Progression Of Radiographic Joint Damage Research Articles

Applications of Diffusion-Weighted MRI to the Musculoskeletal System.

Diffusion-weighted imaging (DWI) is an established MRI technique that can investigate tissue microstructure at the scale of a few micrometers. Musculoskeletal tissues typically have a highly ordered structure to fulfill their functions and therefore represent an optimal application of DWI. Even more since disruption of tissue organization affects its biomechanical properties and may indicate irreversible damage. The application of DWI to the musculoskeletal system faces application-specific challenges on data acquisition including susceptibility effects, the low T2 relaxation time of most musculoskeletal tissues (2-70 msec) and the need for sub-millimetric resolution. Thus, musculoskeletal applications have been an area of development of new DWI methods. In this review, we provide an overview of the technical aspects of DWI acquisition including diffusion-weighting, MRI pulse sequences and different diffusion regimes to study tissue microstructure. For each tissue type (growth plate, articular cartilage, muscle, bone marrow, intervertebral discs, ligaments, tendons, menisci, and synovium), the rationale for the use of DWI and clinical studies in support of its use as a biomarker are presented. The review describes studies showing that DTI of the growth plate has predictive value for child growth and that DTI of articular cartilage has potential to predict the radiographic progression of joint damage in early stages of osteoarthritis. DTI has been used extensively in skeletal muscle where it has shown potential to detect microstructural and functional changes in a wide range of muscle pathologies. DWI of bone marrow showed to be a valuable tool for the diagnosis of benign and malignant acute vertebral fractures and bone metastases. DTI and diffusion kurtosis have been investigated as markers of early intervertebral disc degeneration and lower back pain. Finally, promising new applications of DTI to anterior cruciate ligament grafts and synovium are presented. The review ends with an overview of the use of DWI in clinical routine. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 3.

68Ga-FAPI PET/CT for Rheumatoid Arthritis: A Prospective Study.

Background In rheumatoid arthritis (RA), fibroblast-like synoviocyte cells, which are involved in inflammation of the articular cartilage and bone, overexpress fibroblast activation protein (FAP). This is a feature that could be leveraged to improve imaging assessment of disease. Purpose To determine the performance of gallium 68 (68Ga)-labeled FAP inhibitor (FAPI) in assessing joint disease activity of RA and to compare with fluorine 18 (18F) fluorodeoxyglucose (FDG) imaging. Materials and Methods Twenty participants with RA (15 women; mean age, 55 years ± 10 [SD]) were prospectively enrolled from September 2020 to December 2021 and underwent clinical and laboratory assessment of disease activity and dual-tracer PET/CT (68Ga-FAPI and 18F-FDG) imaging. Imaging-derived variables of PET joint count (the number of joints positive for RA at PET) and PET articular index (a sum of the points of the joints using a three-point scale) were correlated to clinical and laboratory variables of disease activity. Results The combined output of both PET/CT techniques helped detect 244 affected joints, all of which showed positive results at 68Ga-FAPI PET/CT. However, fifteen of 244 (6.1%) FAPI-avid joints in six of 20 (30%) participants were not detected at 18F-FDG PET/CT. The maximum standardized uptake value of the most affected joint in each participant was higher in 68Ga-FAPI than in 18F-FDG PET/CT (9.54 ± 4.92 vs 5.85 ± 2.81, respectively; P = .001). The maximum standardized uptake values of the joints at both 68Ga-FAPI and 18F-FDG PET/CT were positively correlated with laboratory evaluation of C-reactive protein levels (r = 0.49 [P = .03] and 0.54 [P = .01], respectively). The PET joint count and PET articular index scores at 68Ga-FAPI PET/CT were also positively correlated with most clinical disease activity variables and radiographic progression of joint damage (P < .05). Conclusion In participants with rheumatoid arthritis who underwent gallium 68 fibroblast activation protein inhibitor PET/CT, the extent of joint involvement correlated with clinical and laboratory variables of disease activity and showed a greater amount and degree of affected joints than at fluorine 18 fluorodeoxyglucose PET/CT. Clinical trial registration no. NCT04514614 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Williams and Ahlman in this issue.

Frequency of joint inflammation is associated with local joint damage progression in rheumatoid arthritis despite long-term targeted treatment

ObjectivesTo investigate whether in rheumatoid arthritis (RA) frequency of local joint inflammation is associated with radiographic joint damage progression in that joint.MethodsData from 473 patients with RA and available radiographs...

Effectiveness of Telemedicine Compared with Standard Care for Patients with Rheumatic Diseases: A Systematic Review.

Objective: The aim of this study was to systematically review the evidence on the effectiveness of telemedicine compared to standard care for patients with rheumatic diseases. Methods: A search was performed in MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews; for the gray literature, GREYNET databases and a snowball search were used. MeSH or Emtree terms. Three authors independently selected systematic reviews, randomized controlled trail (RCTs), or non-RCTs with patients with autoimmune or inflammatory rheumatic diseases, where telemedicine was compared with standard care. Effectiveness was measured in terms of disease activity, quality of life, and functional activity. The patients' satisfaction was also measured. The risk of bias was assessed by the Cochrane collaboration tool for RCTs and AMSTAR II for systematic reviews. Results: Four RCTs, one cross-out study, and five systematic reviews were included. The studies were conducted with rheumatoid arthritis patients, and one study involved patients with systematic lupus erythematosus. The interventions mainly involved teleconsultation and telemonitoring, with patient-reported outcomes (PROs) being compared with standard care. Four studies measured the effectiveness of telemedicine using PROs, in which three of the RCTs did not find differences in the clinical outcomes, and one found that telemedicine improved the remission of diseases, functional impairment, and radiographic joint damage progression. Two studies measured patient satisfaction with telemedicine and standard care without a significant difference between the groups. Conclusions: Despite heterogeneity between studies, the findings were remarkably consistent in demonstrating that there was no significant difference between the telemedicine group and the control group in terms of PROs and patient satisfaction. Patients should be offered the option of telemedicine to manage their diseases as part of health-care support. Further research is needed on the effectiveness of telemedicine in the long term for patients with rheumatic diseases.

Filgotinib in Rheumatoid Arthritis: A Profile of Its Use

Filgotinib (Jyseleca®), an oral Janus kinase (JAK) inhibitor, is approved as monotherapy or in combination with methotrexate to treat moderate to severe active rheumatoid arthritis (RA) in adults who have an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs). In phase 3 trials, once-daily filgotinib was generally well tolerated and associated with an improvement in RA signs and symptoms as well as physical function in patients with an inadequate response to ongoing methotrexate, an inadequate response to ongoing conventional synthetic DMARDs plus an inadequate response or intolerance to prior biologic DMARDs, or limited or no prior exposure to methotrexate. In addition, filgotinib was noninferior to adalimumab in terms of low disease activity response rate (DAS28-CRP ≤ 3.2) in patients with an inadequate response to methotrexate. Filgotinib also appeared to inhibit the radiographic progression of joint damage and led to low disease activity or disease remission (DAS28-CRP < 2.6). Filgotinib showed sustained efficacy, and the safety profile of filgotinib longer term was similar to that in the phase 2 and 3 trials.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40261-021-01055-0.

OP0019 STABLE VERSUS TAPERED AND WITHDRAWN TREATMENT WITH TUMOR NECROSIS FACTOR INHIBITOR IN RHEUMATOID ARTHRITIS REMISSION (ARCTIC REWIND): A RANDOMISED, OPEN-LABEL, PHASE 4, NON-INFERIORITY TRIAL

Background:Remission is the preferred treatment target in rheumatoid arthritis (RA), and many patients require biologic DMARDs to reach this state. It is debated whether tapering of tumor necrosis factor inhibitor (TNFi) treatment to discontinuation should be considered in RA patients who sustain remission on treatment (1).Objectives:The primary study objective was to assess the effect of tapering and withdrawal of TNFi on the risk of flares in RA patients in clinical remission.Methods:In the non-inferiority ARCTIC REWIND trial, RA patients in remission for at least 12 months on stable TNFi therapy were randomly assigned to continued stable TNFi or tapering (half-dose TNFi for 4 months, thereafter withdrawal of TNFi), with visits every four months. csDMARD co-medication was kept stable in both arms. Patients had to be in DAS remission at inclusion with 0/44 swollen joints. The primary endpoint was the proportion of patients with disease flare during the 12-month study period (defined as DAS&gt;1.6, change in DAS&gt;0.6 and 2 or more swollen joints, or the physician and patient agreed that a clinically significant flare had occurred). Full-dose TNFi was reinstated in case of flares in the tapering arm. The non-inferiority margin was 20%, with a predefined superiority test if non-inferiority was not shown. The inferiority null-hypothesis was tested in the per-protocol population by mixed effect logistic regression. Radiographs were scored by van der Heijde modified Sharp score (0 and 12 months, average of two readers, progression: ≥1 unit change). ClinicaltrialsNCT01881308.Results:We randomised 99 patients, 92 received the allocated treatment strategy, 84 were included in the per-protocol population. Baseline characteristics, clinical and ultrasound disease activity were balanced (Table). csDMARD co-medication was used by 93% in the stable and 88% in the tapering arm. In the primary analysis, 5% of patients in the stable TNFi arm experienced a flare during 12 months, compared to 63% in the tapering TNFi arm. The risk difference (95% CI) was 58% (42% to 74%, Fig 1), with stable treatment being deemed superior to tapering. 90% in the stable and 81% in the tapering arm did not show progression of radiographic joint damage, difference (95% CI) -9% (-24%, 6%). At 12 months, DAS scores, DAS remission and function were similar between groups (Fig 2). The numbers of adverse events (AE)/serious AE in the stable and tapering arm were 57/2 and 50/3, respectively, with 26 and 15 infections.Conclusion:In a randomised clinical trial assessing patients in prolonged and deep RA remission, we observed a large increase in the flare rate in patients who tapered and discontinued TNFi. Patients responded well to reinstated treatment and remission rates in the two study arms were comparable at 12 months.

Successful cessation of tumor necrosis factor inhibitor treatment in rheumatoid arthritis patients and potential predictors for early flare: An observational study in routine clinical care

Objectives: To investigate the prevalence and the consequence of tumor necrosis factor inhibitor (TNFi) cessation after clinical improvement in rheumatoid arthritis (RA) patients in clinical practice and predictors of flare after TNFi cessation.Methods: We retrospectively assessed the prevalence of TNFi cessation after achieving sustained improvement, disease flare and joint damage progression after TNFi cessation in consecutive RA patients who started TNFi due to insufficient response to methotrexate were studied. Predictors for flare after TNFi cessation were investigated using Cox regression analysis.Results: In 135 patients who started TNFi with methotrexate, 95 stopped TNFi after sustained improvement and continued methotrexate thereafter. Over 1 year, 33 patients had a flare and 26 restarted TNFi therapy. In 78 patients whose radiographs adequate for evaluation were available, 73 did not exhibit joint damage progression. Female gender, smoking, the interval from starting methotrexate to starting TNFi of more than 9 months and glucocorticoid use at starting TNFi were independently associated with shorter time to flare.Conclusion: Sixty-five percent of patients were successfully discontinued TNFi over 1 year. Radiographic joint damage progression was rare. Early intervention with TNF inhibitor may contribute to successful TNF inhibitor cessation in patients with insufficient response to methotrexate.Key messageSuccessful TNF inhibitor cessation is achievable in two-third of RA patients after achieving sustained remission.Female gender and smoking may predispose to flare after TNF inhibitor cessation.Early intervention with TNF inhibitor may contribute to successful TNF inhibitor cessation.

Effectiveness and safety over 3 years after the 2-year U-Act-Early trial of the strategies initiating tocilizumab and/or methotrexate.

ObjectivesU-Act-Early was a 2-year, randomized placebo controlled, double-blind trial, in which DMARD-naïve early RA patients were treated to the target of sustained remission (SR). Two strategies initiating tocilizumab (TCZ), with and without methotrexate (MTX), were more effective than a strategy initiating MTX. The aim of the current study was to determine longer-term effectiveness in daily clinical practice.MethodsAt the end of U-Act-Early, patients were included in a 3-year post-trial follow-up (PTFU), in which treatment was according to standard care and data were collected every 3 months during the first year and every 6 months thereafter. Primary end point was disease activity score assessing 28 joints (DAS28) over time. Mixed effects models were used to compare effectiveness between initial strategy groups, correcting for relevant confounders. Between the groups as randomized, proportions of patients were tested for DMARD use, SR and radiographic progression of joint damage.ResultsOf patients starting U-Act-Early, 226/317 (71%) participated in the PTFU. Over the total 5 years, mean DAS28 was similar between groups (P > 0.20). During U-Act-Early, biologic DMARD use decreased in both TCZ initiation groups and increased in the MTX initiation group, but during follow-up this trend did not continue. SR was achieved at least once in 99% of patients. Of the 226 patients, only 30% had any radiographic progression over 5 years, without significant differences between the groups.ConclusionAlthough in the short-term the strategies initiating TCZ yielded the most clinical benefit, in the longer-term differences in important clinical outcomes between the strategies disappeared, probably due to continuation of the treat-to-target principle.

Plasma pentraxin 3 is associated with progression of radiographic joint damage, but not carotid atherosclerosis, in female rheumatoid arthritis patients: 3-year prospective study

Background: Pentraxin 3 (PTX3) has an important role in inflammation, immunity, and atherosclerosis. Rheumatoid arthritis (RA) is a chronic inflammatory disease featuring both joint damage and atherosclerosis. We investigated whether the plasma PTX3 level was associated with progression of joint destruction and subclinical atherosclerosis in RA patients.Methods: Plasma PTX3 levels were measured in 72 women with RA and 80 female control subjects. In RA patients, we also evaluated clinical characteristics, medications, and at one and three years, joint damage and atherosclerosis. Then we investigated whether PTX3 was associated with progression of joint destruction or an increase of carotid intima-media thickness (IMT).Results: Plasma PTX3 levels were significantly higher in the RA patients than in healthy controls (4.05 ± 2.91 ng/mL vs. 1.61 ± 1.05 ng/mL, p < .001). By multivariate linear regression analysis, the plasma pentraxin 3 level was independently associated with radiographic progression of joint damage for 3 years in the RA patients after adjustment for age, disease duration, body mass index, rheumatoid factor, MMP-3, Disease Activity Score 28-ESR, postmenopausal status, current use of corticosteroids and biologic use. On the other hands, pentraxin 3 was not associated with an increase of carotid intima-media thickness in RA patients.Conclusion: Female RA patients had elevated plasma PTX3 levels compared with control female subjects. PTX3 was independently associated with radiographic progression of joint damage in the RA patients, but not with carotid atherosclerosis.

Synovial cellular and molecular signatures stratify clinical response to csDMARD therapy and predict radiographic progression in early rheumatoid arthritis patients

ObjectivesTo unravel the hierarchy of cellular/molecular pathways in the disease tissue of early, treatment-naïve rheumatoid arthritis (RA) patients and determine their relationship with clinical phenotypes and treatment response/outcomes longitudinally.Methods144 consecutive...

Role of reproductive and menopausal factors in functional and structural progression of rheumatoid arthritis: results from the SCQM cohort.

To study the relationship between female reproductive and menopausal factors on functional and structural joint damage progression in women with RA. This is an observational cohort study of RA patients enrolled in the Swiss Clinical Quality Management Program for Rheumatoid Arthritis. Information about female hormonal factors, such as pregnancies, menopause and hormonal therapy, were retrospectively retrieved using a specific questionnaire. The primary outcome was functional disability progression (HAQ) and the secondary outcome radiographic joint damage progression. We compared the functional progression between pre- and post-menopausal women using a multilevel regression model for longitudinal data, adjusting for potential confounders, such as baseline age, years of education, disease duration, seropositivity, DAS28 and treatment. A total of 1667 women were analysed, of whom 1025 (61%) were post-menopausal. Participants had a median of 6 HAQ assessments (interquartile range 3-10) during 5.1 (interquartile range 2.2-9.8) years of follow-up. At baseline, post-menopausal women had higher HAQ and erosion scores than pre-menopausal women. The evolution of HAQ scores over time differed between pre- and post-menopausal women (P < 0.001), with a less favourable evolution in post-menopausal women, particularly with earlier age at menopause. Erosion progression did not differ between pre- and post-menopausal women. In women with RA, functional disability progression differed between pre- and post-menopausal women. The more favourable evolution of function in pre-menopausal women was not explained by disease duration, age or radiographic damage.

Affinity maturation shapes the function of agonistic antibodies to peptidylarginine deiminase type 4 in rheumatoid arthritis

ObjectivesThe citrullinating enzyme peptidylarginine deiminase type 4 (PAD4) is the target of a polyclonal group of autoantibodies in patients with rheumatoid arthritis (RA). A subgroup of such antibodies, initially identified...

Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis

BackgroundBaricitinib is an oral, reversible inhibitor of the Janus kinases JAK1 and JAK2 that may have therapeutic value in patients with rheumatoid arthritis.MethodsWe conducted a 52-week, phase 3, double-blind, placebo- and active-controlled trial in which 1307 patients with active rheumatoid arthritis who were receiving background therapy with methotrexate were randomly assigned to one of three regimens in a 3:3:2 ratio: placebo (switched to baricitinib after 24 weeks), 4 mg of baricitinib once daily, or 40 mg of adalimumab (an anti–tumor necrosis factor α monoclonal antibody) every other week. End-point measures evaluated after adjustment for multiplicity included 20% improvement according to the criteria of the American College of Rheumatology (ACR20 response) (the primary end point), the Disease Activity Score for 28 joints (DAS28), the Health Assessment Questionnaire–Disability Index, and the Simplified Disease Activity Index at week 12, as well as radiographic progression of joint damage as measured by the van der Heijde modification of the total Sharp score (mTSS) (range, 0 to 448, with higher scores indicating greater structural joint damage) at week 24.ResultsMore patients had an ACR20 response at week 12 with baricitinib than with placebo (primary end point, 70% vs. 40%, P<0.001). All major secondary objectives were met, including inhibition of radiographic progression of joint damage, according to the mTSS at week 24 with baricitinib versus placebo (mean change from baseline, 0.41 vs. 0.90; P<0.001) and an increased ACR20 response rate at week 12 with baricitinib versus adalimumab (70% vs. 61%, P=0.014). Adverse events, including infections, were more frequent through week 24 with baricitinib and adalimumab than with placebo. Cancers were reported in five patients (two who received baricitinib and three who received placebo). Baricitinib was associated with reductions in neutrophil counts and increases in levels of creatinine and low-density lipoprotein cholesterol.ConclusionsIn patients with rheumatoid arthritis who had had an inadequate response to methotrexate, baricitinib was associated with significant clinical improvements as compared with placebo and adalimumab. (Funded by Eli Lilly and Incyte; ClinicalTrials.gov number, NCT01710358.)

Rheumatoid arthritis: an evolutionary force in biologics.

The advent of biologic therapy has transformed the outcomes of patients with Rheumatoid Arthritis (RA), but has also highlighted important issues for their development. Early attempts at T-cell driven therapies gave mixed results with difficulties extrapolating from non-human models to first in man trials. There is currently one T-cell modulating therapy - abatacept - licenced for use in RA. Cytokine inhibition has proven to be more fruitful with a number of anti-TNF and IL6 agents either licenced for use in RA or in development. The B-cell depleting therapy rituximab has also shown good efficacy as a chemotherapy agent repurposed for RA treatment. Overall the biologics show good efficacy in RA and have been shown to retard progression of radiographic joint damage. However, this benefit comes with a burden of increased infection risk and a financial cost significantly higher than conventional disease modifying therapies. As a result current UK licencing holds the biologics in reserve following failure of a conventional therapy and the presence of moderate to severely active disease. The long term use of the biologics in RA has highlighted the risk of immunogenicity, with significant proportions of patients developing anti-drug antibodies and losing therapeutic effect. The side effect profile and cost also raise the question around duration of therapy and trials of drug tapering following disease remission are now taking place with several biologic agents. Our inability to stratify patients to the most appropriate biologic drug (stratified or precision medicine) has also catalysed a large and critically important research agenda. Beyond identifying new biologic targets, the development of biosimilar agents will likely drive the future shape of the RA biologics market as lower cost alternatives are developed, thereby improving access to these therapies.

Progress in imaging in rheumatology.

For decades, diagnostic imaging in rheumatology has used conventional radiography. Over the past 10 years, MRI and ultrasonography have clearly shown their potential in diagnostic imaging in rheumatology and their use is revolutionizing the management of chronic arthritis, revealing subclinical inflammation and predicting progression of joint damage. Although validation processes for these imaging modalities are still ongoing, several investigations have now established the positive correlation between subclinical synovitis and radiographic progression of joint damage. Despite the available evidence and the diagnostic potential, there remains a substantial proportion of rheumatologists for whom MRI and ultrasonography findings do not influence their clinical decision-making. This Perspectives will discuss the key issues related to diagnostic imaging in patients with chronic arthritis, outlining how new imaging techniques have evolved over the past two decades and presenting the most attractive technological advances in this field.

THU0131 Long Term Results of Inhibition of Radiographic Joint Damage Progression in Small and Medium and Large Joints in Patients with Rheumatoid Arthritis Treated with Tofacitinib Monotherapy

BackgroundTofacitinib is a novel oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). There was a study concerned with the efficacy for inhibiting the progression of radiographic...

AB0274 The Influence of Continuous Remission Rate on Functional Disability and Radiographic Progression for Rheumatoid Arthritis in A Japanese Observational Cohort

BackgroundOne goal of clinical remission in rheumatoid arthritis (RA) is to halt joint damage. The continuous clinical remission in established RA may result in improved function and reduced radiographic progression.ObjectivesThe...

THU0257 Acpa-Negative RA Patients Benefit from Initial Combination Therapy with Early Clinical Improvement - A Sub-Analysis of the Best Study

BackgroundAnti-citrullinated protein antibodies (ACPA)-positive (+) and ACPA-negative (−) rheumatoid arthritis (RA) patients may have different disease outcomes and may require different therapies.ObjectivesTo determine which treatment strategy in Disease Activity Score...

A11: Assessment of Radiographic Progression in Patients With Polyarticular‐Course Juvenile Idiopathic Arthritis Treated With Tocilizumab: 2‐Year Data From CHERISH

Background/Purpose:The phase 3 CHERISH trial demonstrated the efficacy of tocilizumab (TCZ), an interleukin‐6 receptor inhibitor, in patients with polyarticular‐course juvenile idiopathic arthritis (pcJIA). This analysis investigated the progression of radiographic joint damage in patients with pcJIA treated with TCZ for up to 104 weeks in CHERISH.Methods:Patients 2 to 17 years old with ≥6 months' active pcJIA for whom methotrexate failed received open‐label (OL) TCZ according to body weight (BW) (BW ≥30 kg, 8 mg/kg [n = 119]; BW &lt;30 kg, randomly assigned 1:1 to 8 mg/kg [n = 34] or 10 mg/kg [n = 35]) every 4 weeks for 16 weeks. At 16 weeks, eligible patients (≥JIA ACR30 response) entered a 24‐week, randomized, double‐blind withdrawal period and were assigned 1:1 to placebo or continued TCZ. All patients entered an OL extension through week 104. Those receiving TCZ in all 3 parts were included in the continuous TCZ subgroup for which key radiographic end points were assessed. Radiographic progression was indicated as a positive change in adapted Sharp/van der Heijde score () (aSH) and/or a negative change in Poznanski score (), assessed on hand and wrist radiographs, from baseline to weeks 52 and 104.Results:Baseline and ≥1 postbaseline aSH and Poznanski scores were available for 45 and 35 patients, respectively, in the continuous TCZ subgroup and for 87 and 61 patients, respectively, in the total population. Reasons for missing data included early withdrawal, no consent, or unreadable radiographs (because of advanced damage resulting in unreliable measurements or growth plate fusion in postpubertal children), preventing assessment of Poznanski scores. Baseline demographics and disease characteristics were balanced for aSH and Poznanski populations and were similar to those for the full study population. At weeks 52 and 104, median changes from baseline aSH score of 0.5 (p = 0.70) and −1.0 (p = 0.11), respectively, and median changes from baseline Poznanski score of 0.3 (p = 0.07) and 0.6 (p = 0.004), respectively, indicating a lack of radiographic progression. With a cutoff of the smallest detectable difference, no radiographic progression was seen in 87.5% and 97.1% of patients based on aSH scoring and 93.5% and 96.0% of patients based on Poznanski scoring at weeks 52 and 104, respectively. Comparable proportions of the total radiographic population, including those exposed to placebo, remained radiographic progression free at week 104. Among the radiographic population, the annualized rates of progression to week 104 for aSH and Poznanski scores were 0.00 and 0.18, respectively.Conclusion:TCZ halted the progression of radiographic damage, leaving a large majority of pcJIA patients free of radiographic progression after 2 years of treatment.

A66: Assessment of Radiographic Progression in Patients With Systemic Juvenile Idiopathic Arthritis Treated With Tocilizumab: 2‐Year Results From the TENDER Trial

Background/Purpose: A phase 3 trial (TENDER) demonstrated the efficacy of the interleukin-6 receptor inhibitor tocilizumab (TCZ) in patients with systemic juvenile idiopathic arthritis (sJIA) ([1, 2]). The aim of this study was to investigate the progression of radiographic joint damage in patients with sJIA treated with TCZ for up to 2 years in TENDER. Methods: One hundred twelve patients 2 to 17 years old with active, refractory sJIA of ≥6 months' duration and inadequate response to previous nonsteroidal anti-inflammatory drugs and oral corticosteroids were enrolled in TENDER. Patients were randomly assigned 2:1 to receive TCZ according to body weight (12 mg/kg <30 kg or 8 mg/kg ≥30 kg) or placebo intravenously every 2 weeks for 12 weeks. Patients then received open-label TCZ in the ongoing long-term extension. Radiographic progression was calculated as change in adapted Sharp/van der Heijde score (aSH) score and/or Poznanski score, assessed on hand and wrist radiographs, from baseline to weeks 52 and 104. Radiographic progression was indicated by a positive aSH score change or a negative Poznanski score change. Clinical efficacy end points included American College of Rheumatology (ACR) Pediatric (Pedi) 70/90 responses. Results: Baseline and ≥1 postbaseline aSH and Poznanski scores were available for 47 and 33 patients, respectively (reasons for missing x-rays: early withdrawal, no consent, unreadable x-rays). Baseline characteristics for patients with radiographic data were similar in the whole TCZ population (1). Patients with assessable aSH/Poznanski scores had 5.2-/4.8-year disease duration, 21.3/19.2 active joints, 20.0/18.2 joints with limitation of movement, and 53.9/59.2 mm/h erythrocyte sedimentation rate. At weeks 52 and 104, 20 and 19 patients, respectively, had aSH progression, and 8 and 8 patients, respectively, had Poznanski score progression. Median changes in aSH score from baseline to weeks 52 and 104 were 0 and 0.5, respectively (1). Median changes in Poznanski score from baseline to weeks 52 and 104 were 0.29 and 0.16, respectively (1). Table 1. Week 52 Week 104 a IQR, interquartile range. aSH score (n = 47), median (IQR) 0.00 (−8.70: 4.00) 0.50 (−7.50: 12.00) Poznanski score (n = 33), median (IQR) 0.29 (−0.05: 1.05) 0.16 (−0.01: 1.04) ACR Pedi 70 (n = 112), n/N (%) 92/106 (86.8) 57/65 (87.7) ACR Pedi 90 (n = 112), n/N (%) 67/106 (63.2) 46/65 (70.8) Conclusion: Although changes in radiographic scores over time were seen in many patients, on average, patients with sJIA did not experience noticeable progression of radiographic damage over 2 years of treatment with TCZ.