Objectives The use of immune checkpoint inhibitors (ICI) for cancer treatment continues to increase as indications expand, both in the palliative and adjuvant setting. Immune related adverse events (irAE) can affect any organ due to immune system stimulation. ICI associated large vessel vasculitis (ICI-LVV) is a rare irAE, with descriptions limited to small case series and reports.[1] We aimed to identify and characterize the manifestations, management and outcomes of ICI-LVV in a national multi-center cohort. Methods We searched the Canadian Research Group of Rheumatology in Immuno-Oncology (CanRIO) retrospective and prospective cohorts for cases of de novo ICI-LVV. Cases of pre-existing LVV were excluded. Demographic, clinical and laboratory data were extracted from the study databases. Results We identified 13 patients who developed LVV after ICI exposure, most commonly for melanoma (n=5) and non-small cell lung cancer (n=3). Most patients received single agent ICI (69%). The median time from ICI exposure to symptom onset was 4.0 months (IQR 1.5-15). Isolated large vessel (n=5) or isolated cranial involvement (n=5) were the most common presentations. In those with cranial involvement (n=8), headache (n=8), jaw claudication (n=6) and scalp tenderness (n=6) were the most common symptoms. In those with confirmed large vessel involvement, (n=8), the most common radiographic finding was hypermetabolism on PET scan (n=6), often found incidentally without associated symptoms. There was 1 case of stenosis, and no aneurysms identified on imaging. Six patients had temporal artery biopsy and 2 were consistent with LVV, without clear histopathologic differences from idiopathic giant cell arteritis. Eleven patients were treated with glucocorticoids: Two relapsed during taper, 1 required additional immunosuppression (methotrexate and tocilizumab). Two patients with normal inflammatory markers and isolated large vessel involvement (hypermetabolism on PET) had remission without treatment. Only 2 patients continued ICI after ICI-LVV diagnosis, both without vasculitis recurrence/progression. There was no vision loss or death attributable to ICI-LVV. Conclusion Isolated cranial or large vessel involvement were the most common presentations of ICI-LVV. Like idiopathic GCA, headache was the most common clinical manifestation in those with cranial involvement. In contrast, isolated large vessel involvement was commonly found on PET, incidentally and without clinical symptoms. Careful clinical correlation is required in cases of isolated large vessel involvement, as not all may require treatment. This has important implications given the potential impact of immunosuppression on ICI and tumor outcomes. Further studies are needed into the clinical presentation, underlying pathological mechanisms and optimal management of ICI-LVV. References [1.] Cottu A. Rheumatology (Oxford) 2025;64:4546-54.

Given the high rate of cardiovascular comorbidities in anti-HMG–CoA reductase (HMGCR)–immune-mediated necrotizing myopathy (IMNM), a glucocorticosteroids (GC)-free treatment approach remains an appealing strategy. While intravenous immunoglobulins (IVIg) represents an effective therapy in most subgroups of idiopathic inflammatory myositis (IIM), there remains limited evidence supporting the use subcutaneous immunoglobulins (SCIg), a potentially safer, more convenient and cost-effective alternative. We present a case of a 68-year-old male of European descent with a 2-year history of progressive proximal bilateral lower extremity weakness. He had been treated for his dyslipidemia with atorvastatin for 2 years, then with rosuvastatin for 2 additional years until discontinued a year before our assessment. His other comorbidities included hypertension and diabetes mellitus type II. Physical examination demonstrated proximal weakness of his bilateral hip flexors and deltoids, and no rash. His creatine kinase (CK) was elevated at 1644 IU/L. Electromyography revealed a generalized myopathic disorder with proximal predominance and muscle biopsy of the right quadriceps showed typical findings of an IMNM. Serum HMG–CoA reductase antibody was positive. Due to accumulating evidence supporting the effectiveness of IVIg in anti-HMGCR–IMNM, even without concomitant GC or other immunosuppressive agent, we opted for a GC-free approach through shared-decision making in light of patient’s preference regarding potential GC side effects with his comorbidities. As he lived a considerable distance from any center, where IVIg infusions could be offered, and given the patient was unable to drive himself due to his symptoms we opted for SCIg (0.5 g/kg/week). Within 1 month, his CK decreased and weakness resolved. SCIg monotherapy was tapered over 3 years and this patient remains in remission 7 years after SCIg initiation. The patient did not have any adverse effects related to SCIg use. To our knowledge, this is the first case report describing a successful corticosteroid-free management of anti-HMGCR immune-mediated necrotizing myopathy using SCIg as monotherapy. This case highlights the potential for steroids-free induction and maintenance strategies in IMNM. Larger studies are required to confirm the effectiveness and safety of SCIg in IMNM and other subtypes of IIM, and to provide guidelines for dosing recommendations.

BACKGROUND:Anti-synthetase syndrome (aSS) is a rare autoimmune disorder primarily affecting the lungs and musculoskeletal system, with ocular involvement often underreported. While dry eye disease is the most frequently documented manifestation, other anterior and posterior segment involvement can also occur. METHODS:A case report and a systematic review. CASE PRESENTATION:We report a 47-year-old woman with aSS presenting with bilateral panuveitis and occlusive retinal vasculitis, a previously unreported combination. Ophthalmologic examination revealed compromised vision, anterior chamber reaction, posterior synechiae, papillitis, uveitic macular edema, and neovascularization of the disc (NVD). Extensive infectious and autoimmune workups guided the diagnosis, emphasizing the role of ocular findings in identifying aSS. The patient required multidisciplinary assessment and multifaceted treatment approach, including systemic corticosteroids, mycophenolate mofetil, intravenous immunoglobulin, and posterior sub-Tenon's triamcinolone injections, with consideration of anti-VEGF therapy for NVD. RESULTS:Our systemic review of 19 studies (86 patients) identified dry eye disease as the most common ocular manifestation (36%), with retinal vasculitis reported in only two cases (2.3%). Other reported manifestations included blurry vision, diplopia, ptosis, blepharitis, lagophthalmos, periorbital edema, and corneal disease. Compared to prior reports, our case represents one of the most severe ophthalmic presentations of aSS, highlighting the need for early recognition and intervention to prevent vision threatening sequelae. CONCLUSION:This case broadens the spectrum of ocular findings in aSS and highlights the importance of ophthalmologic evaluation in diagnosing systemic autoimmune diseases. Given the potential for vision-threatening complications, multidisciplinary collaboration is essential for holistic patient management.

Objectives:Serum creatine kinase (CK) is widely used in the diagnostic evaluation of neuromuscular disorders, including idiopathic inflammatory myopathies (IIM). As most laboratories define reference ranges using the central 95% of values from white populations, elevated CK levels are common in otherwise healthy individuals. We investigated the predictive value of baseline CK at defined cutoffs for diagnosing an underlying myopathic illness including IIM. Methods:A retrospective chart review was performed of consecutive adult patients attending a tertiary neuromuscular clinic from January 2018 to June 2022. We investigated the test characteristics of CK based on several a priori defined thresholds. Results:From a total of 488 patients, we identified 276 IIM cases, 89 with a non-inflammatory myopathy and 123 had an alternative/reassuring aetiology. Baseline CK levels were significantly higher in the IIM and non-inflammatory myopathy groups vs the alternative/reassuring group. The laboratory defined cutoffs for CK yielded a sensitivity of 77.0%, a specificity of 66.7% and a positive predictive value (PPV) of 87.3% for identifying IIM or other neuromuscular disorders, which only marginally improved when evaluating the 97.5th percentile (75.6, 67.5 and 87.3%) or the European Federation of Neurological Societies (EFNS) thresholds (68.8, 78.0 and 90.3%). Conclusion:The current thresholds defined by the EFNS guidelines compared with laboratory defined cutoff to pursue investigations for elevated CK only marginally improve specificity. A baseline CK >1000 IU/l is highly predictive of an IIM or other neuromuscular disorders. This study highlights the role of baseline CK levels in suspected IIM and neuromuscular disorders, clarifying its diagnostic value.

Immune checkpoint inhibitors (ICIs) are known to cause a wide spectrum of immune-related adverse events (irAEs). Among these, eosinophilic fasciitis (EF) is a rare, fibrosing disorder causing inflammatory infiltration of subcutaneous fat and fascia. It is characterized clinically by edema and subsequent induration and tightening of the skin and subcutaneous tissues. Several case reports have documented EF secondary to ICIs in patients on active treatment. Herein, we present two cases of delayed EF following treatment cessation with avelumab for metastatic urothelial carcinoma (Case 1) and following adjuvant nivolumab completion for stage IIIC melanoma (Case 2). Both patients had typical exam findings including erythema/edema of the extremities and trunk and diffuse thickening of subcutaneous fat and fascia, leading to severe respiratory restriction in Case 1. Both patients were diagnosed with EF by full-thickness skin biopsy showing sclerosis and lymphocytic infiltration of the subcutaneous fat and/or fascia. Only one of the two patients presented with definite eosinophilia. Both cases were treated with glucocorticoids and had early recurrence of symptoms post steroid taper, necessitating subsequent protracted steroid and steroid sparing agent use. Overall, we demonstrate the importance of considering delayed irAEs, specifically autoimmune fibrotic skin diseases even when ICI therapy has been discontinued. We underscore the need for collaboration between oncology and rheumatology as the scope of ICI treatments for cancer continues to expand.

BACKGROUND:Digital ulcers (DUs) are among the most painful and functionally disabling complications of systemic sclerosis (SSc), affecting up to 50% of patients. Despite their clinical relevance, interventional studies on DUs are limited and vary widely in design, definitions, and outcome reporting, hindering comparability and the development of standardized treatment approaches. OBJECTIVES:This initiative, led by an international expert group under the World Scleroderma Foundation (WSF), aims to establish points to consider for the standardized reporting of DUs in interventional studies, improving study quality, interpretability, and clinical relevance. METHODS:A steering committee of SSc experts developed these recommendations based on three systematic literature reviews on local, surgical, and systemic treatments for SSc-DUs. Consensus was achieved through iterative discussion among committee members, without external funding or third-party influence. RESULTS:Seven domains were identified as essential for standardization: (1) a uniform definition and classification of DUs; (2) consistent inclusion and exclusion criteria; (3) standardized primary and secondary outcome measures, including clinical and patient-reported outcomes; (4) detailed reporting of background and concomitant therapies; (5) harmonized local wound care protocols; (6) predefined timing and frequency of assessments; and (7) consideration of seasonal and environmental influences. CONCLUSION:Adopting these standardized reporting principles in future DU trials will enhance the quality and comparability of data, support more robust meta-analyses, and facilitate the development of effective, patient-centered treatment strategies for SSc-related DUs.

BACKGROUND:The OMERACT Scleroderma Vascular Disease Working Group sought to identify essential core outcome domains for inclusion in clinical trials focusing on Raynaud's phenomenon (RP) and/or digital ulcers (DUs) related to systemic sclerosis (SSc). METHODS:Candidate domains identified from previous qualitative work and systematic literature reviews were included in separate Delphi exercises for SSc-RP and SSc-DUs. Patients with SSc and other participants (clinicians with experience in treating patients with SSc and/or conducting clinical trials) were invited to participate through international patient advocacy groups and clinical networks. Core domains were defined as the domains reaching group consensus agreement (≥ 70% ratings of 'critical' in both patient and other participant groups) after three rounds of the Delphi. RESULTS:The 3-round Delphi exercises were completed by 78 patients and 116 others from 39 countries for SSc-RP, and by 26 patients and 99 others from 36 countries for SSc-DUs. For SSc-RP, nine domains reached consensus agreement as critically important: three domains in the Pathophysiological Manifestations core area and six in the Life Impact core area. For SSc-DUs, 16 domains reached consensus: five domains in the Pathophysiological Manifestations core area, seven in the Life Impact core area, and four in the Resource Use area. CONCLUSION:Patients with SSc and clinicians identified core domains for use in clinical trials in SSc-associated RP and DUs, with several Life Impact domains common to both vascular manifestations of disease. These results will inform development of a final Core Domain Set for use in clinical trials.

Objectives Physician global assessments (PhyGAs) are commonly performed in randomized controlled trials (RCTs) in SSc. However, there is no single PhyGA applied across RCTs. We performed an exploratory qualitative study to explore perceptions of the PhyGA, its role in RCTs and how physicians perform their own assessment.Methods Participants with expertise in the clinical assessment and, or actively involved in research on SSc were invited to participate. Participants were asked to define disease constructs of activity, damage, severity, and overall health, and to describe how they perform a PhyGA and their perception of what a PhyGA should assess. Interview transcripts were analysed using deductive and inductive thematic analysis.Results Eighteen rheumatologists and one patient research partner were interviewed. Four major themes were identified: (i) physician uncertainty; (ii) variation in the conduct of a PhyGA; (iii) physician efforts to improve PhyGA consistency; (iv) utility of a PhyGA. Most participants felt a PhyGA should assess changeable aspects of SSc, commonly conceived of as disease activity. There was considerable uncertainty about the optimal method for assessing disease activity. Participants were uncertain about their own methods of performing a PhyGA, and variability in the application of the instrument was identified. Despite these limitations, physicians generally agreed that the PhyGA is useful and can assess unquantifiable aspects of SSc.Conclusion We identified significant heterogeneity in the approach to PhyGAs in SSc. This variation was considered a limitation of the PhyGA. Overall, a PhyGA was viewed as a useful instrument that can aid the assessment of treatment response in RCTs.

ObjectiveImmune checkpoint inhibitors (ICIs) have revolutionized cancer outcomes but are limited by immune-related adverse events (irAEs), including rheumatic irAEs (Rh-irAEs). Aging is associated with increased inflammation, referred to as "inflammaging." In this study, we explore the effect of age on severity, frequency, and treatment of Rh-irAEs.MethodsAdults with new Rh-irAEs after ICI exposure are followed prospectively across 10 Canadian sites as part of the Canadian Research Group of Rheumatology in Immuno-Oncology (CanRIO) prospective cohort. In this study of patients seen between January 2020 and March 2023, we compare the severity of Rh-irAEs and number of irAEs between patients aged ≥ 65 years and < 65 years and explore potential epidemiologic, treatment-related, and phenotypic differences between the older and younger patients.ResultsA total of 139 patients with de novo Rh-irAEs were included, 58 in the younger (aged < 65 yrs) and 81 in the older (aged ≥ 65 yrs) group. There were no significant differences in severity of Rh-irAEs (P= 0.84) or number of irAEs (P= 0.21), although there was a nonsignificant trend toward more younger patients than older patients with ≥ 3 irAEs (24% vs 14%). Types of treatment for Rh-irAEs were similar between the groups. ICI continuation did not differ. Within the ICI-related inflammatory arthritis subgroup, there was also no significant difference in the incidence of severe Rh-irAEs (P= 0.51).ConclusionSimilar numbers of overall irAEs and severity of Rh-irAEs were observed between older vs younger patients who developed Rh-irAEs after treatment with ICI therapy, suggesting that inflammaging does not play a significant role in Rh-irAEs. Larger studies are needed to explore potential differences in patient phenotypes.

BACKGROUND:The use of immune checkpoint inhibitor (ICI) therapy is increasing in pediatric oncology. ICIs can cause rheumatic-immune related adverse events (Rh-irAEs) such as inflammatory arthritis and myositis. Few case reports detail Rh-irAEs and their management in the pediatric population. Our objective was to assess the familiarity of pediatric rheumatologists (PRs) worldwide with Rh-irAEs, gauge confidence in managing these conditions, and identify knowledge gaps to guide future educational efforts. METHODS:We circulated an online survey to 2084 PRs via the "Dr. Peter Dent Pediatric Rheumatology Bulletin Board." Responses were collected from June 2024 to September 2024. We collected data on practitioner demographics, knowledge of ICIs and Rh-irAEs, confidence in managing Rh-irAEs, and preferred educational resources. RESULTS:Sixty-nine participants responded, of which 55 (80%) were PRs from academic centers. Despite global distribution, 56 (81%) responses came from North America. Thirty-four (49%) respondents were not aware of ICIs and their related mechanisms, indications, and side effects, and 40 (58%) were not familiar with irAEs. Fifty-five (80%) had never managed a patient with Rh-irAEs. Among those who had (14/69, 21%), the median number of cases managed was 2.0 (IQR 0.0). Thirty-nine respondents were "not confident at all" managing Rh-irAEs, 34 were "not confident at all" managing pre-existing autoimmune diseases (PAD) in ICI users, and 46 were "not confident at all" advising oncology colleagues on initiating or discontinuing ICIs in the context of Rh-irAEs or pre-existing autoimmune diseases (PAD). No respondents felt "completely confident" managing these conditions. Participants identified knowledge gaps in long-term management, acute management, and recognition and diagnosis. Forty-three indicated the need for pediatric-specific clinical guidelines. Of the 14 respondents with clinical experience treating Rh-irAEs, treatment varied, with 4 using nonsteroidal anti-inflammatory drugs, 3 using prednisone, and 4 combining prednisone with methotrexate. Long-term management also varied, with 5 using methotrexate, and 3 using tumor necrosis factor inhibitors. CONCLUSIONS:Significant knowledge gaps and a lack of confidence exist among PRs managing ICI-related Rh-irAEs. As ICI use increases in pediatric oncology, PRs' exposure to Rh-irAEs will follow. Targeted educational programs and clinical guidelines may be valuable to address these gaps.

Systemic sclerosis (SSc) is a progressive autoimmune disease characterized by significant multi-organ damage. Its intricate pathophysiology involves various immune pathways, including the activation of B-cells, which are thought to play a crucial role in disease progression by driving fibrosis and causing vascular damage.[1] Historically, treatment options were limited; however, a larger range of treatments targeting the immune system have been tested over the last decade, including CAR-T therapy,[2] a treatment modality that Ottawa is working toward in collaboration with the CLIC pan-Canadian CAR-T network.[3] We conducted a scoping review to summarize trends of immunosuppressive therapies used for SSc treatment, particularly relating to skin and lung involvement. A scoping review was conducted in adherence to the PRISMA-ScR methodology. We searched 3 databases (MEDLINE, EMBASE, Cochrane Central) for studies published from January 2004 to January 2024. Titles and abstracts, then full-text articles were screened, focusing on skin and lung function outcomes in SSc. A total of 3891 abstracts were screened, resulting in the inclusion of 294 studies −149 abstracts and 145 full-text articles (Figure 1). Overall, 41 unique therapies studied were identified. The 10 most commonly studied treatments were: rituximab (n=84, 20.6%), cyclophosphamide (n=77, 18.9%), mycophenolate mofetil (n=52, 12.8%), autologous hematopoietic stem cell transplantation (autoHSCT) (n=29, 7.1%), tocilizumab (n=23, 5.7%), glucocorticoids (n=23, 5.7%), azathioprine (n=19, 4.7%), methotrexate (n=14, 3.4%), imatinib (n=14, 3.4%), and nintedanib (n=10, 2.5%). The peak number of studies pertaining to cyclophosphamide (28.9%) and mycophenolate mofetil (17.4%) treatments occurred in 2014-2018. However, from 2019-2024, studies of rituximab (27.2%) and autoHSCT (11.3%) became more prevalent. Figure 1. Immunosuppressive therapies for Systemic Sclerosis, with skin and/or lung involvement, studied between 2004–2024. Over the past 2 decades, SSc treatment has progressed significantly, shifting between immunosuppressive agents and autoHSCT. These advancements highlight the evolving landscape of SSc management and emphasize the need for innovative approaches, including advanced cellular therapies such as CAR-T-based treatments. [1.] Thoreau B. Role of B-cell in the pathogenesis of systemic sclerosis. Frontiers in Immunology 2022;13:933468. [2.] Bergmann C. Annals of the Rheumatic Diseases 2023;82(8):1117-20. [3.] Kekre N. Frontiers in immunology 2022;13:1074740.

Immune checkpoint inhibitors (ICI) have transformed oncology care, but their use is limited by immune-related adverse events (irAEs) and optimal use in patients with rheumatic pre-existing autoimmune disease (Rh-PAD) is unknown.[1] We report on ICI management, baseline immunosuppression, and irAE treatment strategies, using data from the CanRIO retrospective and prospective cohorts from 10 Canadian sites. Patients with Rh-PAD recruited to the prospective cohort between Jan 2020 and April 2023 and retrospective cohort from Jan 2013 to June 2022 and who received at least 1 dose of CTLA-4, PD-1, or PDL-1 ICI therapy were included. Data on irAE treatment, baseline immunosuppression, and cancer outcomes are collected in a REDCap database as per standardized protocol. Eighty-three eligible patients (40 from prospective and 43 from retrospective cohort) were identified and stratified by baseline immunosuppression (IS), with 44 on baseline IS and 39 not on baseline IS. Baseline IS included corticosteroids, conventional DMARDs, and biologic DMARDs. Of those on baseline IS, 37 had inflammatory arthritis (48.65% active) and 7 had other rheumatic disease (57.14% active). Of those not on baseline IS, 26 had inflammatory arthritis (26.92% active) and 13 had other rheumatic disease (23.08% active). Patients on baseline IS were more likely to have a PAD flare (OR 4.19, P=0.003) and less likely to develop a new unrelated irAE (OR 0.36, P=0.027) compared to those not on baseline IS. In both cohorts, 4 patients experienced both a flare of their Rh-PAD and a de novo irAE. Those with de novo irAE generally responded to analgesics, corticosteroids or csDMARDs. There was a non-significant trend toward patients on baseline IS being more likely to require bDMARD compared to those not on baseline IS (P = 0.057). Grade 1-2 irAEs were more likely to be treated while continuing immunotherapy, while ICIs were either stopped or held in all patients with grade 3-5 events (Baseline IS P = 0.026; No Baseline IS P = 0.052; All Patients P < 0.001). Our findings suggest those on baseline IS have higher rates of active PAD at start of ICI therapy. We found 1) Continuing baseline DMARDs may not protect from flares but may prevent de novo irAEs. If de-novo irAEs occur, bDMARD may be required for treatment 2) Continuing immunotherapy during irAE treatment can be considered for patients with low grade irAEs. Future analyses will explore the impact of baseline IS on cancer outcomes. [1.] Khalil DN. Nat Rev Clin 2016;13:273-90.

Introduction:Digital ulcers (DUs) stand out as one of the most prevalent and clinically meaningful manifestations of systemic sclerosis (SSc) and are associated with significant morbidity. While systemic (pharmacological) therapy is currently established as the 'standard of care', effective local ulcer management remains crucial for all cases of DUs. This is particularly true for patients who cannot tolerate systemic treatments or in the case of refractory SSc-DUs. On this background, there is a pressing demand for the formulation of evidence-based guidelines to assist clinicians and patients in navigating the local treatment options for DUs. Methods:A steering committee of international experts was established by the World Scleorderma Foundation (WSF) Digital Ulcer (DU) ad hoc committee. Two systematic literature reviews on local non-surgical and surgical treatments for the management of SSc-DUs were performed to inform the development of local treatment recommendations for SSc-DUs. Consensus methodology was used to develop the final treatment recommendations. Results:Six overarching treatment principles and eight local treatment recommendations (five non-surgical and three surgical) were agreed upon for the management of SSc-DU. Among topical non-surgical options, botulin toxin can be conditionally recommended for refractory and/or severe DUs. Among surgical treatments, autologous adipose tissue grafting might be recommended for DU healing when combined with background systemic treatments. Conclusion:These recommendations are specifically tailored to guide treatment decisions concerning both local and non-pharmacological approaches to managing SSc-related DUs. Our work has highlighted a notable quality gap in comparison to systemic treatments, underscoring the scarcity of high-quality studies concerning this topic.

Research results are often not communicated to study participants or others with relevant lived experience. Effective communication of research results would help study participants understand their contribution to research and could improve trust in research and likelihood of research participation. Few randomized controlled trials (RCTs), however, have compared the effectiveness of research communication tools, and it is not known which tools work best for different people. We will conduct the Scleroderma Patient-centered Intervention Network—Communicating Latest Evidence and Results (SPIN-CLEAR) trial series via the multi-national SPIN Cohort to compare tool effectiveness. Primary objectives of each RCT will be to compare tools based on (1) information completeness, (2) understandability, and (3) ease of use. We will additionally evaluate comprehension of key aspects of disseminated research; likelihood that participants would enroll in a similar future study; and, for all primary and secondary outcomes, outcomes by participant characteristics (gender, age, race or ethnicity, country, language, education level, health literacy). An advisory team of people with systemic sclerosis (SSc, also known as scleroderma) participated in developing research questions, selecting outcomes, and designing the series of parallel-arm RCTs that will each compare two or more tools or tool variations to a plain-language summary comparator; the common comparator will facilitate across-trial comparisons. In each RCT, people with SSc and researchers will select a recent SSc research study to disseminate. Tools will be developed by experienced tool developers and people with SSc. SPIN Cohort participants (current N eligible = 1522 from 50 SPIN sites in Australia, Canada, France, UK, USA) and additional participants recruited via social media and patient organization partners who consent to participate will be randomized to a dissemination tool or plain-language summary comparator and complete outcomes. Analyses will be intent-to-treat and use linear regression models. Each trial in the planned series of trials will build upon knowledge from previous trials. Results will contribute to the evidence base on how to best disseminate results to study participants and others with relevant lived experience. ClinicalTrials.gov NCT06373263. Registered on April 17, 2024 (first trial in series).

Immune checkpoint inhibitor (ICI) therapy is increasing in pediatric oncology. Immune-related adverse events (irAEs) can affect various organ systems, including rheumatic-irAEs (Rh-irAEs) such as inflammatory arthritis, myositis, sicca syndrome, systemic lupus erythematosus, sarcoidosis, and vasculitis.[1] Few cases report detail Rh-irAEs and their management in the pediatric population.[2] Our objective was to assess the familiarity of pediatric rheumatologists (PR) worldwide with ICI-induced Rh-irAEs, gauge their confidence managing these conditions, and identify knowledge gaps to guide future educational efforts. We circulated a 21-question online survey to 2084 PR via the “Dr. Peter Dent Pediatric Rheumatology Bulletin Board.” Responses were collected from June 2024 to September 2024. We collected data on practitioner demographics, knowledge of ICIs and Rh-irAEs, confidence in managing Rh-irAEs, and preferred educational resources. Sixty-nine responses were received of which 55 (80%) were PR from academic centers, and 9 (13%) were from community practices (Table 1). 24 (35%) had >20 years of clinical experience. Despite global distribution, 56 (81%) of responses came from North America. 34 (49%) of respondents were not aware of ICIs and their related mechanisms, indications, and side effects, and 40 (58%) were not familiar with irAEs. 55 (80%) had never managed a patient with Rh-irAEs. Among those who had (14/69), the median number of cases managed was 2.75 (IQR 1.75). Confidence in managing these conditions was limited: 39 (57%) were “not confident at all” managing Rh-irAEs, 34 (49%) were “not confident at all” managing pre-existing autoimmune diseases (PAD) in ICI users, and 46 (67%) were “not confident at all” advising oncology colleagues on initiating or discontinuing ICIs in the context of Rh-irAEs or PADs. No one felt “completely confident” managing these conditions. Several knowledge gaps were identified: 59 (86%) in long-term management, 55 (80%) in acute management, and 51 (74%) in recognition and diagnosis. 43 (62%) indicated the need for pediatric-specific clinical guidelines. Of the 14 (20%) respondents with clinical experience treating Rh-irAEs, initial treatment approaches varied, with 4/14 (29%) using NSAIDs, 3/14 (21%) using prednisone, and 4/14 (29%) combining prednisone with methotrexate. Long-term management also varied, with 5/14 (36%) using methotrexate, and 3/14 (21%) using TNF inhibitors. Table 1: Respondent Demographics, Knowledge & Confidence Assessment Significant knowledge gaps and a lack of confidence exist among PR in managing ICI-related Rh-irAEs. As ICI use increases in pediatric oncology, PR exposure to Rh-irAEs will follow. Targeted educational programs and clinical guidelines will be valuable to address these gaps and improve patient care. [1.] Ghosh N. Rheum Dis Clin North Am 2022; 48(2):411-28. [2.] Storwick JA. Pediatr Rheumatol Online J 2024;22(1):49.

Introduction: Digital ulcers are an important disease manifestation of systemic sclerosis and are associated with significant morbidity. As such, there is an urgent need for the development of evidence-based recommendations to guide clinicians in the treatment of digital ulcers.Methods: A steering committee of international experts was established. A systematic review of the literature pertaining to the use of pharmacologic treatments in the management of digital ulcers was performed to inform the development of treatment recommendations for systemic sclerosis digital ulcers. Consensus methodology was used to develop the final treatment recommendations.Results: The World Scleroderma Foundation committee agreed on 8 overarching treatment principles and 10 pharmacologic treatment recommendations for the management of systemic sclerosis digital ulcers. Phosphodiesterase 5 inhibitors and intravenous iloprost were recommended for the management of acute digital ulcers. Bosentan was recommended for prevention of digital ulcers.Conclusion: This study has yielded pragmatic treatment recommendations to direct treatment decisions for the management of systemic sclerosis digital ulcers. In addition, results have highlighted areas in need of future research in order to improve patient outcomes.

Systemic sclerosis (SSc) is a severe, progressive disease with limited treatment options. Autologous hematopoietic stem cell transplantation (AHSCT) has been shown to be an effective treatment for rapidly progressive SSc. The objective of this study was to evaluate the effectiveness of AHSCT for SSc compared to real-world clinical care. SSc patients from France who underwent AHSCT were compared to patients from Canada who met criteria for AHSCT (as defined in the ASTIS trial) but received conventional care. The primary outcome was overall survival. Secondary outcomes included modified Rodnan skin score (mRSS) and forced vital capacity (FVC). Overall survival was estimated by Kaplan-Meier survival curves. Measures of mRSS and FVC were compared using linear regression models. Analyses were adjusted for baseline scores and incorporated stabilized inverse probability of treatment weights to account for confounding by indication. Propensity scores were estimated using logistic regression. Forty-one AHSCT patients and 85 conventional care patients were compared. AHSCT was associated with a suggestive, though not statistically significant trend toward improvement in overall survival (log-rank P = .115). In follow-up, the mRSS was lower with AHSCT compared to conventional care: between group difference of 8.81; P < .0001 at 12 months and 11.28; P = .011 at 60 months. There was no significant difference in FVC between groups at 12 months but at 24 months, AHSCT was associated with a higher FVC (between group difference of 10.53 (P = .05)). This study demonstrates with real-world long-term data that compared with conventional care, treatment with AHSCT may offer superior outcomes for SSc patients. (c) 2025 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.