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Objective To comprehensively assess multimorbidity burden in patients with rheumatoid arthritis (RA) in order to unify the multimorbidity definition for RA research and clinical practice. Methods In this population-based study, residents of eight Minnesota counties with prevalent RA on 1 January 2015 were identified. Age, sex and county-matched non-RA comparators were selected from the same population. Diagnostic codes were retrieved for 5 years before 1 January 2015. Using two codes ≥30 days apart, 44 previously defined morbidities and 78 non-overlapping chronic disease categories based on Clinical Classification Software were defined. Prevalence of each morbidity in the RA versus non-RA cohorts was compared using false discovery rate to adjust for multiple comparisons. Morbidities more common in RA than non-RA and those with prevalence ≥5% were retained. Results 1643 patients with RA and 1643 non-RA subjects (72% women; mean age 63.1 years) were studied. Using the 44 morbidities, multimorbidity (defined as 2+ morbidities) was present in 1411 (86%) of RA and 1164 (71%) of non-RA subjects (p<0.001) with 5+ morbidities present in 907 (55%) of RA and 619 (38%) of non-RA (p<0.001). Patients with RA had significantly higher prevalence of 24 of the 44 morbidities compared with non-RA, especially interstitial lung disease, fibromyalgia, osteoarthritis and osteoporosis. Among the additional 78 categories, 7 were significantly higher in RA than non-RA, including organic sleep disorders, vitamin D deficiency and foot ulcers. Conclusion Patients with RA have a higher prevalence of multimorbidity compared with non-RA subjects. These results confirm the list of 44 morbidities and add several other morbidities of interest in RA.

ObjectiveTo identify the incidence, risk factors, and outcomes of rheumatoid arthritis–associated interstitial lung disease (RA‐ILD) and to assess time trends in the incidence and mortality in RA‐ILD.MethodsWe included adult residents of Olmsted County, Minnesota with incident RA between 1999 and 2014. Subjects were followed until death, emigration, or April 30, 2019. ILD was defined as the presence of a radiologist‐defined pattern consistent with ILD on chest computed tomography (CT). When chest CT was absent, the combination of chest radiograph abnormalities compatible with ILD and restrictive pattern on pulmonary function testing was considered consistent with ILD. Potential risk factors included age, sex, smoking, obesity, seropositivity, extraarticular manifestations (EAMs), and medications. For survival analysis, we matched RA‐ILD patients to RA–non‐ILD comparators. The frequency and mortality from clinician‐diagnosed RA‐ILD from 1999 to 2014 was compared against a cohort from 1955 to 1994.ResultsDuring the 1999–2014 time period, 645 individuals (70% women) had incident RA, were a median age of 55.3 years, and 53% never smoked. Twenty‐two patients had ILD before RA, and 51 (67% women) developed ILD during follow‐up. The 20‐year cumulative incidence of RA‐ILD was 15.3%. Ever‐smoking (hazard ratio [HR] 1.92), age at RA onset (HR 1.89 per 10‐year increase), and severe EAMs (HR 2.29) were associated with incident RA‐ILD. The RA‐ILD cases had higher mortality than their matched RA comparators (HR 2.42). Incidence of RA‐ILD was non‐significantly lower from 1999 to 2014 than from 1955 to1994, but mortality was improved.ConclusionsRA‐ILD occurs in nearly 1 in 6 patients with RA within 20 years and is associated with shorter survival. Lack of significant change in RA‐ILD incidence over 6 decades deserves further investigation.

Objective To test the ability of machine learning (ML) approaches with clinical and genomic biomarkers to predict methotrexate treatment response in patients with early rheumatoid arthritis (RA). Methods Demographic, clinical, and genomic data from 643 patients of European ancestry with early RA (mean age 54 years; 70% female) subdivided into a training (n = 336) and validation cohort (n = 307) were used. The genomic data comprised 160 single‐nucleotide polymorphisms (SNPs) previously associated with RA or methotrexate metabolism. Response to methotrexate monotherapy was defined as good or moderate by the European Alliance of Associations for Rheumatology (EULAR) response criteria at the 3‐month follow‐up. Supervised ML methods were trained with 5 repeats and 10‐fold cross‐validation using the training cohort. Prediction performance was validated in the independent validation cohort. Results Supervised ML methods combining age, sex, smoking, rheumatoid factor, baseline Disease Activity Score in 28 joints (DAS28) scores and 160 SNPs predicted EULAR response at 3 months with the area under the receiver operating curve of 0.84 ( P = 0.05) in the training cohort and achieved a prediction accuracy of 76% ( P = 0.05) in the validation cohort (sensitivity 72%, specificity 77%). Intergenic SNPs rs12446816, rs13385025, rs113798271, and ATIC (rs2372536) had variable importance above 60.0 and along with baseline DAS28 scores were among the top predictors of methotrexate response. Conclusion Pharmacogenomic biomarkers combined with baseline DAS28 scores can be useful in predicting response to methotrexate in patients with early RA. Applying ML to predict treatment response holds promise for guiding effective RA treatment choices, including timely escalation of RA therapies.

Abstract Background: MGTA-145, a CXCR2 agonist, has shown promising activity for hematopoietic stem cell (HSC) mobilization with plerixafor in pre-clinical models and healthy volunteers. It has the potential to become the first GCSF free regimen for HSC mobilization/apheresis in preparation for transplant, with fewer side effects, better patient experience and optimal resource utilization. Methods: We conducted a single center phase 2 trial of MGTA-145 + plerixafor for HSC mobilization in patients with multiple myeloma (MM), NCT04552743. Primary endpoint was collection of ≥2 x 10 6 CD34+ cells/kg in up to 2 days of mobilization/apheresis. Secondary endpoints were collection of 4 and 6 x 10 6 CD34+ cells/kg, safety and engraftment. Patients with MM, 18-70 years of age, within 1 year of starting treatment & CrCl &gt; 30 ml/min were eligible. Patients received plerixafor 0.24 mg/kg (0.16 mg/kg if renal dysfunction) SQ, followed 2 hours later by MGTA-145 (0.03 mg/kg) IV over 3-10 minutes and apheresis within 30 minutes. Mobilization and collection were repeated for a second consecutive day if day 1 yield was &lt; 6 x 10 6 CD34+ cells/kg. The study was open-label single arm trial of 15 patients. If 13 or more patients met primary endpoint, an expansion cohort of 10 patients was planned. The trial has 85% power at a 5% one-sided type I error rate. Our analysis is based on aggregated results from total cohort of 25 patients. Results: Median age was 62 years, 52% were female, 24% had ISS stage 3, 57% had high-risk FISH (primarily gain1q). Induction therapy was VRD in 68% (17), daratumumab VRD in 24% (6), CyBorD in 8% (2) patients. Median duration of induction was 4 months (3-6) and median lenalidomide exposure was 5 cycles (1-8), with &gt; VGPR in 88% of patients. (Table 1) Plerixafor 0.24 mg/kg was given in 24 (96%) patients. Median pre-apheresis CD34 count was day 1, 24/uL (3-99) & day 2, 15/uL (5-46). Median total HSC cell yield (CD34+ cells/kg x 10 6) was 5.0 (1.1-16.2), day 1 yield was 3.4 (0.3-16.2) and day 2 yield was 1.9 (0.5-4.6) (Fig1). 88% (n=22) of patients met the primary endpoint of collecting sufficient HSCs in &lt; 2 days of mobilization + apheresis to proceed to transplant, 68% (17) in 1 day (2 x 10 6 CD34+ cells/kg). 3 patients who did not meet primary endpoint successfully collected HSCs with standard GCSF + plerixafor dosing & 2-3 apheresis sessions. Secondary endpoints of 4 and 6 x 10 6 CD34+ cells/kg in &lt; 2 days were met in 68% (17) and 40% (10) patients. MGTA-145+plerixafor was well tolerated. At least 1 treatment emergent AE (TEAE) with MGTA-145 was seen in 60% of patients (grade 1, n= 14, grade 2, n=1). Pain (all grade 1) was most common, seen in 44% (11), with 38% (9) patients experiencing acute onset transient bone pain with MGTA-145 (duration: 7 minutes, range: 3-28). Using the validated Brief Pain Inventory, 56% (14) patients self-reported pain with mobilization vs 40% (10) at baseline. 7/15 patients without baseline pain reported pain with mobilization. An increase for worst pain was seen on mobilization day 1, that returned to the baseline, but no difference for aggregate score of pain severity/interference (linear mixed effects model). At last follow-up, 18 patients have completed transplant with MGTA-145 mobilized graft, with melphalan 200 mg/m 2 in 15 (83%) patients. Median of 3.5 (2.2-8.1) x 10 6 CD34+ cells/kg were infused. All patients have engrafted. Median time to neutrophil engraftment of 12 days (range: 11-15) & platelet engraftment (platelets &gt; 20,000, no transfusion in 7 days) of 17.5 days (15-33) are comparable to historical data (DiPersio et al. 2009). RBC transfusion was needed in 3 (17%) patients. 14 patients have day 100 follow-up, all with durable engraftment. MGTA-145 + plerixafor mobilized grafts had a favorable graft composition. We observed high enrichment for CD90+CD45RA- among CD34+ cells, a CD34 subset of long term engrafting HSCs (median: 36% of CD34+ cells, range 10-66%, N=25). 74% (17 of 23) grafts were minimal residual disease negative with next generation flow cytometry. Conclusions: This is the first study to evaluate the novel G-CSF-free regimen of MGTA-145 + plerixafor for HSC cell mobilization & collection for hematologic malignancies. The study cohort was representative of transplant eligible patients with MM, with 88% patients meeting the primary endpoint. The regimen was well tolerated. Patients achieved timely & durable engraftment. Our data support further development of this regimen for rapid HSC mobilization. Figure 1 Figure 1. Disclosures Sidana: Janssen: Consultancy, Research Funding; Allogene: Research Funding; Magenta Therapeutics: Consultancy, Research Funding; BMS: Consultancy. Kumar: Bluebird Bio: Consultancy; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Carsgen: Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Oncopeptides: Consultancy; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Tenebio: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Beigene: Consultancy; Antengene: Consultancy, Honoraria; Amgen: Consultancy, Research Funding; Roche-Genentech: Consultancy, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; BMS: Consultancy, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding. Muffly: Pfizer, Amgen, Jazz, Medexus, Pfizer: Consultancy; Astellas, Jasper, Adaptive, Baxalta: Research Funding; Adaptive: Honoraria, Other: fees for non-CME/CE services: , Research Funding. Arai: Magenta Therapeutics: Research Funding. Meyer: Indee, Jura: Consultancy; Orca Biosystems: Research Funding; GigaImmune: Current holder of stock options in a privately-held company; Triursus Therapeutics: Current holder of stock options in a privately-held company. Rezvani: US Department of Justice: Consultancy; Kaleido: Other: One-time scientific advisory board; Nohla Therapeutics: Other: One-time scientific advisory board; Pharmacyclics-Abbvie: Research Funding. Weng: Kite Pharma: Research Funding. Frank: Kite-Gilead: Membership on an entity's Board of Directors or advisory committees; Allogene Therapeutics: Research Funding; Adaptive Biotechnologies: Research Funding. Shiraz: Kite Pharma-Gilead: Research Funding. Girgenti: Magenta Therapeutics: Current Employment. Goncalves: Magenta Therapeutics: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties. Schmelmer: Magenta Therapeutics: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties. Davis: Magenta Therapeutics: Current equity holder in publicly-traded company, Ended employment in the past 24 months. Shizuru: Jasper Therapeutics, Inc.: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: Chair of scientific advisory board; Forty seven Inc: Other: Inventor on a patent licenses by Forty Seven. Forty seven was acquired by Gilead in 2020. Miklos: Pharmacyclics: Patents & Royalties; Kite, a Gilead Company, Amgen, Atara, Wugen, Celgene, Novartis, Juno-Celgene-Bristol Myers Squibb, Allogene, Precision Bioscience, Adicet, Pharmacyclics, Janssen, Takeda, Adaptive Biotechnologies and Miltenyi Biotechnologies: Consultancy; Pharmacyclics, Amgen, Kite, a Gilead Company, Novartis, Roche, Genentech, Becton Dickinson, Isoplexis, Miltenyi, Juno-Celgene-Bristol Myers Squibb, Allogene, Precision Biosciences, Adicet, Adaptive Biotechnologies: Research Funding; Adaptive Biotechnologies, Novartis, Juno/Celgene-BMS, Kite, a Gilead Company, Pharmacyclics-AbbVie, Janssen, Pharmacyclics, AlloGene, Precision Bioscience, Miltenyi Biotech, Adicet, Takeda: Membership on an entity's Board of Directors or advisory committees.

ObjectiveWe aimed to determine the population‐based incidence, prevalence, and mortality of dermatomyositis (DM) using European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) criteria.MethodsThis population‐based cohort study included incident DM from January 1, 1995 to December 31, 2019. We manually reviewed all individuals with at least 1 code for DM or polymyositis to determine if they met EULAR/ACR criteria, subspecialty physician diagnosis, and/or Bohan and Peter criteria. We age‐ and sex‐adjusted incidence and prevalence estimates to the US non‐Hispanic White year 2000 population and estimated prevalence on January 1, 2015. Standardized mortality ratios (SMRs) with 95% confidence intervals (95% CIs) compared observed to expected mortality adjusting for age, sex, and year.ResultsWe identified 40 cases of verified DM, with 29 cases incident in Olmsted County from 1995 to 2019. The mean age was 57 years, 26 (90%) were female, and 12 (41%) had clinically amyopathic DM (CADM). The median follow‐up time was 8.2 years. The overall adjusted incidence of DM was 1.1 (95% CI 0.7–1.5) per 100,000 person‐years, and prevalence was 13 (95% CI 6–19) per 100,000. The SMR was significantly elevated among the myopathic DM cases (3.1 [95% CI 1.1–6.8]) but not CADM cases (1.1 [95% CI 0.2–3.3]). The positive predictive value of ≥2 DM codes was only 40 of 82 (49%).ConclusionThis population‐based study found that DM incidence and prevalence were higher than previously reported. Mortality was significantly elevated for myopathic DM but not for CADM.

ObjectiveTreat‐to‐target (T2T) and shared decision‐making are valued features of current guidelines for rheumatoid arthritis (RA) management. Although T2T has demonstrated value for improving RA outcomes, implementation remains inconsistent and lacks standardization and procedures for including patient input. We sought to better understand the impact of shared decisions on T2T and how treatment goal discussions between patients and providers impact RA treatment improvement and satisfaction.MethodsAn anonymous, web‐based questionnaire was presented to United States residents aged 18 years or older with a self‐reported diagnosis of RA by a medical professional with 28 questions regarding socio‐demographics, RA disease activity (DA), diagnosis, treatments, outcomes, and goals. Analyses included descriptive statistics with χ2 and rank sum tests for comparisons.ResultsThe questionnaire was completed by 907 people (mean age of 58 years; mean 11 years since diagnosis; 90% female). The majority (571; 63%) did not discuss RA treatment goals with providers. Patients engaging in treatment goal discussions with their providers were three times more likely to be satisfied with their treatment plans. Patients discussing treatment goals with their providers were more likely to have improved DA levels and 68% more likely to reach remission.ConclusionA majority of patients with RA report having no treatment goal discussion with their providers; however, these discussions are associated with greater DA improvement and treatment satisfaction. Further research should seek understanding of how shared treatment goal discussions relate to successful RA management and explore the development of practical tools to implement them in regular clinic practice as part of a T2T regimen.

8023 Background: MGTA-145 (GroβT), a CXCR2 agonist, has shown promising activity for HSC mobilization with plerixafor in pre-clinical models and healthy volunteers. Methods: This phase 2 single center study evaluates HSC mobilization with MGTA-145 + plerixafor and same day apheresis in patients with multiple myeloma. Patients received plerixafor 0.24 mg/kg (0.16 mg/kg if renal dysfunction) SQ, followed 2 hours later by MGTA-145 (0.03 mg/kg) IV over 3-10 minutes and apheresis within 30 minutes. Mobilization was repeated for a second day if day 1 yield was < 6 x 106 CD34+ cells/kg. This interim analysis reports on mobilization in 10 patients (of 25 planned), including safety cohort of first 6 patients completing transplant. Primary endpoint is collection of 2 x 106 CD34+ cells/kg. Results: Median age was 63 years (range: 46-68), 50% were female, 22% had ISS stage 3 & 50% had high-risk FISH. Induction therapy was VRD in 7 and daratumumab + VRD in 3 patients; median induction duration: 4 months (3-6) & median lenalidomide exposure: 6 cycles (4-6), with > VGPR in 70%. Median total stem cell yield (CD34+ cells/kg x 106) was 7.1 (3-16.2), day 1 yield was 5.4 (1.1-16.2) & yield per apheresis session was 4 (1.1-16.2). 100% of patients met the primary endpoint of collecting sufficient HSCs in < 2 days of mobilization + apheresis to proceed to transplant (2 x 106 CD34+ cells/kg). Secondary endpoints of 4 and 6 x 106 CD34+ cells/kg in < 2 days were met in 90% & 80% patients. 30% patients underwent 1 apheresis, while 70% underwent 2 sessions. MGTA-145 was well tolerated. At least 1 adverse event (AE) was seen in 90% of patients, 20% had grade 2 AEs (anemia, hypokalemia) and 20% had grade 3 AEs (worsening of baseline grade 3 anemia; hypocalcemia); all resolved. Acute & transient bone pain was seen in 40% of patients (back-2, hip-1, sternum-1), all grade 1, all on day 1, & resolved without intervention after 6 minutes (3-10). All 6 patients in the safety cohort have completed transplant with melphalan 200 mg/m2. Median of 4.1 (3.4-5.6) x 106 CD34+ cells/kg were infused. All patients have engrafted timely (DiPersio Blood 2009); median time to neutrophil engraftment: 12 days (11-13) & platelet engraftment: 17 days (16-19). Apheresis graft analysis is available in these 6 patients. Grafts with MGTA-145+plerixafor showed high enrichment for CD90+CD45RA- among CD34+ cells, a CD34 subset of long term engrafting HSCs (median: 31% of CD34+ cells, 27-52), higher than seen with G-CSF (6%, Goncalves TCT 2021). 67% of grafts were minimal residual disease negative with next generation flow cytometry. Conclusions: This is the first study to evaluate the novel regimen of MGTA-145 + plerixafor for same day stem cell mobilization & collection in myeloma/hematologic malignancies, with 100% efficacy in interim analysis and the first to demonstrate successful engraftment in patients with cells collected with this GCSF free regimen. Clinical trial information: NCT04552743.