Daniel J. Lovell

Objective: The purpose of this study was to assess the pharmacokinetics, effectiveness, safety, and immunogenicity of certolizumab pegol (CZP) in polyarticular‐course juvenile idiopathic arthritis (pcJIA). Methods: Pediatric Arthritis Study of Certolizumab Pegol (NCT01550003), a multicenter, open‐label study, enrolled patients aged 2 to 17 years with active pcJIA and inadequate response or intolerance to at least one disease‐modifying antirheumatic drug. Original CZP doses, based on pharmacokinetic model simulations, included loading and then 50, 100, or 200 mg maintenance doses once every two weeks for patients 10 to <20, 20 to 79.0% by Wk12) and associated with lower CZP concentrations, but it maintained response to CZP. Conclusion: Open‐label CZP treatment demonstrated rapid, long‐term clinical improvements, an acceptable safety profile, and tolerability in patients with pcJIA. No new safety signals were identified.

Objective: To evaluate the timeline for resolution of sacroiliac joint (SIJ) inflammation, changes in structural lesions, and their correlation with patient‐reported outcomes (PROs) in youth with axial juvenile spondyloarthritis (axJSpA) initiating tumor necrosis factor inhibitor (TNFi). Methods: This prospective, multicenter study included youth aged 8 to 18 years with a clinical diagnosis of axJSpA starting TNFi. Assessments were conducted at baseline and 12 weeks, including clinical evaluation, magnetic resonance imaging (MRI), and PROs. Participants with persistent SIJ inflammation at 12 weeks were reassessed at 24 weeks. Three blinded reviewers evaluated MRIs using Spondyloarthritis Research Consortium of Canada SIJ inflammation scores (SIS) and SIJ structural scores. Results: Of 75 enrolled participants, 73 completed baseline visits, and 62 had MRI‐confirmed axJSpA. Fifty‐seven completed a 12‐week follow‐up; 89% (51 of 57) showed SIS improvement, and 63% (36 of 57) achieved inflammation resolution (SIS <2). Median SIS change from baseline to 12 weeks was −8 (interquartile range: −18 to −3). Among those with persistent inflammation at 12 weeks (n = 26), 85% reported at least moderate clinical improvement. At 24 weeks, 56% (14 of 25) had ongoing inflammation. A total of 84% of SIS improvement occurred within the first 12 weeks. In patients with at least two scans, structural lesion scores decreased, increased, or stayed the same from baseline to the 12‐week scan for erosions (58%/25%/18%), sclerosis (21%/9%/70%), fat metaplasia (0%/30%/70%), and backfill (4%/28%/68%). Conclusion: Most participants showed early imaging response to TNFi, with most improvement occurring within 12 weeks. Despite residual inflammation persisting in nearly half of patients, most reported symptom improvement, underscoring both the rapid impact of TNFi and the heterogeneity of treatment effects. image

Objective: We aimed to validate the Pediatric Arthritis Ultrasound Scoring System (PAUSS) for upper extremity joints in children with juvenile idiopathic arthritis (JIA). Methods: Children with JIA were evaluated for elbow, wrist, or finger arthritis by clinical examination (CE) and musculoskeletal ultrasound (MSUS) with images scored according to the joint‐specific PAUSS. A subset of children received contrast‐enhanced magnetic resonance imaging (ceMRI) of the affected joint(s). The performance of the PAUSS as a measure of arthritis activity was compared to CE and ceMRI, using ceMRI as the reference standard. Results: Seventy‐five children contributed 44 elbows, 55 wrists, and 106 fingers for MSUS and 15 elbows, 16 wrists, and 40 fingers for ceMRI. B‐mode PAUSS scores for the finger joints demonstrated moderate correlations with CE findings of arthritis, and the PAUSS‐elbow noted a strong correlation. PAUSS scores for all joints showed a sensitivity of 75% to 94% in detecting synovitis when compared to ceMRI and good to excellent diagnostic accuracy for elbow and finger arthritis. The addition of MSUS to CE markedly improved the sensitivity of CE to 92% to 100%. The PAUSS and ceMRI scores for assessment of disease severity had strong correlation for each specific joint ( r = 0.65–0.84, P ≤ 0.005). Conclusion: There is moderate to high sensitivity and diagnostic accuracy of the PAUSS in detecting synovitis in elbow, wrist, and finger joints, as well as a strong correlation of the PAUSS severity scores with the ceMRI severity scores, providing strong support that the PAUSS enhances the clinical assessment of disease activity in children with JIA.

Objective: Juvenile idiopathic arthritis (JIA) is associated with impaired overall health‐related quality of life (HRQoL). We evaluated the impact of tofacitinib on patient‐reported outcomes (PROs) in patients with JIA. Methods: This was a post hoc analysis of a phase 3, randomized, double‐blind, placebo‐controlled withdrawal trial (NCT02592434) in patients with JIA. In the open‐label phase (part 1; weeks 0–18), patients received body weight–based doses of tofacitinib. During the double‐blind phase (part 2; weeks 18–44), responders (per JIA‐American College of Rheumatology 30 response criteria) were randomized 1:1 to continue tofacitinib or switch to placebo for up to 26 weeks. Assessed PROs included the validated parent and/or legal guardian versions of the Childhood Health Assessment Questionnaire for evaluation of disability, arthritis pain, overall well‐being, and the Child Health Questionnaire (CHQ). Results: Overall, 225 patients were enrolled and received open‐label tofacitinib in part 1, and 173 patients were randomized in part 2. During part 1, least‐squares (LS) mean (SE) disability, arthritis pain, and overall well‐being scores numerically improved from mean 1.04 (SE 0.05), mean 5.53 (SE 0.20), and mean 5.07 (SE 0.20) at baseline to mean 0.57 (SE 0.05), mean 2.46 (SE 0.18), and mean 2.47 (SE 0.18) at week 18, respectively. LS mean (SE) CHQ physical summary and psychological summary scores numerically improved from mean 29.51 (SE 1.15) and mean 47.24 (SE 0.85) at baseline to mean 42.70 (SE 0.98) and mean 51.53 (SE 0.80) at week 18, respectively. Improvements were generally maintained to week 44 in part 2. Conclusion: Tofacitinib improved a range of PROs in patients with JIA, suggesting potential HRQoL benefits.

Objective: We evaluate tofacitinib efficacy and safety in patients with juvenile idiopathic arthritis (JIA) stratified by concomitant methotrexate and prior biologic disease‐modifying antirheumatic drug (bDMARD) treatment. Methods: In this two part, double‐blind, randomized withdrawal Phase 3 trial (NCT02592434), patients (2–<18 years) with JIA received open‐label tofacitinib (5 mg twice daily/weight‐based equivalent) in Part 1 (Day 1–Week 18). Those eligible were randomized to continue tofacitinib or switch to placebo in Part 2 (Weeks 18–44). In this post hoc analysis, patients were stratified by concomitant methotrexate (MTX+/−) and prior bDMARD treatment (bDMARD+/−). Efficacy outcomes included JIA disease flare, JIA/American College of Rheumatology (ACR) 50/70 response rates, and JIA/ACR clinical inactive disease (CID). Safety was assessed throughout the trial. Results: Of 225 patients in Part 1, 147 (65.3%) were MTX+; 85 (37.8%) were bDMARD+. Across subgroups, JIA flare rate at Week 44 was lower with tofacitinib than placebo: patients who were MTX+ (29.8% vs 47.5%), patients who were MTX− (32.3% vs 73.1%), patients who were bDMARD+ (29.0% vs 70.4%), patients who were bDMARD− (31.6% vs 48.3%). Greater JIA/ACR50/70 and JIA/ACR‐CID responses with tofacitinib than with placebo were observed across subgroups. In tofacitinib‐treated patients, adverse events (AEs) were more common in the subgroups of patients who were MTX− (85.9%) and patients who were bDMARD+ (81.2%) than the subgroups of patients who were MTX+ (74.1%) and patients who were bDMARD− (76.4%). Similar findings were observed with serious AEs/discontinuations due to AEs. Conclusion: Tofacitinib was efficacious for patients regardless of baseline concomitant MTX treatment or prior bDMARD exposure; MTX may have a protective effect for flare upon tofacitinib withdrawal. Safety was consistent with the known tofacitinib profile, and no new risks were identified in these subgroups.

Background/Objectives: Juvenile Idiopathic Arthritis (JIA) is the most common autoimmune rheumatic disease in children and can vary in presentation based on the properties of the JIA subtypes. Timely diagnosis and intervention are essential for maximizing quality of life, healthy growth and development, and prevention of long-term disability. This review aims to provide a clinically practical framework for the core elements important in recognition, monitoring, and management of JIA. Methods: We performed a narrative review of the current literature, complemented by real-world clinical experience from academic rheumatology practice. The review synthesizes evidence-based knowledge with practical insights to develop an approach that can be applied in daily clinical decision-making. Results: We propose a structured, stepwise method for evaluating suspected JIA, emphasizing the integration of pattern recognition with differential diagnosis. Our framework emphasizes two principal parameters: (1) the distribution of joint involvement (peripheral vs. axial) and (2) the presence of extra-articular manifestations, including uveitis, cutaneous findings, and gastrointestinal symptoms. This format aids in distinguishing major JIA subtypes and highlights their distinctive features. In addition, we review overarching principles for monitoring, assessing risk for uveitis, and treatment, and the importance of multidisciplinary care. Conclusions: This structured approach is intended to support clinicians in the accurate recognition of JIA and its subtypes, facilitate early diagnosis, and provide insights on management strategies that improve patient outcomes.

Objective: The objective of this study was to determine a core set of measures for youth with juvenile spondyloarthritis and axial disease (axJSpA), using the juvenile arthritis working group Outcome Measures in Rheumatology framework.Methods: This was a prospective multicenter study of youth with axJSpA. Participants (aged 8–18 years) all initiated tumor necrosis factor inhibitor (TNFi) therapy and completed questionnaires, examinations, and magnetic resonance imaging (MRI) at baseline and 12 weeks. Responsiveness and discrimination were assessed using standardized response mean (SRM) and standardized mean difference (SMD). For highly correlated (r > |0.80|) items within domains, larger SRM and SMD were prioritized, and minimal clinically important improvement was determined for each.Results: Of the evaluable cohort (N = 57), 68.4% were male, and the median age was 15.3 years; 70.2% of youth treated with TNFi had clinical response (change ≥2 in patient global assessment). Although 58% had continued MRI inflammation, 77% of those patients reported moderate clinical improvement. The final axJSpA core set contained the following: Patient‐Reported Outcomes Measurement Information System (PROMIS) pain interference (SRM 0.77, SMD 0.5), the sacroiliac joint inflammation score (SRM 1.02, SMD 0.52), PROMIS mobility (SRM 0.83, SMD 0.75), and patient global well‐being (SRM 0.88, SMD not applicable). All overall and composite disease activity measures tested, except the physician global assessment, had high SRM and SMD. Subgroup analysis demonstrated differences by biologic sex and overweight status. Improvement in the MRI inflammation score was greater in male patients. Improvement in the PROMIS pain interference and mobility measures was greater in those with normal body mass index.Conclusion: A set of measures was developed for youth with axJSpA. image

Objective: To evaluate rates of clinically inactive disease (CID) and remission in patients with juvenile idiopathic arthritis (JIA) receiving tofacitinib using the 2021 Juvenile Arthritis Disease Activity Score (JADAS) thresholds and American College of Rheumatology (ACR) criteria. Methods: This post hoc analysis included patients with active JIA (polyarticular-course JIA, psoriatic arthritis, or enthesitis-related arthritis) enrolled in a phase III randomized withdrawal study of tofacitinib. In part 1 (weeks 0-18), patients received open-label tofacitinib. In part 2 (weeks 18-44), patients who achieved ACR improvement ≥ 30% were randomized to tofacitinib or placebo for 26 weeks or until JIA flare. Disease activity was assessed using the JADAS in 10 joints (JADAS10) based on C-reactive protein, with interpretation according to 2021 polyarthritis thresholds. JADAS10 remission was defined as ≥ 24 continuous weeks of JADAS10 CID (JADAS10-CID). ACR CID (ACR-CID) and ACR clinical remission were also assessed. Results: Of 225 patients with JIA in part 1, 173 (76.9%) were randomized in part 2 to continue tofacitinib or switch to placebo. Rates of JADAS10-CID and ACR-CID increased throughout part 1 to 30.5% and 15.8% (week 18), respectively. In part 2, these were sustained with tofacitinib (week 44: 35.2% [JADAS10-CID], 25% [ACR-CID]) and decreased when patients switched to placebo (week 44: 25.9% [JADAS10-CID], 15.3% [ACR-CID]). A small proportion of patients achieved JADAS10 remission at week 44 (tofacitinib: 14.8%; placebo: 7.1%). Conclusion: In patients with JIA receiving tofacitinib, JADAS10-CID and ACR-CID rates improved rapidly and were sustained over time, and a small proportion of patients achieved JADAS10 remission. Inactive disease is a feasible treatment target in patients receiving tofacitinib. (ClinicalTrials.gov: NCT02592434)

Objective: We evaluated the efficacy and safety profiles of JAK inhibitors (JAKi) and biologic disease‐modifying antirheumatic drugs (bDMARDs) when used with or without methotrexate (MTX) for the treatment of nonsystemic forms of juvenile idiopathic arthritis (nsJIA).Methods: Randomized clinical trials (RCTs) investigating efficacy and safety outcomes of JAKi or bDMARDs for the nsJIA population up to 2023 were searched in ClinicalTrial.gov, PubMed, EMBASE, and Cochrane databases. Bayesian arm‐based network meta‐analysis compared efficacy as measured by Juvenile Idiopathic Arthritis‐American College of Rheumatology 70 (JIA‐ACR70) improvement and safety based on rates of serious adverse events (SAEs) among all therapies.Results: Eligible studies included 45 citations from 16 RCTs (7 parallel and 9 withdrawal trials) with a total of 1,821 participants that investigated nine bDMARDs, three with and six without MTX co‐treatment, and two JAKis (tofacitinib and baricitnib). The reported SAE incidence rates ranged from 0 to 0.3 per person‐year of follow‐up; none of the pairwise comparisons were statistically significant. The JIA‐ACR70 improvement by 16 weeks of treatment ranged from 11.3% to 89.5%. Compared with controls, significant JIA‐ACR70 improvements were observed for etanercept, golimumab, and all three combination therapies (adalimumab+MTX, etanercept+MTX, and infliximab+MTX), with odds ratios ranging from 2.97 to 3.99. No significant pairwise comparisons between bDMARDs and JAKi versus bDMARDs were noted.Conclusion: Overall, no significant evidence was found for efficacy and safety profiles in pairwise comparisons of JAKis and bDMARDs. Future studies will expand the meta‐analysis by including non‐RCT studies and individual participant data. image