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At the end of 2015, INFN formally approved a new experiment, PADME, to search for invisible decays of the A' dark photon at the DAFNE Linac in Frascati. The experiment is designed to detect the A' produced in positron-on-fixed target annihilation, by measuring the final state missing mass. The collaboration aims to complete the design and construction of the experiment by the end of 2017 and to collect ∼1013 positrons on target by the end of 2018, thus reaching a sensitivity on the coupling constant of ∼103 and on the dark photon mass up to ∼ 23.7 MeV/c2

Metastasis suppressors comprise a growing class of genes whose downregulation triggers metastatic progression. In contrast to tumor suppressors, metastasis suppressors are rarely mutated or deleted, and little is known regarding the mechanisms by which their expression is downregulated. Here, we demonstrate that the metastasis suppressor, NM23-H1, is degraded by lysosomal cysteine cathepsins (L,B), which directly cleave NM23-H1. In addition, activation of c-Abl and Arg oncoproteins induces NM23-H1 degradation in invasive cancer cells by increasing cysteine cathepsin transcription and activation. Moreover, c-Abl activates cathepsins by promoting endosome maturation, which facilitates trafficking of NM23-H1 to the lysosome where it is degraded. Importantly, the invasion- and metastasis-promoting activity of c-Abl/Arg is dependent on their ability to induce NM23-H1 degradation, and the pathway is clinically relevant as c-Abl/Arg activity and NM23-H1 expression are inversely correlated in primary breast cancers and melanomas. Thus, we demonstrate a novel mechanism by which cathepsin expression is upregulated in cancer cells (via Abl kinases). We also identify a novel role for intracellular cathepsins in invasion and metastasis (degradation of a metastasis suppressor). Finally, we identify novel crosstalk between oncogenic and metastasis suppressor pathways, thereby providing mechanistic insight into the process of NM23-H1 loss, which may pave the way for new strategies to restore NM23-H1 expression and block metastatic progression.

Background:Treatment of polymyalgia rheumatica (PMR), a common inflammatory rheumatic disease in older adults, is hindered by a paucity of glucocorticoid (GC)-sparing therapies with proven efficacy. A retrospective study showed treatment with IL-6 receptor inhibitors (IL-6Ri) vs. conventional synthetic immunomodulatory drugs (csIM [methotrexate, leflunomide, and azathioprine]) was associated with greater likelihood of GC discontinuation (HR [95% CI]: 1.32 [1.09–1.58]) at 1 year1. Frailty, a syndrome characterized by increased vulnerability to stressors and poor health outcomes is associated with aging and inflammation. Frailty may be accelerated and more prevalent in patients with PMR vs. the general population2. Prolonged GC treatment may exacerbate frailty3, highlighting the need to reduce GC use in these patients. IL-6 is involved in the pathogenesis of PMR and frailty2 and thus, patients with both may particularly benefit from IL-6Ri therapy.Objectives:To compare effectiveness of IL-6Ri vs. csIM therapy as second (2L) and third (3L) line treatment for frail patients with PMR.Methods:A subgroup analysis of patients with frailty from a retrospective cohort study comparing the effectiveness of IL-6Ri to csIM in 2L and 3L treatment of patients with PMR identified from 3/2016–6/2019 using Medicare claims data was conducted. IL-6Ri and csIM PMR patients were direct matched on multiple factors (e.g. baseline GC dose category, and history of giant cell arteritis) and then propensity matched pairs were assessed with a validated claims-based frailty index (CFI)4. Although CFI ≥0.25 and ≥0.254 have been used as thresholds for frailty, due to sample size median CFI was used as the threshold to identify more frail patients. Matched pairs of patients with CFI ≥median, were retained for comparison. The primary outcomes were time-to-GC discontinuation (>60-day gap) and time-to-GC discontinuation or minimal GC dose (≤2 mg/day of prednisone equivalent) using Cox proportional hazards models stratified by 2L or 3L treatment. Patients were censored at 1 year, 60 days prior to the end of enrollment, death, outcome achievement, stopping csIM/IL-6Ri therapy or switching csIM/IL-6Ri therapy. Cumulative GC dose was also compared.Results:Of the 187 2L and 228 3L PS matched pairs from the parent cohort, 89 (35 [39.3%] 2L and 54 [60.7%] 3L) had CFI ≥0.2, the median. The most common csIM therapy in 2L and 3L was methotrexate (77.1%) and leflunomide (64.8%), respectively. Patient characteristics were generally balanced (Table 1) though patients with IL-6Ri were less likely to enroll in Medicare due to disability than csIM initiators (19.1% vs. 31.5%) and they had more inpatient days during baseline (Mean [SD] 2.1 [6.2] vs. 0.9 [2.6]) (Table 1). IL-6Ri vs. csIM initiators were significantly more likely to discontinue GC (HR [95% CI] 2.32 [1.35–3.99], P=0.002) and achieve discontinuation of GC or minimal GC dose (HR [95% CI] 2.23 [1.34–3.71], P=0.002), and had a lower cumulative GC dose (Mean [SD], mg; (3017.6 [4327.1] vs. 5764.0 [14690.3], P=0.025)) (Table 2). Results of sensitivity analyses for discontinuation of GC varying the censoring rules by removing censoring for 1 year, stopping or switching csIM or IL-6Ri, and stopping csIM or IL-6Ri resulted in similar findings with HR (95% CI) of 1.88 (1.14–3.10), P=0.013; 2.49 (1.59–3.89), P<0.001 and 2.71 (1.71–4.29), P<0.001, respectively.Conclusion:Compared with csIM, IL-6Ri therapy had a greater GC-sparing effect in frail patients with PMR. The effect size seen in patients with frailty appears to be larger than previously reported in a general PMR cohort1, suggesting patients with frailty may derive even greater benefit from IL-6Ri therapy compared with csIM therapy.REFERENCES:[1] Curtis JR et al. AMCP 2023 Poster No. M18.[2] Sattui SE et al. Rheumatology (Oxford) 2022;61:4455–64.[3] Motta F et al. Front Immunol 2020;11:576134.[4] Kim DH et al. J Gerontol A Biol Sci Med Sci 2019;74:1271–6.[5] Halawa OA et al. Ophthalmology 2023;130:646–54.Acknowledgements:The study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Medical writing support for this abstract was provided by Kritika Dhamija, M.S. (Pharm.), of Sanofi.Disclosure of Interests:Sebastian E. Sattui Research funding from Bristol Myers Squibb Foundation Robert A. Winn Diversity in Clinical Trials Career Development Award, Research support AstraZeneca and Glaxo Smith Kline (clinical trials), Consulting and advisory boards for Sanofi and Amgen (all funds toward research support), Christian Dejaco Consulting/speaker’s fees from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, Sparrow, Roche, Galapagos, and Sanofi, Editorial board member of ARD, Kerri Ford Employee of Sanofi and may hold stock and/or stock options in the company, Stefano Fiore Employee of Sanofi and may hold stock and/or stock options in the company, Sebastian Unizony Consulting fees from Kiniksa, Janssen, and Sanofi, Research support from Genentech, Fenglong Xie: None declared, Jeffrey R Curtis Consulting, research grants from AstraZeneca, Amgen, AbbVie, Bendcare, Genentech, GSK, Horizon, Janssen, Lilly, Novartis, Pfizer, Sanofi, Scipher Medicine, Setpoint, and UCB.

Background:Polymyalgia rheumatica (PMR), a common inflammatory rheumatic disease in older adults, is primarily treated with glucocorticoids (GC). A high comorbidity burden in PMR may increase the risk of GC toxicity. Frailty, characterized by poor health outcomes and increased vulnerability to stressors is more frequent in PMR (17%) [1] than in community dwelling elderly (11%) [2]. There are limited data on the prevalence of patients with PMR and comorbidities or frailty that may warrant more personalized PMR management (earlier specialist care, screening, lower GC dose/faster taper).Objectives:To describe the prevalence and management over time of frailty and comorbidities in patients with new onset PMR that may result from or worsen due to long term GC use.Methods:An inception cohort of patients with PMR aged ≥50 years was identified in fee-for-service U.S. Medicare claims data from 10/1/2016 to 12/31/2019 with 1) no history of PMR or giant cell arteritis, 2) ≥1 inpatient or ≥2 outpatient PMR diagnosis codes (ICD-10-CM M35.3) ≥30 to <365 days apart. Initial GC (prednisone equivalent) use had to be 7.5–25 mg/day ≤30 days after 1st inpatient code or from 1st outpatient to ≤30 days after 2nd outpatient code, ≥200 mg in first ≤30 days and continuous ≥ 4 months. Patients with seropositive rheumatoid arthritis, other systemic rheumatic disease, organ transplant, multiple sclerosis, active malignancy treatment or prescription for methotrexate, leflunomide, azathioprine or interleukin-6 receptor inhibitor during baseline were excluded. We report the prevalence of comorbidities (based on diagnosis, procedure or drug codes) that might be relative contraindications to long term GC use and frailty (assessed with a validated claims-based frailty index [CFI] [3]; defined as CFI ≥0.2 [4]), GC use, care by rheumatology, and screening with Dual-energy X-ray absorptiometry (DXA).Results:Of 5,499 patients with new onset PMR, at baseline 4.7%, 22.8% and 72.5%, had no, 1 and ≥2 comorbidities, respectively and frailty was seen in 33.8%. Patients with no vs. 1/≥2 comorbidities, and no frailty vs. frailty were younger (75.3 vs. 76.3/77.3; 76.5 vs. 77.9, years), fewer were female (49.2% vs. 54.7%/69.7%; 61.7% vs 72.5%) and fewer entered Medicare due to disability (7.8% vs 8.4%/14.5%; 8.8% vs 20.5%). Patients with no/1 vs. ≥2 comorbidities and frailty vs. no frailty were less likely to have ≥1 non excluded chronic inflammatory condition (asthma, psoriasis etc.) where GC may be used (41.1%/38.7% vs. 45.7%; 38.3% vs. 54.8%). Frailty occurred more in blacks vs. whites (43.1% vs. 33.4%). Comorbidities and frailty increased over 3 years, with a 4-fold increase in moderate-severe frailty (Table 1). Patients with a higher burden of comorbidities and who were frail were more likely to be on long term GCs (Table 2). DXA was obtained ≤2 years prior to GC use to ≤3 months after in 42.8%, 72.4%, 56.7%, and 35.6% of all patients, those with low bone mineral density (BMD), those with fracture (other comorbidities range: 24.4%–49.6%) and those with moderate-severe frailty, respectively. Although 57.4% of patients with PMR visited rheumatology within the first 6 months, 36.7% did not in ≤3 years. Rheumatology consultations for PMR were similar regardless of comorbidity or frailty.Conclusion:In this observational study, a majority of patients with new onset PMR had or developed comorbidities and frailty over 3 years that may be relative contraindications to long term GC use. Some patients developed these conditions (e.g. fracture) possibly due to GC use and/or other factors. Frailty was higher than previously reported in PMR and community dwelling elderly patients. Despite increased vulnerability to GC toxicity, no substantial difference was observed in GC use in frail patients, possibly due to lack of highly effective alternative treatments. Additional measures are needed to improve BMD screening which was underutilized in PMR patients and rheumatology referral.REFERENCES:[1] Sattui SE, et al. Rheumatology (Oxford). 2022.[2] Collart RM, et al. J Am Geriatr Soc. 2012.[3] Halawa OA, et al. Ophthalmology. 2023.[4] Kim DH, et al. J Gerontol A Biol Sci Med Sci. 2018.Acknowledgements:The study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Medical writing support for this abstract was provided by Pritha Bhunia, MSc., and Kritika Dhamija, M.S. (Pharm.), of Sanofi.Disclosure of Interests:Sebastian E. Sattui Consulting and advisory boards for Sanofi and Amgen (all funds toward research support), Research funding from Bristol Myers Squibb Foundation Robert A. Winn Diversity in Clinical Trials Career Development Award, Research support AstraZeneca and Glaxo Smith Kline (clinical trials), Frank Buttgereit Speaker/honoraria - AbbVie, Sanofi, Pfizer, Consultant - AbbVie, Sanofi, Gruenenthal, and Horizon Therapeutics, Grant/research support - AbbVie, Sanofi, and Horizon Therapeutics, Merav Lidar Speaker/honoraria - Abbvie, Pfizer, Lilly, Novartis, Sanofi, Janssen, GSK, and Astra, Kerri Ford Sanofi, Sanofi, Stefano Fiore Sanofi, Sanofi, Lita Araujo Sanofi, Sanofi, Timothy Beukelman Consulting - UCB, Fenglong Xie: None declared, Jeffrey Curtis Consulting - AstraZeneca, Amgen, AbbVie, Genentech, GSK, Horizon, Janssen, Lilly, Novartis, Pfizer, Sanofi, Scipher, Setpoint, UCB, ongoing, Research grants - AstraZeneca, Amgen, AbbVie, Genentech, GSK, Horizon, Janssen, Lilly, Novartis, Pfizer, Sanofi, Scipher, Setpoint, UCB, ongoing.

The Frascati Neutron Generator (FNG) started operations in November 1992 making available to EU fusion community 14 MeV neutrons at an emission rate of 1011 s-1. The fusion community strongly supported the idea of international collaboration in neutronics experiments, data base and code improvement, development of (new) experimental techniques and detectors. FNG was designed and built in ENEA that also operates the machine at its own expenses. FNG is extensively used to perform benchmarks or mock-up experiments of interest to Fusion neutronics in turn validating nuclear data and codes. A number of activities in different fields within a series of collaborations are carried out at FNG so far.

BackgroundThe SAPHYR study (NCT03600818) in patients with polymyalgia rheumatica (PMR) who were resistant to glucocorticoid (GC) taper met the primary endpoint with a significantly higher proportion of patients in the sarilumab arm versus the comparator arm achieving sustained remission from weeks 12 to 52 (28.3% vs 10.3%; P=0.0193) [1]. Sarilumab, when administered to patients with rheumatoid arthritis at a dose of 200 mg subcutaneously, achieved a steady state within 14 to 16 weeks [2]. Patients treated with sarilumab in SAPHYR may not have reached steady state concentrations by week 12 when disease remission was assessed for the primary endpoint of sustained remission.ObjectivesThis post-hoc analysis of the SAPHYR study assessed the proportion of patients achieving sustained remission up to week 52 from week 16 and from week 24.MethodsPatients were randomized (1:1 ratio) to 52 weeks of treatment with sarilumab 200 mg every 2 weeks (Q2W) + 14 week GC tapered regimen (sarilumab arm) or placebo Q2W + 52 week GC tapered regimen (comparator arm).Here, we assessed the proportion of patients achieving sustained remission and each of the sustained remission components from week 16 and from week 24 to the end of study. Sustained remission was defined as having met all of the following: disease remission at 16 weeks and 24 weeks (no PMR signs and symptoms + CRP normalization [<10 mg/L]); absence of disease flare from weeks 16 to 52 and weeks 24 to 52; sustained reduction of CRP (to <10 mg/L, with no successive elevations to ≥10 mg/L) from weeks 16 to 52 and weeks 24 to 52; and successful adherence to protocol specified GC taper dose from weeks 16 to 52 and weeks 24 to 52. Patients who did not achieve remission, received rescue treatment with open label prednisone (or equivalent), withdrew from the study before week 52, or had missing data that prevented assessment of the primary endpoint were considered as non-responders.ResultsBetween Oct 2018 and Jul 2020, 60 patients were randomized to the sarilumab arm and 58 patients to the comparator arm (intent to treat population). A higher proportion of patients in the sarilumab arm, versus the comparator, achieved sustained remission from weeks 16 to 52 (30.0% vs 8.6%; difference [95% CI]: 21.4 [7.7, 35.0]; P=0.0047) and from weeks 24 to 52 (31.7% vs 10.3%; difference [95% CI]: 21.3 [7.2, 35.5]; P=0.0063). This improvement in sustained remission rate in the sarilumab arm was due to additional responses seen between weeks 12 to 24 (Figure 1).Similarly, all the independent components of the sustained remission were achieved by a higher proportion of patients in the sarilumab arm, versus the comparator arm, during each assessment period. In both the sarilumab arm and the comparator arm, the disease remission rates decreased slightly at weeks 16 and 24 compared with week 12; sarilumab arm 40.0% and 41.7%, respectively vs 46.7% and comparator arm 31.0% and 20.7%, respectively vs 37.9%. Disease remission rates declined due to missing or abnormal CRP, as the proportion of patients with no PMR signs and symptoms increased over time.In the sarilumab arm, the proportion of patients with no disease flare increased from weeks 12 to 52 assessment to weeks 16 to 52 and weeks 24 to 52 assessments, whereas the proportion of patients with sustained CRP normalization or those who adhered to protocol-defined GC taper remained the same during the three assessment periods (Figure 1).Safety data were consistent with the know profile of sarilumab and were presented previously [1].ConclusionThis post-hoc analysis showed that a higher proportion of patients in the sarilumab arm, versus the comparator arm, achieved sustained remission when assessed from week 16 and week 24 up to week 52. Most patients who achieved sustained remission did so rapidly by week 12 with some additional responses seen between week 12 and 24.Reference[1]Dasgupta B, et al. Ann Rheum Dis. 2022;81:210-211; 2McCarty D & Robinson A. Ther Adv Musculoskelet Dis. 2018; 10(3): 61–67.AcknowledgementsScientific writing support was provided by Vijay Kadasi of Sanofi.Disclosure of InterestsBhaskar Dasgupta Speakers bureau: Cipla and Roche Chugai, Consultant of: Roche Chugai and Sanofi, Grant/research support from: Abbvie, Roche Chugai, and Sanofi, Amy Praestgaard Shareholder of: Sanofi, Employee of: Sanofi, Stefano Fiore Shareholder of: Sanofi, Employee of: Sanofi, Kerri Ford Shareholder of: Sanofi, Employee of: Sanofi, Jennifer Sloane Lazar Shareholder of: Sanofi, Employee of: Sanofi, Anisha Dua Consultant of: Abbvie, Sanofi, Chemocentryx, and Novartis, Robert Spiera Consultant of: GSK, Regeneron, Abbvie, Sanofi, Chemocentryx, Novartis, Galderma, Vera, Chemomab, Boehringer Ingelheim, and BMS, Grant/research support from: Roche-Genetech, Astra-Zeneca, GSK, Kadmon, Boehringer Ingelheim, Chemocentryx, Corbus, Formation Biologics, Novartis, Inflarx, and Principia.

Background:Glucocorticoids (GCs) are the mainstay of treatment for polymyalgia rheumatica (PMR). However, a substantial proportion of patients treated with GC may not achieve GC-free remission or may not be able to taper GC without experiencing flares.[1] It is estimated that almost 50% of patients experience a disease flare upon GC taper or discontinuation.[2,3] The clinical and economic burden of continuing GC in these patients could provide important insight into the potential value of steroid sparing therapy. Previous analyses defined inadequate response to GC/GC taper to include patients with comorbidities that may result from or worsen with GC use.[4] However, these occur at a high rate in this population and may not preclude use of GC in some patients. This analysis evaluates the clinical and economic outcomes in patients with PMR who are presumed to flare with GC use or relapse after discontinuation in a real-world setting.Objectives:To estimate the clinical and economic outcomes of continuing GCs in patients with PMR who are IR to GC or unable to taper GCMethods:A PMR inception cohort was derived using fee-for service Medicare claims data,[4] included patients aged ≥50 years with no prior history of PMR or giant cell arteritis who had 1) ≥1 inpatient or ≥2 outpatient claims for PMR (ICD-10-CM M35.3) ≥30 to <365 days apart, 2) prescription for GC (prednisone equivalent) 7.5–25 mg/day <30 days from 1st inpatient code or from 1st outpatient code to 30 days after 2nd code with GC dose ≥200 mg in first ≤30 days and continuous GC use ≥4 months 3) continuous enrollment ≥1 year prior to index and 4) ≥2 years follow-up. Index date was latter of the date the diagnosis or GC dose/use criteria was met; and was between 10/1/2016 and 12/31/2019. Patients with seropositive rheumatoid arthritis, other systemic rheumatic disease, solid organ transplant, multiple sclerosis, active treatment for malignancy or prescription for conventional immunomodulatory drugs [csIM (methotrexate [MTX], leflunomide, azathioprine)]/interleukin-6 receptor inhibitors during baseline (1 year prior to and including index) were excluded. Patients were divided into two groups: 1) IR-GC/GC taper, i.e., those with GC dose ≥7.5 mg/day at 6 months or persistent GC use >12 months (i.e., presumed flare) or relapse [GC use after discontinuation (>60-day gap)] or 2) non-IR-GC/GC taper (all others).All-cause healthcare resource utilization (HCRU) costs, and incidence rate of GC-related adverse events (GC-AEs) as per ICD-10-CM diagnosis, drug, or procedure codes were reported beginning 6 months after index and updated at 6-months intervals. For hospitalized infections and fractures, repeat events were allowed; for all other AEs, only the 1st event was counted. Exact Poisson methods were used to estimate event rates per 100 patient-years and 95% confidence intervals. A subgroup analysis of the IR-GC/GC taper group estimated outcomes by cumulative GC dose quartiles, updated every 6 months.Results:This analysis included 6054 patients with new onset PMR (65.4% females) with mean age 77.1 years. The rates of GC-AEs and all-cause HCRU costs were generally higher in the IR-GC/GC taper group vs. non-IR-GC/GC taper group in the months >6–18 and remained higher through months 42–54, except for osteonecrosis (Table 1). In the IR-GC/GC taper group, all-cause HCRU costs and most GC-AEs decreased over time. A GC dose-response relationship was noted between cumulative GC dose and most outcomes (Table 2).Conclusion:The clinical and economic burden of continuing GCs in PMR patients with inability to taper GCs are considerable and may endure even after GC discontinuation. These results underscore the need for effective GC-sparing therapies for PMR to avoid/minimize the clinical and economic burden of long-term GCs.REFERENCES:[1] Hutchings A, et al Arthritis Rheum 2007; 57:803–9.[2] Salvarani C, et al Arthritis Rheum 2005; 53:33–38.[3] Kremers HM, et al J Rheumatol 2005; 32:65–73[4] Curtis J, et al Arthritis Rheumatol. 2023; 75 (suppl 9)Acknowledgements:This study was funded by Sanofi and Regeneron Pharmaceuticals, Inc. Medical writing assistance was provided by Arohi Sarang M.Pharm. of Sanofi.Disclosure of Interests:Jeffrey R Curtis AstraZeneca, Amgen, AbbVie, Bendcare, Genentech, GSK, Horizon, Janssen, Lilly, Novartis, Pfizer, Sanofi, Scipher, Setpoint, and UCB, AstraZeneca, Amgen, AbbVie, Bendcare, Genentech, GSK, Horizon, Janssen, Lilly, Novartis, Pfizer, Sanofi, Scipher, Setpoint, and UCB, Lita Araujo Employee of Sanofi and may hold stocks/stock options in the company, Stefano Fiore Employee of Sanofi and may hold stocks/stock options in the company, Sebastian E. Sattui Research funding from Bristol Myers Squibb Foundation Robert A. Winn Diversity in Clinical Trials Career Development Award; research support from AstraZeneca and GlaxoSmithKline (clinical trials) and consultant and participated in advisory boards for Sanofi and Amgen (all funds towards research support)., John H. Stone Consultant: Sanofi, Brandon Yip Employees of Sanofi and may hold stocks/stock options in the company, Kerri Ford Employee of Sanofi and may hold stocks/stock options in the company, Fenglong Xie: None declared.

Background:Polymyalgia Rheumatica (PMR) is a common inflammatory rheumatic condition in people aged ≥50 years with incidence peaking at 70–80 years. PMR is primarily treated with glucocorticoids (GC) with guideline recommended treatment duration of 36–48 weeks without a flare or 40–52 weeks with a single flare.[1] However, it is estimated that 77%, 51%, and 25% of PMR patients remain on GC at 1, 2, and 5 years, respectively.[2] Extended GC therapy can increase the risk of GC-related toxicity, particularly in this elderly population. Thus, early recognition of patients who may require GC treatment for >1 year will help identify patients at risk of GC toxicity who could benefit from GC sparing therapies. Few studies have evaluated factors that could be indicators of patients likely to require extended GC therapy.[3,4]Objectives:To identify characteristics at 6 months in new onset PMR patients associated with extended GC use beyond 1 year.Methods:This was an exploratory analysis of an inception cohort of PMR patients identified from fee-for-service Medicare claims from 10/01/2016 to 12/31/2020.[5] Patients included had no history of PMR or giant cell arteritis, were ≥50 years, had ≥1 inpatient or ≥2 outpatient claims for PMR (ICD-10-CM M35.3) ≥30 days and <365 days apart. They initiated GC (prednisone equivalent) 7.5–25 mg/day ≤30 days after 1st inpatient code or from 1st outpatient to ≤30 days after 2nd outpatient code, had GC dose ≥200 mg in first ≤30 days and ≥4 months continuous GC use. Continuous enrollment ≥1 year prior to first diagnosis date was required. Patients with other systemic rheumatic disease, active malignancy treatment, multiple sclerosis, solid organ transplant, or prescription for conventional synthetic immunomodulatory drugs [csIM (methotrexate [MTX], leflunomide, azathioprine)] or interleukin-6 receptor inhibitors, ≤1 year prior to first (inpatient) or second (outpatient) PMR diagnosis to 6 months after GC initiation (baseline period), were also excluded (GC cohort). A supplemental analysis evaluated patients who met other criteria and received a csIM ≤6 months from GC initiation (csIM cohort). The primary outcome was comparison of characteristics (demographic, clinical, and healthcare resource utilization) at 6 months between patients who were on GC vs. off GC (>60-day gap) at 1 year. Comorbidities were defined using diagnosis, procedure, or drug codes. Frailty was assessed by a validated claims-based frailty index[6] and defined using a published threshold.[7]Results:A total of 4,748 patients were included in the GC cohort and 318 in the csIM cohort. MTX was the most common csIM [200/318 (62.9%)]. Of patients in the GC cohort and csIM cohort, 3,038 (64.0%) and 183 (57.5%) were on GC at 1 year, respectively. In both GC and csIM cohorts, significantly more patients on GC vs. off GC at 1 year were on GC dose ≥5 mg at 6 months. Patients on GC vs. off GC at 1 year also had significantly higher cumulative GC use at 6 months in both cohorts (Table 1). In the GC cohort, demographic characteristics and presence of comorbidities or frailty at 6 months, were not associated with GC use at 1 year while in the csIM cohort, age, year GC was initiated, initial GC dose, and glaucoma were significantly associated with GC use at 1 year (Tables 1,2). A sensitivity analysis including patients who initiated MTX within 6 months found 55.5% (111/200) of patients were on GC at 1 year and MTX use was significantly associated with GC use at 1 year: fewer patients on GC vs. off GC at 1 year had received MTX within 6 months [111/3149 (3.5%) vs 89/1799 (4.9%); p=0.015].Conclusion:More than half of PMR patients remained on GC beyond 1 year. Evaluation of GC dose at 6 months may be useful to identify patients who may benefit from GC sparing therapy.REFERENCES:[1] Dejaco C et al. Arthritis Rheumatol 2015, 67:2569–80.[2] Floris A et al. Clin Rheumatol 2022, 41:19–31.[3] Perricone C et al. Clin Exp Med 2023, 23:3391–7.[4] Birra D et al. Clin Exp Rheum 2020, 38:436–41.[5] Curtis J, et al. Arthritis Rheumatol 2023, 75.[6] Kim DH et al. J Gerontol A Biol Sci Med Sci 2018, 73:980–7.[7] Halawa OA, et al, Ophthalmology 2023, 130: 646-54.Acknowledgements:This study was funded by Sanofi and Regeneron Pharmaceuticals, Inc. Medical writing support for this abstract was provided by Kavita Garg, PhD, CMPP, of Sanofi.Disclosure of Interests:Anisha B Dua Consultant: AbbVie, Amgen, Astra Zeneca, GSK, Sandoz, Sanofi, Andrea Rubbert-Roth Honoraria for consultation and lectures from AbbVie, BMS, Gilead, Lilly, Pfizer, Roche, Sanofi, UCB, Kerri Ford Employee of Sanofi and may hold stock and/or stock options in the company, Stefano Fiore Employee of Sanofi and may hold stock and/or stock options in the company, Lita Araujo Employee of Sanofi and may hold stock and/or stock options in the company, Timothy Beukelman Consultant: UCB, Fenglong Xie: None declared, Jeffrey R Curtis Consulting and research grants from AstraZeneca, Amgen, AbbVie, Bendcare, Genentech, GSK, Horizon, Janssen, Lilly, Novartis, Pfizer, Sanofi, Scipher, Setpoint, and UCB.