome. CONCLUSION: Sjögren's syndrome is surprisingly common in pediatric patients who present with recurrent parotitis. Otolaryngologists who treat pediatric parotitis should have a high index of suspicion for Sjögren's syndrome. LEVEL OF EVIDENCE: 4.

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.

Consensus Treatment Plans for Chronic Nonbacterial Osteomyelitis Refractory to Nonsteroidal Antiinflammatory Drugs and/or With Active Spinal Lesions.

OBJECTIVE: To develop standardized treatment regimens for chronic nonbacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis (CRMO), to enable comparative effectiveness treatment studies. METHODS: Virtual and face-to-face discussions and meetings were held within the CNO/CRMO subgroup of the Childhood Arthritis and Rheumatology Research Alliance (CARRA). A literature search was conducted, and CARRA membership was surveyed to evaluate available treatment data and identify current treatment practices. Nominal group technique was used to achieve consensus on treatment plans for CNO refractory to nonsteroidal antiinflammatory drug (NSAID) monotherapy and/or with active spinal lesions. RESULTS: Three consensus treatment plans (CTPs) were developed for the first 12 months of therapy for CNO patients refractory to NSAID monotherapy and/or with active spinal lesions. The 3 CTPs are methotrexate or sulfasalazine, tumor necrosis factor inhibitors with optional methotrexate, and bisphosphonates. Short courses of glucocorticoids and continuation of NSAIDs are permitted for all regimens. Consensus was achieved on these CTPs among CARRA members. Consensus was also reached on subject eligibility criteria, initial evaluations that should be conducted prior to the initiation of CTPs, and data items to collect to assess treatment response. CONCLUSION: Three consensus treatment plans were developed for pediatric patients with CNO refractory to NSAIDs and/or with active spinal lesions. Use of these CTPs will provide additional information on efficacy and will generate meaningful data for comparative effectiveness research in CNO.

Autoinflammatory bone diseases.

Autoinflammatory bone disease is a new branch of autoinflammatory diseases caused by seemingly unprovoked activation of the innate immune system leading to an osseous inflammatory process. The inflammatory bone lesions in these disorders are characterized by chronic inflammation that is typically culture negative with no demonstrable organism on histopathology. The most common autoinflammatory bone diseases in childhood include chronic nonbacterial osteomyelitis (CNO), synovitis, acne, pustulosis, hyperostosis, osteitis syndrome, Majeed syndrome, deficiency of interleukin-1 receptor antagonist, and cherubism. In this article, the authors focus on CNO and summarize the distinct genetic autoinflammatory bone syndromes.