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Acromial (ASF) and scapular spine (SSF) stress fractures are well-recognized complications of reverse shoulder arthroplasty (RSA), but much of the current data are derived from single-center or single-implant studies with limited generalizability. This study from the American Shoulder and Elbow Surgeons (ASES) Complications of Reverse Shoulder Arthroplasty Multicenter Research Group determined the incidence of ASF/SSF after RSA and identified preoperative patient characteristics associated with their occurrence.Fifteen institutions including 21 ASES members across the United States participated in this study. Patients undergoing either primary or revision RSA between January 2013 and June 2019 with a minimum 3-month follow-up were included. All definitions and inclusion criteria were determined using the Delphi method, an iterative survey process involving all primary investigators. Consensus was achieved when at least 75% of investigators agreed on each aspect of the study protocol. Only symptomatic ASF/SSF diagnosed by radiograph or computed tomography were considered. Multivariable logistic regression was performed to identify factors associated with ASF/SSF development.We identified 6755 RSAs with an average follow-up of 19.8 months (range, 3-94). The total stress fracture incidence rate was 3.9% (n = 264), of which 3.0% (n = 200) were ASF and 0.9% (n = 64) were SSF. Fractures occurred at an average 8.2 months (0-64) following RSA with 21.2% (n = 56) following a trauma. Patient-related factors independently predictive of ASF were chronic dislocation (odds ratio [OR] 3.67, P = .04), massive rotator cuff tear without arthritis (OR 2.51, P.01), rotator cuff arthropathy (OR 2.14, P.01), self-reported osteoporosis (OR 2.21, P.01), inflammatory arthritis (OR 2.18, P.01), female sex (OR 1.51, P = .02), and older age (OR 1.02 per 1-year increase, P = .02). Factors independently associated with the development of SSF included osteoporosis (OR 2.63, P.01), female sex (OR 2.34, P = .01), rotator cuff arthropathy (OR 2.12, P = .03), and inflammatory arthritis (OR 2.05, P = .03).About 1 in 26 patients undergoing RSA will develop a symptomatic ASF or SSF, more frequently within the first year of surgery. Our results indicate that severe rotator cuff disease may play an important role in the occurrence of stress fractures following RSA. This information can be used to counsel patients about potential setbacks in recovery, especially among older women with suboptimal bone health. Strategies for prevention of ASF and SSF in these at-risk patients warrant further study. A follow-up study evaluating the impact of prosthetic factors on the incidence rates of ASF and SSF may prove highly valuable in the decision-making process.

ZUSAMMENFASSUNGDie systemische juvenile idiopathische Arthritis nimmt unter den Kategorien der JIA eine Sonderstellung ein, klinisch aufgrund der obligat extraartikulären, systemischen Beteiligung, aber auch aufgrund der der vital bedrohlichen Komplikationen, Makrophagenaktivierungssyndrom und Lungenbeteiligung. Untersuchungen legen ein biphasisches Krankheitsgeschehen mit konsekutiven Eigenschaften einer autoinflammatorischen mit denen einer Autoimmunerkrankung nahe. Diese Erkenntnisse führten zu Therapieoptionen wie der IL-1- und IL-6-Blockade mit Biologika und zu Therapiealgorithmen, die zwischen früher Erkrankung und später Erkrankung unterscheiden, letztlich mit dem Ziel, der Nutzung eines „windows of opportunity“ zur Erreichung des Therapieziels der Remission.

Background Limiting opioid use in perioperative pain management is currently an important focus in orthopedic surgery. The ability of acetaminophen to reduce postoperative opioid consumption while providing acceptable pain management has not been thoroughly investigated in patients undergoing rotator cuff repair (RCR). Methods Patients undergoing primary arthroscopic RCR were prospectively randomized to 1 of 3 treatment groups: Group 1 (control) received both 5 mg of oxycodone every 6 hours as needed and 1000 mg of acetaminophen orally every 6 hours as needed after surgery and had the option to take either medication or both. Group 2 (control) received only 5 mg of oxycodone every 6 hours as needed without any additional acetaminophen after surgery. Group 3 received 1000 mg of acetaminophen orally every 6 hours for 1 day prior to and after surgery, which was subsequently decreased to administration every 8 hours during postoperative days 2-5. Group 3 patients were also allowed to take 5 mg of oxycodone every 6 hours as needed after surgery. All patients received interscalene blocks with liposomal bupivacaine (Exparel). Opioid use, pain scores, side effects, and overall satisfaction were assessed daily for the first week after surgery. Results A total of 57 patients (mean age, 57.8 ± 9.55 years) were included in this study. Baseline demographic characteristics including age, sex, and body mass index were similar between the groups (P > .05). Patients in group 3 took significantly fewer narcotics overall (P = .017) and took significantly fewer pills each day compared with group 2. Group 3 also reported significantly better overall pain control compared with the other groups (P = .040). There were no significant differences in overall patient satisfaction between the groups (P > .05). Additionally, there were no significant differences between groups regarding postoperative medication-associated side effects (P > .05). Conclusion Perioperative acetaminophen represents an important component of multimodal analgesia in appropriately selected patients undergoing shoulder surgery. In this study, the use of perioperative acetaminophen significantly decreased opioid consumption and improved overall pain control after primary arthroscopic RCR.

Background Degenerative disease of the elbow is a unique dilemma due to the different pathologies of arthritis. Outcome measures are used by physicians to provide a quantitative measure of patient progression. While there has been a substantial number of case series and studies on treatment of elbow arthritis, the heterogeneity of outcome measures reported in the literature makes it difficult for surgeons to compare results between treatment options. There is no consensus on outcome measure reporting as no measure has been found to be superior to others in the literature. The purpose of this study was to examine the elbow arthritis literature for the most commonly reported outcomes measures after treatment of elbow arthritis and recommend a guideline for reporting in future studies in an attempt to standardize the literature. Methods A query was performed of all studies written in English literature from 2010 to 2020 using PubMed and Scopus databases utilizing PRISMA guidelines. Articles that met inclusion criteria were reviewed for reporting of patient-reported outcome, range of motion, return to work/sport, complication rate, satisfaction rate, revision rate, number of patients, minimum and mean follow-up time, type of treatment, journal, journal impact factor, level of evidence, and number of citations as of April 2020. Results Eighty three studies met inclusion criteria with a mean number of 39 patients per study with a mean age of 53 years. Mayo elbow performance score (MEPS) was the most commonly reported outcome measure (81%) followed by quick Disabilities of Arm Shoulder Hand (qDASH; 23%), DASH (16%), and modified American Shoulder and Elbow Surgeons score (m-ASES; 16%). The average number of outcome measures per study was 1.6. Studies that reported MEPS had higher number of citations compared to studies that did not (14.21 vs. 7.62 citations; P = .031). Studies that reported MEPS were found to publish more in journals with higher impact factors (ie, impact factor of ≥2) (88% vs. 71%; P = .051). Discussion Outcome measures are inconsistently reported in elbow arthritis literature. Studies that report MEPS were found to be cited more. We recommend reporting of at least two outcome measures in future studies as well as range of motion for easier cross-study analysis. Additional measures such as return to work/sport, satisfaction rate, complication rate, and revision rate should be reported to provide more complete understanding of post-treatment outcome. Conclusion Increased standardization of outcome measure reporting may improve future patients’ outcomes following treatment of elbow arthritis. Levels of Evidence Level IV

Background: As youth participation in contact and overhead sports has increased in recent decades, so has the occurrence of injuries of the shoulder. Rotator cuff injury (RCI) is an infrequent shoulder pathology in pediatric patients and its description in the literature has been scarce. A greater understanding of RCI characteristics and treatment outcomes in children and adolescents would improve our understanding of this pathology and help to better guide clinical decision-making. Hypothesis: To identify pediatric patients with magnetic resonance imaging-confirmed RCI treated at a single center to summarize injury characteristics, treatment, and outcomes. It was hypothesized that injuries would occur predominantly in overhead throwing athletes and would demonstrate good outcomes among both operatively and nonoperatively treated patients. Study Design: Cross-sectional study. Level of Evidence: Level 4. Methods: A retrospective review of pediatric patients (Results: A total of 52 pediatric patients treated for a rotator cuff avulsion, partial tear, or complete tear were identified. Mean age was 15 years and 67% of patients were male. Injuries were related most commonly to participation in throwing sports. Operative management occurred in 23% of patients, while 77% were managed nonoperatively. Treatment cohorts differed based on tear type, with all complete tears being managed operatively ( P < 0.01). Associated shoulder pathology was common, with the most frequent finding being anterior shoulder instability pathology. Return to play was longer for operatively managed patients (7.1 vs 4.5 months; P < 0.01). Conclusion: The present study expands the limited data available regarding RCIs in pediatric patients. Most injuries are associated with sports and involve the supraspinatus tendon. RCIs were associated with good outcomes and low rates of reinjury in patients managed both nonoperative and operatively. RCI should be considered in throwing athletes with shoulder pain, even in skeletally immature patients. Clinical Relevance: This retrospective study fills the hole in the literature by detailing the patterns associated with RCI characteristics and treatment outcomes. In contrast to studies of adult RCIs, our results suggest that outcomes are good regardless of treatment type.

Background Humeral stem designs for total shoulder arthroplasty have varied over the years, with a recent trend toward shorter stems. The purpose of this study was to examine the impact of humeral component stem length on the ability to restore the native humeral head anatomy. Methods We performed a retrospective review including patients who underwent total shoulder arthroplasty for primary osteoarthritis between 2007 and 2017 with complete operative reports and adequate radiographs. Surgical data including stem design were collected. Preoperative and postoperative radiographic measurements of the center of rotation (COR), humeral head height (HH), and neck-shaft angle were performed. Restoration of the native humeral anatomy was deemed “acceptable” based on postoperative differences in the COR ≤ 3 mm, HH ≤ 5 mm, and neck-shaft angle > 130°. Deviations between preoperative and postoperative measurements were compared across stem types. All available 2-year stemless implant radiographs were also analyzed. Results In total, 261 patients were included, with 31 stemless, 43 short-stem, and 187 standard-stem implants. There was no significant difference in COR restoration in the x-axis direction (P = .060) or y-axis direction (P = .579). There was no significant difference in restoration of acceptable HH by stem type (P = .339). Stemless arthroplasty implants were more likely to be placed in varus (22.6%) compared with short-stem (7.0%) and standard-stem (3.7%) designs (P Conclusion Restoration of humeral anatomic parameters occurred significantly less with stemless implants than with short- and standard-stem implants. The stem of a shoulder arthroplasty implant aids surgeons in accurately restoring patient-specific anatomy.

Introduction Critical shoulder angle (CSA) has been shown to influence rates of rotator cuff tears and glenohumeral arthritis with larger CSA associated with rotator cuff tears and smaller CSA associated with glenohumeral arthritis. There has been no study to determine whether such radiographic measurement influences the function of patients with demonstrated cuff tear arthropathy (CTA). The purpose of this study was to examine whether smaller CSAs were associated with greater range of motion (ROM) in patients diagnosed with cuff tear arthropathy (CTA). Materials and Methods Ninety-three patients with a diagnosis of CTA with adequate anteroposterior shoulder radiographs were obtained. Patient demographics were recorded. Presence of a rotator cuff tear was confirmed via advanced imaging or when applicable via operative report. Patients’ ROM was evaluated through physician’s office note. Shoulder radiographs were used to measure CSA, glenoid inclination (GI), acromial index (AI), and acromiohumeral interval (AHI). Patient ROM was measured and grouped into two different tiered cohorts; cohort one had 4 subgroups of forward elevation (i.e. ≤45°, 45-90°, 91-135° and 136-180°) and cohort two had 2 subgroups of forward elevation (i.e. ≤90°, >90°). We then analyzed forward elevation between these groups in the context of their radiographic measurements. Results The average patient age was 73.8 ± 8.0 years old. There was no significant difference in AHI. AI was found to be significantly different between patients presenting with ≤90° in forward elevation (FE) compared to those >90° (p=0.02). Average CSA was significantly lower in patients with forward elevation greater than 90° at 33.7° ± 3.9° compared to patients with forward elevation less than 90° at 37.1° ± 6.3° (p=0.002). There was also a significant difference with regard to CSA angles, with those patients with FE 45o having a mean CSA of 38.2o ± 8.3 compared to those patients with FE > 135o having a mean CSA of 33.3o ± 4.3 (p=0.02). Conclusion Patients diagnosed with cuff tear arthropathy can significantly vary in their shoulder function and ability to forward elevate. Lower CSA was found to be associated with higher forward elevation in CTA patients preoperatively. In addition, patients with a smaller acromial index were also found to have better overhead function. Analyzing CSA on plain radiographs may help manage functional expectations in CTA patients.

Cutibacterium acnes is a lipophilic, anaerobic, gram-positive bacillus that mainly colonizes the pilosebaceous glands of human skin. It has been implicated as the leading cause of prosthetic joint infection (PJI) after shoulder arthroplasty. However, PJI caused by C acnes rarely manifests as overt clinical, laboratory, or imaging features. In fact, more than 40% of shoulders undergoing revision arthroplasty are likely to be culture positive. However, rates of infection following a positive culture can be as low as 5%. The purpose of this review was to put forth alternative explanations for this discordance between positive cultures and infection. We describe C acnes roles as a commensal, bystander, and/or contaminant organism; the role of cultures in diagnosis and other methods that may be more accurate; its existence in a shoulder microbiome; and the variable virulence of C acnes. C acnes is an important cause of shoulder PJI in some patients. However, there is a large body of literature that suggests other functions that need to be considered. Further research is needed to define the role of C acnes that is logically explained by all of the literature and not only some.

Background The number of primary total elbow arthroplasties (TEAs) performed is increasing annually, necessitating a rise in the number of revision procedures. No studies exist to illustrate reliable indications for revision arthroplasty. The purpose of this study was to determine the impact of the etiology of primary TEA failure on the failure rate of revision surgery. Methods We retrospectively analyzed the patient charts of all revision TEAs performed at a single institution between 2006 and 2016. The primary outcome was revision failure, defined as the need for a second revision surgical procedure. Patients were organized into cohorts by etiology of primary implant failure. Failure rates, time to second revision, and average number of additional revisions were compared among cohorts. Results A total of 46 patients with a mean age of 62.7 years and minimum 2-year follow-up were included. The etiologies of failure identified were infection (n = 20), aseptic loosening (n = 17), periprosthetic fracture (n = 6), and bushing wear (n = 3). All noninfectious etiologies were grouped into an additional cohort. Patients who underwent revision for infection demonstrated a significantly greater failure rate and greater number of additional revisions per patient than those with aseptic loosening, those with periprosthetic fracture, and the noninfectious group, as well as a shorter time to failure than the noninfectious group. Conclusion Patients in whom primary TEA fails because of infection are more likely to experience revision failure and require a greater number of subsequent operations than patients with other etiologies of primary TEA failure. These data question the efficacy of revision surgery in the treatment of infected TEAs.

The success of total shoulder arthroplasty is dependent on both proper patient selection and restoration of the native anatomy. After proper patient selection, preoperative planning is essential to select implants that will allow the surgeon to properly restore soft-tissue tension and correct for deformity. Although it is possible to template implants with plain radiographs, these do not allow accurate measurements of the complex three-dimensional anatomy of the glenohumeral joint. CT can be used to further examine version of the glenoid and humerus, as well as humeral head subluxation. Three-dimensional reconstructions also allow for virtual implantation, resulting in a more reliable prediction of implant appearance. Commercial software is available that calculates parameters such as version; however, these have been shown to have variability when compared with measurements obtained by surgeons. Patient-specific instrumentation can also be obtained based on preoperative measurements; however, although it allowed for improved measurements when compared with two-dimensional imaging, there has been no difference in version error, inclination error, or positional offset of the glenoid implant when comparing patient-specific instrumentation with standard instrumentation. Intraoperative navigation can also be used to give real-time feedback on implant positioning; however, additional studies are needed to fully evaluate its benefit.

Proximal humerus fractures (PHFs) are common, and their incidence is increasing as the population ages. Despite this, postoperative rehabilitation remains unstandardized and little is known about surgeon preferences. The aim of this study was to assess differences in postoperative rehabilitation preferences and patient education between orthopedic trauma and shoulder surgeons.An electronic survey was distributed to members of the Orthopaedic Trauma Association and the American Shoulder and Elbow Surgeons to assess differences in postoperative rehabilitation preferences and patient counseling. Descriptive statistics were reported for all respondents, trauma surgeons, and shoulder surgeons. Chi-square and unpaired 2-sample t tests were used to compare responses. Multinomial regression was used to further elucidate the influence of fellowship training independent of confounding characteristics.A total of 293 surgeons completed the survey, including 172 shoulder and 78 trauma surgeons. A greater proportion of trauma surgeons preferred an immediate weightbearing status after arthroplasty compared to shoulder surgeons (45% vs. 19%, P = .003), but not after open reduction and internal fixation (ORIF) (62% vs. 75%, P = .412). A greater proportion of shoulder surgeons preferred home exercise therapy taught by the physician or using a handout following reverse shoulder arthroplasty (RSA) (21% vs. 2%, P = .009). A greater proportion of trauma surgeons began passive range of motion (ROM)2 weeks after 2-part fractures (70% vs. 41%, P .001). Conversely, a greater proportion of shoulder surgeons began passive ROM between 2 and 6 weeks for 2-part (57% vs. 24%, P .001) and 4-part fractures (65% vs. 43%, P = .020). On multinomial regression analysis, fellowship training in shoulder surgery was associated with preference for a nonweightbearing duration of12 weeks vs. 6-12 weeks after ORIF. Similarly, fellowship training in shoulder surgery was associated with increased odds of preferring a nonweightbearing duration of6 weeks vs. no restrictions and12 weeks vs. 6-12 weeks after arthroplasty. Training in shoulder surgery was associated with greater odds of preferring a nonweightbearing duration prior to beginning passive ROM of 2-6 weeks vs.2 weeks or6 weeks for 2-part fractures, but not 4-part fractures.Trauma surgeons have a more aggressive approach to rehabilitation following operative PHF repair compared to shoulder surgeons regarding time to weightbearing status and passive ROM. Given the increasing incidence of PHFs and substantial variations in reported treatment outcomes, differences in rehabilitation after PHF treatment should be further evaluated to determine the role it may play in the outcomes of treatment studies.

Variable neck-shaft angle (NSA) stemmed humeral components have been incorporated into certain implant designs to better re-create normal anatomy in total shoulder arthroplasty (TSA). The purpose of this study was to determine if premorbid glenohumeral joint anatomy is better restored with a fixed- vs. variable-NSA prosthesis.A randomized controlled trial was performed including 50 patients with osteoarthritis indicated for primary anatomic TSA. Patients were randomized preoperatively to receive either a variable- (n = 26) or fixed-NSA (n = 24) prosthesis. Humeral neck cut in the variable-NSA group matched the patient's anatomic neck, with prosthetic NSA of 127.5°, 132.5°, and 137.5° available. Fixed-NSA cuts were made with an intramedullary guide of 132.5°. Preoperative and postoperative radiographs were evaluated for specific radiographic anatomic variables: NSA, head thickness, tuberosity-to-head height, head offset, articular arc, greater tuberosity offset, and center of rotation (COR). Postoperative radiographic criteria were compared between groups.No differences were found between groups in demographics or preoperative radiographic measures. When comparing average difference in preoperative and postoperative measurements in the fixed-NSA group, the humeral head offset from the humeral shaft axis significantly decreased by 1.4 mm (P = .046), and the COR moved superiorly (3.0 mm, P = .002) without significant medialization or lateralization. In the variable angle group, humeral head offset decreased but did not reach significance (1.2 mm, P = .091), and the COR also moved superiorly (2.9 mm, P .001) without significant medialization or lateralization. All remaining radiographic parameters did not significantly change from pre- to postoperative imaging. In comparing the fixed- and variable-NSA groups' net change from the premorbid measurements, no significant differences were found in tuberosity-to-head height, head offset, or COR position in both the horizontal and vertical planes.Both fixed- and variable-NSA anatomic TSA humeral components demonstrate adequate restoration of premorbid anatomy radiographically.

BackgroundPsychiatric comorbidities can be a significant additional burden in chronic diseases. The most common chronic inflammatory rheumatic disease in children and adolescents is juvenile idiopathic arthritis (JIA). Data on mental illness in children and adolescents with JIA are heterogeneous.ObjectivesTo assess the frequency of depressive and anxious symptoms in patients with JIA compared to healthy peers.MethodsData were analysed from JIA patients and healthy controls of the same age included in the inception cohort of newly diagnosed children and adolescents with JIA (ICON). Depressive symptoms (using the Patient Health Questionnaire (PHQ-9, score 0-27) and anxious symptoms (Generalised Anxiety Disorder Scale (GAD-7, score 0-21) were captured 7 or 9 years after inclusion in ICON in patients aged thirteen years or older at the time of filling in these questionnaires. Symptom severity for both instruments was assessed by sum score with the following cut-off values: PHQ-9 score < 5: none, 5-9: mild, 10-14: moderate, 15-19: severe, ≥ 20: very severe. GAD-7 Score < 5: none, 5-9: mild, 10-14: moderate, ≥ 15: severe. Disease parameters such as Physician Global Assessment of Disease Activity (PhGA Disease Activity, numerical rating scale, (NRS),0-10, 0=best), joint count (n) and patient-reported outcomes on functional limitations ((C)HAQ, score 0-3, 0=best), Patient Global Assessment of Well-being (PGA Well-being), pain and fatigue (NRS, 0-10, 0=best) were also documented.ResultsThe analysis included 344 patients, 157 (45.6%) < 18 years old (mean 15.5 ± 1.5 years, 64.3% female), 187 (54.4%) ≥ 18 years old (mean 21.5 ± 2.1 years, 65.2% female) and 224 control subjects, 115 (51.3%) < 18 years old (mean 15.2 ± 1.5 years, 60% female), 109 (48.7%) ≥ 18 years old (mean 21.4 ± 1.9 years, 58.7% female). Almost 40% of patients had oligoarthritis (26% persistent OA, 12.5% extended OA), 27% rheumatoid factor (RF)-negative polyarthritis, 6% psoriatic arthritis, 17% enthesitis-related arthritis; 3% each had systemic JIA and RF-positive polyarthritis. In the total cohort, 14% of patients and 7% of controls had a PHQ-9 ≥ 10 and 10% of patients and 2% of controls had a GAD-7 ≥ 10. Within the categories of JIA, the rate of a PHQ-9 ≥ 10 ranged from 9.3% (oligoarthritis extended) to 33.3% (RF-positive polyarthritis) and a GAD-7 ≥ 10 ranged from 0% (systemic arthritis) to 22.2% (psoriatic arthritis).Patients aged ≥ 18 years had higher scores for both PHQ-9 (≥ 10: 18.7%) and GAD-7 (≥ 10: 14.4%) compared to patients < 18 years (PHQ-9 ≥ 10: 8.3%, GAD-7 ≥ 10: 5.1).In patients < 18 years with PHQ-9 < 10 versus ≥ 10, there were no significant differences in either PhGA disease activity (0.8±1.6 / 1.0±2.0, p = 0.673) or joint count (0.5±1.3 / 0.5±1.6, p = 0.999). In contrast, there was a significant difference in PhGA disease activity (0.8±1.5 / 1.6±1.4, p = 0.005) but not in joint count (0.7±3.1 / 0.8±1.3, p = 0.850) in patients ≥ 18 years with PHQ-9 < 10 versus PHQ-9 ≥ 10.Female patients were more often found to have higher scores for depression and anxiety than male patients (PHQ-9 ≥ 10: female 17.5%, male 7.4%, GAD-7 ≥ 10: female 13.5%, male 4.1%) and patients more often had higher scores for depression than controls (PHQ-9 ≥ 10: female patients 17.5%, female controls 8.3%, male patients 7.4%, male controls 4.4%). The difference in the proportion of female patients with GAD-7 ≥ 10 (13.5%) compared to control subjects (2.3%) was remarkable, but in male patients this proportion (4.1%) was only slightly higher than in male control subjects (2.2%).ConclusionDepressive and anxious symptoms are common in adolescents and young adults with JIA, especially in females. In the continuous care of these patients, standardised diagnostic tools should be implemented to detect these comorbidities, to optimise therapy and thereby reduce the burden of disease. Further research is needed to identify possible predictors of the development of depression and anxiety in JIA patients in order to pursue preventive approaches.Disclosure of InterestsPrasad Oommen: None declared, Jens Klotsche: None declared, Frank Dressler: None declared, Ivan Foeldvari: None declared, Dirk Foell: None declared, Gerd Horneff Speakers bureau: Pfizer, Novartis, Janssen, Chugai, Abbvie, Grant/research support from: Pfizer, Novartis, MSD, Chugai, Roche, Abbvie, Toni Hospach Consultant of: SOBI, Novartis, Tilmann Kallinich: None declared, Jasmin Kuemmerle-Deschner: None declared, Ina Liedmann: None declared, Kirsten Moenkemoeller: None declared, Martina Niewerth: None declared, Caroline Siemer: None declared, Frank Weller-Heinemann: None declared, Daniel Windschall: None declared, Kirsten Minden Speakers bureau: AbbVie, Pfizer, Novartis, Claudia Sengler: None declared

BackgroundEnthesitis-related Arthritis (ERA) is a category of juvenile idiopathic arthritis (JIA) characterised by heterogeneous and insidious manifestations comprising axial and/or peripheral arthritis, and enthesitis.1 Secukinumab (SEC) demonstrated efficacy and safety in both ERA and juvenile psoriatic arthritis (JPsA) in the JUNIPERA trial.2ObjectivesTo evaluate the rate of flare risk reduction and efficacy of SEC on axial and peripheral manifestations in patients (pts) with active ERA.MethodsERA pts (2 to 3 Evaluation of axial and peripheral manifestations at the end of TP1 and TP2 in pts who experienced these symptoms at BL included modified Schober test (lumbar flexion), inflammatory back pain, FABER (Flexion, ABduction, External Rotation) test, JIA-ACR responses, Juvenile Arthritis Disease Activity Score (JADAS)-27, and resolution of enthesitis and dactylitis for peripheral disease. These outcomes were also used to assess JIA disease course at the end of TP2.ResultsA total of 52/86 (60.5%) pts with ERA were enrolled in the OL period TP1 (mean age, 13.7 years; male, 78.8%). In total, 51/52 (98.1%) pts completed TP1 and 41/44 (93.2%) completed TP2. At BL, mean JADAS-27 was 14.8, mean JSpADA index was 3.9, mean enthesitis and dactylitis counts were 2.7 and 0.4, respectively, mean number of active joints was 6.2 and of mean joints with limited range of motion 4.9. The relative risk reduction of experiencing a disease flare in TP2 was 55% (HR 0.45, 95% CI: 0.16–1.28, p=0.075) in ERA pts (Figure 1). The overall axial and peripheral disease symptoms improved over time and are presented in the Table 1. At the end of TP1, 84.6% (44/52) of pts achieved JIA-ACR 30 and 65.4% (34/52) achieved JIA-ACR 70. Clinically relevant reduction of functional ability as assessed by Childhood Health Assessment Questionnaire (CHAQ) also occurred (see Table 1).Table 1.Resolution of axial and peripheral disease symptoms and JIA ACR responses at the end of TP1 and 2Clinical response, mean (SD) change from BL (unless otherwise stated)TP1-Wk 12End of TP2*SEC (N=52)SEC (N=22)PBO (N=22)JSpADA index−2.4 (1.7)−2.7 (1.7)−2.3 (2.1)JSpADA Schöber, %58.3100.0100.0Inflammatory back pain, %77.8100.050.0FABER test, %52.6100.083.3Clinical sacroiliitis, %53.3100.050.0Enthesitis−2.2 (1.9)−2.5 (2.1)−1.3 (1.8)Dactylitis−0.2 (0.8)−0.2 (1)−0.1 (0.4)JIA ACR30, %84.690.968.2JIA ACR50, %78.881.868.2JIA ACR70, %65.468.254.5JIA ACR90, %32.745.550.0JIA ACR100, %26.936.445.5Inactive disease, %38.550.050.0CHAQ−0.5 (0.5)−0.6 (0.7)−0.4 (0.5)CRP, median (SD) change from BL−1.8 (38.7)−5.8 (38.3)0 (35.9)JADAS-27−9.6 (7.5)−11.0 (8.9)−7.6 (8.9)Resolution of enthesitis#, %72.378.683.3Resolution of dactylitis#, %5066.70*End of TP2 is based on individual pts’ last visit at TP2. #At BL, in TP1, enthesitis (n= 46); dactylitis (n=5). In TP2, no. of pts who had presence at BL and showed complete resolution at the end of TP2: enthesitis, SEC 14, PBO 18; dactylitis, SEC 3, PBO, 0. CRP, C-reactive proteinConclusionIn pts with ERA, SEC demonstrated longer time to disease flare vs PBO and exhibited rapid and sustained improvement of axial and peripheral manifestations up to Wk 104.References[1]Pagnini I, et al. Front Med 2021;8:6673052.[2]Brunner H, et al. Arthritis Rheumatol 2021;73 (suppl 10).[3]Weiss PF, et al. Arthritis Care Res 2014;66:1775-82.Disclosure of InterestsNicolino Ruperto Speakers bureau: Eli Lilly, GlaxoSmith and Kline, Pfizer, SOBI and UCB, Paid instructor for: Eli Lilly and Pfizer, Consultant of: Ablynx, Amgen, Astrazeneca-Medimmune, Aurinia, Bayer, Bristol Myers and Squibb, Cambridge Healthcare Research (CHR), Celegene, Domain therapeutic, Eli Lilly, EMD Serono, GlaxoSmith and Kline, Idorsia, Janssen, Novartis, Pfizer, SOBI and UCB, Grant/research support from: Bristol Myers and Squibb, Eli Lilly, F Hoffmann-La Roche, Novartis, Pfizer and SOBI, Elena Chertok: None declared, Joke Dehoorne Speakers bureau: Abbvie, Roche, Consultant of: Abbvie, Roche, Pfizer, Grant/research support from: Abbvie, Roche, Gerd Horneff Speakers bureau: Novartis, Pfizer, Janssen, Grant/research support from: Pfizer, Novartis, Roche, MSD, Tilmann Kallinich Speakers bureau: Roche, Ingrid Louw Speakers bureau: Pfizer, Abbvie, BMS, Consultant of: Pfizer, Abbvie, Janssen, Amgen and Cipla, Sandrine Compeyrot-Lacassagne: None declared, Bernard Lauwerys Employee of: UCB Pharma, Neil Martin: None declared, Katherine Marzan Grant/research support from: Novartis, Sanofi, William Knibbe Speakers bureau: Novartis, Amgen, UCB, Abbvie, Ruvie Martin Shareholder of: Novartis, Employee of: Novartis, Xuan Zhu Shareholder of: Novartis, Employee of: Novartis, sarah whelan Shareholder of: Novartis, Employee of: Novartis, Luminita Pricop Shareholder of: Novartis, Employee of: Novartis, Alberto Martini Speakers bureau: Aurinia, Bristol Myers and Squibb, Eli Lilly, EMD, Janssen, Pfizer, Roche and Serono, Consultant of: Aurinia, Bristol Myers and Squibb, Eli Lilly and EMD, Daniel J Lovell Consultant of: Astra Zeneca, Boehringer Ingelheim, GSK, Hoffman LaRoche, Novartis, UBC, Grant/research support from: Astra Zeneca, Boehringer Ingelheim, GSK, Hoffman LaRoche, Novartis, UBC, Hermine Brunner Consultant of: Novartis, Grant/research support from: Novartis

BackgroundAutoinflammatory diseases (AID) are characterized by severe systemic and organ inflammation as well as high burden of disease for patients and their families. Treatment with the monoclonal antibody canakinumab (CAN), an interleukin-1β inhibitor, has been proven to be safe and effective in clinical trials and real-life.ObjectivesThe present study explores the long-term efficacy and safety of CAN in routine clinical practice conditions in pediatric (age ≥2 years) and adult patients with CAPS (cryopyrin-associated periodic syndromes), FMF (familial Mediterranean fever), TRAPS (tumor necrosis factor receptor-associated periodic syndrome) and HIDS/MKD (hyperimmunoglobulinemia D syndrome/mevalonate kinase deficiency).MethodsRELIANCE is a prospective, non-interventional, observational study based in Germany. Patients with clinically confirmed diagnoses of AID routinely receiving CAN are enrolled. Besides efficacy parameters regarding disease activity and remission, safety parameters were recorded at baseline and assessed at 6-monthly intervals.ResultsHere, we present the interim analysis of patients with AID (N=199) enrolled in the RELIANCE Registry between October 2017 and December 2021. Mean age in this cohort was 24.4 years (2–79 years) and the proportion of female patients was 53% (N=104). At baseline, median duration of prior CAN treatment was 2 years (0–12 years).A total of 123 patients (62%) experienced any AE (N=653) among which nasopharyngitis, increase of inflammatory markers and pyrexia were the most frequent AE with incidence rates per 100 patient years (IR) of 8.3, 6.2, and 6.2, respectively.29 patients (15%) were affected by severe AE (SAE, total number N=90) including 11 patients (6%) with SAE suspected to be drug-related (SADR; total number N=30) with IR from 0.2 to 0.7 (Table 1). Overall, 16 AE comprised upper respiratory tract infections (URI). One death (COVID-19, not related) and one malignancy (skin papilloma, not related) were reported. No vertigo and no hypersensitivity reactions were observed. N=10 (IR 2.36) vaccination reactions were reported (no SAE).Table 1.Overview of the CAN safety data of the RELIANCE study across all study indications (N=199 patients).Type of eventNumber of eventsIR‡AE total653154.43AE non-serious563133.15AE, non-serious, not related31774.97AE, URI163.78AE, non-serious adverse drug reaction24658.18SAE, total9021.28SAE, not related6014.19SADR#, total307.09#Abdominal pain; Alport’s syndrome, appendicitis, arthralgia, blister, cardiovascular disorder, chest pain, circulatory collapse, dehydration, diplopia, dyspnoea, erythema, febrile convulsion, gastroenteritis, glomerulonephritis, Haemophilus test positive, myalgia, oedema, pneumonia, premature delivery, skin discoloration, tachycardia, tonsillitis bacterial, tonsillitis streptococcal, vision blurred (each n=1 event, IR 0.24‡), tonsillectomy (2 events, IR 0.47‡), pyrexia (3 events, IR 0.71‡), not yet coded (hospital admission due to exsiccosis upon gastroenteritis, 1 event, IR 0.35‡)‡IR, incidence rate per 100 patient years; AE, adverse event; URI, upper respiratory tract infection; SAE, severe adverse event, SADR, severe adverse drug reactionIncidence rate = number of events * 36,525 / sum of observation days (=154,442)ConclusionThe interim data from the RELIANCE study, the longest running real-life canakinumab registry, confirm safety of long-term canakinumab treatment across the entire study population. A trend for dose-related increase of SAE/SADR requires continuous close monitoring and awareness in patient groups (children, severe phenotypes, certain genotypes) requiring greater than standard dose treatment regimens.Disclosure of InterestsJ. B. Kuemmerle-Deschner Consultant of: Novartis, AbbVie, Sobi, Grant/research support from: Novartis, AbbVie, Sobi, Jörg Henes Consultant of: Novartis, AbbVie, Sobi, Roche, Janssen, Boehringer-Ingelheim, Grant/research support from: Novartis, Roche, Birgit Kortus-Goetze Consultant of: Novartis, Tilmann Kallinich Consultant of: Sobi, Novartis, Roche, Grant/research support from: Novartis, Prasad Oommen Grant/research support from: Novartis, Jürgen Rech Speakers bureau: Abbvie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD; Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Consultant of: Abbvie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD, Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Grant/research support from: Novartis, Sobi, Tobias Krickau Speakers bureau: Novartis, Consultant of: Novartis, Grant/research support from: Novartis, Frank Weller-Heinemann: None declared, Gerd Horneff Speakers bureau: AbbVie, Bayer, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Grant/research support from: AbbVie, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Ales Janda: None declared, Ivan Foeldvari Consultant of: Novartis, Hexal, Medac, Pfizer, Catharina Schuetz: None declared, Frank Dressler Consultant of: Abbvie, Mylan, Novartis, Pfizer, Grant/research support from: Novartis, Michael Borte Grant/research support from: Pfizer, Shire, Markus Hufnagel Consultant of: Novartis and SOBI, Florian Meier Speakers bureau: Novartis, Michael Fiene: None declared, Julia Weber-Arden Employee of: Novartis, Norbert Blank Consultant of: Novartis, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Actelion, UCB, Boehringer-Ingelheim, Roche, Grant/research support from: Novartis, Sobi

BackgroundTocilizumab (TCZ) has been approved for treatment of juvenile idiopathic arthritis (JIA) for 10 years.ObjectivesEvaluation of 12-month efficacy and safety of TCZ compared to TNF inhibitors (TNFi).MethodsBIKER WA 29358 is a 5-year multi-centre prospective, observational cohort study including polyarticular JIA patients in Germany starting treatment between 2015 and 2020 with TCZ and matched 1:1 by date of treatment start and region to patients starting an approved TNFi. Clinical disease activity (JADAS10), JADAS MDA (≦3.8)/remission (≦1.0), safety and drug adherence at 12 months were assessed and compared between cohorts.ResultsThe analysis included 342 participants with 12-month treatment data (TCZ n=171; TNFi n=171). TCZ was used as 2nd line biologic in the majority of patients (84%) while TNFi were mostly 1st line biologics (86%). Patients starting TCZ had a longer disease duration. Efficacy was demonstrated by a marked decrease in JADAS10 in both cohorts (TCZ vs. TNFi at baseline: 15.0+/-6.7 vs. 14.6+/-6.3; at month 12: 3.8+/-5.1 vs. 3.4+/-4.5). Proportions of patients in TCZ/TNFi cohorts achieving JADAS remission at 12 months were 48%/41% in 1st line biologic users and 32%/33% in 2nd line biologic users. JADAS MDA was achieved in 64%/69% in 1st line and 52%/58% in 2nd line users of TCZ/TNFi.After 12 months of treatment JADAS10 (mean +/SD) was higher in the 2nd line TNFi cohort compared to the 1st line (4.5+/-5.6 vs. 3.2+/-4.3), similar to patients receiving 2nd or 1st line TCZ (4.0+/-5.2 vs. 2.9+/-4.4). Patients receiving TCZ or TNFi as first biologic reached JADAS10 remission and MDA numerically more frequently but not statistically significant compared to 2nd line users.Safety was assessed based on adverse event (AE) reporting. 57 (33%) patients in the TCZ cohort and 43 (25%) patients in the TNFi cohort reported AE. The AE rate was significantly higher in the TCZ cohort (69 vs. 44.8/100 patient years, RR 1.5 [95%CI 1.1-2.0], p=0.006, Wald-test). There were 6 serious AE in the TCZ and 3 in the TNFi cohort. Injection site reactions were more common in the TNFi cohort (9 vs. 1, p=0.043). No further differences were identified to date. There was no death and no opportunistic infection.In the TCZ cohort, 32 patients discontinued treatment, 27 due to lack of efficacy, while in the TNFi cohort only 6 patients discontinued treatment. Treatment discontinuation was more frequent among the 2nd biologic users (n=29; 17.4%) than in first line users (n= 9; 5.1%).ConclusionIn this first interim analysis, treatment targets were reached with similar frequency after 12 months of treatment with TCZ or TNFi. TCZ was used predominantly as 2nd line biologic. Higher rates of remission /MDA were observed in 1st line compared to 2nd line biologic users. Although more AE were reported in the TCZ cohort, the occurrence of serious AE and infections was comparable in both cohorts. No new safety signals were identified. Observation is ongoing.Table 1.Baseline characteristics and discontinuations with reasons.Number, nTNFi 1st 147TNFi 2nd 24TNFi total 171TCZ 1st 27TCZ 2nd 144TCZ total 171Female, %119(81%)20 (83%)139(81%)20(74%)123(85%)143(84%)Disease duration, years2.7+/-2.76.5+/-3.33.2+/-3.12.5+/-2.75.9+/-4.15.4+/-4.1Pre-treatmentn.a.None=147 (86%)n.a.None=27 (16%)1 biologic14 (58%)14 (8%)80 (56%)80 (47%)2 biologics7 (29%)7 (4%)54 (38%)54 (32%)≥ 3 biologics3 (13%)3 (2%)10 (7%)10 (6%)CHAQ-DI, mean +/- SD0.67+/-0.640.31+/-0.450.63+/-0,630.43+/-0.440.65+/-0.650.61+/-0.62JADAS 10, mean +/- SD14.8+/-6.313.4+/-6.814.6+/-6.313.3+/-6.015.3+/-7.015.0+/-6.7ConcomitantMTX, n (%)120 (82%)13 (54%)133 (78%)17 (63%)75 (52%)92 (54%)Steroid, n (%)37 (25%)4 (17%)41 (24%)8 (30%)35 (24%)43 (25%)Discontinuations, n (%)5 (3.4%)1 (4.2%)6 (3.5%)4 (16%)28 (19%)32 (19%)-Inefficacy1 (0.7%)2 (1.2%)3 (12%)24 (17%)27 (16%)-Intolerance2 (1.4%)1 (4.2%)2 (1.2%)2 (1.4%)2 (1.2%)-Other2 (1.4%)2 (1.2%)1 (4%)4 (2.8%)5 (3.0%)Disclosure of InterestsAriane Klein Speakers bureau: Novartis fee chairing a lunch symposium, Angela Zimmer: None declared, Toni Hospach: None declared, Frank Weller-Heinemann: None declared, Sandra Hansmann: None declared, Jasmin Kuemmerle-Deschner: None declared, Maria Fasshauer: None declared, Kirsten Minden Speakers bureau: Honoraries from Novartis, Pfizer, Medac, Ivan Foeldvari: None declared, Christoph Rietschel: None declared, Daniel Windschall Speakers bureau: Pfizer, Novartis, Abbvie, MEDAC, Canon, Grant/research support from: Novartis, Pfizer, Ralf Trauzeddel: None declared, Markus Hufnagel: None declared, Dirk Foell: None declared, Rainer Berendes: None declared, Gundula Boeschow: None declared, Prasad Oommen: None declared, Frank Dressler Speakers bureau: Honoraries from Novartis, Pfizer, Abbvie, Consultant of: Advisory board Novartis, Mylan, Gerd Horneff Speakers bureau: Novartis, Pfizer, Janssen, Grant/research support from: Pfizer, Novartis, Roche, MSD

BackgroundFor classification in juvenile spondyloarthritis (JSpA), it is important to develop cut-offs for active and structural lesions typical of axial disease on MRI that are readily and consistently interpreted. Since the maturing sacroiliac joint (SIJ) looks different from the adult SIJ, the criteria developed for positive MRI in adults may not be applicable in JSpA.ObjectivesAs part of a study developing classification criteria for axial disease in JSpA, we aimed to determine quantitative SIJ imaging lesion cut-offs for inflammatory and structural lesions typical of axial JSpA using majority imaging expert decision as the reference criterion.MethodsSubjects were a retrospective cohort of children with SpA who met the provisional Pediatric Rheumatology International Trials Organization criteria for enthesitis/spondylitis-related juvenile idiopathic arthritis or had a rheumatologist JSpA diagnosis. All subjects had symptom onset prior to age 18 years and underwent MRI as part of a diagnostic evaluation for axial disease. To enable SIJ quadrant-based scoring, all MRIs included semi-coronal slices through the cartilaginous part of the joint on fluid sensitive sequences and on T1-weighted sequences for the assessment of inflammation and structural lesions, respectively. MRIs were reviewed by 6 musculoskeletal imaging experts who were blinded to clinical details. MRI evaluation of the SIJ was based on standardized lesion definitions that were decided by consensus of the central imaging team and represented a mix of definitions from ASAS and the Juvenile Arthritis MRI Score Outcome Measures in Rheumatology working group. Using a web-based interface, raters globally assessed the presence or absence of lesions typical of axial SpA and performed SIJ quadrant or joint based scoring. Lesion scores were generated by averaging the scores of all raters. Sensitivity and specificity of lesion cut-offs were calculated using rater majority (≥4/6 raters) on a global assessment of the presence/absence of active or structural lesions typical of axial SpA with high confidence (confidence of ±3 or stronger on confidence scale from -5, “Definitely No”, to +5, “Definitely Yes”) as the reference standard.ResultsImaging from 243 subjects, 61% male, median age 14.9 years, had sequences available for detailed MRI scoring. Active inflammatory lesion typical of axial disease in JSpA was defined as bone marrow edema (BME) in at least 3 SIJ quadrants (sensitivity 98.6%, specificity 96.5%). For structural lesion typical of axial JSpA, the optimal cut-off was erosion in at least 3 quadrants or at least one of the following lesions in at least 2 SIJ quadrants: sclerosis, fat lesion, backfill, ankylosis (sensitivity 98.6%, specificity 95.5%).ConclusionWe propose data-driven cut-offs for active inflammatory and structural lesions on MRI typical of axial disease in JSpA that have high specificity and sensitivity using central imaging global assessment as the reference standard.Table 1.Performance of cut-offs for inflammatory and structural lesions of axial diseaseCut-offs for number of SIJ quadrants (any location)Sensitivity (95% CI)Specificity (95% CI)Definite active lesionBME score ≥2100 (95.0-100)93.5 (88.7-96.7)BME score ≥398.6 (92.5-100)96.5 (92.5-98.7)BME, same location on ≥3 consecutive slices88.6 (78.7-94.9)98.8 (95.8-99.9)Definite structural lesionErosion ≥295.7 (88-99.1)96.8 (92.7-99)Erosion, same location on ≥2 consecutive slices94.3 (86-98.4)98.1 (94.5-99.6)Erosion ≥391.4 (82.3-96.8)98.7 (95.4-99.8)Sclerosis ≥262.9 (50.5-74.1)98.1 (94.5-99.6)Fat lesion ≥222.9 (13.7-34.4%)98.7 (95.4-99.8%)Backfill ≥220 (11.4-31.3)100 (97.7-100)Ankylosis ≥21.3 (0.2-4.7)100 (94.9-100)ANY of the following in ≥2 SIJ quadrants: erosion, sclerosis, fat lesion, backfill, ankylosis98.6 (92.3-100)93.6 (88.5-96.9)Erosion ≥3 quadrants OR ≥2 quadrants of at least one of the following lesions: sclerosis, fat, backfill, ankylosis98.6 (92.3-100.0)95.5 (91.0-98.2)Disclosure of InterestsPamela F. Weiss Consultant of: PfizerNovartisBiogenLilly(All Novartis, Consultant of: Not in the last four years.BMS, Lilly, Novartis, Robert A. Colbert: None declared, Gerd Horneff Speakers bureau: Pfizer, Novartis, Janssen, Chugai, Abbvie, Grant/research support from: Pfizer, Novartis, MSD, Chugai, Roche, Abbvie, Rik Joos Speakers bureau: Galapagos, Pfizer, AbbVie, Novartis, Amgen, BMS, Lilly, Grant/research support from: Pfizer, AbbVie, Roche, Ronald Laxer Consultant of: Abbvie, Novartis, Sobi, Sanofi, Eli Lilly Canada, Eli Lilly, Kirsten Minden Speakers bureau: Pfizer, Novartis, Consultant of: Pfizer, Novartis, Angelo Ravelli Speakers bureau: Abbvie, Novartis, SOBI, Angelini, Reckitt-Benkiser, Roche, Pfizer, Alexion, Grant/research support from: Novartis, Pfizer, Nicolino Ruperto Speakers bureau: NR has received honoraria for consultancies or speaker bureaus from the following pharmaceutical companies in the past 3 years: 2 Bridge, Amgen, AstraZeneca, Aurinia, Bayer, Brystol Myers and Squibb, Celgene, inMed, Cambridge Healthcare Research, Domain Therapeutic, EMD Serono, Glaxo Smith Kline, Idorsia, Janssen, Eli Lilly, Novartis, Pfizer, Sobi, UCB., Consultant of: NR has received honoraria for consultancies or speaker bureaus from the following pharmaceutical companies in the past 3 years: 2 Bridge, Amgen, AstraZeneca, Aurinia, Bayer, Brystol Myers and Squibb, Celgene, inMed, Cambridge Healthcare Research, Domain Therapeutic, EMD Serono, Glaxo Smith Kline, Idorsia, Janssen, Eli Lilly, Novartis, Pfizer, Sobi, UCB., Grant/research support from: The IRCCS Istituto Giannina Gaslini (IGG), where NR works as full-time public employee has received contributions from the following industries in the last 3 years: Bristol Myers and Squibb, Eli-Lilly, F Hoffmann-La Roche, Novartis, Pfizer, Sobi. This funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment with third parties., Judith Smith Consultant of: Consulting panel of pediatric rheumatologists identifying issues in juvenile spondyloarthritis for Novartis. Paid < $5000, Matthew L. Stoll Consultant of: Currently consulting for Novartis, Shirley ML Tse: None declared, Filip van den Bosch Speakers bureau: Abbvie, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, UCB, Paid instructor for: Amgen, Eli Lilly, Consultant of: Abbvie, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, UCB, Robert G Lambert Paid instructor for: Novartis, Consultant of: CARE Arthritis, Calyx, Image Analysis Group, Novartis, David M. Biko Employee of: Merck (1998-2000), Nancy A. Chauvin Employee of: Forest Pharmaceuticals - Research scientist (1996) and Novartis - Pharmaceutical sales representative (1997), Michael L. Francavilla: None declared, Jacob L Jaremko: None declared, Nele Herregods: None declared, Ozgur Kasapcopur Speakers bureau: Pfizer, Abbvie, Novartis and Roche, Mehmet YILDIZ: None declared, Alison M. Hendry: None declared, Walter P Maksymowych Speakers bureau: Abbvie, Eli-Lilly, Janssen, Novartis, Pfizer, UCB Pharma, Consultant of: AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, UCB Pharma, Grant/research support from: Abbvie, Novartis, Pfizer

BackgroundAlthough the risk for severe COVID-19 progression in children is low, this may be aggravated by the underlying disease and/or immunosuppressive drugs.ObjectivesWe analyzed clinical data of COVID-19 cases among paediatric patients with rheumatic diseases reported to the BIKER registry.MethodsThe main task of the German BIKER (Biologics in Pediatric Rheumatology) registry is to monitor the safety of biologics therapies in JIA. After the onset of the COVID-19 pandemic, the survey was expanded with a standardized form to proactively interview all participating centers about the occurrence, presentation, and outcome of SARS-CoV-2- infections in children with rheumatic diseases. Interviews were conducted with 68 centers initially weekly and later biweekly.ResultsA total of 68 centres participated in the survey. Clinical data from 194 COVID-19 cases reported to the BIKER registry from 41 German and 1 Austrian pediatric rheumatology institutions between February 2020 and December 2021 were analyzed. Juvenile idiopathic arthritis (JIA, n=144) was the most common diagnosis followed by genetic autoinflammation (n=18; i.e. FMF, TRAPS, CAPS, HIDS, DADA2), systemic autoimmune diseases (n=11; i.e. SLE, dermatomyositis, vasculitis) and 16 with other rheumatic diseases (i.e. CRMO, Uveitis). 5 patients with no rheumatic disease were excluded. 104 (54%) patients were receiving conventional DMARDs, 81 (43%) received biologics, mainly TNF inhibitors (n=66 (35%)).Of the 189 rheumatic patients with SARS-CoV2 infection, 123 (63%) were female. The mean age was 12.4+/-4.4 years in females and 13.2+/-4.1 in males. The duration of SARS-Co2 infection associated symptoms was 13.8+/-15.3 days (max. 113 days), in 35 (43%) patients they lasted for > 12 days. 46 (24%) were asymptomatic. Patients with autoinflammation and systemic autoimmunopathies reported more symptoms such as fever, head and throat ache. 4 patients only complained about dyspnea.Only 3 patients were hospitalized and received Oxygen-supplementation. The only patients admitted to ICU, received ventilation but succumbed. This 3½-year-old patient, initially diagnosed with systemic JIA, developed fatal disease with intracranial edema and respiratory failure, as well as typical pulmonary texture changes. Prior to her SARS-CoV-2 infection, the patient was treated with MTX and low-dose steroids. Genetic testing revealed a so far unrecognized congenital immunodeficiency.In the total JIA cohort, treatment with corticosteroids, conventional DMARDs, biologics or combinations did not influence the number of reported symptoms or the favorable outcome of the cohort. However, the duration of symptoms was lower in the TNF-treated cohort (10.4+/-6.4 days vs. 15.7 +/- 19.7 days). In the cohort with autoinflammation, fever was observed in 11 (61%). Those 6 who received IL-1-inhibitors did not show a different outcome than those 12 who did not. No case of PIMS/MISC in children with rheumatic diseases was reported.ConclusionExcept for one patient with congenital immunodeficiency who died from her COVID-19 infection, no case of severe COVID-19 was reported in our cohort. At the time of infection, over 80% of patients in our cohort had been treated with conventional DMARDs and/or biologics. This did not appear to have a negative impact on the severity or outcome of SARS-CoV2 infection. Interestingly, no case of PIMS/MISC was observed.Disclosure of InterestsGerd Horneff Speakers bureau: Novartis, Pfizer, Janssen, Grant/research support from: Pfizer, Novartis, Roche, MSD, Frank Dressler Speakers bureau: Pfizer, Novartis, Abbvie, Paid instructor for: Advisory boards Novartis, Mylan, Daniel Windschall Speakers bureau: Pfizer, Novartis, Abbvie, MEDAC, Canon, Grant/research support from: Novartis, Pfizer, Sonja Mrusek: None declared, Toni Hospach: None declared, Alexander Kühn: None declared, Maria Haller: None declared, Philipp von Bismarck: None declared, Wolfgang Emminger: None declared, Peggy Ruehmer: None declared, Markus Hufnagel: None declared, Ariane Klein Speakers bureau: Novartis

BackgroundThe cryopyrin-associated periodic fever syndromes (CAPS) are hereditary monogenic autoinflammatory diseases with severe systemic and organ inflammation due to increased production of Interleukin-1β (IL-1β). The subcutaneously administered monoclonal antibody canakinumab (CAN) effectively inhibits IL-1β and results in rapid remission of CAPS symptoms in clinical trials as well as in real-life.ObjectivesThe RELIANCE registry is designed to explore long-term safety and effectiveness of CAN under routine clinical practice conditions in pediatric (≥2 years) and adult patients with CAPS, including Muckle-Wells syndrome (MWS), familial cold autoinflammatory syndrome (FCAS), and neonatal onset multisystem inflammatory disease (NOMID)/chronic infantile neurological cutaneous and articular syndrome (CINCA).MethodsThis prospective, non-interventional, observational study with a 3-year follow-up enrolls patients in Germany with clinically confirmed diagnoses of CAPS routinely receiving CAN. In 6-monthly visits, clinical data, physician assessments and patient-reported outcomes are evaluated starting at baseline.Results98 CAPS patients (52% female; 15 [15%] NOMID/CINCA subtypes) were enrolled by December 2021 (Table 1). At baseline, median age was 20 years and median duration of prior CAN treatment was 6 years. At the 36 months visit, 74% of patients reached disease remission by physicians´ assessment along with increasing rates of absent disease activity (patient’s assessment, median 2.0 at baseline and 0.0 month 36). In addition, patients reported low levels of fatigue (absent to mild/moderate: 87% at baseline and 95% at month 36). At baseline, CAPS impaired social life in 47% of patients (37% at month 36) and 33% (23% at month 36) reported days off from school/work. Lab parameters were within normal limits. Remission and disease control were sustained as evaluated parameters remained stable or even decreased over time.Table 1.Patient and physician assessment of clinical CAPS disease activity and laboratory markers over time.Baseline12 months36 monthsNumber of patients, N987240Number (%) of patients in disease remission (physician assessment)64 (68)48 (70)28 (74)Patient’s assessment of current disease activity; 0–10, median (min; max)2.0 (0; 7)2.0 (0; 7)0.0 (0; 6)Patient’s assessment of current fatigue; 0–10, median (min; max)3.0 (0; 9)2.0 (0; 8)1.0 (0; 8)Number (%) of patients without impairment of social life by the disease34 (53)35 (65.0)17 (63)CRP (mg/dl) | SAA (mg/dl); median0.1 | 0.30.1 | 0.50.1 | 0.3Number (%) of patients with disease-related symptomsprior to inclusion into the study | at baseline12 months36 monthsFever75 (80) | 14 (15)19 (28)4 (11)Fatigue84 (89) | 49 (52)36 (52)17 (46)Conjunctivitis/Uveitis63 (67) | 27 (29)21 (30)7 (19)Headache68 (72) | 30 (32)30 (43)9 (24)Arthralgia/arthritis80 (85) | 32 (34)30 (43)14 (38)Impairment of hearing35 (37) | 23 (25)18 (26)11 (30)Trigger (cold, stress, infections, vaccinations, hormones)71 (76) | 32 (34)21 (30)3 (8)SAENumber of eventsIncidence rate* per 100 patient yearsAll types of SAE | SADR63 | 28#25.98 | 11.55CRP, c-reactive protein; ESR, erythrocyte sedimentation rate; n. a., not annotated; SAA, serum amyloid A; SADR, serious adverse drug reaction; SAE, serious adverse event*Incidence rate = number of events * 36,525 / sum of observation days (=88,558)#Abdominal pain, Alport’s syndrome, appendicitis, arthralgia, blister, cardiovascular disorder, chest pain, circulatory collapse, dehydration, diplopia, dyspnoea, erythema, febrile convulsion, gastroenteritis, glomerulonephritis, haemophilus test positive, myalgia, oedema, pneumonia, premature delivery, skin discoloration, tonsillectomy, tonsillitis bacterial, tonsillitis streptococcal, vision blurred (all N=1 event), pyrexia (3 events)ConclusionThe 36-month interim analysis of the RELIANCE study demonstrates that long-term CAN treatment is safe and effective in patients with CAPS, independent of subtype severity.Disclosure of InterestsJ. B. Kuemmerle-Deschner Consultant of: Novartis, AbbVie, Sobi, Grant/research support from: Novartis, AbbVie, Sobi, Birgit Kortus-Goetze Paid instructor for: Novartis, Prasad Oommen Grant/research support from: Novartis, Ales Janda: None declared, Jürgen Rech Speakers bureau: Abbvie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD; Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Consultant of: Abbvie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD, Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Grant/research support from: Novartis, Sobi, Catharina Schuetz: None declared, Tilmann Kallinich Consultant of: Sobi, Novartis, Roche, Grant/research support from: Novartis, Frank Weller-Heinemann: None declared, Gerd Horneff Speakers bureau: AbbVie, Bayer, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Grant/research support from: AbbVie, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Ivan Foeldvari Consultant of: Novartis, Hexal, Medac, Pfizer, Florian Meier Speakers bureau: Novartis, Michael Borte Grant/research support from: Pfizer, Shire, Tobias Krickau Speakers bureau: Novartis, Consultant of: Novartis, Grant/research support from: Novartis, Julia Weber-Arden Employee of: Novartis, Norbert Blank Consultant of: Novartis, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Actelion, UCB, Boehringer-Ingelheim, Roche, Grant/research support from: Novartis, Sobi

Proximal humerus fractures (PHFs) are managed with open reduction and internal fixation (ORIF), hemiarthroplasty (HA), reverse shoulder arthroplasty (RSA), or nonoperatively. Given the mixed results in the literature, the optimal treatment is unclear to surgeons. The purpose of this study was to survey orthopedic shoulder and trauma surgeons to identify the patient- and fracture-related characteristics that influence surgical decision-making.We distributed a 23-question closed-response email survey to members of the American Shoulder and Elbow Surgeons and Orthopaedic Trauma Association. Questions posed to respondents included demographics, surgical planning, indications for ORIF and arthroplasty, and the use of surgical augmentation with ORIF. Numerical and multiple-choice responses were compared between shoulder and trauma surgeons using unpaired t-tests and χRespondents included 172 shoulder and 78 trauma surgeons. When surgery is indicated, most shoulder and trauma surgeons treat 2-part (69%) and 3-part (53%) PHFs with ORIF. Indications for managing PHFs with arthroplasty instead of ORIF include an intra-articular fracture (82%), bone quality (76%), age (72%), and previous rotator cuff dysfunction (70%). In patients older than 50 years, 90% of respondents cited a head-split fracture as an indication for arthroplasty. Both shoulder and trauma surgeons preferred RSA for treating PHFs presenting with a head-split fracture in an elderly patient (94%), pre-existing rotator cuff tear (84%), and pre-existing glenohumeral arthritis with an intact cuff (75%). Similarly, both groups preferred ORIF for PHFs in young patients with a fracture dislocation (94%). In contrast, although most trauma surgeons preferred to manage PHFs in low functioning patients with a significantly displaced fracture or nonreconstructable injury nonoperatively (84% and 86%, respectively), shoulder surgeons preferred either RSA (44% and 46%, respectively) or nonoperative treatment (54% and 49%, respectively) (P .001). Similarly, although trauma surgeons preferred to manage PHFs in young patients with a head-split fracture or limited humeral head subchondral bone with ORIF (98% and 87%, respectively), shoulder surgeons preferred either ORIF (54% and 62%, respectively) or HA (43% and 34%, respectively) (P .001).ORIF and HA are preferred for treating simple PHFs in young patients with good bone quality or fracture dislocations, whereas RSA and nonoperative management are preferred for complex fractures in elderly patients with poor bone quality, rotator cuff dysfunction, or osteoarthritis. The preferred management differed between shoulder and trauma surgeons for half of the common PHF presentations, highlighting the need for future research.

Indications for total elbow arthroplasty (TEA) were traditionally reserved for patients with advanced rheumatoid disease and posttraumatic conditions of the elbow. The indications have expanded for TEA to include patients with acute elbow trauma, dysfunctional instability, and end-stage osteoarthritis. Many of these patients are younger and place a greater demand on their TEA. This evolution of TEA use combined with the concern of soft tissue handling and triceps function has led to increased interest regarding surgical exposure for TEA. Three generalized approaches to TEA are predicated on the handling of the triceps tendon: triceps reflecting, triceps splitting, and triceps sparing. Each of these approaches has its own inherent advantages and disadvantages. As indications grow for TEA and the possibility of revision surgery increases with use in younger, higher demand patients, it is important for treating surgeons to use these various exposures so that they are capable of treating patients in a variety of settings.

Massive irreparable rotator cuff tears remain a difficult problem to treat in orthopaedics. The reverse shoulder arthroplasty has revolutionized how we approach patients without a functional rotator cuff, but there is a large patient population that remains unsuitable for this procedure. The subacromial interpositional balloon spacer is one of the latest techniques designed to address this challenging problem for such patients. The biodegradable spacer is designed to restore glenohumeral mechanics by reversing proximal humeral migration and providing a counterbalance to the superiorly directed force vector of the deltoid muscle. This helps to restore the fulcrum necessary for elevation of the arm. Placement of the biodegradable device is relatively quick and does not require extensive rehabilitation postoperatively. In addition, the surgery does not prohibit the patient from any future surgeries should the condition of the shoulder worsen over time. The subacromial balloon spacer has had widespread use in Europe with good success and limited complications. It is currently being evaluated for use in the United States in The Food and Drug Administration trial.

ObjectivesDue to their underlying disease as well as therapeutic immunosuppression, children and adolescents with rheumatic and musculoskeletal diseases (RMD) may be at higher risk for a severe course or worse outcome of COVID-19, and SARS-CoV2 infection may trigger a flare of the RMD. To address these issues, a specific SARS-CoV-2 questionnaire was implemented in the National Pediatric Rheumatology Database (NPRD) in Germany.MethodsDemographic, clinical and treatment data from juvenile patients with RMD as well as data about SARS-CoV-2 infection like test date and method, clinical characteristics, disease course, outcome and impact on the disease activity of the RMD documented on this questionnaire were analyzed.ResultsFrom April 17th, 2020, to February 14th, 2021, data were collected from 79 patients (53% female) with RMD with median age of 14 years, diagnosed with juvenile idiopathic arthritis (57%), autoinflammatory (23%) and connective tissue disease (8%). Sixty-one patients (77%) received disease-modifying antirheumatic drugs (DMARDs), 43% biologic DMARDs, and 9% systemic glucocorticoids. Sixty patients (76%) developed symptoms of COVID-19. Disease severity was mild and outcome was good in the majority of patients. Two patients were hospitalized, one of whom required intensive care and died of cardiorespiratory failure. In 84% of SARS-CoV-2-positive patients, no relevant increase in disease activity of the RMD was observed.ConclusionsIn our cohort, COVID-19 in juvenile patients with RMD under various medications was mild with good outcome in the majority of cases. SARS-CoV-2 infection does not appear to have a relevant impact on disease activity of the underlying condition.

Introduction Patients with a worker compensation claim are associated with a greater probability of continued symptoms and activity intolerance. This study aims to determine predictors of improved patient-reported outcomes in the workers’ compensation population. Methods Patients with workers’ compensation claims undergoing arthroscopic rotator cuff repair between 2010 and 2015 were included. Age, gender, dominant hand, occupation, and number of tendons involved were analyzed. At a minimum of two years, patients were contacted to complete American Shoulder and Elbow Surgeons (ASES) Survey, Simple Shoulder Test (SST), and return-to-work status (RTW). Preoperative characteristics and scores were then compared. Results Seventy patients were available for follow-up at an average of 5.4 years (range: 2.1-8.8 years). Average age was 55 years (range: 37-72); 55 (78.6%) were males, 23 (32.9%) were laborers; and 59 (84.2%) patients returned to work. The sole predictor for RTW was surgery on the non-dominant arm (96.5% versus 75.6%; p = 0.021). Laborers showed decreased RTW (p = 0.03). Patients who completed RTW had excellent outcomes with higher ASES (87 versus 50; p value < 0.001) and SST scores (10.4 versus 4.6; p < 0.001). Patients with three tendon tears had inferior ASES (p = 0.026) and SST (p = 0.023) scores than those with less. Conclusion Most workers’ compensation patients have excellent outcomes from rotator cuff repair. Patients with three tendon tear repairs demonstrated the worst functional outcomes. Laborers showed decreased ability to RTW with nearly one-third unable.

Background The purpose of this analysis was to analyze outcomes of distal biceps reconstruction with soft tissue allograft in the setting of chronic, irreparable distal biceps ruptures. The outcomes of these cases were then compared with a matched cohort of distal biceps ruptures that were able to be repaired primarily. Methods Retrospective review of an institutional elbow surgery database was conducted. All cases of distal biceps repairs were identified by Common Procedural Terminology, ICD-9, and ICD-10 codes from January 2009 to March 2018. A direct review of operative reports was then conducted to identify which cases required allograft reconstruction. After identification of this population, a 2:1 manually matched cohort of patients who underwent primary repair was generated using age, gender, body mass index, and age-adjusted Charlson Comorbidity Index. Finally, the allograft reconstruction and matched primary repair cohorts were compared for reoperation, range of motion, and patient-reported outcomes scores. Results There were 46 male patients who underwent distal biceps reconstruction with allograft (14 Achilles tendon, 32 semitendinosus) and they were matched to 92 male patients that underwent primary distal biceps repair. Mean patient age (46.9 ± 10.3 vs. 47.0 ± 9.8 years, P = .95), BMI (31.3 ± 5.3 vs. 31.3 ± 4.8 kg/m2, P = .60), and Charlson Comorbidity Index (1.2 ± 1.1 vs. 1.3 ± 0.9, P = .64) were similar between allograft reconstruction and primary repair groups. Disability of the Arm, Shoulder and Hand score (7.4 ± 18.0 vs. 1.6 ± 4.1, P = .23), Mayo Elbow Performance Score (92.1 ± 19.7 vs. 97.3 ± 6.4, P = .36), and Oxford Elbow Score (43.4 ± 11.0 vs. 46.8 ± 3.2, P = .25) were not significantly different between groups at mean 5.1 years (range, 1.5-10.9 years) after surgery. There were 1 of 42 (2.2%) allograft patients who require revision compared with 3 of 92 (3.3%, P = .719) in the primary repair group. In addition, one primary repair required reoperation for scar tissue excision and lateral antebrachial cutaneous neurolysis. Final range of motion data (twelve-week follow-up) for the allograft reconstruction group was similar to primary repair group in flexion (136.1° ± 5.3° vs. 135.9° ± 2.7°, P = .81), extension (0.8° ± 2.9° vs. 0.4° ± 1.7°, P = .53), pronation (78.0° ± 9.0° vs. 76.4° ± 15.4°, P = .50), supination (77.4° ± 10.7° vs. 77.5° ± 11.9°, P = .96). Conclusion Patients who underwent distal biceps reconstruction with a graft had similar failure rates, reoperation rates, final range of motion, and patient-reported outcomes scores as those treated without a graft. Patients can be consulted that direct repair in the acute setting is preferred; however, even in the setting of a distal biceps reconstruction with graft augmentation, they can expect low complications and good functional results.

Introduction Given the limitations of anchor-based rotator cuff repair, surgeons have considered and investigated the use of an arthroscopic transosseous repair technique using only sutures to repair tendon tissue. Returning full circle to the gold standard of transosseous repair, but with the modern adaptation of arthroscopy, advocates of arthroscopic transosseous rotator cuff repair believe that many of the risks associated with suture anchors can be avoided. The purpose of this study was to examine the capabilities of a novel needle-based arthroscopic transosseous tunneling device (OmniCuff™ arthroscopic transosseous device, MinInvasive Ltd., Magal, Israel) and evaluate the short-term clinical outcomes and patient satisfaction of patients treated with this technique. Materials and methods This study was a prospective, single-arm, multi-center study performed on patients from January 2014 to March 2015. During the study period, thirty-two patients underwent arthroscopic transosseous rotator cuff repair using the OmniCuff™ arthroscopic transosseous device. Results The average age of patients was 58.2 years (range, 44 to 80 years). The sizes of the tears were as follows: seven small, 18 medium, four large, and three massive. The average number of tunnels used per repair was 1.9 with the following breakdown: six one-tunnel repairs, 22 two-tunnel repairs, and four three-tunnel repairs. The mean American Shoulder and Elbow Surgeon (ASES) score improved from 45.1 to 87.7, the mean Simple Shoulder Test (SST) score improved from 42.6 to 92. Overall patient satisfaction was high with an average Likert scale of 4.6. Conclusion Our study demonstrated significantly improved outcomes for patients undergoing arthroscopic transosseous rotator cuff repair using the needle based Omnicuff device. Patients were overall very satisfied with the outcome of their surgery and their ASES and SST scores demonstrated this appropriately.

BACKGROUND: Multiple surgical techniques for fixation of Neer type IIB distal clavicle fractures have been described without consensus on optimal treatment. The purpose of this study is to compare functional and radiographic results with surgical management of Neer type IIB distal clavicle fractures at a single institution. METHODS: Sixty-three patients with acute Neer type IIB fractures treated operatively were evaluated. Patients with a minimum of two year follow up were included. Functional scores included American Shoulder and Elbow Surgeons (ASES), Single Assessment Numeric Evaluation (SANE), Simple Shoulder Test (SST), and Likert patient satisfaction (1 to 5). Radiographs were assessed for osseous union and coracoclavicular (CC) distance. RESULTS: Thirty-eight patients met inclusion with a mean follow-up of 5.3 years. Patients were divided into five groups based on fixation technique: suture-only CC fixation (n=6), CC screw fixation only (n=3), open reduction internal fixation (ORIF) without CC fixation (n=8), hook plate fixation (n=4), and ORIF with suture CC reconstruction (n=17). Outcome scores for the entire cohort were 91.8 for ASES, 90.2 for SANE, and 10.8 for STT. Patients with hook plates had significantly lower SANE score (p=0.016), but no other significant differences in functional, satisfaction, or radiographic outcomes were found between groups. Sixteen patients (42.1%) required reoperation. CONCLUSION: Treatment of Neer type IIB fractures via suture- only fixation, plate-only fixation, or a combination of both demonstrated satisfactory mid to long term outcomes. While implant removal was more common in the CC screw and ORIF groups, no fixation technique proved functionally superior.

BackgroundCLIPPER2 was an 8-year, open-label extension of the phase 3b, multicenter, 2-year CLIPPER study of the safety and efficacy of etanercept (ETN) in the treatment of patients (pts) with juvenile idiopathic arthritis (JIA) categorized as extended oligoarticular arthritis (eoJIA), enthesitis-related arthritis (ERA), or psoriatic arthritis (PsA).ObjectivesThe objective of this analysis was to describe the safety of ETN in this population after 10 years of follow up.MethodsPts (n=127) with eoJIA (2-17 years), ERA, or PsA (each 12-17 years) who received ≥1 ETN dose (0.8 mg/kg once weekly [max, 50 mg]) in CLIPPER were eligible to enter CLIPPER2. The primary outcome measure was the occurrence of malignancy. Long-term safety was assessed as the total incidence of events from CLIPPER baseline (BL) to month (mth) 120, frequency of events per 100 patient-years (EP100PY), and frequency of events in each study year.ResultsA total of 109/127 (86%) pts entered CLIPPER2; 99 (78%) continued in the active treatment period. At mth 120, 84 (66%) pts had completed the study; 27 (21%) while actively taking ETN; 7 (6%) had withdrawn from treatment due to low/inactive disease; 5 (4%) had re-started ETN following an earlier withdrawal from treatment; and 45 (35%) had stopped ETN (but remained under observation); 25 (20%) pts permanently discontinued from the CLIPPER2 study. In CLIPPER/CLIPPER2, 1 case of malignancy (Hodgkin’s disease) was reported (1 pt with eoJIA in Year 3). There was 1 case of uveitis (1 pt with eoJIA in Year 8) and 3 of Crohn’s disease (2 pts with ERA, Year 1/Year 6; 1 pt with eoJIA, Year 5). There were 2 cases of opportunistic infections (both herpes zoster), and no deaths. Overall, there were 559 (81.82 EP100PY) treatment-emergent adverse events (TEAEs) excluding infections and injection-site reactions (ISRs). The overall rate of TE serious infections was low (N=14; 2.05 EP100PY) (Table 1), with the most common TE serious infection being gastroenteritis (N=2; 0.29 EP100PY). The most frequently reported TEAEs (N [EP100PY]) were headache (28 [4.10]), arthralgia (24 [3.51]), pyrexia (21 [3.07]), diarrhea (14 [2.05]), and leukopenia (12 [1.76]). Overall, 39 patients reported serious AEs (excluding infections/ISRs). The number and frequency (N [EP100PY]) of TEAEs (excluding infections/ISRs) decreased over the 10-year study period from 193 [173.81] in Year 1 to 9 [27.15] in Year 10. The number and frequency of TE infections and TE serious infections also decreased over the 10-year study period. There was no clear trend of a decrease over time for the incidence of TE serious AEs (Figure 1).Table 1.ETN Safety Summary (from CLIPPER BL to mth 120), N (EP100PY) (FAS)*eoJIA, n=60(EXP=313.667 PY)ERA, n=38(EXP=206.971 PY)PsA, n=29(EXP=162.576 PY)Total, n=12(EXP=683.214 PY)TEAEs†269 (85.76)176 (85.04)114 (70.12)559 (81.82)TE serious AEs†16 (5.10)17 (8.21)7 (4.31)40 (5.85)TE ISRs23 (7.33)29 (14.01)12 (7.38)64 (9.37)TE infections418 (133.26)99 (47.83)155 (95.34)672 (98.36)TE serious infectionsǂ5 (1.59)4 (1.93)5 (3.08)14 (2.05)Opportunistic infections§01 (0.48)1 (0.62)2 (0.29)TEAEs causing withdrawal†7 (2.23)9 (4.35)2 (1.23)18 (2.63)TE infections causing withdrawal2 (0.64)01 (0.62)3 (0.44)*While on active ETN treatment or within 30 days of last dose†Excluding infections/ISRsǂGastroenteritis, 2 (0.29); acute tonsillitis, anal abscess, bronchopneumonia, gastrointestinal infection, helicobacter gastritis, influenza, peritonitis, pharyngitis, pyelocystitis, sepsis, urinary tract infection, viral infection, all 1 (0.15)§Both herpes zosterEXP, exposure to ETN; FAS, full analysis set; n, number of patients; N, number of eventsConclusionETN treatment to mth 120 was well tolerated in this patient population and consistent with the known safety profile. Frequency of TEAEs and TE infections decreased over time. Over 10 years, there was 1 reported event of malignancy and the overall rate of TE serious infections was low.References[1]NCT00962741/NCT01421069AcknowledgementsMedical writing support was provided by Iain McDonald, PhD, of Engage Scientific Solutions and was funded by Pfizer.Disclosure of InterestsJelena Vojinovic Speakers bureau: Abbvie, Roche, Sandoz, Joke Dehoorne Speakers bureau: Abbvie, Roche, Consultant of: Abbvie, Roche, Violeta Panaviene: None declared, Gordana Susic: None declared, Gerd Horneff Speakers bureau: Chugai, Eli-Lilly, Glaxo Smith and Kline, Janssen, Novartis, Pfizer, Roche and Sobi, Grant/research support from: Novartis, Janssen, Roche, Valda Stanevicha Speakers bureau: Sandoz, Abbvie, Roche, Katarzyna Kobusinska: None declared, Zbigniew Żuber: None declared, Bogna Dobrzyniecka: None declared, Jonathan Akikusa: None declared, Tadej Avcin Speakers bureau: AbbVie, Octapharma, and Takeda, Consultant of: AbbVie, Alexion, Octapharma, and Takeda, Alberto Martini Speakers bureau: Aurinia, Bristol Myers and Squibb, Eli-Lilly, EMD Serono, Janssen, Pfizer, Roche, Consultant of: Aurinia, Bristol Myers and Squibb, Eli-Lilly, EMD Serono, Janssen, Pfizer, Roche, Cecilia Borlenghi Shareholder of: Pfizer, Employee of: Pfizer, Edmund Arthur Employee of: Pfizer, Svitlana Y Tatulych Shareholder of: Pfizer, Employee of: Pfizer, Chuanbo Zang Shareholder of: Pfizer, Employee of: Pfizer, Bonnie Vlahos Shareholder of: Pfizer, Employee of: Pfizer, Nicolino Ruperto Speakers bureau: Ablynx, Amgen, Astrazeneca-Medimmune, Aurinia, Bayer, Bristol Myers and Squibb, Cambridge Healthcare Research (CHR), Celgene, Domain therapeutic, Eli-Lilly, EMD Serono, Glaxo Smith and Kline, Idorsia, Janssen, Novartis, Pfizer, Sobi, UCB., Consultant of: Ablynx, Amgen, Astrazeneca-Medimmune, Aurinia, Bayer, Bristol Myers and Squibb, Cambridge Healthcare Research (CHR), Celgene, Domain therapeutic, Eli-Lilly, EMD Serono, Glaxo Smith and Kline, Idorsia, Janssen, Novartis, Pfizer, Sobi, UCB.

BackgroundFamilial Mediterranean Fever (FMF) is a chronic disease characterized by recurrent attacks of fever as well as serositis and bears the risk of serious complications (e. g. amyloidosis). Treatment of FMF according to EULAR aims to control acute attacks and subclinical inflammation as well as to improve patient´s quality of life1. Clinical data indicate that the inhibition of interleukin-1β with canakinumab (CAN) is effective in controlling and preventing flares in FMF patients2.ObjectivesThe present study explores the long-term efficacy and safety of canakinumab in routine clinical practice conditions in pediatric (age ≥2 years) and adult FMF patients.MethodsRELIANCE is a prospective, non-interventional, multi-center, observational study based in Germany with a 3-year follow-up period. Patients with clinically confirmed FMF diagnosis who routinely receive canakinumab are enrolled in order to evaluate effectiveness and safety of canakinumab. Disease activity and remission by physicians´ assessment, disease activity, fatigue and impact on social life by patients’ assessment, inflammatory markers and AIDAI (Auto-Inflammatory Diseases Activity Index) score were recorded at baseline and assessed at 6-monthly intervals within the 3-year observation period of the study.ResultsThis interim analysis of FMF patients (N=74) enrolled by December 2021 includes baseline as well as 6- to 24-month data. Mean age in this cohort was 25 years (2−61 years) and the proportion of female patients was 51 % (N=38). At baseline, median duration of prior CAN treatment was 1.0 years (0−6 years).At month 24, physician ratings report around 63% of patients in disease remission and patient-reported disease activity (mean PPA) decreased from moderate (3.0) to low (2.6) during the observation period. Other disease activity parameters also decreased (Table 1). A total of 18 serious adverse events were reported, of which 2 (1 case of tonsillectomy and 1 case of tachycardia) were classified as drug - related.Table 1.Baseline characteristics and 4th interim analysis data of patients with FMFBaseline12 months24 monthsNumber of patients, N744624Number (%) of patients with days absent from work/school during last 6 months6 (8)11 (24)9 (38)Number (%) of patients in disease remission (physician assessment)22 (45)23 (72)12 (63)Patient’s assessment of current disease activity; 0–10, median (min; max)2.0 (0; 10)2.0 (0; 7)2.0 (0; 10)Patient’s assessment of current fatigue; 0–10, median (min; max)5.0 (0; 10)2.0 (0; 10)4.0 (0; 10)Number (%) of patients without impairment of social life by the disease27 (50)28 (80)8 (67)CRP (mg/dl) | SAA (mg/dl) | ESR (mm/h); median0.2 | 0.7 | 8.00.2 | 0.5 | 4.00.2 | 0.7 | 6.0Number (%) of patients with disease-related symptomsprior to inclusion into the study | at baseline12 months24 monthsFever68 (93) | 14 (29)8 (25)3 (16)Abdominal pain67 (92) | 20 (41)10 (31)4 (21)Thoracic pain45 (62) | 5 (10)3 (9)1 (5)Headache34 (47) | 11 (22)7 (22)5 (26)Myalgia23 (32) | 6 (12)4 (13)2 (11)Arthralgia/arthritis39 (54) | 16 (33)9 (28)5 (26)Dermal symptoms (urticarial, maculopapulose)15 (21) | 5 (10)3 (9)0 (0)SAENumber of eventsIncidence rate# per 100 patient yearsAll types of SAE1814.03SADR21.56Incidence rate = number of events * 36,525 / sum of observation days (=46,848).CRP, c-reactive protein; ESR, erythrocyte sedimentation rate; n. a., not annotated; SAA, serum amyloid A; SADR, serious adverse drug reaction; SAE, serious adverse events.ConclusionInterim data of FMF patients from the RELIANCE study, the longest running real-life canakinumab registry confirm efficacy and safety of long-term canakinumab treatment.References[1]Ozen S, et al. EULAR recommendations for the management of familial Mediterranean fever. Ann Rheum Dis 2016;75:644–651. doi:10.1136/annrheumdis-2015-208690[2]De Benedetti F, et al. Canakinumab for the treatment of autoinflammatory recurrent fever syndromes. N Engl J Med 2018;378:1908–19.Disclosure of InterestsJörg Henes Consultant of: Novartis, AbbVie, Sobi, Roche, Janssen, Boehringer-Ingelheim, Grant/research support from: Novartis, Roche, J. B. Kuemmerle-Deschner Consultant of: Novartis, AbbVie, Sobi, Grant/research support from: Novartis, AbbVie, Sobi, Tobias Krickau Speakers bureau: Novartis, Consultant of: Novartis, Grant/research support from: Novartis, Tilmann Kallinich Consultant of: Sobi, Novartis, Roche, Grant/research support from: Novartis, Frank Dressler Consultant of: Abbvie, Mylan, Novartis, Pfizer, Grant/research support from: Novartis, Gerd Horneff Speakers bureau: AbbVie, Bayer, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Grant/research support from: AbbVie, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Florian Meier Speakers bureau: Novartis, Ivan Foeldvari Consultant of: Novartis, Hexal, Medac, Pfizer, Frank Weller-Heinemann: None declared, Birgit Kortus-Goetze Consultant of: Novartis, Markus Hufnagel Grant/research support from: Novartis, Jürgen Rech Speakers bureau: Abbvie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD; Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Consultant of: Abbvie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD, Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Grant/research support from: Novartis, Sobi, Prasad Oommen Grant/research support from: Novartis, Julia Weber-Arden Employee of: Novartis, Norbert Blank Consultant of: Novartis, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Actelion, UCB, Boehringer-Ingelheim, Roche, Grant/research support from: Novartis, Sobi.

BackgroundThe ProKind Commission of the Society for Paediatric and Adolescent Rheumatology (GKJR) has developed evidence- and consensus-based protocols for the diagnosis and therapy of children and adolescents with defined rheumatic diseases (e.g., [1]). In the ProKind-Rheuma project, it is now investigated whether the protocols are followed in everyday clinical practice and what the treatment-associated outcomes are.ObjectivesTo investigate the mode of treatment and treatment response in patients with polyarticular juvenile idiopathic arthritis (pJIA).MethodsProKind-Rheuma is a multicenter prospective non-interventional observational study. Patients with pJIA enrolled until 17/1/2022 were included into this analysis. Treatments and outcomes up to the 3-month follow-up visit (3FU) were analyzed. Disease states were categorized based on the 2021 cJADAS10 cutoffs [2].ResultsTo date, 18 pediatric rheumatology facilities have participated in ProKind-Rheuma. Data from 203 patients with JIA are available. Of those, 44% have oligoarthritis, 36% polyarthritis, 9% systemic JIA, 6% enthesitis-related arthritis and 3% psoriatic arthritis.In total, 76 patients were diagnosed with pJIA, 38 with already completed 3FU:For 23 patients with pJIA and completed 3FU, we were able to analyze the protocol-defined [1] treatment goal of at least “minimal improvement”. In total, 18 (78%) achieved minimal improvement, 5 (22%) missed it. For 4 of those 5 patients, the underlying MTX therapy was escalated to a bDMARD (3 changed to MTX+bDMARD-combi, 1 to bDMARD-mono). In 3 other patients, therapy was also escalated to an MTX+bDMARD-combi.Between baseline and 3FU, 72% achieved cJADAS10-disease state improvement (Table 1) by at least one category (range 1 - 2), 0% decreased.Table 1.*based on non-missing valuesAt Baseline allAt Baseline with 3FUAt 3FUTotal7638Female, n (%)58 (76)30 (79)Age (years), Mdn (IQR)9 (3-12)7 (2-12)7.5 (3-12)Time since diagnosis (months), Mdn (IQR)0 (0-1)0 (0-1)4 (3-4)RF-positivity, n (%)8 (11)3 (8)Number of active joints (arthritis), Mdn (IQR)7 (4-12)7 (5-12)2 (0-4)JADAS10 (0-40), Mean (SD) (NBL+3FU= 23)18.6 (7.4)19.6 (7.6)7.2 (4.2)cJADAS10 (0-30), Mean (SD) (NBL+3FU= 29)16.3 (5.9)16.7 (6.1)7.1 (4.1)State of inactive disease (cJADAS10≤2.5), n (%*)0 (0)0 (0)4 (13)State of minimal disease activity (2.51 (2)1 (3)9 (28)State of moderate disease activity (533 (54)17 (50)18 (56)State of high disease activity (cJADAS10>16), n (%*)27 (44)16 (47)1 (3)CHAQ (0-3), Mean (SD)0.8 (0.8)0.9 (0.8)0.3 (0.5)Pain (NRS 0 - 10), Mean (SD)4.3 (3)4.7 (3)2.2 (2.7)PedsQL 4.0 total score, Mean (SD)66.3 (22.2)65.4 (21.8)78.4 (17.6)Intraarticular glucocorticoids > 4 joints (ever), n (%)12 (16)5 (13)7 (18)Glucocorticoid pulses (ever), n (%)22 (29)12 (32)13 (34)Methotrexate, n (%)56 (74)31 (82)34 (90)bDMARDs, n (%)7 (9)2 (5)9 (24)Within the first 3 months after diagnosis, the treatment pathways proposed by the ProKind Commission [1] were followed in about three-quarters of patients: i) 5 (13%) received MTX and intra-articular glucocorticoid injections in more than 4 joints (IAGC), but no high-dose intravenous glucocorticoid pulse (HDGC) or bDMARD; ii) 8 (21%) received MTX and HDGC (no bDMARD, no IAGC); iii) 16 (42%) patients received MTX, of whom 4 received a bDMARD up to or at the 3FU (no HDGC, no IAGC). Nine (24%) patients were not treated with MTX or did not fit any of these categories, mostly due to starting bDMARD therapy in conjunction with HDGC or IAGC.ConclusionIn the routine care of JIA patients with polyarthritis, the proposed treatment protocol and treat-to-target strategy are followed in most patients. At 3FU, improvements of JADAS10 and other outcomes were evident, with 41% having achieved inactive or minimal active disease.ProKind is funded by the Innovation Fund “Gemeinsamer Bundesausschuss”, FKZ: 01VSF18031References[1]Horneff et al. Pediatric Rheumatology 2017; 15:78[2]Trincianti et al. Arthritis Rheumatol. 2021 Nov; 73(11):1966-1975AcknowledgementsWe are grateful to all physicians, medical professionals and everyone else who has so far contributed and supported the ProKind-Rheuma project.Moreover, we want to express special gratitude to all patients and their parents for their participation.Disclosure of InterestsSascha Eulert: None declared, Kristina Vollbach: None declared, Klaus Tenbrock: None declared, Jens Klotsche: None declared, Dirk Foell Speakers bureau: Speaker fees/honoraria from Boehringer, Novartis, Werfen and Sobi, Grant/research support from: Novartis and Sobi, Johannes-Peter Haas: None declared, Frank Weller-Heinemann: None declared, Sonja Mrusek: None declared, Prasad Oommen: None declared, Daniel Windschall Speakers bureau: Research support and speakers fee: Pfizer, Novartis, Abbvie, Medac, Sobi, Canon, Grant/research support from: Research support and speakers fee: Pfizer, Novartis, Abbvie, Medac, Sobi, Canon, Kirsten Moenkemoeller: None declared, Tilmann Kallinich: None declared, Markus Hufnagel: None declared, Ivan Foeldvari Consultant of: Addvisory board: Hexal, Novartis, Pfizer, Toni Hospach Consultant of: Advisory board: Sobi, Novartis, Moritz Klaas: None declared, Michael Rühlmann: None declared, Ralf Trauzeddel: None declared, Normi Brueck: None declared, Catharina Schütz: None declared, J. B. Kuemmerle-Deschner: None declared, Ariane Klein: None declared, Kirsten Minden Speakers bureau: Speaker: Pfizer, Novartis, Gerd Horneff: None declared

BackgroundJuvenile systemic sclerosis (jSSc) is an orphan disease with a prevalence of 3 in 1 000 000 children (1). In adult patients there are significant differences between the clinical presentation of diffuse and limited subtypes (2). We reviewed clinical differences in presentation of subtypes in patients in the juvenile systemic scleroderma inception cohort up to 2021.ObjectivesTo study the clinical presentation of jSSc patients with diffuse (djSSc) and limited (ljSSc) subtypes.MethodsWe reviewed the clinical baseline characteristics of the patients, who were recruited to the juvenile scleroderma inception cohort (jSScC) (3, 4) till 1st of December 2021. jSScC is a prospective cohort of jSSc patients, who developed the first non-Raynaud´s symptom before the age of 16 years and are under the age of 18 years at the time of inclusion.Results210 patients with jSSc were included in the cohort, 71% (n=162) had diffuse subtype. The median age at onset of Raynaud phenomenon was 10.4 years (7.3 – 12.9) and the median age at the first non-Raynaud symptom was 10.9 years (7.4 – 13.2). Median disease duration was 2.5 years (1 – 4.4) at the time of inclusion. The female/male ratio was significantly lower in the djSSc subtype (3.7:1 versus 5:1, p< -2 z score (20% versus 4%, p=0.003) and decreased joint range of motion (64% versus 46%, p=0.019). Patients with ljSSc had significantly higher rate of cardiac involvement (13% versus 2%, p=0.001).Regarding patient related outcomes djSSc patients had more severe disease, looking at patient reported global disease activity (VAS 0 – 100) (40 versus 25, p=0.039), patient reported global disease damage (VAS 0 – 100) (40 versus 25, p=0.021) and patient reported assessment of ulceration activity (10 versus 0, p=0.044). Regarding physician related outcomes the physician reported global disease activity (VAS 0 – 100) (32 versus 20, pConclusionIn this jSSc cohort, the largest in the world, djSSc patients have a significantly more severe disease than ljSSc patients. Interestingly, we found no differences regarding interstitial lung disease and pulmonary hypertension.References[1]Beukelman T, Xie F, Foeldvari I. Assessing the prevalence of juvenile systemic sclerosis in childhood using administrative claims data from the United States. Journal of Scleroderma and Related Disorders. 2018;3(2):189-90.[2]Dougherty DH, Kwakkenbos L, Carrier ME, Salazar G, Assassi S, Baron M, et al. The Scleroderma Patient-Centered Intervention Network Cohort: baseline clinical features and comparison with other large scleroderma cohorts. Rheumatology (Oxford). 2018;57(9):1623-31.[3]Foeldvari I, Klotsche J, Kasapcopur O, Adrovic A, Terreri MT, Sakamoto AP, et al. Differences sustained between diffuse and limited forms of juvenile systemic sclerosis in expanded international cohort. www.juvenile-scleroderma.com. Arthritis Care Res (Hoboken). 2021.[4]Foeldvari I, Klotsche J, Torok KS, Kasapcopur O, Adrovic A, Stanevica V, et al. CHARACTERISTICS OF THE FIRST 80 PATIENTS AT TIMEPOINT OF FIRST ASSESSMENT INCLUDED IN THE JUVENILE SYSTEMIC SCLEROSIS INCEPTION COHORT. WWW.JUVENILESCLERODERMA.COM. Journal of Scleroderma and Related Disorders. 2018;4(1-13).Disclosure of InterestsNone declared

BackgroundAlthough regular physical activity (PA) is known to have many health-related benefits for children and adolescents with chronic conditions, JIA has been associated with reduced physical activity (PA) and increased time spent sedentary [1]. Sedentary behaviour is an important consideration alongside PA when examining the contribution of both behaviours to the health of young patients. Because young people show more complex but less structured movement behaviour than adults, capturing their many spontaneous and impulsive movements is a great challenge for PA assessment.ObjectivesSince accurate, objective measures of PA related to potential factors promoting PA have been scarce, this study aimed i) to objectively assess moderate to vigorous PA (MVPA) as well as sedentary behaviour and ii) to identify facilitators for PA in patients with JIA.MethodsWithin the framework of the ActiMON study as part of the TARISMA research network, data were collected at several German paediatric rheumatology centres. Objectively assessed PA of adolescent patients with JIA was recorded exclusively during school months in the period June - December 2021 using the accelerometer ActiGraph wGT3X-BT laterally on the right hip. In accordance with the International Children’s Accelerometry Database criteria [2], ActiGraphs were worn on seven consecutive days during all waking hours, including at least 4 valid weekdays and 1 weekend day (wear time >8 hours) in the evaluation. Self-reported PA-related data were measured using a physical activity questionnaire (PAQ), while clinical parameters were used from the National Paediatric Rheumatologic Database (NPRD). Achievement of the WHO recommendation of at least 60 minutes MVPA per day and compliance with the national recommendation of no more than 120 minutes of daily screen time were determined among 12- to 18-year-olds.ResultsData of 41 patients (mean age 14.6 ± 1.9 years, female 73%, patients’ disease duration 7.9 ± 4.6 years, polyarthritis 40%, cJADAS-10 2.3 ± 2.4) were available for evaluation. Almost 71% of participating patients met the WHO-recommended minimum level of MVPA, while the average daily step count achieved was 7804. Almost 80% of the patients rated their motor and coordination skills as being good. The most frequently mentioned reasons for doing sports (multiple answers possible) included feeling good (78%), giving energy (70%), pleasure (65%) and enjoyment (60%). Patients whose parents are active in sports and support their child in finding a suitable offer were more likely to fulfil the WHO recommendation than patients without family support. The average daily time spent sedentary was 10.5 ± 1.9 hours. About half of the patients reported spending more than 4 hours a day with screen-based media, especially video games.ConclusionThese preliminary results suggest that while a large proportion of patients achieve the WHO recommended minimum level of PA, they exhibit very pronounced sedentary behaviour with increased screen use. In addition to controlled disease activity as a well-known prerequisite for achieving PA recommendations, these results also point to the importance of family support and emotional well-being. With ongoing recruitment, further potential facilitators and barriers to PA should be identified in more in-depth analyses.References[1]Gualano B et al. Physical activity for paediatric rheumatic diseases: standing up against old paradigms. Nat Rev Rheumatol 2017;13:368-379.[2]Sherar LB et al. International children’s accelerometry database (ICAD): design and methods. BMC Public Health 2011;11:485.AcknowledgementsActiMON is funded by the Federal Ministry of Education and Research (01EC1902F).Disclosure of InterestsFlorian Milatz: None declared, Ralf Trauzeddel: None declared, Tilmann Kallinich: None declared, Moritz Klaas: None declared, Hermann Girschick: None declared, Sandra Hansmann: None declared, Gerd Horneff: None declared, Daniel Windschall Speakers bureau: Pfizer, Novartis, Abbvie, Medac, Sobi, Canon, Johannes-Peter Haas: None declared, Nadja Baumeister: None declared, Martina Niewerth: None declared, Kirsten Minden Speakers bureau: Pfizer; Novartis

BackgroundCLIPPER2 was an 8-year, open-label extension of the phase 3b, 2-year CLIPPER study of the safety and efficacy of etanercept (ETN) in patients (pts) with juvenile idiopathic arthritis (JIA), categorized as extended oligoarticular JIA (eoJIA), enthesitis-related arthritis (ERA), or psoriatic arthritis (PsA).ObjectivesEvaluation of the efficacy of ETN and its effect on health outcomes over 10 years of follow-up were secondary objectives and are reported here.MethodsPts (n=127) with eoJIA (n=60; 2-17 years of age), ERA (n=38; 12-17), or PsA (n=29; 12-17) who received ≥1 ETN dose (0.8 mg/kg once weekly [max, 50 mg]) in CLIPPER were eligible to enter CLIPPER2. The study design has been reported previously.1 Efficacy endpoints included proportions of pts achieving JIA American College of Rheumatology (ACR) 30/50/70/90/100 criteria, Juvenile Arthritis Disease Activity Score (JADAS) inactive disease and clinical remission criteria, and sustained clinical remission (ACR criteria) or JADAS ≤1 for 12 continuous months (mths). Exploratory efficacy endpoints included time to flare following ETN withdrawal (based on ≥30% worsening in ≥3/6 ACR Pedi components, with ≥30% improvement in Observed Cases were used (i.e., there was no imputation for missing data) for pts who were in the Active Treatment Period.ResultsA total of 109/127 (86%) CLIPPER participants entered CLIPPER2 (n=55 eoJIA, n=31 ERA, n=23 PsA), with 99 (78%) pts continuing in the Active Treatment Period. Overall, 84 (66%) pts completed 120 mths of follow-up; 27 (21%) while actively taking ETN. Thirty (24%) pts entered the Withdrawal Period from the Active Treatment Period (i.e., they discontinued ETN, either by meeting the Wallace definition for clinically inactive disease for at least 6 months on ETN, or by having had a good clinical response and being deemed to benefit from withdrawal in the investigator’s judgment). Of the pts in the Active Treatment Period, over 90% achieved JIA ACR 50 response at all study time points. Sustained JADAS and ACR remission was achieved by 42 (33%) pts and 17 (13%) pts, respectively. The mean improvements from baseline in JADAS disease activity at mth 24 of CLIPPER were largely maintained through CLIPPER2 A total of 109/127 (86%) CLIPPER participants entered CLIPPER2 (n=55 eoJIA, n=31 ERA, n=23 PsA), with 99 (78%) pts continuing in the Active Treatment Period. Overall, 84 (66%) pts completed 120 mths of follow-up; 27 (21%) while actively taking ETN. Thirty (24%) pts entered the Withdrawal Period from the Active Treatment Period (i.e., they discontinued ETN, either by meeting the Wallace definition for clinically inactive disease for at least 6 months on ETN, or by having had a good clinical response and being deemed to benefit from withdrawal in the investigator’s judgment). Of the pts in the Active Treatment Period, over 90% achieved JIA ACR 50 response at all study time points. Sustained JADAS and ACR remission was achieved by 42 (33%) pts and 17 (13%) pts, respectively. The mean improvements from baseline in JADAS disease activity at mth 24 of CLIPPER were largely maintained through CLIPPER2.ConclusionThe low numbers of evaluable pts notwithstanding, efficacy results were consistent with the profile of ETN, and treatment responses were considered clinically meaningful and durable with long-term treatment.References[1]Foeldvari I, et al. Arthritis Res Ther 2019;21:125.[2]Trincianti C, et al. Arthritis Rheumatol 2021:73;1966-75.Trial Registration:NCT00962741/NCT01421069AcknowledgementsMedical writing support was provided by Iain McDonald, PhD, of Engage Scientific Solutions and was funded by Pfizer.Disclosure of InterestsJelena Vojinovic Speakers bureau: Abbvie, Roche, Sandoz, Joke Dehoorne Speakers bureau: Abbvie, Roche, Consultant of: Abbvie, Roche, Violeta Panaviene: None declared, Gordana Susic: None declared, Gerd Horneff Speakers bureau: Chugai, Eli-Lilly, Glaxo Smith and Kline, Janssen, Novartis, Pfizer, Roche and Sobi, Grant/research support from: Novartis, Janssen, Roche, Valda Stanevicha Speakers bureau: Sandoz, Abbvie, Roche, Katarzyna Kobusinska: None declared, Zbigniew Żuber: None declared, Bogna Dobrzyniecka: None declared, Jonathan Akikusa: None declared, Tadej Avcin Speakers bureau: AbbVie, Octapharma and Takeda, Consultant of: AbbVie, Octapharma and Takeda, Alberto Martini Speakers bureau: Aurinia, Bristol Myers and Squibb, Eli-Lilly, EMD Serono, Janssen, Pfizer, Roche, Consultant of: Aurinia, Bristol Myers and Squibb, Eli-Lilly, EMD Serono, Janssen, Pfizer, Roche, Cecilia Borlenghi Shareholder of: Pfizer, Employee of: Pfizer, Edmund Arthur Employee of: Pfizer, Svitlana Y Tatulych Shareholder of: Pfizer, Employee of: Pfizer, Chuanbo Zang Shareholder of: Pfizer, Employee of: Pfizer, Vasileios TSEKOURAS Shareholder of: Pfizer, Employee of: Pfizer, Bonnie Vlahos Shareholder of: Pfizer, Employee of: Pfizer, Nicolino Ruperto Speakers bureau: Ablynx, Amgen, Astrazeneca-Medimmune, Aurinia, Bayer, Bristol Myers and Squibb, Cambridge Healthcare Research (CHR), Celgene, Domain therapeutic, Eli-Lilly, EMD Serono, Glaxo Smith and Kline, Idorsia, Janssen, Novartis, Pfizer, Sobi, UCB., Consultant of: Ablynx, Amgen, Astrazeneca-Medimmune, Aurinia, Bayer, Bristol Myers and Squibb, Cambridge Healthcare Research (CHR), Celgene, Domain therapeutic, Eli-Lilly, EMD Serono, Glaxo Smith and Kline, Idorsia, Janssen, Novartis, Pfizer, Sobi, UCB.

BackgroundThe lack of pediatric classification criteria for axial disease is a major impediment to the conduct of clinical trials for juvenile spondyloarthritis (JSpA).ObjectivesWe aimed to develop classification criteria for axial JSpA that will enable identification of a more homogeneous group representative of children with SpA and axial disease for entry into observational or clinical trials. These criteria are not intended to capture all possible subjects, but instead most patients with shared key features of axial disease. Treatment and diagnostic decisions should adhere to evidence-based recommendations.Methods304 cases with JSpA and suspected axial disease from 6 international centers were collected on a standardized case report form; all had an MRI that was reviewed by an independent team of experts in musculoskeletal imaging. Candidate criteria were developed in an earlier phase of the project through an iterative process that included an international Delphi exercise for item generation, systematic literature review, and an item reduction exercise. Using the preliminary candidate criteria, 14 international clinical SpA experts scored and rank-ordered 20 representative SpA cases. During four, 3-hour virtual meetings, the clinical expert panel reviewed the interrater reliability of case ranking, refined the criteria definitions and domain levels, and participated in a multi-criterion decision consensus methodology exercise to generate relative weights of the criteria. The expert panel assessed whether the criteria weighting was in accordance with their consensus clinical judgment as a test of face validation of the weighting/scoring system and revisions were made as necessary. Next, 30 cases from the derivation cohort were scored and ranked using the relative weights for each category and domain. Each expert independently determined the score or “threshold” below which they were no longer confident enough that a patient had axial disease to enroll the child in a Phase 3 randomized clinical trial of a drug with unclear efficacy and safety. Results of this exercise were discussed and a provisional threshold score for classification was achieved by consensus.ResultsThe preliminary axial disease criteria for JSpA included the PRINTO provisional criteria for enthesitis/spondylitis-related JIA or a rheumatologist diagnosis of SpA as obligatory entry criteria as well as additive weighted criteria for 7 domains (SIJ active inflammation on imaging, SIJ structural lesions on imaging, pain chronicity, pain pattern, pain location, morning stiffness, and genetics) (Figure 1). Interrater reliability of the pre-consensus meeting case rankings was poor (Kendall’s correlation coefficient was 0.20 for clinical data-only and 0.23 for clinical plus imaging data). The multi-criterion decision analysis was repeated for the imaging domains when the initial criteria weighting was not in accordance with the expert panel’s opinion. The multi-criterion decision analysis involved a total of 58 pairwise decisions agreed by expert consensus. After criteria weights and additive scores were re-calculated, experts reached consensus for axial disease in JSpA for all cases scoring 55 and greater.Figure 1.Axial juvenile spondyloarthritis (AxJSpA) classification criteria domains and levels. The first ring represents the domains and the items branching out are the levels moving from highest level (closest to center) to lowest level (farthest from center) in each domain. Assigned weights are shown below each item description.ConclusionUsing an iterative process, the JSpA axial disease criteria definitions were refined, preliminary weights were generated, and a provisional threshold score for classification was determined. The most heavily weighted domains were active inflammation and structural lesions on imaging. Imaging typical of sacroiliitis was necessary, but not sufficient without any clinical criterion, to surpass the axial disease classification threshold.Disclosure of InterestsPamela F. Weiss Consultant of: PfizerNovartisBiogenLilly(All < $5K in the past fiscal year), Timothy G. Brandon: None declared, Amita Aggarwal: None declared, Ruben Burgos-Vargas Speakers bureau: not in the last three yearsNovartis, Consultant of: Not in the last four yearsBMS, Lilly, Novartis, Robert A. Colbert: None declared, Gerd Horneff Speakers bureau: Pfizer, Novartis, Janssen, Chugai, Abbvie, Grant/research support from: Pfizer, Novartis, MSD, Chugai, Roche, Abbvie, Rik Joos Speakers bureau: Galapagos, Pfizer, AbbVie, Novartis, Amgen, BMS, Lilly, Grant/research support from: Pfizer, AbbVie, Roche, Ronald Laxer Consultant of: Abbvie, Novartis, Sobi, Sanofi, Eli Lilly Canada, Eli Lilly, Kirsten Minden Speakers bureau: Pfizer, Novartis, Consultant of: Pfizer, Novartis, Angelo Ravelli Speakers bureau: Abbvie, Novartis, SOBI, Angelini, Reckitt-Benkiser, Roche, Pfizer, Alexion, Grant/research support from: Novartis, Pfizer, Nicolino Ruperto Speakers bureau: NR has received honoraria for consultancies or speaker bureaus from the following pharmaceutical companies in the past 3 years: 2 Bridge, Amgen, AstraZeneca, Aurinia, Bayer, Brystol Myers and Squibb, Celgene, inMed, Cambridge Healthcare Research, Domain Therapeutic, EMD Serono, Glaxo Smith Kline, Idorsia, Janssen, Eli Lilly, Novartis, Pfizer, Sobi, UCB., Consultant of: NR has received honoraria for consultancies or speaker bureaus from the following pharmaceutical companies in the past 3 years: 2 Bridge, Amgen, AstraZeneca, Aurinia, Bayer, Brystol Myers and Squibb, Celgene, inMed, Cambridge Healthcare Research, Domain Therapeutic, EMD Serono, Glaxo Smith Kline, Idorsia, Janssen, Eli Lilly, Novartis, Pfizer, Sobi, UCB., Grant/research support from: The IRCCS Istituto Giannina Gaslini (IGG), where NR works as full-time public employee has received contributions from the following industries in the last 3 years: Bristol Myers and Squibb, Eli-Lilly, F Hoffmann-La Roche, Novartis, Pfizer, Sobi. This funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment with third parties., Judith Smith Consultant of: Consulting panel of pediatric rheumatologists identifying issues in juvenile spondyloarthritis for Novartis. Paid < $5000, Matthew L. Stoll Consultant of: Currently consulting for Novartis, Shirley ML Tse: None declared, Filip van den Bosch Speakers bureau: Abbvie, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, UCB, Paid instructor for: Amgen, Eli Lilly, Consultant of: Abbvie, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, UCB, Walter P Maksymowych Speakers bureau: Abbvie, Eli-Lilly, Janssen, Novartis, Pfizer, UCB Pharma, Consultant of: AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, UCB Pharma, Grant/research support from: Abbvie, Novartis, Pfizer, Robert G Lambert Paid instructor for: Novartis, Consultant of: CARE Arthritis, Calyx, Image Analysis Group, Novartis, David M. Biko Employee of: Employee of Merck from 1998 to 2000, Nancy A. Chauvin Employee of: Forest Pharmaceuticals - Research scientist (1996) and Novartis - Pharmaceutical sales representative (1997), Michael L. Francavilla: None declared, Jacob L Jaremko: None declared, Nele Herregods: None declared, Ozgur Kasapcopur Speakers bureau: Pfizer, Abbvie, Novartis and Roche, Mehmet YILDIZ: None declared, Alison M. Hendry: None declared

BackgroundIn recent years, transition clinics have been set up at an increasing number of paediatric rheumatology sites in Germany to reduce identified deficits in the care of young people with rheumatic diseases1. In addition, the German Rheumatic Diseases League (Deutsche Rheuma-Liga, DRL), the largest self-help organisation in Germany, has been offering support services for young people in transition since 2016, including the interactive website www.mein-rheuma-wird-erwachsen.de.ObjectivesTo assess the transition competence of young people with juvenile idiopathic arthritis (JIA) and their knowledge of self-help services.MethodsCross-sectional data of the National Paediatric Rheumatology Database (NPRD) from 2016 to 2020 were used to evaluate the health-related transition competence of young people with JIA aged ≥16 years. Health-related knowledge and health-care competence were assessed using a modified self-report instrument2 on a 4-point Likert scale as part of routine documentation in the NPRD. Young people were also asked about their information behaviour and knowledge of new support services. Linear mixed models were used to determine whether health-related transition competence changed between 2016 and 2020, adjusted for disease duration.ResultsDuring the years 2016 to 2020, between 1.908 to 2.536 patients with JIA aged ≥16 years were annually recorded in the NPRD from 56 to 61 paediatric rheumatology sites. The annual patient collectives comprised 34-39% oligoarthritis, 23-26% RF-negative or RF-positive polyarthritis and 22-27% enthesitis-related arthritis cases. In the years from 2016 to 2020, about one-third of patients had inactive disease (cJADAS-10≤1) and about 60% had no functional limitations (CHAQ=0).Over the years, the proportions of patients who rated their disease knowledge and health care competence as “very well” increased significantly in most areas. Although over time, no increase in numbers of patients seeking information about their disease outside of rheumatology consultations were recorded (2016: 22.8%; 2020: 20.9%), awareness of the DRL’s new website for young people with rheumatic diseases increased from 7.7% in 2016 to 26.9% in 2020. Compared to those who were unaware of the new website, those who knew about the website were more likely to have received care in rheumatology settings that offer transition clinics and were more likely to be girls (75% vs 65%), to attend high school (51% vs 46%) and to be slightly older (17.6 vs 17.1 years).ConclusionThe transition competence of young people with JIA seems to have improved over the last five years. During this time, more transition services were made available for young people with rheumatic diseases. However, most young people are not yet aware of these services. Moreover, the effectiveness of the different measures/interventions has yet to be evaluated.References[1]Luque Ramos A et al. Semin Arthritis Rheum 2017;47:269-75.[2]Herrmann-Garitz C et al. Gesundheitswesen 2017;79:491–6.Table 1.Health-related transition competence in JIA patients ≥16 years who participated in the NPRD201620182020p (difference over time)PatientsN=2536N=2068N=1908Disease duration, years6.7±4.97.2±5.07.6±5.1DMARDs at documentation, %576263Disease-related knowledge (best answer “very well”), %N=1992N=1598N=1265name of illness3542420.001names of medicines5459560.717what medicines are for5054520.357who to contact in case of health problems5965650.015influence of smoking, drugs, and alcohol on disease4955540.002how to make a doctor’s appointment6868650.087which doctors are responsible after leaving paediatric care4246490.031Health-care competence (best answer “most of the time”), %N=1784N=1443N=1143inform my doctor of any unusual changes in my health6672690.038keep information about my illness8184840.281ask my own questions5156550.016answer the questions I am asked6973740.014take care of my health concerns and needs6671690.041attend the consultation alone5961610.599speak up for myself and say what I need6468680.537AcknowledgementsThe NPRD has been funded by the Federal Ministry of Health and the companies Abbvie, Chugai, ask, Novartis, PfizerDisclosure of InterestsKirsten Minden Speakers bureau: Pfizer, Novartis, Consultant of: Pfizer, Novartis, Martina Niewerth: None declared, Susanne Schalm: None declared, Ivan Foeldvari: None declared, Johannes-Peter Haas: None declared, Gerd Horneff: None declared, Daniel Windschall Speakers bureau: Pfizer, Novartis, Abbvie, Medac, Sobi, Canon, Grant/research support from: Pfizer, Novartis, Abbvie, Medac, Sobi, Canon, Tilmann Kallinich: None declared, Frank Dressler: None declared, Frank Weller-Heinemann: None declared, Rainer Berendes: None declared, Toni Hospach Consultant of: SOBI, Novartis, Markus Hufnagel: None declared, Maria Haller: None declared, Sandra Hansmann: None declared, Jens Klotsche: None declared

BackgroundJuvenile systemic sclerosis (jSSc) is an orphan disease with a prevalence of 3 in 1 000 000 children (1). The Juvenile Systemic Scleroderma Inception cohort (jSScC) is the largest cohort of jSSc patients in the world. The jSScC collects longitudinal data prospectively in jSSc, allowing the evaluation of the development of organ involvement and patients and physician reported outcomes in jSSc over time.ObjectivesTo review the changes in the clinical characteristics and patient and physician reported outcomes over 12 months observation period from the time of inclusion into the cohort.MethodsThe jSScC cohort enrolls jSSc patients who developed the first non-Raynaud´s symptom before the age of 16 years and are under the age of 18 years at the time of inclusion (2, 3). We reviewed jSScC patient clinical data and patient and physician reported outcomes, who had 12 months follow up from the time of inclusion until 1st of December 2021.ResultsWe could extract data of 113 patients. The female/male ratio was 3.5:1. Median age of onset of Raynaud´s was 10.1 years and the median age of onset of non-Raynaud´s was 10.8 years. Eighty-eight percent of the patients were treated with disease modifying anti-rheumatic drugs (DMARDs) at time of inclusion in the cohort (T0) and 93% after 12 months (T12). Median disease duration was 2.5 years at T0. Antibody profile stayed unchanged. Only 3 clinical parameters changed and improved significantly, the median modified Rodnan skin score improved from 13 to 8 (p=0.002), the number of patients with swollen joints decreased from 17% to 8% (p=0.043) and number of patients with joints with pain on motion decreased from 20% to 12% (p=0.048). All other organ involvement did not show any statistically significant change from T0 to T12.All collected patient reported outcomes improved significantly from T0 to T12: the patient reported disease activity (VAS 0 – 100) from 40 to 20 (p=0.011), the patient reported disease damage (VAS 0 – 100) from 40 to 20 (p=0.001), patient reported ulceration activity (VAS 0 – 100) from 10 to 0 (p=0.02) and the CHAQ score from 0.3 to 0.1 (p=0.002). Two of the three physician reported outcomes improved significantly, the physician global disease activity (VAS 0 – 100) from 30 to 20 (p=0.011) and physician reported global disease damage (VAS 0 – 100) from 30 to 25 (p=0.028).ConclusionSkin and musculoskeletal clinical features improved over 12 months, with almost all patients on DMARDs, supporting likely response of these features to therapy. It was promising that internal organ involvement, like cardiac and lung, although potentially stable, did not significantly worsen or increase. The most striking observation in the positive direction is improvement across several patient and physician reported outcome measures over the 12 month time period in this large international cohort.References[1]Beukelman T, Xie F, Foeldvari I. Assessing the prevalence of juvenile systemic sclerosis in childhood using administrative claims data from the United States. Journal of Scleroderma and Related Disorders. 2018;3(2):189-90.[2]Foeldvari I, Klotsche J, Kasapcopur O, Adrovic A, Terreri MT, Sakamoto AP, et al. Differences sustained between diffuse and limited forms of juvenile systemic sclerosis in expanded international cohort. www.juvenile-scleroderma.com. Arthritis Care Res (Hoboken). 2021.[3]Foeldvari I, Klotsche J, Torok KS, Kasapcopur O, Adrovic A, Stanevica V, et al. CHARACTERISTICS OF THE FIRST 80 PATIENTS AT TIMEPOINT OF FIRST ASSESSMENT INCLUDED IN THE JUVENILE SYSTEMIC SCLEROSIS INCEPTION COHORT. WWW.JUVENILESCLERODERMA.COM. Journal of Scleroderma and Related Disorders. 2018;4(1-13).Disclosure of InterestsNone declared

BackgroundJuvenile systemic scleroderma (jSSc) is an orphan disease with a prevalence of 3 in 1,000,000 children. Currently no medications are licensed for the treatment of jSSc. Due to its rarity, only recently have the first management and treatment guidelines been published, the jSSc SHARE (Single Hub and Access point for paediatric Rheumatology in Europe) recommendations, reflecting consensus opinion upon pediatric rheumatologists (1).ObjectivesTo better understand treatment practices internationally for jSSc, both at baseline and over 24 months observation period and to compare if real world therapies are congruent with the recent SHARE recommendations.MethodsThe juvenile systemic sclerosis inceptions cohort (jSScC) is a multinational cohort that prospectively collects clinical data, including medications at baseline and subsequent visits. The jSScC enrollment criteria include age of onset of the first non-Raynaud symptom younger than 16 years and age younger than 18 years at cohort entrance. The frequency of medications (general category and specific medication) was calculated across the cohort at timepoint 0 (enrollment), 12 months and 24 months.ResultsWe extracted data from the jSScC of patients who were followed for 12 or 24 months. 109 patients were followed at time point 0 (T0) and 12 months (T12), and data was available for 77 of them up at 24 months (T24). The mean age of the patients was 13.2 years at the timepoint 0. 77% were female and 75% had diffuse subtype. Disease duration at baseline visit was 3.1 years. The medications the patients were on recorded by the physician were captured at T0, T12 and T24 listed in Table 1.Table 1.MEDICATIONSTime point 0N=109T12 monthsN=109T24 months N=77Any Medication92% (100)97% (106)97% (75)Vascular medications Endothelial receptor antagonist16% (17)24% (26)21% (16) PDE-5-Blocker5% (5)8% (9)9% (7)ImmunomodulatorsCorticosteroids52% (57)44% (48)44% (21)All csDMARDs:81% (88)93% (101)92% (71) csDMARDs monotherapy61% (67)66% (72)60% (46) csDMARDs combination therapy17% (18)15% (16)14% (11) Methotrexate51% (56)50% (55)39% (30) Mycophenolate Mofetil26% (28)44% (48)47% (36) Hydroxychloriquine11% (12)15% (16)21% (16) Cyclophosphamide12% (13)2% (2)1% (1) Azathioprine2% (2)2% (2)3% (2)All bDMARDs:5% (5)14% (15)18% (14) bDMARDs monotherapy2%(2)2%(2)1% (1) bDMARDs combined with csDMARDs3% (3)12% (13)17% (13) Tocilizumab2% (2)10% (11)14% (11) Rituximab2% (2)4% (4)4% (3) Adalimumab1% (1)0% (0)0% (0)Autologous Stem cell transplantation0% (0)1% (1)0% (0)csDMARDs: Conventional synthetic disease-modifying antirheumatic drugsb DMARDs: Biological disease-modifying antirheumatic drugsConclusionAt baseline half of the patients were on corticosteroids. This is more frequent than typical adult SSc practice but coincides with jSSc SHARE treatment recommendations (#1). After 12 months observation in the cohort over 90% of patients received a DMARD therapy. Methotrexate and mycophenolate mofetil were the most commonly prescribed DMARDs, which also reflects the SHARE treatment recommendations (#2, #3). At 12 months the use of glucocorticoid decreased and the use of bDMARDs increased. In general, biological DMARDs are typically considered in severe or refractory (SHARE recommendation #7), reflecting the lower percentage compared to csDMARDs. Autologous stem cell transplantation was observed in one patient at 12 months, reflecting an option in jSSc with progressive and refractory disease (SHARE recommendation #8). Endothelial receptor antagonists, such as bosentan, were used over time in approximately 20% of the patients, reflecting SHARE recommendation #6 for pulmonary hypertension and/or digital tip ulcers. This is the first evaluation looking at clinical medication practice pattern in jSSc, and its comparison to recently published consensus guidelines.References[1]Foeldvari I, Culpo R, Sperotto F et al. Consensus-based recommendations for the management of juvenile systemic sclerosis. Rheumatology (Oxford). 2021;60(4):1651-8.Disclosure of InterestsNone declared

BackgroundJuvenile systemic sclerosis (jSSc) is an orphan autoimmune disease with a prevalence of 3 in 1 000 000 children. Information on long-term development of organ involvement and clinical characteristics of jSSc patients in adulthood are lacking. It was believed that patients in adult cohorts may represent a survival biased population.ObjectivesTo assess differences in clinical characteristics of jSSc-onset patients from the pediatric age group, with a mean disease duration of 3 years, compared to the adult age jSSc-onset group, with a mean disease duration of 18.5 years.MethodsWe extracted clinical data at time of inclusion into the cohorts from the Juvenile Scleroderma Inception Cohort (jSScC) and data from juvenile-onset adult SSc patients from the European Trials and Research Group (EUSTAR) cohort. We compared the clinical characteristics of the patients by descriptive statistics.ResultsWe extracted data of 187 jSSc patients from the jSScC and 236 patients from EUSTAR. The mean age at time of assessment was 13.4 years old in the jSScC and 32.4 years old in EUSTAR. The mean disease duration since first non-Raynaud was 3.0 years in jSScC and 18.5 years in the EUSTAR (Table 1).We found significant differences between the cohorts. There were more female patients in EUSTAR (87.7% versus 80.2%, p=0.04). More patients had diffuse subtype in jSScC (72.2% versus 40%, pTable 1.Clinical characteristics of juvenile onset SSc patients at time point of the inclusion into the juvenile scleroderma inception (jSScC) cohort and in the adult EUSTAR- cohortjSScCEUSTAR CohortP valueNumber of patients1872360.04Age in years, mean (SD)13.4 (3.6)32.4 (15.4)Female patients, n (%)150 (80.2%)207 (87.7%)jSSC Subtype, n (%)diffuse135 (72.2%)87 (38.1%)limited52 (27.8%)121 (53.3%)Age at Raynaud onset in years, mean (SD)10.0 (3.9)13.7 (9.1)Age at non-Raynaud onset in years, mean (SD)10.3 (3.9)11.7 (3.7)Duration since first Raynaud symptoms in years, mean (SD)3.4 (2.7)20.6 (15.9)Duration since first non-Raynaud symptoms in years, mean (SD)3.0 (2.7)18.5 (15.6)Raynaud´s, n (%)170 (90.9%)222 (94.9%)ANA positive, n (%)166 (91.7%)210 (92.9%)0.99Anti-Scl 70 positive, n (%)62 (34.4%)73 (33.3%)0.68Modified Rodnan Skin Score, mean (SD)5%Data missingModified Rodnan Skin Score, mean (SD)14.2 (11.7)12.1 (14.5)0.02Digital ulceration, n (%)At the time of inclusion33 (17.8)21 (26.6%)0.01In the past history100 (54.1%)34 (43%)Telangiectasia62 (37.4%)42 (53.2%)0.04FVC, mean (SD)84.1 (18.6)84 (22.4)0.96DLCO, mean (SD)75.4 (19.2)86.3 (19.9)Arterial hypertension, n (%)10 (5.4%)20 (8.5%)0.26Renal crisis, n (%)03 (1.3%)0.26Esophageal involvement, n (%)63 (33.7%)149 (63.7%)Intestinal involvement, n (%)62 (33.2%)56 (23.8%)0.04Articular involvement, n (%)34 (18.3%)27 (11.6%)0.06Muscular involvement, n (%)31 (19.3%)46 (19.8%)0.45ConclusionPatients with jSSc-onset who are currently adult age (defined as >18 years of age) are less frequently male and from the diffuse subset, have lower mRSS, less digital ulcers and intestinal involvement. This might represent a combination of both survival bias and/or be explained by the longer observation time with less active disease (i.e. natural progression decreased mRSS over time). Further long-term observational studies with jSSc patients are required to address this issue.Disclosure of InterestsNone declared

BackgroundUveitis is an extra-articular manifestation of Juvenile idiopathic arthritis (JIA) with a prevalence of up to 20% developing most frequently in young girls and patients positive for antinuclear antibodies (ANA). Untreated and uncontrolled uveitis may lead to vision-threatening complications and even blindness.ObjectivesThe main objectives of the analyses were to determine the visual prognosis, uveitis complications and necessity of ocular surgery during the first five years of ocular disease. The likelihood of achieving an inflammation-free phase or even a remission without medication were investigated.MethodsThe Inception Cohort of Newly diagnosed patients with JIA (ICON) was initiated in 2010 in order to prospectively follow JIA patients up to 10 years after JIA disease onset. 953 Patients were assessed at enrollment, three-monthly during the first year, and six-monthly afterwards by a standardized physician’s and patient’s case report form including clinical parameters, treatment data and several laboratory parameters such as ESR, CRP or S100A12. Patients who developed uveitis underwent a regular ophthalmological assessment. The treating ophthalmologist three-monthly completed an additional questionnaire, documenting the anterior chamber (AC) cell grade, current uveitis activity (UA) and UA during the previous three months, best corrected visual acuity (BCVA), uveitis-related complications, previous ocular surgery, current topical treatment and clinical course of uveitis and additional parameters. Inactive uveitis was defined by AC cell grade of 0, quiescence of uveitis by inactive uveitis for at least 6 months, and remission by inactive uveitis for at least 6 months without topical steroids or systemic anti-inflammatory medication (steroids or DMARDs).ResultsA total of 133 children developed uveitis in the JIA disease course, of which 97 patients were documented via the ophthalmological questionnaire for at least two years resulting in a mean follow-up of 5.8 years (SD 1.8). 76% were female, 86% ANA positive, 70% oligoarthritis, and 22% rheumatoid factor negative polyarthritis and mean age at JIA onset was 3.1 (SD 2.1) and uveitis onset at 4.4 (SD 2.2) years. The mean duration between JIA onset and uveitis onset was 15.7 (SD 15.6) months. At least one ocular complication was reported for 24% of patients at first uveitis documentation and 47% of patients had at least one ocular complication until the five year follow-up. Among those, posterior synechiae (31%) and cataract (27%) were the most frequent, followed by an increased IOP (12%) with or without glaucomatous changes. Ocular surgery was rarely necessary, and visual acuity remained quite good in the majority of patients: After five years, >90% had BCVA of ConclusionThe rate of ocular complications is already remarkable at uveitis diagnosis, and increases during uveitis disease course despite anti-inflammatory treatment. However, the visual acuity frequently remains unaffected, and the majority of patients achieve uveitis quiescence and even 40% uveitis remission within 5 years of follow-up.AcknowledgementsThe ICON study is funded by a research grant of the Federal ministry of education and research (BMBF, FKZ 01ER0812, FKZ 01ER1504A-C)Disclosure of InterestsJens Klotsche: None declared, Claudia Sengler: None declared, Frank Dressler: None declared, Dirk Foell: None declared, Ivan Foeldvari: None declared, Johannes-Peter Haas: None declared, Gerd Horneff Speakers bureau: Pfizer, Novartis, Janssen, Chugai, Abbvie, Grant/research support from: Pfizer, Novartis, MSD, Chugai, Roche, Abbvie, Toni Hospach Consultant of: SOBI, Novartis, Tilmann Kallinich: None declared, Ina Liedmann: None declared, Kirsten Moenkemoeller: None declared, Martina Niewerth: None declared, Frank Weller-Heinemann: None declared, Daniel Windschall: None declared, Arnd Heiligenhaus: None declared, Kirsten Minden: None declared, Karoline Baquet-Walscheid: None declared

BackgroundFor children with polyarticular juvenile idiopathic arthritis (pJIA) and inadequate response or intolerance to initial treatment with MTX, treatment options include abatacept.1 Abatacept, a selective T-cell co-stimulation modulator, has a distinct mechanism of action from other current treatments for rheumatic diseases,2 and factors predicting clinical response can help determine optimal treatment strategy. Two phase 3 studies demonstrated the efficacy and safety of IV and SC abatacept in patients with pJIA and an inadequate response to other DMARDs.2,3ObjectivesTo determine baseline and post-baseline factors that may predict a clinical response in children and adolescents with pJIA treated with abatacept for 2 years.MethodsBaseline demographic and disease characteristics and post-baseline factors (50% and 70% improvement in ACR criteria [ACR50, ACR70] at days 57 and 85) were analyzed using data from 2 phase 3 studies of abatacept in patients with JIA aged 2–17 years (SC administration) and 6–17 years (IV administration). Efficacy endpoints were Juvenile Arthritis Disease Activity Score in 10 joints based on CRP (JADAS10-CRP) inactive disease (ID; score of ≤ 2.7),4 and remission, defined as 6 consecutive months of post-baseline JADAS10-CRP ID. Data were analyzed over the entire 2-year study period. The earliest time point at which patients achieved these outcomes was reported. The aforementioned study factors were subjected to a time-to-event analysis, including Cox proportional hazards univariate regression analysis and Cox proportional hazards multivariate regression analysis using stepwise regression; results of the multivariate analysis are reported. Kaplan–Meier analysis was used to estimate time to achieve clinical response. Receiver operating characteristic curves were used to determine threshold values for continuous variables.ResultsOverall, 347 patients were included in the analysis (SC, n = 219; IV, n = 128; 73.8% female; mean [SD] age, 11.3 [4.0] years). Following abatacept treatment, both time to JADAS10-CRP ID and time to JADAS10-CRP remission were predicted (nominal P ≤ 0.05) by age (≤ 11 years: hazard ratio [HR], 1.52 [95% CI, 1.14–2.02] and ≤ 10 years: HR, 1.73 [95% CI, 1.20–2.48], respectively), high-sensitivity CRP (hsCRP; ≤ 0.6 mg/dL: HR, 1.67 [95% CI, 1.22–2.28] and ≤ 0.21 mg/dL: HR, 1.67 [95% CI, 1.15–2.42], respectively), Parent/Patient Global Assessment of well-being (≤ 35.86: HR, 1.88 [95% CI, 1.41–2.51] and ≤ 43.16: HR, 2.05 [95% CI, 1.35–3.10], respectively), and Childhood HAQ-DI (CHAQ-DI; ≤ 1.63: HR, 2.23 [95% CI, 1.47–3.39] and ≤ 0.75: HR, 1.84 [95% CI, 1.24–2.73], respectively) (remission data shown in Figure 1). Disease duration ≤ 2 years from baseline (HR, 1.66 [95% CI, 1.25–2.21]) and SC route of administration (HR, 2.05 [95% CI, 1.45–2.91]) also predicted ID. Among the post-baseline factors, ACR50 at days 57 and 85 predicted both ID (HR, 1.57 [95% CI, 1.04–2.36] and HR, 1.88 [95% CI, 1.41–2.51], respectively) and remission (HR, 1.96 [95% CI, 1.11–3.45] and HR, 3.05 [95% CI, 1.47–6.34], respectively); ACR70 at day 57 also predicted ID (data not shown). Patients with predictive factors for age, hsCRP, Parent/Patient Global Assessment of well-being, and CHAQ-DI, and with lower disease activity achieved ID and/or remission earlier than patients with high disease activity.ConclusionWe identified baseline and post-baseline factors that predicted JADAS10-CRP ID and remission in patients with pJIA treated with abatacept for 2 years. Screening of abatacept-treated patients with pJIA for such factors may help predict earlier achievement of ID and/or remission.References[1]Ringold S, et al. Arthritis Rheumatol 2019;71:846–63.[2]Brunner HI, et al. Arthritis Rheumatol 2018;70:1144–54.[3]Ruperto N, et al. Lancet 2008;372:383–91.[4]Trincianti C, et al. Arthritis Rheumatol 2021;73:1966–75.AcknowledgementsThis study was sponsored by Bristol Myers Squibb. Writing and editorial assistance were provided by Candice Judith Dcosta, MSc, of Caudex, funded by Bristol Myers Squibb. We would like to acknowledge Mara Becker, Duke Clinical Research Institute, Durham, NC, USA, for her contribution to the study analysis.Disclosure of InterestsNicolino Ruperto Speakers bureau: Honoraria for consultancies or speaker bureaus from the following pharmaceutical companies in the past 3 years: 2 Bridge, Amgen, AstraZeneca, Aurinia, Bayer, Brystol Myers Squibb, Cambridge Healthcare Research, Celgene, Domain Therapeutic, Eli Lilly, EMD Serono, GlaxoSmithKline, Idorsia, inMed, Janssen, Novartis, Pfizer, Sobi, UCB, Consultant of: Honoraria for consultancies or speaker bureaus from the following pharmaceutical companies in the past 3 years: 2 Bridge, Amgen, AstraZeneca, Aurinia, Bayer, Brystol Myers Squibb, Cambridge Healthcare Research, Celgene, Domain Therapeutic, Eli Lilly, EMD Serono, GlaxoSmithKline, Idorsia, inMed, Janssen, Novartis, Pfizer, Sobi, UCB, Hermine Brunner Speakers bureau: GlaxoSmithKline, Novartis, Pfizer, Consultant of: AbbVie, AstraZeneca-Medimmune, Biogen, Boehringer, Bristol Myers Squibb, Celgene, Cerocor, Eli Lilly, EMD Serono, F. Hoffmann-La Roche, GlaxoSmithKline, Idorsia, Janssen, Merck, Novartis, R-Pharm, Sanofi, Grant/research support from: The Cincinnati Children’s Hospital, where HIB works as a full-time public employee, has received contributions from the following industries in the past 3 years: Bristol Myers Squibb, F. Hoffmann-La Roche, Janssen, Novartis, and Pfizer. This funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment to third parties, Alberto Berman Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Lilly, Novartis, Pfizer, Roche, Francisco Avila Zapata: None declared, Gerd Horneff Speakers bureau: AbbVie, Chugai, Janssen, Novartis, Pfizer, Grant/research support from: AbbVie, Chugai, MSD, Novartis, Pfizer, Roche, Linda Wagner-Weiner Grant/research support from: Abbott, Bristol Myers Squibb, Merck, Pfizer, UCB, Alexander Belot Speakers bureau: Chugai, GlaxoSmithKline, Novartis, Roche (punctual scientific intervention), Grant/research support from: Boehringer Ingelheim, Merck (joint research project), Ruben Burgos-Vargas: None declared, Maria Luz Gámir Gámir: None declared, Claudia Goldenstein-Schainberg Speakers bureau: AbbVie, Janssen, Novartis, Consultant of: AbbVie, Janssen, Novartis, Maria T. Terreri: None declared, Margarita Askelson Consultant of: Acerta Pharma, Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Robert Wong Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Alberto Martini Consultant of: AbbVie, Eli Lilly, EMD Serono, Idorsia, Janssen, Novartis, Pfizer, Daniel J Lovell Consultant of: AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Hoffman LaRoche, Novartis, UBC (all contracts with employer, CCHMC), Grant/research support from: Bristol Myers Squibb, Janssen, Pfizer, Roche (all contracts with employer, CCHMC); NIH grants: NIAMS, NICHD

Background: The IL-1 receptor-antagonist anakinra is recommended for the treatment of systemic juvenile idiopathic arthritis (sJIA) and was recently approved for first-line treatment. Long-term dat...

BACKGROUND: We sought to characterize humeral-sided radiographic changes at a minimum of 2 years after reverse shoulder arthroplasty (RSA) to determine their association with specific implantation techniques. METHODS: The immediate and most recent postoperative anteroposterior radiographs of 120 shoulders with primary RSA and a minimum of 2-years of radiographic follow-up were analyzed (mean follow-up 35.2 months). Stress shielding was evaluated by measuring cortical thickness at 4 different locations. Three independent examiners evaluated radiographs for humeral osteolysis, radiolucent lines, stress shielding, stem loosening, and scapular notching. RESULTS: The cortical diameter, marker of external stress shielding, significantly decreased from initial to most recent measurement (P