Janssen Global Services Research Articles

Updated Results of Talquetamab, a GPRC5D×CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Multiple Myeloma with Prior Exposure to T-Cell Redirecting Therapies: Results of the Phase 1/2 MonumenTAL-1 Study

Introduction: Novel T-cell redirecting therapies (TCR), including chimeric antigen receptor T-cell therapy (CAR-T) and bispecific antibodies (BsAbs), are important new treatment options for patients (pts) with relapsed/refractory multiple myeloma (RRMM) but result in a new unmet need for pts who relapse following these therapies. Talquetamab is the most advanced BsAb therapy targeting G protein-coupled receptor family C group 5 member D (GPRC5D), a novel antigen that is overexpressed on malignant plasma cells but is expressed at low levels on B cells and bone marrow progenitors. Previous results from the phase 1/2 MonumenTAL-1 study (NCT03399799/NCT04634552) demonstrated deep and durable responses with talquetamab in pts with RRMM, with an overall response rate (ORR) of >71% in 288 pts naive to TCR and 65% in 51 pts with prior TCR. Here, we present updated results in pts with prior TCR, including an additional 19 pts enrolled since the prior analysis. Methods: Eligible pts for phase 1 of the study had progressed on or could not tolerate established multiple myeloma therapies.In phase 2, eligible pts had been exposed to ≥3 prior lines of therapy including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody. The current analysis includes all pts across phase 1 and 2 of the study who received 1 of the 2 recommended phase 2 doses of subcutaneous talquetamab (0.4 mg/kg weekly [QW] or 0.8 mg/kg every other week [Q2W]) and who were exposed to a TCR (prior CAR-T and BsAb), as well as pts exposed to both a TCR and a B-cell maturation antigen (BCMA)-targeting antibody-drug conjugate (ADC). Results: As of Jan 17, 2023, 70 pts were enrolled with prior TCR. Overall, 44 (63%) were <65 years old; 65 (93%) received ≥4 prior lines of therapy; 58 (83%) and 29 (41%) were triple-class and penta-drug refractory, respectively; 21 (30%) had extramedullary disease, 24 (34%) had high-risk cytogenetics, and 12 (17%) had International Staging System stage III disease. Fifty of 70 pts received prior CAR-T (48/50 anti-BCMA CAR-T), 25 pts received prior BsAb (23/25 anti-BCMA BsAb), and 5 pts received both. Eight of 70 pts received prior treatment with BCMA ADC. Among BCMA-exposed pts, ORR was comparable between pts receiving prior BCMA CAR-T and prior BCMA ADC, and similar to the overall population; ORR was lower in pts receiving prior BCMA BsAb (Table). Median duration of response (mDOR) was similar between the overall population (12.3 mo; 95% CI, 6.5-not estimable [NE]) and pts with prior BCMA CAR-T (12.3 mo; 95% CI, 4.8-NE), but was shorter in pts with prior BCMA BsAb (6.5 mo; 95% CI, 1.9-NE). In the prior CAR-T group, ORR was comparable in those who received CAR-T as immediate prior line vs at any prior line of therapy before talquetamab (75.9% [22/29] vs 71.4% [15/21], respectively). In the prior BsAb group, ORR was lower in those who received BsAb as immediate prior line vs at any prior line of therapy before talquetamab (28.6% [2/7] vs 61.1% [11/18], respectively). In the prior BsAb group, ORR was 62.5% (5/8) in pts who had ≥9 mo interval between last dose of the prior BsAb and talquetamab, 50% (3/6) in those who had ≥6 to <9 mo interval, and 45.5% (5/11) in those who had <6 mo interval. Conclusions: These updated results from pts with prior TCR in the phase 1/2 MonumenTAL-1 study show continued strong efficacy of GPRC5D-targeting talquetamab across populations exposed to TCR (predominantly anti-BCMA), with notable ORR of 73% and mDOR of >1 year in the post-CAR-T setting. More than 50% of pts exposed to prior BsAb responded, and outcomes data in these pts may offer insight into optimal sequencing. Together with previously published data, these results support talquetamab as a versatile treatment option that provides robust responses in TCR/BCMA-naive and TCR/BCMA-exposed pts with RRMM. Acknowledgments: This study was funded by Janssen Research & Development, LLC. Medical writing support was provided by Michelle Yang, PharmD, of Eloquent Scientific Solutions, and funded by Janssen Global Services, LLC.

227-LB: Kynurenine Pathway Is Associated with Preservation of Beta-Cell Function in Autoimmune Diabetes

Background: Autoimmune diabetes (AD) results from a loss of immune tolerance leading to the destruction of β-cells in the pancreas. Heterogeneity in severity of β-cell damage among people with AD is well-recognized, with some patients retaining a certain amount of insulin-producing cells for years despite the presence of pancreatic autoimmunity. Cellular and molecular mechanisms driving the preservation of β-cell function in AD remain unclear. Aim & Methods: To identify metabolic pathways associated with preservation of β-cell function we conducted a metabolomic study using gas and liquid chromatography-mass spectrometry (GC- and LC-MS) based platform on plasma samples collected from 32 subjects with adult-onset AD (median [Q1-Q3] age: 57 [52-62]; disease duration: 4.5 [3.0-9.0] years) with different severity of β-cell dysfunction, compared with data from people with rheumatoid arthritis (RA, n=28). Metabolome profiles of pancreatic islets from healthy donors after in vitro treatment with proinflammatory cytokines was also evaluated. Results: Metabolomic analyses showed decreased plasma Kynurenine/Tryptophan ratio (KynTr), a marker of indoleamine 2,3 dioxygenase-1 (IDO1) activity, in people with AD compared to RA (0.023 vs 0.027, p=0.03). Among people with AD, KynTr was directly associated with fasting C-peptide levels (rho=0.365), independently of age, gender, body mass index, diabetes duration and Hba1c (p-value after adjustments= 0.003). Lower concentrations of Tryptophan was observed in pancreatic islets from healthy donors after treatment with proinflammatory cytokines. Conclusions: While confirming that IDO1 impairment is involved in the pathogenesis of AD and in the regulation of inflammatory response of pancreatic islets, our results show that KynTr is a marker of beta-cell damage in AD. Overall, this suggests that the kynurenine pathway may be studied as a possible target for therapies aimed at preserving beta-cell function also after a diagnosis of AD Disclosure E. Maddaloni: Consultant; Abbott, Merck KGaA, PIKDARE S. p. A., Speaker's Bureau; Medical Technology & Devices. F. Dotta: None. P. Marchetti: None. R. Buzzetti: None. A. Gastaldelli: Advisory Panel; Pfizer Inc., Novo Nordisk, Merck Sharp & Dohme Corp., Boehringer Ingelheim International GmbH, Consultant; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Fractyl Health, Inc., Merck Sharp & Dohme Corp., Other Relationship; Pfizer Inc., Speaker's Bureau; Eli Lilly and Company. L. Navarini: Consultant; AbbVie Inc., Pfizer Inc., Bristol Myers, Celgene, MSD Life Science Foundation, Eli Lilly and Company, Novartis, Janssen Global Services, LLC. R. Amendolara: None. S. Fenizia: None. S. Pezzica: None. M. Tesi: None. L. D'onofrio: None. E. Bosi: None. Funding Italian Ministry of University and Research (PRIN 2017: 20175L9H7H)

(247) Complication Rates After Penile Prostheses In Men with History of Priapism – A Retrospective Claims Database Cohort Analysis

Abstract Introduction Penile prostheses can be placed in men with a history of priapism who develop erectile dysfunction, or as initial management of acute ischemic priapism. However, little is known about long-term complications associated with prostheses in these men. Objective To assess the risk of penile prosthesis complications in men with a history of priapism. Methods We searched the TriNetX insurance claims database to create a cohort of men ages ≥16 years old with 1) a diagnosis of priapism (ICD-10: N48.4), 2) a diagnosis of erectile dysfunction (ICD-10: N52), and 3) had undergone prosthesis placement (insertion of penile prosthesis inflatable and self-contained [CPT: 54401], insertion of semi-rigid penile prosthesis [CPT 54400], or insertion of multiple component inflatable penile prosthesis [CPT: 54405]). Three complications were assessed: penile prosthesis infection (ICD-10: T83.61), penile prosthesis mechanical breakdown (ICD-10: T83.410A), and penile prosthesis displacement or migration (ICD-10: T83.420). Rates of and duration to IPP removal (CPT: 54415-17, 54406, 54410-11) were also assessed. To compare rates of complications, the priapism cohort was compared to a cohort of men with a diagnosis of erectile dysfunction and prosthesis placement but without a history of priapism or corpora cavernosal irrigation, matched by age, race, diabetes status, and obesity (E66). When assessing risk of prosthesis complications, we utilized 1:1 greedy nearest-neighbor propensity score matching to control for confounding variables. Results A total of 665 men were identified with a diagnosis of priapism and erectile dysfunction who subsequently received a penile prosthesis. A control group of 31,345 patients with erectile dysfunction and a penile prosthesis but without priapism or history of irrigation was identified, and ultimately 660 men in the case and control cohorts were matched by age, race, diabetes status, and obesity. Men of with a history of priapism were more likely to experience penile prosthesis infection (5.0% vs 2.7%; Risk Ratio (RR): 1.83, 95% Confidence Interval (CI) 1.04-3.22) and mechanical breakdown of the prosthesis (7.3% vs 3.8%, RR: 1.92, 95%CI 1.20-3.08). There was no difference in the rate of penile prosthesis displacement or migration (3.5% vs 2.4%, RR: 0.76, 95%CI 0.77-2.70). Overall rates of penile prosthesis explantation were higher in men with a history of priapism 14.6% vs 8.4% (RR: 1.73, 95%CI 1.27-2.36). Rates of early explantation (within 6 months of placement) were similar between the two groups, 3.3% vs 2.9% (RR: 1.16, 95%CI 0.63-2.11). Rate of explantation of semi-rigid prostheses were significantly higher in men with a history of priapism, 27% vs 9.6% (RR: 2.54, 95%CI 1.62-3.93). Of the 17 men undergoing explantation of semi-rigid prosthesis with history of priapism, only 4 men (23%) went on to have a 3-piece penile prosthesis placed. Conclusions In this US claims-based database comparison between prosthetic complications in men with and without a history of priapism, men with priapism were more likely to experience infection, mechanical breakdown and explantation. There was no difference in rate of device displacement or migration, or in timing of device explantation. This real-world data provides context for counseling men with priapism who undergo prosthesis placement. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Urogen Pharma, Janssen Global Services, Regeneron Pharmaceuticals

(111) Clinical Practice Patterns for Surgical Shunts and Penile Prosthesis Placement in Men with Priapism – A Retrospective Claims Database Analysis

Abstract Introduction New AUA/SMSNA guidelines for management of acute ischemic priapism have been released, but actual practice patterns can be difficult to assess as overall incidence is low and men often seek care at multiple institutions. Objective To assess the rates of surgical shunting and prosthetic placement for acute ischemic priapism using a large multi-institutional claims database. Methods A US claims database network (TriNetX Diamond Network) was queried from 2010 to 2020. We constructed a cohort of men ages ≥16 years old with 1) a diagnosis of priapism (ICD-10: N48.4) and 2) who had undergone an irrigation of the corpora cavernosa for priapism (CPT: 54220). We assessed the number of men who then had a surgical penile shunt (corpora cavernosa-glans penis fistulation [CPT: 54435], corpora cavernosa-corpus spongiosum shunt [CPT: 54430], or corpora cavernosa-saphenous vein shunt [CPT: 54420]) or penile prosthesis placement (insertion of penile prosthesis inflatable and self-contained [CPT: 54401], insertion of semi-rigid penile prosthesis [CPT 54400], or insertion of multiple component inflatable penile prosthesis [CPT: 54405]). Time to surgical procedure and order of procedures were collected, as well as background information including age, race, diabetes status (ICD-10: E11), hyperlipidemia status (ICD-10: E78), sickle cell status (ICD-10: D57.0-1), and if men were classified to have drug-induced priapism (ICD-10: N48.33). Results 6,392 men were identified with the diagnosis of priapism and the procedure of corpora cavernosa irrigation. Of these men, 693 (11%) proceeded to surgical shunt (94 had corpora cavernosa-glans penis fistulation, 321 men had corpora cavernosa-corpus spongiosum shunt, and 78 men had corpora cavernosa-saphenous vein shunt). 144 men (2%) underwent initial penile prosthesis placement (Figure 1). Of the men undergoing initial penile prosthesis 94 (65%) occurred within the first year of the initial corpora cavernosal irrigation with the majority (81 of 94, 86%) being 3-piece inflatable penile prostheses and the majority in a “delayed” manner between 3 to 12 months after initial priapism irrigation (Table 1). Men who underwent initial penile prosthesis placement were older (55.1±13.0 vs 43.0±13.7 years, p<0.0001) and more often white (23% vs 16%, p=0.03), with higher rates of erectile dysfunction (56% vs 9%, p<0.0001), type 2 diabetes (32% vs 13%, p<0.0001), and hyperlipidemia (47% vs 20%, p<0.0001) when compared to men who underwent initial penile shunt procedure (Table 2). Finally, when assessing choice of initial shunts versus initial penile prosthesis pre- and post-2015, overall rates of initial shunt (10.0% vs 8.5%, p<0.0001) and initial prosthesis (3.1% vs 2.1%, p<0.0001) were significantly lower after 2015 when compared with rates prior to 2015. Conclusions In this US claims-based analysis of men presenting with ischemic priapism and treated with initial irrigation, we found that a small percentage (11%) continued to surgical shunting. Only 2% were managed with an initial prosthesis, most often a 3-piece device in a delayed manner. Men receiving initial prostheses were more likely to have more comorbidities, and overall surgical management of priapism has decreased overtime. In the setting of the new AUA/SMSNA guidelines, this data provides real-world practice patterns. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Urogen Pharma, Janssen Global Services, Regeneron Pharmaceuticals

P128 Long-term safety and efficacy of upadacitinib in patients with rheumatoid arthritis: final results from the BALANCE-EXTEND open-label extension study

Abstract Background/Aims Upadacitinib (UPA) was previously evaluated in two Phase 2, randomized, controlled trials (RCTs) in patients (pts) with rheumatoid arthritis (RA) and inadequate response to tumor necrosis factor inhibitors (BALANCE-1) or methotrexate (BALANCE-2). Objectives: To assess the final safety and efficacy of UPA in BALANCE-EXTEND, a 312-week open-label extension (OLE) enrolling pts who completed either BALANCE1 or BALANCE-2. Methods All pts initially received UPA 6 mg twice daily (BID). Increase to 12 mg BID was required for pts with <20% improvement in swollen or tender joint counts (S/TJC) at Week 6 or 12, and permitted for those not achieving Clinical Disease Activity Index (CDAI) low disease activity (LDA). Pts with <20% improvement in SJC or TJC 6 weeks after escalation, or at any two consecutive visits, discontinued. Return to 6 mg BID was permitted for safety or tolerability reasons. After January 2017, the 6 and 12 mg BID doses were replaced by 15 and 30 mg once-daily (QD) extended-release equivalents. As-observed efficacy data are shown at Week 312 for three subgroups: pts who received 6 mg BID/15 mg QD throughout (“Never titrated”), those titrated up to 12 mg BID/30 mg QD for efficacy (“Titrated up”), and those titrated up to 12 BID/30 mg QD and then back to 6 mg BID/15 mg QD due to safety concerns (“Titrated up and down”). Exposure-adjusted adverse events (EAERs) per 100 patient-years (PY) of exposure were summarized from OLE Day 1 in all pts who received UPA (Any UPA). Results Overall, 493 pts entered the OLE, receiving UPA for ≤6.2 years (Never titrated, n = 306; Titrated up, n = 149; Titrated up and down, n = 38), and 270 pts (54.8%) discontinued, mostly due to withdrawal of consent (16.8%; n = 83) or AEs (14.6%; n = 72). Mean (standard deviation) duration of UPA exposure was 3.8 (2.4) years (range <1-6.2 years); cumulative exposure was 1863 PY. The AE profile in pts receiving UPA 15 mg was generally similar to the Any UPA population, and to that observed in the Phase 3 UPA 15 mg clinical trial population. Efficacy was maintained to Week 312, with 84.5% and 86.6% of pts in the Never titrated group achieving DAS28-CRP ≤3.2 and CDAI LDA, respectively. Conclusion In this OLE, UPA treatment over ∼312 weeks showed sustained long-term efficacy in pts with RA who had completed Phase 2 RCTs. Overall safety results showed that UPA was well tolerated over time; the types and frequencies of AEs were consistent with those in pts with similar populations of moderately to severely active RA receiving Janus kinase inhibitors. Disclosure A. Kivitz: Consultancies; A Kivitz has received consulting fees and/or honoraria from AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly and Company, Flexion, Genzyme, Gilead, Horizon, Janssen, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sanofi Aventis, SUN Pharma Advanced Research, and UCB. Shareholder/stock ownership; A Kivitz owns stocks or options in Amgen, Gilead, GlaxoSmithKline, Novartis, Pfizer, and Sanofi. Honoraria; A Kivitz has received honoraria from AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly and Company, Flexion, Genzyme, Gilead, Horizon, Janssen, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sanofi Aventis, SUN Pharma Advanced Research, and UCB. Grants/research support; A Kivitz's institution received fees from AbbVie for his role as a Principal Investigator in the study. A.F. Wells: Consultancies; AF Wells has received consulting fees from AbbVie. J.I. Vargas: Honoraria; JI Vargas has received honoraria from AbbVie. Grants/research support; JI Vargas has received fees from AbbVie as Principal Investigator in the study. H.S.B. Baraf: Consultancies; HSB Baraf has acted as a consultant for Gilead and Janssen. Grants/research support; HSB Baraf has received grant/research support from AbbVie, Eli Lilly, Genentech, Gilead, and Janssen. M. Rischmueller: Consultancies; M Rischmueller has acted as a consultant for AbbVie, Bristol-Myers Squibb, CSL Behring, Eli Lilly, Gilead Sciences, Janssen Global Services, Pfizer, Sanofi US Services, and UCB Biosciences. Grants/research support; M Rischmueller has received grant/research support from AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Janssen Global Services, Novartis, Pfizer, Sanofi Pasteur Biologics, and UCB Biosciences. J. Klaff: Shareholder/stock ownership; J Klaff is employee of AbbVie and may own stocks or options. N. Khan: Shareholder/stock ownership; N Khan is an employee of AbbVie and may own stocks or options. Y. Li: Shareholder/stock ownership; Yihan Li is an employee of AbbVie and may own stocks and options. K. Carter: Shareholder/stock ownership; K Carter is an employee of AbbVie and may own stocks and options. A. Friedman: Shareholder/stock ownership; A Friedman is an employee of AbbVie and may own stocks and options. P. Durez: Corporate appointments; P Durez has received speaker fees from Eli Lilly and Galapagos.

P135 Efficacy and safety of upadacitinib in TNFi inadequate responders with rheumatoid arthritis from three Phase 3 clinical trials

Abstract Background/Aims For patients with RA who are refractory to biologic disease-modifying antirheumatic drugs (bDMARDs), such as tumor necrosis factor inhibitors (TNFis), optimal disease control is less likely to be achieved with subsequent therapy. In line with recommendations from EULAR and ACR, switching to a treatment with a different mechanism of action is appropriate for these patients. Objectives To describe the efficacy and safety of upadacitinib (UPA) 15 mg once daily in patients with RA and an inadequate response or intolerance to TNFis (TNFi-IR). Methods A post hoc subgroup analysis was conducted in TNFi-IR patients who were treated with UPA 15 mg once daily in three Phase 3 clinical trials: SELECT-BEYOND, -CHOICE, and -COMPARE. For COMPARE, only patients treated with adalimumab and switched to UPA as rescue therapy were included. ≥20/50/70% improvement in ACR criteria, DAS28-CRP, Clinical Disease Activity Index, and Simple Disease Activity Index, as well as change from baseline in HAQ-DI and other patient-reported outcomes (PROs) were reported through 24 weeks. Non-responder imputation was used for all missing categorical outcomes; as observed (COMPARE) or multiple imputation (CHOICE, BEYOND) were used for missing continuous outcomes. Pooled safety results were presented as exposure-adjusted event rates (EAERs) with a cut-off of June 30, 2021. Results 568 TNFi-IR patients were included: 146 from BEYOND, 263 from CHOICE, and 159 from COMPARE. Mean duration since RA diagnosis was longer for BEYOND and CHOICE versus COMPARE; CV risk factors were common among this refractory population. ACR20/50/70 and disease activity outcomes observed in the TNFi-IR population were generally consistent with the overall BEYOND and CHOICE bDMARD-IR populations, and consistent across the three studies in the TNFi-IR subgroups. Improvements in PROs including HAQ-DI, fatigue, pain, and morning stiffness over 24 weeks were observed (data not shown). Pooled safety results reporting 1574.8 PY of exposure in the TNFi-IR subgroup showed similar results to the overall BEYOND and CHOICE bDMARD-IR study populations, with EAERs of 3.1 events/100 PY for herpes zoster and 0.8 events/100 PY for adjudicated major adverse CV events and venous thromboembolism, and malignancy excluding non-melanoma skin cancer. The EAER of any AE leading to death was 1.4 events/100 PY. Conclusion In this post hoc subgroup analysis, TNFi-IR patients treated with UPA 15 mg achieved clinically meaningful efficacy responses over 24 weeks, with safety consistent with the overall bDMARD-IR patient population in the Phase 3 program. Disclosure R. Fleischmann: Consultancies; Consultant for AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Galvani, Gilead, GSK, Janssen, Novartis, Pfizer Inc, and UCB. Grants/research support; Grant/research support from AbbVie, Amgen, Biosplice, Bristol-Myers Squibb, Flexion, Gilead, Horizon, Eli Lilly, Galvani, Janssen, Novartis, Pfizer Inc, Sanofi-Aventis, Selecta, Teva, UCB, Viela, and. L. Bessette: Consultancies; AbbVie, Amgen, Bristol-Meyers Squibb, Celgene, Eli Lilly, Fresenius Kabi, Gilead, Janssen, Merck, Novartis, and Pfizer, Roche, Sanofi-Aventis, Teva, and UCB. Member of speakers’ bureau; AbbVie, Amgen, Bristol-Meyers Squibb, Celgene, Eli Lilly, Fresenius Kabi, Gilead, Janssen, Merck, Novartis, and Pfizer, Roche, Sanofi-Aventis, Teva, and UCB. Grants/research support; AbbVie, Amgen, Bristol-Meyers Squibb, Celgene, Eli Lilly, Fresenius Kabi, Gilead, Janssen, Merck, Novartis, and Pfizer, Roche, Sanofi-Aventis, Teva, and UCB. S. Hall: Consultancies; AbbVie, Amgen, Bristol-Meyers Sqibb, Eli Lilly, Gilead, Janssen, Merck, Novartis, and UCB. Grants/research support; AbbVie, Amgen, Bristol-Meyers Sqibb, Eli Lilly, Gilead, Janssen, Merck, Novartis, and UCB. J. Sparks: Consultancies; Consulted for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer. M. Jain: Consultancies; Amgen, Abbvie, Eli Lilly, Pfizer, and Novartis. Grants/research support; Amgen, Abbvie, Eli Lilly, Pfizer, and Novartis. A. Kakehasi: Consultancies; Amgen, Janssen, UCB, AbbVie, Pfizer, Eli Lilly, Novartis, Sandoz, Fresenius Kabi. Member of speakers’ bureau; Amgen, Janssen, UCB, AbbVie, Pfizer, Eli Lilly, Novartis, Sandoz, Fresenius Kabi. Grants/research support; Amgen, Janssen, UCB, AbbVie, Pfizer, Eli Lilly, Novartis, Sandoz, Fresenius Kabi. Y. Song: Shareholder/stock ownership; full-time employees of AbbVie and may own stock or options. S. Meerwein: Shareholder/stock ownership; full-time employees of AbbVie and may own stock or options. R. DeMasi: Shareholder/stock ownership; full-time employees of AbbVie and may own stock or options. J. Suboticki: Shareholder/stock ownership; full-time employees of AbbVie and may own stock or options. A. Rubbert-Roth: Consultancies; AbbVie, AbbVie Deutschland, Amgen, Bristol-Myers Squibb, Chugai Pharmaceuticals, Eli Lilly, F. Hoffman-La Roche, Gilead Sciences, Janssen Global Services, Novartis, and Sanofi Pasteur.

Budget impact of introducing once-every-6-months paliperidone palmitate in US health care plans.

BACKGROUND: In the United States, most patients with schizophrenia have Medicaid coverage. Antipsychotic treatments are the cornerstone of schizophrenia management; most patients are treated with daily oral antipsychotics but struggle with medication adherence. Evidence suggests that medication adherence is inversely correlated with dosing frequency. Once-monthly paliperidone palmitate (PP) has been demonstrated to improve adherence compared with oral antipsychotics; transitioning to once-every-3-months PP (PP3M) further improved adherence. In 2021, once-every-6-months PP (PP6M) was approved by the US Food and Drug Administration to provide even longer between-dose intervals. Public health stakeholders who aim to improve medication adherence are interested in understanding how introducing PP6M to the formulary will impact the budget. OBJECTIVE: To evaluate the budget impact of introducing PP6M to the formulary from the perspectives of a hypothetical US multistate health care payer and state Medicaid programs using California, Georgia, and Ohio as examples. METHODS: The budget impact model was developed from a payer perspective, comparing the reference scenario (without PP6M in the market) with a new scenario (with PP6M). The study population included patients with schizophrenia who were eligible to receive PP6M. Market shares were assigned to the reference and new market scenarios. Efficacy was measured by the relative risk of relapse while receiving treatment. Adherence effects were included in the model and affected costs of treatment and relapse rates. A deterministic 1-way sensitivity analysis was performed. RESULTS: Base-case results for a multistate payer with 1 million members demonstrate that adding PP6M to the market results in total incremental plan-level costs ranging from $7,747 in year 1 to $11,501 in year 5. Increased drug costs were offset by administration and relapse cost savings ($105 and $881 in year 5, respectively). The average incremental cost per treated patient per year was stable at $180.06 for each year, and the incremental cost per member per month stayed below $0.01 for each year. The results of the model from the state-level Medicaid scenarios are broadly similar to those of the multistate base-case perspective. The 1-way sensitivity analysis demonstrated the model is most sensitive to the per-package costs of PP6M and PP3M, along with the proportion of patients fully adherent with PP3M. CONCLUSIONS: The budget impact of introducing PP6M as a treatment option is minimal. With the expected cost offsets from reduced administration and relapse costs due to adherence benefits, these results suggest that PP6M can be a viable treatment option from a clinical and a budgetary perspective. DISCLOSURES: This study was funded by Janssen Scientific Affairs, LLC. The study sponsor provided funds to Xcenda and ApotheCom for medical writing, editorial support, and submission of the manuscript. Hilary Phelps was an employee of Janssen Global Services, LLC, at the time of the development and finalization of the manuscript. Alex Keenan is an employee of Janssen Global Services, LLC, and holds stock in Johnson & Johnson, Inc. Dee Lin and Carmela Benson are employees of Janssen Scientific Affairs, LLC, and hold stock in Johnson & Johnson, Inc. Aditya Raju was an employee of Xcenda at the time of the development and finalization of the manuscript, and Danmeng Huang is an employee of Xcenda, a health care consulting firm that was contracted by Janssen Scientific Affairs, LLC. Chih-Yuan Cheng is an employee of Janssen NV.

1061. Evaluation of Measures for the Assessment of Covid-19 Signs and Symptoms in Children and Adolescents

Abstract Background The Symptoms of Infection with Coronavirus-19 (SIC) is a 30-item patient-reported outcome (PRO) measure developed to assess the presence and severity of COVID-19 signs and symptoms in adults. To further facilitate the evaluation of new vaccines and treatments in development, similar tools are needed for use within pediatric populations. The objectives of this study were to support adolescent self-completion and create an adaptation of the measure for caregiver assessment of signs and symptoms in children aged < 12 years (henceforth, the Pediatric SIC [PedSIC]). Methods After developing draft versions of the PedSIC and reference materials with definitions to facilitate accurate completion of both measures, iterative rounds of cognitive debriefing interviews were conducted from November 2020 through January 2021 to evaluate understanding of the SIC (in adolescents aged 12-17), and inform refinement of the PedSIC for caregivers of children aged < 12. Recruitment quotas were employed to support sample diversity. Results Nine adolescents (mean [SD, range] age, 14 [1.76, 12-17] years, 56% female, 78% white; round 1, n=6; round 2, n=3) and 17 caregivers (mean [SD, range] age, 34 [6.28, 26-41] years, 59% female, 65% white; round 1, n=9; round 2, n=8) completed interviews. All adolescents understood and completed the adult version of the SIC without instrument modification. Ease and accuracy of self-completion was improved through the use of reference materials. Caregiver feedback resulted in modification of the PedSIC to include two sections: observable signs (ages < 12), and symptoms assessed with input from children (ages ≥ 5-< 12). Reference materials provided standardization of item intent. Conclusion Results support using the SIC, PedSIC, and their associated reference materials to assess the presence and severity of COVID-19 signs/symptoms in adolescents and children aged < 12 years, respectively, who participate in vaccine and treatment clinical trials. Supported by Janssen Vaccines & Prevention B.V. Disclosures Carla Romano, MS, Janssen Pharmaceuticals: Grant/Research Support Margaret Mayorga, MS , MPH, Janssen Pharmaceuticals: Grant/Research Support Javier Ruiz-Guiñazu, MD, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds Géralyn C. Trudel, PhD, Janssen Pharmaceuticals: Stocks/Bonds Sheri Fehnel, PhD, Janssen Pharmaceuticals: Grant/Research Support Kelly McQuarrie, BSN, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds Eric K. H. Chan, PhD, Janssen Global Services, LLC: Employee|Janssen Pharmaceuticals: Stocks/Bonds Eva G. Katz, PhD, MPH, RD, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds.

1820. Clinical Characteristics of Invasive Extraintestinal Pathogenic Escherichia coli Disease Among Older Adult Patients Treated in Hospitals in the United States

Abstract Background The risk of invasive extraintestinal pathogenic Escherichia coli disease (IED) increases with age and can lead to severe outcomes, including sepsis and death. Aim To describe the clinical outcomes of IED in older adults in the United States (US). Methods The Premier Healthcare Database (10/01/2015-03/31/2020) was used to identify IED encounters among patients ≥ 60 years old. The index encounter was defined as the first encounter with a positive E. coli culture in a normally sterile body site (Group 1) or a positive E. coli culture in urine with signs of sepsis (Group 2), in the absence of other pathogens. Outcomes included medical resource utilization, antibiotic use, IED recurrence, and in-hospital death, and were descriptively reported during the index encounter and over the subsequent year. Results Overall, 19,773 patients with IED were included (mean age: 76.8 years; 67.4% female; 82.1% white). Approximately half of index encounters were from Group 1 (51.8%), and the vast majority of patients had community-onset IED (94.3%). Most index encounters led to inpatient hospitalization (96.5%; mean duration: 6.9 days) and 32.4% required transfer to an intensive care unit (mean duration: 3.7 days). During the index encounter, patients received a mean [SD] of 2.9 [1.4] antibiotic agents, and 30.1% received ≥ 4 agents. The 3 most prevalent antibiotics received were ceftriaxone (66.2%), vancomycin (36.3%), and piperacillin (35.0%; Fig 1). The majority of E. coli isolates showed resistance to ≥ 1 antibiotic category (61.7%), and 34.4% were classified as multi-drug resistant (i.e., ≥ 3 categories). Following discharge, 34.8% of patients were transferred to a skilled nursing/intermediate care facility. In-hospital death reached 6.8% during the index encounter and increased to 10.9% 1-year post-index (Fig 2). One-year post-index, 2.4% of patients had an IED recurrence and 36.8% were readmitted to the hospital for any reason (Fig 3). Conclusion Our findings suggest that IED is a severe disease that is associated with substantial burden and far-reaching consequences beyond the initial encounter. These findings emphasize the need for increased awareness and surveillance of IED and its consequences and the potential benefit of preventative measures. Disclosures Elie Saade, MD, Janssen: Grant/Research Support|Pfizer: Board Member|Pfizer: Grant/Research Support|Sanofi Pasteur: Grant/Research Support|Sanofi Pasteur: Speaking/lecture fees, travel reimbursement|Seqirus: Grant/Research Support Jeroen Geurtsen, PhD, Janssen: Employee of Janssen Vaccines & Prevention BV Bryan Baugh, MD, Janssen Research & Development LLC: Employee|Janssen Research & Development LLC: Stocks/Bonds Antoine El Khoury, PhD, Janssen: Employee of Janssen Global Services, LLC. Nnanya Kalu, PhD, Janssen: Employee of Janssen Scientific Affairs, LLC. Marjolaine Gauthier-Loiselle, PhD, Janssen: Advisor/Consultant|Janssen: Advisor/Consultant Rebecca Bungay, MScPH, Janssen: Employees of Analysis Group, Inc. which has received consultancy fees from Janssen Scientific Affairs, LLC for the conduct of this studies. Martin Cloutier, MSc, Janssen: Employees of Analysis Group, Inc. which has received consultancy fees from Janssen Scientific Affairs, LLC for the conduct of this studies. Luis Hernandez Pastor, PharmD, PhD, Janssen: Employee of Janssen Pharmaceutica NV.

EFFICACY AND SAFETY OF NIPOCALIMAB, AN FCRN BLOCKER, IN WARM AUTOIMMUNE HEMOLYTIC ANEMIA (WAIHA): ENERGY PHASE 2/3 STUDY DESIGN

Warm autoimmune hemolytic anemia (wAIHA) is characterized by the destruction of red blood cells (RBCs) by pathogenic autoantibodies which bind to RBCs and lead to their clearance in the spleen and liver. Patients with wAIHA can experience acute worsening of anemia, which can be a medical emergency, and have an increased risk of thromboembolic events and premature death. Nipocalimab is a fully human, aglycosylated, effectorless IgG1 monoclonal antibody that blocks the IgG binding site on the neonatal Fc receptor (FcRn) with high affinity. FcRn, which is expressed in endothelial cells, is responsible for recycling IgG into the circulation and for the relatively long half-life of IgG antibodies compared to other Igs. It is expected that nipocalimab, by blocking IgG binding to FcRn, will prevent IgG recycling and lower pathogenic IgG autoantibodies that cause many autoantibody diseases, including wAIHA. Nipocalimab has been studied in multiple phase 1 studies in healthy subjects and in a completed phase 2 study in subjects with Generalized Myasthenia Gravis (gMG). Treatment with nipocalimab was associated with rapid and durable total serum IgG and pathogenic IgG autoantibody reduction and meaningful clinical response. Here we share the rationale and study design for an adaptive, phase 2/3 multicenter, randomized, double-blind, placebo-controlled study in patients with wAIHA whose aim is to evaluate the efficacy, safety, tolerability, PK, and PD of nipocalimab compared with placebo (NCT04119050). Male or female subjects ≥18 years of age who have been diagnosed with primary or secondary wAIHA and have not experienced a sufficient response or have not tolerated currently available treatments will be included in the study. Subjects with cold antibody AIHA, cold agglutinin syndrome, mixed type (i.e., warm and cold) AIHA, or paroxysmal cold hemoglobinuria will be excluded. Participants will be randomized 1:1:1 to receive nipocalimab at two different dose schedules or placebo. Following completion of 24 weeks of double-blind treatment, participants may enter an open-label extension period to receive nipocalimab. The primary endpoint is percentage of participants achieving durable response of improvement in hemoglobin (Hgb). The main secondary endpoints are change from baseline in the total score from the FACIT-Fatigue Scale, number of participants who attain normal lactate dehydrogenase, normal haptoglobin, and normal indirect bilirubin levels at a minimum of 3 consecutive visits after baseline. ENERGY is a phase 2/3 study that will evaluate the efficacy and safety of nipocalimab in wAIHA. ENERGY is currently enrolling globally. IM received research support from Alexion, Annexon, Incyte, Kezar, Momenta, Rigel, and Sanofi; and served as a consultant for Apellis, Janssen, Momenta, Novartis, Rigel, and Sanofi. BF is a consultant of Alexion, Amgen, Janssen, Momenta, and Novartis. DC is an employee of Janssen Global Services, LLC, which is a wholly owned subsidiary of Johnson & Johnson, and may own stock or stock options in Johnson & Johnson; was an employee of Momenta. AMBP is an employee of Janssen Latin America, which is a wholly owned subsidiary of Johnson & Johnson, and may own stock or stock options in Johnson & Johnson. MHJ was an employee of Momenta.

856-P: Cardiovascular (CV) and Kidney Outcomes with Canagliflozin (CANA) According to Type 2 Diabetes (T2D) Treatment Targets at Baseline (BL) : Data from the CANVAS Program and CREDENCE

In T2D, treatment targets include maintaining HbA1c ≤7.0%, LDL-C <2 mmol/L (<77 mg/dL) , and BP <130/80 mmHg. It is also recommended to improve urinary albumin:creatinine ratio (UACR) , a marker of renal damage and CV risk. We examined effects of CANA vs. placebo on CV and kidney outcomes in patients with T2D and high CV risk and/or chronic kidney disease according to BL treatment targets and risk factors. Pooled data from the CANVAS Program (N=10,142) and the CREDENCE trial (N=4401) were analyzed according to treatment target achievement and by number of targets achieved at BL. Hazard ratios and 95% CIs were estimated using Cox regression models. Of 14,432 participants at BL, 3683 (26%) had achieved 0, 5851 (41%) had achieved 1, 3680 (25%) had achieved 2, and 1218 (8%) had achieved either 3 or 4 targets. At BL, 8415 (58%) participants had UACR >2 mg/mmol. CANA consistently reduced risk of MACE, HHF/CV death, and ESKD or doubling of serum creatinine vs. placebo, regardless of whether BL targets were met or if UACR was elevated (Figure) . The number of uncontrolled targets at BL did not impact the beneficial effect of CANA on CV and kidney outcomes (all P interaction >0.17) . In conclusion, CANA demonstrated consistent CV and renal benefits in patients with T2D, regardless of risk factor control. Disclosure V.C.Woo: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly, Novo Nordisk, Speaker's Bureau; Janssen Pharmaceuticals, Inc. M.Tsoukas: Speaker's Bureau; AstraZeneca, Bausch Health, Canada, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Johnson & Johnson, Novo Nordisk Canada Inc. S.Tobe: Other Relationship; Bayer AG, Speaker's Bureau; AstraZeneca, Otsuka Pharmaceutical Co., Ltd. A.Slee: Consultant; Alydia Health, Elixir Medical , IHP Therapeutics , iLumen Scientific, Intuitive Surgical, Janssen Global Services, LLC, Laborie, Providence Medical, Pulse Biosciences, SonoMotion. W.Rapattoni: Employee; Janssen Pharmaceuticals, Inc. F.Ang: Employee; Bristol-Myers Squibb Company, Janssen Pharmaceuticals, Inc. J.Seufert: Advisory Panel; Abbott, Sanofi-Aventis Deutschland GmbH, Research Support; Boehringer Ingelheim International GmbH, Speaker's Bureau; Abbott Diabetes, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Lilly, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. D.C.Wheeler: Advisory Panel; Bayer AG, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., GlaxoSmithKline plc., Janssen Global Services, LLC, Merck Sharp & Dohme Corp., Mundipharma, Tricida, Inc., Vifor Pharma Management Ltd., Consultant; AstraZeneca, Speaker's Bureau; Amgen Inc., Astellas Pharma Inc. Funding Janssen Inc., Toronto, ON, Canada

808-P: Association between Analogue Compared with Human Insulin and the Outcomes of Mortality, Hospitalization, MACE, and Hypoglycemia in Hemodialysis Patients with Type 2 Diabetes: The ARO Research Initiative

Aims: Poor glycemic control may contribute to the very high mortality rate in patients with type 2 diabetes (T2D) receiving hemodialysis (HD) . Whether analogue compared to human insulin therapy associates with different outcomes is unknown. Methods: Incident HD patients with T2D on insulin treatment enrolled at one of the 288 Fresenius Medical Care facilities across 7 European countries between 2007-20were identified using an established administrative data algorithm. All patients were censored after 3 years of observation. Following multiple imputation, inverse probably weighting (IPW) and instrumental variable (IV; using country) analyses were used to generate Cox-proportional hazards to estimate analogue compared to human insulin hazard ratios for all-cause mortality (ACM) , MACE, hospitalization, and confirmed hypoglycemia (<3.0 mmol/L during a dialysis session) . Results: About 713 analogue users were compared to 733 subjects treated with human insulin. Significant variation in prescription by country was observed. IPW hazard ratios [95% confidence intervals] for patients on analogue compared to human insulin were 0.8[0.659-0.991] for ACM (p=0.042) , 0.817 [0.679-0.983] for MACE (p=0.033) , 0.757 [0.665-0.861] for hospitalization (p<0.001) , and 1.6[1.1419-2.268] for hypoglycemia (p=0.008) . Consistent strength and direction of the associations were observed in the IV analysis and across sensitivity analyses. Conclusions: In this large, multinational cohort of patients with T2D on HD, compared to human insulins, analogue insulins were associated with better clinical outcomes, although hypoglycemia rates were increased. Whether analogue insulins represent the preferred therapy in this group requires confirmatory evidence from a clinical trial. Disclosure T. Ebert: Consultant; Sanofi, Santis. Research Support; AstraZeneca, Novo Nordisk. N. Sattar: None. M. Greig: None. C. Lamina: None. K. Eckardt: Consultant; Akebia Therapeutics, Inc. Research Support; Bayer AG, Evotec International GmbH, Fresenius Medical Care. Speaker's Bureau; AstraZeneca, Bayer AG, Otsuka Pharmaceutical Co., Ltd. J. Floege: Other Relationship; Novo Nordisk A/S. F. Kronenberg: Advisory Panel; Amgen Inc., Novartis AG. P. Stenvinkel: Advisory Panel; AstraZeneca, Baxter, Fresenius Medical Care, Reata Pharmaceuticals, Inc., Vifor Pharma Management Ltd. Speaker's Bureau; Astellas Pharma Inc., Bayer AG, Novo Nordisk. D.C. Wheeler: Advisory Panel; Bayer AG, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., GlaxoSmithKline plc., Janssen Global Services, LLC, Merck Sharp & Dohme Corp., Mundipharma, Tricida, Inc., Vifor Pharma Management Ltd. Consultant; AstraZeneca. Speaker's Bureau; Amgen Inc., Astellas Pharma Inc. J. Fotheringham: Advisory Panel; Novartis Pharmaceuticals Corporation. Speaker's Bureau; Fresenius Medical Care, Novartis Pharmaceuticals Corporation, Vifor Pharma Management Ltd. Funding Amgen (Europe) GmbH- Rotkreuz, Switzerland- Swedish Research Council (grant 2009-1068) - Swedish Heart and Lung Foundation (20160384) - Njurfonden- Westmans Foundation- Novo Nordisk (Postdoctoral fellowship program run inpartnership with Karolinska Institutet, Stockholm,Sweden) - Karolinska Institutet Research Foundation - EFSD (EFSD Mentorship Programme supported by AstraZeneca) - German Research Foundation (SFB TRR 219, projects C1 and M1) - National Institute for Health Research (UK) (Clinician Scientist Award)

866-P: Efficacy of Dapagliflozin by Baseline Diabetes Medications: A Prespecified Analysis from the DAPA-CKD Study

Background: The sodium-glucose cotransporter 2 inhibitor dapagliflozin improved kidney and cardiovascular (CV) outcomes in persons with chronic kidney disease (CKD) with and without type 2 diabetes (T2D) in the DAPA-CKD study. In this prespecified analysis we investigate the effects of dapagliflozin on kidney, CV, and mortality outcomes according to baseline diabetes drug class or number of diabetes drugs. Methods: We enrolled participants with CKD with eGFR 25-75 ml/min/1.73m2 and UACR 200-5000 mg/g, and included those with T2D at baseline in this analysis. The primary endpoint was a composite of sustained decline in eGFR of ≥50%, end-stage kidney disease, or death from kidney or CV causes. Secondary outcomes included a kidney-specific composite (the same as the primary without CV death) , composite of hospitalizations for heart failure and CV mortality, and all-cause mortality. We determined the effect of dapagliflozin, compared with placebo, in subgroups by use or not of diabetes drug classes at baseline: metformin, sulfonylureas, DPP4 inhibitors, GLP-1 receptor agonists and insulin, and by the number of diabetes medications at baseline. Results: Of 43participants enrolled 29 (68%) had T2D, of which 1598 (55%) were on insulin, 1244 (43%) on metformin, 774 (27%) on sulfonylureas, 742 (26%) on DPP4 inhibitors, and 122 (4%) on GLP-1 receptor agonists. At baseline 327 (11%) were without diabetes treatment, 1442 (50%) were treated with one diabetes drug, 943 (32%) with two drugs and 194 (7%) with three or more. The effect of dapagliflozin on the primary composite outcome was consistent across comparisons of baseline drug class (all pint>0.19) , and according to number of drugs (pint=0.08) . Similarly, we found consistent benefit of dapagliflozin compared to placebo on the secondary endpoints regardless of background drug class or number of drugs. Conclusion: Dapagliflozin reduced kidney and CV events in T2D with CKD independent of baseline diabetes drug class or number. Disclosure F.Persson: Advisory Panel; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S, Research Support; Boehringer Ingelheim International GmbH, Novo Nordisk A/S, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S, Sanofi. R.D.Toto: Advisory Panel; Bayer AG, Boehringer Ingelheim International GmbH, Chinook Therapeutics Inc., Lilly, Consultant; Amgen Inc., AstraZeneca, Medscape, Vifor Pharma Management Ltd., Other Relationship; Akebia Therapeutics, Inc., Otsuka America Pharmaceutical, Inc., Reata Pharmaceuticals, Inc. A.Langkilde: Employee; AstraZeneca, Stock/Shareholder; AstraZeneca. D.C.Wheeler: Advisory Panel; Bayer AG, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., GlaxoSmithKline plc., Janssen Global Services, LLC, Merck Sharp & Dohme Corp., Mundipharma, Tricida, Inc., Vifor Pharma Management Ltd., Consultant; AstraZeneca, Speaker's Bureau; Amgen Inc., Astellas Pharma Inc. H.L.Heerspink: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Chinook Therapeutics Inc., CSL Behring, Gilead Sciences, Inc., Goldfinch Bio, Inc., Janssen Research & Development, LLC, Mitsubishi Tanabe Pharma Corporation, Mundipharma, Traveere Pharmaceuticals, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Dapa-ckd trial committees and investigators: n/a. P.Rossing: Consultant; Astellas Pharma Inc., AstraZeneca, Bayer AG, Gilead Sciences, Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Speaker's Bureau; Eli Lilly and Company. N.Jongs: None. G.M.Chertow: Other Relationship; AstraZeneca. F.Hou: Other Relationship; AstraZeneca. P.Vart: None. J.J.Mcmurray: Other Relationship; Abbott, Alkem Metabolics, Alnylam Pharmaceuticals, Inc., Amgen Inc., AstraZeneca, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Cardurion, Cytokinetics Inc., DalCor Pharmaceuticals, Eris Lifesciences Ltd., GlaxoSmithKline plc., Ionis Pharmaceuticals, KBP Bioscience, Lupin Pharmaceuticals, Inc., Medscape, Novartis AG, ProAdWise Communications, Radcliffe Group, Servier Laboratories, Sun Pharmaceutical Industries Ltd., The Corpus, Theracos, Inc. R.Correa-rotter: Advisory Panel; Boehringer Ingelheim International GmbH, Consultant; Bayer AG, Other Relationship; AstraZeneca, GlaxoSmithKline plc., Novo Nordisk, Speaker's Bureau; AbbVie Inc., Amgen Inc., Janssen Pharmaceuticals, Inc., Sanofi. B.Stefansson: Employee; AstraZeneca. Funding AstraZeneca

218-LB: Remission of Type 2 Diabetes after Weight Loss in "Normal" Weight People—The ReTUNE Study

Background and aims: Mechanisms underlying weight loss induced remission of type 2 diabetes (T2DM) have been reported only in people with BMI >27kg/m2. The Personal Fat Threshold hypothesis postulated that the same mechanisms in people with BMI <27kg/m2. Pathophysiology during stepwise dietary weight loss was studied in this group. Methods: People with T2DM (13/20 female, mean (±1SD) 59.3±7.1 years, BMI 24.8±1.7kg/m2) were studied before and after up to three 5% weight loss cycles, each comprising a 2-4 week low energy diet (800kcal/day formula meal replacements plus non starchy vegetables) , followed by 4-6 weeks of weight maintenance. All hypoglycemic agents were stopped before weight loss. Studies were repeated at 12 months. Outcomes were compared to normoglycemic matched controls (n=20) . Intrahepatic and intrapancreatic fat was quantified by magnetic resonance, and a standard meal test assessed insulin secretion by Disposition Index (DI) . Results: 70% achieved remission (HbA1c <6.5%; 14/20) , accompanied by decrease in adipose tissue distress (Median (IQR) PAI-1 8.64 (6.97-11.01) to 5.99 (3.94--7.73) p<0.02 [control 4.87 (3.49-7.03] ng/ml; GDF-15 591 (439-872) to 444 (395-554) [446 (383-614] pg/ml p<0.05. Between baseline and 12 months, decrease was (mean±SE; control data in square brackets) : BMI 24.8±0.4 to 22.5±0.4 kg/m2 (p<0.0001) [21.5±0.5]; total body fat 32.1±1.5 to 27.6±1.8% (p<0.0001) [24.6±1.5]; Fasting plasma insulin 47±6 to 24±6pmol/l (p<0.001) [23±2]; liver fat 4.0±0.6 to 1.6±0.2% (p=0.02) [1.9±0.3]; plasma triglycerides 1.4±0.2 to 0.9±0.1mmol/l (p<0.02) [0.9±0.1]; Intrapancreatic fat (6.1±0.5 to 5.0±0.6% (p=0.03) [4.1±0.3]. DI increased from median (IQR) 289 (183-373) to 774 (486-1709) dl/kg/min per pmol/l (p<0.05) but remained subnormal [2751 (1524-3526]. Conclusion: Mechanistic changes underpinning remission after weight loss in non-obese people with T2DM are the same as in obese people. T2DM occurs if a person becomes too heavy for their own constitution, irrespective of BMI. Weight loss of ∼10% can bring about T2DM remission in people classified as having a ‘normal’ BMI. Disclosure R. Taylor: Speaker's Bureau; Janssen Global Services, LLC, Lilly Diabetes, Nestlé Health Science, Novartis AG. C. Cobelli: None. K. M. Irvine: None. A. C. Barnes: None. T. L. Kelly: None. L. G. Clark: None. K. G. Hollingsworth: None. A. Al-mrabeh: None. R. R. Holman: Advisory Panel; Anji Pharmaceuticals, Novartis AG, Novo Nordisk, Consultant; AstraZeneca, Research Support; AstraZeneca, Bayer AG, Merck Sharp & Dohme Corp. D. Romeres: None. Funding Diabetes UK (17/0005645)

Long-term Outcomes With Ibrutinib Treatment for Patients With Relapsed/Refractory Mantle Cell Lymphoma: A Pooled Analysis of 3 Clinical Trials With Nearly 10 Years of Follow-up.

Long-term Outcomes With Ibrutinib Treatment for Patients With Relapsed/Refractory Mantle Cell Lymphoma: A Pooled Analysis of 3 Clinical Trials With Nearly 10 Years of Follow-up.

Definition and Clinical Significance of the MGUS-like Phenotype: A Study in 5,114 Patients (Pts) with Monoclonal Gammopathies

Definition and Clinical Significance of the MGUS-like Phenotype: A Study in 5,114 Patients (Pts) with Monoclonal Gammopathies

LocoMMotion: A Prospective, Non-Interventional, Multinational Study of Real-Life Current Standards of Care in Patients With Relapsed/Refractory Multiple Myeloma Who Received ≥3 Prior Lines of Therapy

LocoMMotion: A Prospective, Non-Interventional, Multinational Study of Real-Life Current Standards of Care in Patients With Relapsed/Refractory Multiple Myeloma Who Received ≥3 Prior Lines of Therapy

Efficacy and Safety of Daratumumab Monotherapy in Newly Diagnosed Patients with Stage 3B Light Chain Amyloidosis: A Phase 2 Study By the European Myeloma Network

Efficacy and Safety of Daratumumab Monotherapy in Newly Diagnosed Patients with Stage 3B Light Chain Amyloidosis: A Phase 2 Study By the European Myeloma Network

Systemic Light Chain Amyloidosis across Europe: Key Outcomes from a Retrospective Study of 4500 Patients

Systemic Light Chain Amyloidosis across Europe: Key Outcomes from a Retrospective Study of 4500 Patients

Graded Renal Response Criteria for Light Chain (AL) Amyloidosis

Graded Renal Response Criteria for Light Chain (AL) Amyloidosis