BACKGROUND:Approximately 17% of patients with non-small cell lung cancer (NSCLC) have epidermal growth factor receptor mutations (EGFRm). Amivantamab received United States Food and Drug Administration approvals in advanced NSCLC for patients with EGFR exon 20 insertions (exon20ins) who progressed after platinum-based chemotherapy (PBC) on 05/21/2021, for first-line (1 L) EGFR exon20ins on 03/01/2024, and for 1 L and second-line or later (2 L+) EGFR exon 19 deletion and L858R on 08/20/2024 and 09/19/2024, respectively. This claims-based study describes real-world treatment patterns and healthcare resource utilization (HRU) among insured patients with advanced NSCLC initiating amivantamab in 2 L or later (2 L+). METHODS:Komodo Research Data closed claims (01/01/2016-10/31/2023) were used to analyze insured adults with a diagnosis of lung cancer who initiated amivantamab on/after 05/21/2021 in 2 L+. Treatment patterns, including prior PBC and immunotherapy (IO) use, were described by line of therapy (LOT). All-cause HRU per-patient-per-month (PPPM) was assessed during the amivantamab LOT and all LOTs preceding amivantamab. Time to next treatment or death (TTNT-D) was reported using Kaplan-Meier analysis for each LOT. RESULTS:Overall, 126 patients initiated amivantamab in 2 L+ (mean age: 60.2 years, 63.5% female). Amivantamab was initiated in 2 L by 51.6% of patients, while 32.5% and 15.9% initiated amivantamab in third-line (3 L) and fourth-line or later (4 L+), respectively. Most patients initiated amivantamab as monotherapy (2 L: 92.3%; 3 L: 73.2%; 4 L+: 80.0%), had prior PBC use (2 L: 83.1%; 3 L: 100.0%; 4 L+: 100.0%), and prior IO use (2 L: 60.0%; 3 L: 63.4%; 4 L+: 85.0%). Mean outpatient service use was 5.87 days PPPM before amivantamab initiation and 6.79 days PPPM during amivantamab treatment. Mean inpatient admissions PPPM were 0.05 before amivantamab and 0.08 during amivantamab treatment. Among patients initiating amivantamab in 2 L, 3 L, or 4 L+, median TTNT-D was 11.0 months, 5.3 months, and 6.1 months, respectively. CONCLUSIONS:Among insured patients with advanced NSCLC receiving amivantamab in 2 L+, TTNT-D aligned with results reported in clinical trials. Before initiating amivantamab, most patients received IO, despite IO use being inconsistent with treatment guidelines and limited demonstrated benefit. HRU was similar before and during amivantamab treatment, suggesting that amivantamab does not contribute to an increase in medical services compared to treatment regimens used in earlier LOTs.

Objective: To describe characteristics, treatment patterns, and outcomes of patients with EGFR exon 20 insertion (exon20ins)-positive advanced or metastatic non–small cell lung cancer (NSCLC) who received amivantamab or mobocertinib monotherapy after platinum-based chemotherapy (PBC). Patients and Methods: This retrospective longitudinal cohort study pooled electronic health records from the Flatiron Health (January 2011-August 2022), Ontada (January 2013-January 2023), and COTA (January 2010-December 2022) databases. Patients (≥20 years) with advanced or metastatic EGFR exon20ins NSCLC who received amivantamab or mobocertinib following PBC were included. Patient characteristics and treatment patterns were analyzed descriptively. Time to next treatment or death (TTNTD) and time to discontinuation (TTD) were assessed using Kaplan-Meier estimates. Results: 44 patients treated with amivantamab and 24 patients with mobocertinib after PBC met the selection criteria. Patient characteristics were consistent with previous studies. Most patients received amivantamab or mobocertinib as second-line (57 % and 50 %) or third-line (32 % and 33 %) therapy. The median TTNTD was 9.2 months for amivantamab and 4.2 months for mobocertinib. Fewer patients in the amivantamab cohort (43 %) experienced a TTNTD event than the mobocertinib cohort (63 %). The median TTD was 8.6 months for amivantamab and 2.3 months for mobocertinib, with a lower discontinuation rate in the amivantamab cohort (46 % vs 67 %). Conclusion: Real-world patients with EGFR exon20ins NSCLC treated with amivantamab after PBC experienced median TTNTD and TTD consistent with the median progression-free survival observed in its registrational trial while patients treated with mobocertinib exhibited faster disease progression and a higher frequency of treatment discontinuation. MicroAbstract: This retrospective study described patient characteristics, treatment patterns, and outcomes in patients with EGFR exon20ins-mutated advanced or metastatic NSCLC who received amivantamab or mobocertinib monotherapy after platinum-based chemotherapy. Real-world patients treated with amivantamab experienced TTNTD and TTD consistent with the median progression-free survival observed in its registrational trial, while patients treated with mobocertinib exhibited faster disease progression and a higher frequency of treatment discontinuation.

Background: The potential association of long-term oral corticosteroid (OCS) use with adverse events (AEs) in patients with bullous pemphigoid (BP) is not well characterized in a real-world setting. Objective: To evaluate the effect of OCS use and treatment duration on the incident AEs in patients with BP. Methods: This retrospective cohort study used medical and pharmacy claims and patient enrollment data from IQVIA PharMetrics (R) Plus from 2006-2021. Eligible patients had a diagnosis of BP between 1 January 2006 and 30 June 2020 (>= 2 claims for BP >= 30 days apart). Patients in the OCS cohort also had a claim for OCS use, >= 7.5 mg daily dose of prednisone or equivalent, and no claims for a nonoral systemic corticosteroid (CS) at any time during the study period. A control cohort of patients with BP not using OCS was also selected. Relative risk ratios were estimated between the incidence of AEs in OCS users with different exposure durations (short-term, <30 days; medium-term, 30-90 days; long-term, >90 days) and nonusers by Poisson regression, after adjusting for age, sex, prior drug use, and baseline Charlson Comorbidity Index score within the follow-up period. Results: At the 1-year follow-up, long-term OCS users had a higher incidence of infections, cataract, osteoporosis, heart failure, depression or anxiety, and diabetes compared with OCS nonusers (p < 0.05). Furthermore, compared with nonusers, long-term users had increased 1-year risks (risk ratio; 95% confidence interval) for heart failure (2.27; 1.50-3.44), diabetes (2.05; 1.30-3.24), osteoporosis (1.72; 1.23-2.41), and infection (1.50; 1.13-1.99). Long-term OCS users also had increased 1-year risks for heart failure (2.00; 1.21-3.28) and osteoporosis (1.70; 1.16-2.50) compared with short-term OCS users. Conclusion: Long-term OCS use (>= 7.5 mg) in patients with BP was associated with an increased risk of AEs. Study findings demonstrate a need for steroid-sparing options with an improved safety profile.

Background: In psoriatic arthritis (PsA), treatment persistence is important for achieving optimal outcomes. The United States Food and Drug Administration (USFDA) approved guselkumab (a fully human interleukin [IL]-23p19-subunit inhibitor) for the treatment of active PsA in July 2020. Objectives: To provide real-world evidence comparing treatment persistence while following USFDA prescribing guidelines (i.e., on-label persistence) for guselkumab (100 mg administered by subcutaneous [SC] injection at Week [W] 0, W4, then Q8W) versus SC tumor necrosis factor inhibitors (TNFi). Methods: Adults with PsA newly initiated on guselkumab or the first observed SC TNFi (i.e., adalimumab, certolizumab pegol, etanercept, or SC golimumab) between 7/14/2020 and 3/31/2022 were selected from the IQVIATM Health Plan Claims Data. The first claim for guselkumab or a SC TNFi was defined as the index date; study cohorts included bio-naïve and bio-experienced patients. Baseline characteristics were assessed during the 12-month pre-index period; the follow-up period spanned from the index date until the earliest date between the end of the continuous insurance eligibility and the end of data availability (09/30/2022; Figure 1). On-label persistence of the index agent was defined as the absence of treatment discontinuation or any dose escalation/reduction relative to the USFDA label dosing instructions for each respective agent. Discontinuation was defined as having a gap in treatment between consecutive days of the index agent supply of twice the duration of days of supply for a claim (i.e., 2 x 56 = 112 days for guselkumab or 2 x 28 = 56 days for SC TNFi) during follow-up. Patients with any dose change were censored on the first observed date of the dose change. Guselkumab and SC TNFi cohorts were balanced for baseline characteristics, using propensity score weighting based on the standardized mortality ratio (SMR) weighting approach. On-label persistence was assessed using weighted Kaplan-Meier (KM) curves. A weighted Cox proportional hazards model, further adjusted for baseline biologic use, was used to compare on-label persistence between cohorts. Results: The guselkumab cohort included 526 patients (mean age: 49.8 years; 61.2% female) and the SC TNFi cohort included 1,953 patients (mean age: 48.5 years; 60.2% female). After IPTW, baseline characteristics were well balanced and the mean follow-up was 12.3 months for the guselkumab cohort and 12.4 months for the SC TNFi cohort. In the guselkumab cohort, 51.5% were bio-experienced versus 16.7% for SC TNFi. Median time to discontinuation was not reached for the guselkumab cohort versus 8.9 months for the SC TNFi cohort. Weighted KM rates of on-label persistence at 3, 6, 9, and 12 months were 91.2%, 84.1%, 75.9%, and 71.5%, for the guselkumab cohort, versus 77.3%, 61.6%, 50.0%, and 43.7%, for the SC TNFi cohort, respectively (all log-rank p<0.001). At 12 months, patients in the guselkumab cohort were approximately three times more likely to remain persistent on treatment than patients in the SC TNFi cohort (hazard ratio: 2.97; 95% confidence interval: 2.36-3.74; p<0.001; Figure 2). Conclusion: This real-world study assessing treatment persistence in PsA using administrative claims data demonstrated that guselkumab was associated with significantly longer on-label persistence through 12 months versus SC TNFi. Acknowledgements: NIL. Disclosure of Interests: Natalie J. Shiff Stockholder of Johnson & Johnson, of which Janssen Scientific Affairs, LLC is a wholly owned subsidiary, Employee of Janssen Scientific Affairs, LLC, Jessica A. Walsh Consultant for AbbVie, Janssen, Eli Lilly, Novartis, and UCB, Research funding from Pfizer, Merck, AbbVie, Iris Lin Stockholder of Johnson & Johnson, of which Janssen Scientific Affairs, LLC is a wholly owned subsidiary, Employee of Janssen Scientific Affairs, LLC, Ruizhi Zhao Stockholder of Johnson & Johnson, of which Janssen Scientific Affairs, LLC is a wholly owned subsidiary, Employee of Janssen Scientific Affairs, LLC, Laura Morrison Employee of Analysis Group, Inc., a consulting company that has received research funding from Janssen Scientific Affairs, LLC, Bruno Emond Employee of Analysis Group, Inc., a consulting company that has received research funding from Janssen Scientific Affairs, LLC, Louise H. Yu Employee of Analysis Group, Inc., a consulting company that has received research funding from Janssen Scientific Affairs, LLC, Samuel Schwartzbein Employee of Analysis Group, Inc., a consulting company that has received research funding from Janssen Scientific Affairs, LLC, Patrick Lefebvre Employee of Analysis Group, Inc., a consulting company that has received research funding from Janssen Scientific Affairs, LLC, Dominic Pilon Employee of Analysis Group, Inc., a consulting company that has received research funding from Janssen Scientific Affairs, LLC, Soumya D. Chakravarty Stockholder of Johnson & Johnson, of which Janssen Scientific Affairs, LLC is a wholly owned subsidiary, Employee of Janssen Scientific Affairs, LLC, Philip J. Mease Speaker fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant for AbbVie, Acelyrin, Aclaris, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, Sun Pharma, UCB, and Ventyx, Research funding from AbbVie, Acelyrin, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB.

This study aims to identify hemolytic disease of the fetus and newborn (HDFN) pregnancies using electronic health records (EHRs) from a large integrated health care system.A retrospective cohort study was performed among pregnant patients receiving obstetrical care at Kaiser Permanente Southern California health care system between January 1, 2008, and June 30, 2022. Using structured (diagnostic/procedural codes, medication, and laboratory records) and unstructured (clinical notes analyzed via natural language processing) data abstracted from EHRs, we extracted HDFN-specific "indicators" (maternal positive antibody test and abnormal antibody titer, maternal/infant HDFN diagnosis and blood transfusion, hydrops fetalis, infant intravenous immunoglobulin [IVIG] treatment, jaundice/phototherapy, and first administrated Rho[D] Immune Globulin) to identify potential HDFN pregnancies. Chart reviews and adjudication were then performed on select combinations of indicators for case ascertainment. HDFN due to ABO alloimmunization alone was excluded. The HDFN frequency and proportion of each combination were fully analyzed.Among the 464,711 eligible pregnancies, a total of 136 pregnancies were confirmed as HDFN pregnancies. The percentage of the HDFN-specific indicators ranged from 0.02% (infant IVIG treatment) to 34.53% (infant jaundice/phototherapy) among the eligible pregnancies, and 32.35% (infant IVIG treatment) to 100% (maternal positive antibody test) among the 136 confirmed HDFN pregnancies. Four combination groups of four indicators, four combination groups of five indicators, and the unique combination of six indicators showed 100% of HDFN pregnancies, while 80.88% of confirmed HDFN pregnancies had the indicator combination of maternal positive antibody test, maternal/infant HDFN diagnosis, and infant jaundice/phototherapy.We successfully identified HDFN pregnancies by leveraging a combination of medical indicators extracted from structured and unstructured data that may be used in future pharmacoepidemiologic studies. Traditional indicators (positive antibody test results, high titers, and clinical diagnosis codes) alone did not accurately identify HDFN pregnancies, highlighting an unmet need for improved practices in HDFN coding. · A case ascertainment method was developed to identify HDFN from structured and unstructured data.. · The method used in this study may be used in future pharmacoepidemiologic studies.. · The study highlighted an unmet need for improved practices in HDFN coding..

Psoriatic arthritis (PsA) is a chronic, autoimmune form of arthritis that is associated with a substantial humanistic and economic burden. Potential differences in patient-reported outcomes (PROs) and economic outcomes among groups of varying PsA severity and different races/ethnicities have not been well studied. This cross-sectional study assessed sociodemographic data, PROs, and economic outcomes for participants with PsA from the National Health and Wellness Survey (2018–2020). Multivariable analyses were used to assess the association of self-reported PsA severity and race/ethnicity with health-related quality of life (HRQoL), work productivity and activity impairment (WPAI), healthcare resource utilization (HCRU), and medical costs. This study included 1544 participants with PsA (1073 non-Hispanic white, 114 non-Hispanic Black, 223 Hispanic, and 134 Other). Self-reported moderate/severe PsA was associated with significantly worse HRQoL and WPAI, greater HCRU, and higher costs than self-reported mild PsA. Black participants reported more absenteeism (31.11

This retrospective cohort study described real-world treatment patterns and healthcare resource utilization (HCRU) of patients with warm autoimmune hemolytic anemia (wAIHA) initiating treatment with first-line (1L) oral corticosteroids (OCS) + rituximab (R) compared to 1L OCS. Patients with a wAIHA diagnosis code (D59.11) between 8/2020–3/2022 were identified using US pharmacy and medical claims databases. Patients initiating 1L OCS ± R were identified (date of initiation = ‘index date’) with a 1-year pre-index period and a variable (minimum 1-year) follow-up period. The final sample comprised 77 1L OCS + R patients and 400 1L OCS patients ( 60

In patients with psoriatic arthritis (PsA), potential differences in care by race/ethnicity have not been well studied. This retrospective, observational cohort analysis utilized the IBM MarketScan® Multi-State Medicaid database. Patients aged ≥ 18 years with two or more PsA-related claims between January 1, 2010 and December 31, 2019, and ≥ 12 months of continuous enrollment before the first diagnosis of PsA (index date) were included. Outcomes evaluated were the use of disease-modifying antirheumatic drugs (DMARDs) overall and by type (conventional synthetic, biologic, targeted synthetic) within 12 months following initial PsA diagnosis, as well as the time to DMARD initiation after initial PsA diagnosis, stratified by race/ethnicity. Multivariate Cox proportional hazards models were used to assess potential associations between patient baseline characteristics and time to DMARD initiation. Among patients with newly diagnosed PsA (N = 3432), the mean age was 44.4 years, 69.9

Topic: 36. Ethics and health economics Background: Warm autoimmune hemolytic anemia (wAIHA) is a rare life-threatening disorder caused by autoantibodies that lead to the premature destruction of healthy red blood cells. Due to a paucity of clinical trials and no approved treatment, the First International Consensus meeting published recommendations in 2020 with goals to provide international guidelines for diagnosis and to create a framework for current treatment of autoimmune hemolytic anemia (AIHA). Oral corticosteroids (OCS) remain as first-line (1L) therapy for wAIHA, while the addition of rituximab (R) in 1L was recommended only in select patients due to limited duration of follow up and power in prospective studies evaluating the effect of 1L OCS plus rituximab (OCS+R) on the need for other treatments or inducing long-term remission. Experts highlighted the limited evidence base and recommended that clinicians should consider discussion of available clinical trials at all stages of treatment. Aims: This study described real-world treatment patterns and healthcare resource utilization (HCRU) of patients with wAIHA initiating 1L OCS+R compared to 1L OCS. Methods: A retrospective cohort study was conducted using IQVIA pharmacy and medical claims databases in the US to identify patients with a diagnosis code for wAIHA (D59.11) from 8/2020-3/2022. Patients initiating 1L OCS +/- R were identified (date of initiation = the ‘index date’) and required to have a 1-year pre-index (baseline) period and a minimum 1-year post-index (follow-up) period. Baseline clinical and demographic characteristics were collected. Treatment and utilization patterns were reported over the follow-up. Data were analysed using descriptive statistics. Study outcomes for the 1L OCS+R and 1L OCS cohorts were reported as a composite for primary and secondary wAIHA. Results: The final sample comprised 77 1L OCS+R patients and 400 1L OCS patients (~60% female and mean age >64 years). The OCS+R cohort had more patients with a hematology/oncology visit associated with the index date compared to the OCS cohort (71.4% and 55.3%, respectively). For both cohorts, hematologic malignancy was the most common associated condition (23.4% OCS+R and 19.0% OCS) followed by solid tumors (18.2% and 14.8%, respectively), and autoimmune disease (7.8% and 11.8%, respectively) (not mutually exclusive). Over the 1-year follow-up, HCRU was higher in the OCS+R cohort with higher mean number of physician office visits (22.9 and 14.4), including hematology/oncology office visits (10.7 and 5.6), and higher utilization of rescue therapy (59.7% and 33.3%), driven by higher use of injectable corticosteroids (50.6% and 24.8%). Use of outpatient red blood cell transfusion and inpatient hospitalization was comparable between groups. Patients in OCS+R and OCS groups completed 1L therapy after a similar mean duration of 103.5 and 134.6 days, respectively. In the majority of patients, treatment with OCS + R did not extend the remission period because second-line (2L) therapy was initiated at a similar timepoint: 66.2% OCS+R and 72.0% OCS cohorts initiated 2L in a mean of 218.3 and 203.2 days after the end of 1L treatment, respectively. Summary/Conclusion: Despite the addition of rituximab in 1L, duration of remission was brief in both cohorts with most patients initiating 2L therapy within less than 1 year of completing 1L treatment. In addition, substantial HCRU burden was observed among patients initiating 1L OCS+R. More effective novel therapies targeted to the underlying pathophysiology are needed to address the high unmet need to maintain long-term remission in patients with wAIHA.Keywords: Autoimmune hemolytic anemia (AIHA), Treatment, Health care

The aim of this work is to evaluate treatment persistence and clinical outcomes after 6 months of on-label guselkumab use in patients with rheumatologist-diagnosed active psoriatic arthritis (PsA) enrolled in the CorEvitas PsA/Spondyloarthritis Registry. Participants with PsA who initiated and persisted with on-label guselkumab use post-Food and Drug Administration (FDA) approval for active PsA (7/13/2020; subcutaneous 100 mg at weeks 0, 4, and every 8 weeks) at their 6-month follow-up visit (occurring through 3/31/2023) comprised the primary analysis population (On-Label Persisters). Hierarchical, multiplicity-controlled primary and secondary outcomes were mean (95

Background Idiopathic inflammatory myopathies (IIM) are a group of rare, heterogeneous diseases in which the hallmark feature is chronic inflammation of skeletal muscle leading to muscle weakness. Initial conventional therapy is based on expert opinion and includes glucocorticoids in combination with methotrexate, azathioprine, or mycophenolate. If this therapy is not sufficiently effective, second line therapy (calcineurin inhibitors or IVIG) may be considered. If still insufficient, escalation to rituximab or cyclophosphamide is considered. Agents not included in conventional recommended therapies have also been used and are being studied in the management of IIM. Objectives To characterize real-world treatment trajectories among individuals with IIM. Methods Data were provided by adults with IIM enrolled in FORWARD, The National Databank for Rheumatic Diseases. Participants with a co-occurring RA, SLE, or SSc diagnosis were excluded. Participant characteristics were assessed at baseline (study entry) by treatment category and significance was assessed by one way ANOVA and Fisher's exact tests, as appropriate (p<0.05). Treatment category (none, steroid alone, first line without steroid, first line, second line, third line, and other DMARD) was assessed at baseline and for ultimate line of treatment reported during observation. First, second, and third line treatments were considered “conventional” and others were considered “nonconventional.” Results A total of 126 participants met inclusion criteria. At baseline, 43% of participants were on first line therapy. Most of the remaining participants were either on a corticosteroid alone (23%) or were on first line therapy but without a corticosteroid (17%). A relatively small number of participants (2%) were on second line therapy, and none were on third line therapy at baseline. About 9% reported use of a nonconventional DMARD, and the remaining 6% reported no treatment. Those who reported no therapy were more likely to be male and had higher global severity scores. Across 504 person-years of observation, 47% reported first line treatment, 10% reported second line, and 3% reported third line as the most advanced conventional therapy received. The remaining 40% reported either nonconventional or no treatment. Conclusion Despite published recommendations to combine glucocorticoids with another immunosuppressive drug as part of first line therapy for IIM, many individuals with IIM are not prescribed concomitant DMARDs. In this cohort, there were no significant differences in IIM subtype, disease duration, or calendar year by conventional vs nonconventional therapy at study entry. A relatively small number of individuals with IIM reported receiving no treatment during observation, which may be due to significantly shorter follow up time in that subgroup. Future work should examine treatment response and changes in disease activity with changing lines of treatment. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests Kristin Wipfler: None declared, Urbano Sbarigia Shareholder of: Johnson & Johnson, Employee of: Janssen, Federico Zazzetti Shareholder of: Johnson & Johnson, Employee of: Janssen, Anna Sheahan Employee of: Janssen, Iris Lin Shareholder of: Johnson & Johnson, Employee of: Janssen, Evo Alemao Shareholder of: Johnson & Johnson, Employee of: Janssen, Kaleb Michaud: None declared.Figure 1Treatment progression among individuals in FORWARD with IIM. Baseline (at study entry) treatment category is shown on the left, and ultimate treatment category (during observation) is shown on the right. First line = glucocorticoid + methotrexate, azathioprine, or mycophenolate. Second line = calcineurin inhibitors or IVIG. Third line = rituximab or cyclophosphamide.Table 1Characteristics of included participants at study entry by baseline treatment category.Conventional TherapyNonconventional TherapyNo Therapyn=57n=61n=8pAge, years54.6 (14.3)57.2 (14.2)57.0 (8.3)0.61Female sex, %77.882.837.50.02White race, %90.688.575.00.62IIM subtypeDM41.144.137.5PM42.932.212.50.19Unspecified16.123.750.0Time since symptom onset, years6.5 (6.0)8.3 (6.3)4.1 (5.2)0.20Study entry prior to 2010, %55.466.137.50.50Observation time, years3.6 (3.4)4.4 (4.8)2.0 (2.4)0.01Rural residence, %30.421.137.50.41Hx smoking, %42.940.775.00.18Pain VAS, 0-103.1 (2.8)3.2 (2.9)5.1 (3.5)0.71Global severity, 0-103.6 (2.8)3.4 (2.7)6.3 (2.8)0.03HAQ-II, 0-31.0 (0.7)0.9 (0.6)1.2 (0.7)0.48PAS-II, 0-33.5 (2.3)3.3 (2.3)5.1 (2.6)0.86

Background Despite major advances in rheumatoid arthritis (RA) treatment and the improved outcomes that have been associated with the expanding number of advanced therapies available, a substantial number of patients are refractory to multiple biologics. To understand the mechanisms behind refractory RA (reRA) and ultimately improve therapies tailored to individuals, a better understanding of associated factors is necessary. The shared epitope (SE) is an amino acid sequence motif coded by several HLA-DRB1 alleles that are overrepresented among people with RA and is associated with the production of anti-citrullinated protein antibodies. Objectives To characterize the relationship between SE status and risk of developing refractory RA. Methods Participants in FORWARD, The National Databank for Rheumatic Diseases, with RA, high-resolution HLA-DRB1 typing, no history of biologic use at study entry, and subsequent exposure to one or more biologics were included. The reRA group included participants with exposure to at least three biologics while under observation. Those who used a single biologic with continued use for at least two years during observation comprised the comparison non-refractory group. Descriptive statistics for each group were calculated at initiation of first biologic. Significance was assessed with Fisher's exact tests and Mann-Whitney U tests (p<0.05), as appropriate. Logistic regression was used to determine the relationship between shared epitope status and baseline odds of becoming refractory. Results Characteristics of the 70 participants that met inclusion criteria are presented in Table 1. Several covariates varied significantly by refractory group, but these differences were attenuated in adjusted models. SE positive individuals had significantly lower odds of becoming refractory, a relationship that remained consistent with varying model complexity (Figure 1; OR [95% CI] 0.16 [0.05, 0.49] in univariate model; p=0.001). HLA-DRB1*04:01 was the only SE positive allele independently associated with nonrefractory status (p=0.036; data for other alleles not shown). Conclusion In this cohort, individuals with RA who are SE positive were less likely to be refractory to multiple biologics. This relationship appears to be primarily the result of the HLA-DRB1*04:01 allele rather than any other alleles associated with SE positivity. These findings suggest that SE positive individuals with RA are more likely to find success with their first biologic, while SE negative individuals may be more likely to cycle through multiple biologics. Ongoing and future work will investigate this relationship further and assess whether these results remain consistent when using varying definitions of reRA. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests Kristin Wipfler: None declared, Sofia Pedro: None declared, Urbano Sbarigia Shareholder of: Johnson & Johnson, Employee of: Janssen, Federico Zazzetti Shareholder of: Johnson & Johnson, Employee of: Janssen, Anna Sheahan Employee of: Janssen, Iris Lin Shareholder of: Johnson & Johnson, Employee of: Janssen, Evo Alemao Shareholder of: Johnson & Johnson, Employee of: Janssen, Kaleb Michaud: None declared.Figure 1Odds of becoming refractory by SE status. Odds ratios for becoming refractory when SE positive are shown for 9 unique models of increasing complexity. Each model includes a new covariate and all previously listed covariates. P-values for the SE positive covariate are displayed to the right of each associated OR and 95% CI.Table 1Baseline (initiation of first biologic) characteristics of study participants. Values are mean (SD) unless otherwise noted.Non-RefractoryRefractoryn=48n=22pSE positive, %81.340.90.002≥1 copy of HLA-DRB1*04:01, %52.122.70.036Age, years57.2 (12.6)55.0 (9.7)0.266Female sex, %93.886.40.370White race, %95.785.70.167Time since symptom onset, years11.3 (11.3)7.3 (7.1)0.132Observation time, years6.9 (4.4)11.6 (5.5)<0.001Hx smoking, %27.136.40.575BMI, kg/m227.0 (5.5)32.4 (7.8)0.011Hx cancer, %14.69.10.709Hx pulmonary disorder, %18.827.30.532Hx GI disorder, %35.459.10.074Concomitant steroid use, %25.050.00.055Concomitant csDMARD use, %89.681.80.448Pain VAS, 0-102.5 (2.3)4.1 (2.8)0.011Global severity VAS, 0-102.7 (2.4)4.4 (2.5)0.013HAQ-II, 0-30.69 (0.56)1.01 (0.52)0.023