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Patient-reported outcome (PRO) data have assumed increasing importance in the care of patients with rheumatoid arthritis (RA), yet physician-derived disease activity measures, such as Clinical Disease Activity Index (CDAI), remain the most accepted metrics to assess disease activity. The possibility that newer longitudinal PRO data might be used as a proxy for the CDAI has not been evaluated.Using data from a large pragmatic trial, we evaluated patients with RA initiating golimumab intravenous or infliximab. The classification target was low disease activity (LDA) (CDAI ≤10) at the first visit between months 3 and 12. Data were randomly partitioned into training (80%) and test (20%) data sets. Multiple machine learning (ML) methods (eg, random forests, gradient boosting, support vector machines) were used to classify CDAI disease activity category, conduct feature selection, and assess feature importance. Model performance evaluated cross-validated error, comparing different ML approaches using both training and test data.A total of 494 patients were analyzed, and 36.4% achieved LDA. The most important classification features included several Patient-Reported Outcomes Measurement Information System measures (social participation, pain interference, pain intensity, and physical function), patient global, and baseline CDAI. Among all ML methods, random forests performed best. Overall model accuracy and positive predictive values for all ML methods were approximately 80%.ML methods coupled with longitudinal PRO data appear useful and can achieve reasonable accuracy in classifying LDA among patients starting a new biologic. This approach has promise for real-world evidence generation in the common circumstance when physician-derived disease activity data are not available yet PRO measures are.

Background Biologic therapies are often prescribed for patients with rheumatoid arthritis (RA) who have inadequate responses to or are intolerant of methotrexate (MTX) and patients with poor prognostic indicators. This post hoc analysis evaluated effectiveness and safety of intravenous golimumab + MTX vs golimumab without MTX in RA patients. Methods AWARE, a real-world, prospective and pragmatic, Phase 4 study, compared effectiveness and safety of golimumab and infliximab in biologic-naïve and biologic-experienced patients. All treatment decisions were at the discretion of the treating rheumatologist. Effectiveness was evaluated by mean change in CDAI scores at Months 6 and 12. Safety was monitored through approximately 1 year. Results Among 685 golimumab-treated patients, 420 (61%) received concomitant MTX during the study and 265 (39%) did not receive MTX after enrollment; 63% and 72%, respectively, discontinued the study. Relative to golimumab without MTX, golimumab + MTX patients had shorter mean disease duration (8.7 vs 10.0 years) and a lower proportion received prior biologics (60% vs 72%); mean ± standard deviation (SD) baseline CDAI scores were similar (30.8 ± 15.1 and 32.6 ± 15.4). Mean ± SD changes from baseline in CDAI scores at Months 6 and 12, respectively, were similar with golimumab + MTX (− 10.2 ± 14.2 and − 10.8 ± 13.8) and golimumab without MTX (− 9.6 ± 12.9 and − 9.9 ± 13.1). The incidence of adverse events/100 patient-years (PY) (95% confidence interval [CI]) was 155.6 (145.6, 166.1) for golimumab + MTX and 191.2 (176.2, 207.1) for golimumab without MTX; infections were the most common type. The incidence of infusion reactions/100PY (95% CI) was 2.1 (1.1, 3.6) for golimumab + MTX versus 5.1 (2.9, 8.3) for golimumab without MTX; none were considered serious. For golimumab + MTX versus golimumab without MTX, rates/100PY (95% CI) of serious infections, opportunistic infections, and malignancies were 2.6 (1.5, 4.3) versus 7.0 (4.4, 10.6), 0.9 (0.3, 2.0) versus 2.6 (1.1, 5.0), and 3.0 (1.7, 4.7) versus 1.0 (0.2, 2.8), respectively. Conclusions Mean change in CDAI score in the golimumab without MTX group was generally similar to that of the golimumab + MTX group through 1 year, regardless of prior biologic therapy. Adverse events were consistent with the known IV golimumab safety profile. These results provide real world evidential data that may assist healthcare providers and patients with RA in making informed treatment decisions. Trial registration: clinicaltrials.gov NCT02728934 05/04/2016.

Objective Evaluate tolerability and effectiveness of golimumab-IV versus infliximab in patients with rheumatoid arthritis (RA) in a real-world setting. Methods AWARE, a prospective, real-world, pragmatic, observational, multicenter, phase 4 study, enrolled RA patients when initiating golimumab-IV or infliximab. Treatment decisions were made by the treating rheumatologist. The approved doses for RA are 2 mg/kg at weeks 0, 4, then Q8W for golimumab-IV and 3 mg/kg at weeks 0, 2, 6, then Q8W (dose escalation permitted) for infliximab. A prespecified formal interim analysis was conducted. The primary endpoint was the incidence of infusion reactions (any adverse event that occurred during or within 1 h of infusion) through week 52. Major secondary endpoints were mean change from baseline in CDAI at months 6 and 12 in biologic-naïve patients (non-inferiority margin in the CDAI = 6). Baseline characteristics were adjusted using propensity scores with inverse probability of treatment weights (IPTW). Results In the formal interim analysis (golimumab-IV, n = 479; infliximab, n = 354), the incidence of infusion reactions was significantly lower with golimumab-IV vs. infliximab (3.6 vs. 17.6%, p

ObjectiveWe describe an open-label study of nipocalimab to determine the effect of nipocalimab in pediatric participants with gMG.BackgroundNipocalimab is a high affinity, fully human, aglycosylated, effectorless IgG1 anti FcRn monoclonal antibody that targets the neonatal Fc receptor (FcRn) with high affinity, thereby lowering IgG pathogenic antibodies in autoimmune disease. Data from Vivacity-MG, a Phase 2, multicenter, randomized, double-blind, placebo-controlled study of nipocalimab demonstrated safety, tolerability, and efficacy of nipocalimab in adult generalized myasthenia gravis (gMG) (clinicaltrials.govNCT03772587).Design/MethodsThis global study will enroll at least 12 participants, aged 2 to ResultsStudy enrollment will begin in 2022.ConclusionsThe vibrance-mg study will assess the PK/PD, safety and activity of Nipocalimab in pediatric gMG.

Background PROMIS (Patient Reported Outcomes Measurement Information System) has been used in rheumatoid arthritis (RA) patients (Pts) to assess disease activity across multiple domains (i.e. physical function, fatigue, pain interference). AWARE (Comparative and Pragmatic Study of Golimumab IV Versus Infliximab in Rheumatoid Arthritis) is an ongoing Phase 4 study designed to provide a real-world assessment of intravenous Tumor Necrosis Factor inhibitor (TNFi) medications in RA pts. The study utilizes PROMIS and Clinical Disease Activity Index (CDAI) to assess effectiveness. Objectives This analysis examined select PROMIS measures to assess (1) relationship between baseline (BL) CDAI and PROMIS-scores, (2) responsiveness of PROMIS after initiation of TNFi and (3) relationship between PROMIS T-scores of the 4 item Profile29v2 Fatigue and Pain Interference domains and respective PROMIS Short Forms (SF). Methods AWARE is a prospective, noninterventional, 3-year study at 100 US sites. RA pts were enrolled when initiating TNFi treatment. Treatment decisions are at the discretion of the treating rheumatologist. We report on data from Pts’ BL PROMIS Pain Interference 6b (PI), Fatigue7a (F), Profile29v2 and CDAI. PROMIS T-scores were compared across CDAI disease category (high, moderate etc) using ANOVA. We dichotomized pts based on whether their BL T-score was within 0.5SD of the population mean (i.e. ‘normal’) or not to evaluate for effect modification in the subsequent change in PROMIS T-scores. Data shown are mean ± std dev. Results Pts (N=1220) were 59.5± 13.2 yrs, disease duration 8.2 ± 9.9 yrs, 83.4% female, body weight 85.1± 24.2 kg, BMI 31.4 ± 8.51, BL CDAI 32.4 ± 15.6. A significant relationship between PROMIS T-scores (PI, F) and BL CDAI disease activity category was confirmed. There was minimal change in T-score of pts with BL PI and F T-scores /=45 over 5 infusions (approx. 5-7 months). Depending on domain, 14.7-27.3% of pts had initial PROMIS T-scores within 0.5SD of normal. There was a significant (p Conclusion Avoiding floor effects in pts who initiated TNFi therapy with near-normal PROMIS scores, PROMIS instruments demonstrated a robust T-score change in response to initiation of TNFi therapy. Disclosure of Interests Clifton Bingham Grant/research support from: BMS, Consultant for: AbbVie, BMS, Eli Lilly, Genentech/Roche, Janssen, Pfizer, Sanofi/Regeneron, Sergio Schwartzman Shareholder of: Amgen, Boston Scientific, Gilead, Medtronic, and Pfizer, Consultant for: AbbVie, Crescendo, Dermtech, Janssen, Gilead, Lilly, Myriad, Novartis, Regeneron, Samsung, Sanofi, and Union Chimique Belge, Speakers bureau: Abbott/AbbVie, Genentech, Janssen, Lilly, Novartis, Pfizer, Regeneron, Sanofi, and Union Chimique Belge, Shelly Kafka Shareholder of: J&J, Employee of: J&J, Dennis Parenti Employee of: Janssen Research & Development, LLC, Shawn Black Employee of: Janssen Research & Development, LLC, Stephen Xu Employee of: Employee of Janssen Research & Development, LLC, Wayne Langholff Employee of: Janssen Research & Development, LLC, Jeffrey Curtis: None declared

Background AWARE (Comparative and Pragmatic Study of Golimumab IV Versus Infliximab in Rheumatoid Arthritis) is an ongoing Phase 4 comparator study designed to provide a real-world assessment of intravenous golimumab (GLM) and intravenous infliximab (IFX) in patients (pts) with rheumatoid arthritis (RA). The primary objective of AWARE is to assess the incidence of infusion reactions, the concomitant use of methotrexate (MTX) is also reported. The FDA approved label for GLM states that it is indicated for the treatment of patients with moderately to severely active RA in combination with MTX; however prospectively obtained real world evidence based data on the rate of GLM use without MTX has not been reported. Objectives Here we compare patient demographics, disease characteristics, response to therapy and discontinuation of GLM treated patients with and without concomitant MTX from an interim analysis (IA) of the AWARE study. Methods AWARE is a prospective, noninterventional, observational, multicenter 3-year study conducted in the US. RA pts (1,200 adults) were enrolled at the time of initiating treatment with GLM or IFX. All treatment decisions including MTX utilization are made at the discretion of the treating rheumatologist. Imputations of CDAI data were not performed at this IA. Data shown are mean ± standard deviation. Results 678 GLM pts were enrolled; of these 487 (71.8%) were GLM Plus-MTX and 191 (28.2%) were GLM No-MTX. Demographics are shown in the table. Response to therapy was assessed with CDAIs and shown in the figure below. Overall, 92.6% of GLM Plus-MTX and 91.5% of GLM No-MTX pts had a baseline (BL) categorical CDAI disease activity of moderate or high, and 7.4% of GLM Plus-MTX and 8.5% of GLM No-MTX pts had a BL categorical CDAI disease activity of low or remission. Discontinuation from the study during the period of this IA was similar between the GLM Plus-MTX (173/487; 35.5%) and GLM No-MTX (64/191; 33.5%). 7.9% of GLM No-MTX pts reported leflunomide use. Conclusion At BL 28.2% of pts on GLM did not report concomitant MTX use. The demographics of the GLM Plus-MTX pts did not differ remarkably from GLM No-MTX pts. The reported early response to treatment, assessed by CDAI score after 3 months and 6 months was similar in the GLM Plus-MTX and GLM No-MTX groups. These preliminary IA data suggest that in a real-world rheumatology practice setting, use of GLM with or without concomitant MTX led to similar CDAI scores at 3 and 6 months in RA pts with predominantly moderate to high BL CDAI disease category. Disclosure of Interests Aaron Broadwell Grant/research support from: Janssen Scientific Affairs, LLC, Vance Bray Grant/research support from: Janssen Scientific Affairs, LLC, Douglas Conaway Grant/research support from: Janssen Scientific Affairs, LLC, Joy Schechtman Grant/research support from: Janssen Scientific Affairs, LLC, Alan Kivitz Shareholder of: Novartis, Consultant for: Abbvie, Janssen, Pfizer, UCB, Genzyme, Sanofi, Regeneron, Boehringer Ingelheim, Sun Pharma Advanced Research, Flexion., Paid instructor for: Celgene, Horizon, Merck, Novartis, Pfizer, Genzyme, Sanofi, Regeneron, Speakers bureau: Celgene, Horizon, Merck and Genetech, Flexion, Dennis Parenti Employee of: Janssen Research & Development, LLC, Shawn Black Employee of: Janssen Research & Development, LLC, Stephen Xu Employee of: Employee of Janssen Research & Development, LLC, Wayne Langholff Employee of: Janssen Research & Development, LLC, Shelly Kafka Shareholder of: J&J, Employee of: J&J

Background:AWARE is a real-world evidence-based (RWE) study evaluating the safety and efficacy of IV golimumab (GLM) and infliximab (IFX) in adults with RA.Objectives:Evaluate safety and efficacy of IV GLM and IFX in elderly AWARE participants.Methods:AWARE, a prospective non-interventional study (88 US sites), enrolled patients (pts) initiating either IV GLM or IFX. Pt management was at the discretion of treating rheumatologists. In a post hoc analysis, pts were grouped by age (Results:1270 pts were enrolled (685 IV GLM; 585 IFX). 1047 (82%) pts were female; mean age was 60 yrs (57% 1 rates of serious AEs (SAEs) and serious infections increased with age for both IV GLM and IFX; however, increases were more notable in IFX- than IV GLM-treated pts ≥65 yrs. The incidence of serious infections was highest in pts ≥75 yrs for both treatments, although small sample size may limit data interpretation. No increase in opportunistic infections, including Varicella, was observed in pts ≥65 vs Table 1.% of pts with ≥1 AE through W52 DBLIV GLMIFX≥65 yrs≥75 yrs≥65 yrs≥75 yrsPatients, n3513349137021546Discontinued due to AE8.5%12.6%16.5%15.1%17.7%21.7%AE52.4%58.4%57.1%63.5%66.5%71.7%Most common AEs (≥5% of pts in either treatment group)Nausea3.7%3.3%3.3%8.4%6.0%2.2%Worsening of RA5.4%4.5%3.3%7.3%7.0%4.3%Upper respiratory tract infection5.7%5.1%4.4%6.2%5.6%2.2%Pruritis1.4%2.4%3.3%6.8%2.8%2.2%Sinusitis7.1%3.3%0%3.8%3.7%2.2%Urinary tract infection4.8%5.1%5.5%4.3%5.1%6.5%SAE7.7%16.8%20.9%9.7%18.6%26.1%Infection30.5%27.2%27.5%32.2%28.8%32.6%Serious infection3.7%6.3%7.7%3.5%7.9%15.2%Neoplasms benign, malignant and unspecified0.6%2.7%1.1%0.8%2.3%6.5%Latent tuberculosis0.3%0%00.3%0%0%Opportunistic infection1.4%1.8%4.4%1.9%1.4%4.3%Infusion reaction5.1%2.7%1.1%17.3%8.8%8.7%Death0.3%2.4%2.2%0%2.3%6.5%Conclusion:Elderly RA pts receiving IV GLM or IFX in this RWE study demonstrated similar safety and efficacy as reported in Phase 3 trials.2,3 The higher rates of AEs, discontinuations due to AE, and SAEs (mainly serious infections) observed in pts ≥65 yrs are in line with increased safety events seen in elderly vs younger individuals in the general population. Rates of AEs, SAEs, and infusion reactions were higher for IFX vs IV GLM. Infusion reactions were more common in pts References:[1]Castle SC. Clin Infect Dis 2000;31:578–85.[2]Lipsky PE, et al. N Engl J Med 2000;343:1594-602.[3]Weinblatt ME, et al. Ann Rheum Dis 2013;72:381-9.Disclosure of Interests:Joy Schechtman: None declared, Aaron Broadwell Speakers bureau: Amgen, AbbVie, Eli Lilly, Horizon, Janssen, Mallinckrodt, Novartis, Pfizer, Radius, Sanofi/Regeneron, and UCB, Consultant of: AbbVie, Amgen, Aurinia, Celegene, Eli Lilly, Janssen, Novartis, Pfizer, and Sandoz, Shelly Kafka Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Shawn Black Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Stephen Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Wayne Langholff Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Sergio Schwartzman Shareholder of: Amgen, Boston Scientific, Gilead, Medtronic, and Pfizer, Speakers bureau: AbbVie, Janssen, Eli Lily, Novartis, Pfizer, Regeneron, Sanofi, and UCB, Consultant of: AbbVie, Gilead, Eli Lilly, Janssen, Myriad, Novartis, Regeneron, Samsung, Sanofi, and UCB

Background:AWARE is a phase-4 observational study designed to provide real-world assessment of Golimumab (GLM) IV & infliximab (IFX) in patients (pts) with rheumatoid arthritis (RA).Objectives:To assess patient-reported aspects of social, mental, & physical health through the 8th infusion (≈1 year of treatment) using Patient Reported Outcomes Measurement Information System (PROMIS), a validated, disease-agnostic set of health assessment instruments.Methods:AWARE enrolled 1270 RA pts initiating treatment with GLM/IFX. The 52 week analysis set included pts with ≥1-year treatment or those discontinued and, while enrolled, completed PROMIS-29 or PROMIS short form (SF) questionnaires. PROMIS instruments were administered at baseline & prior to infusions 2, 5, & 8. The raw score was converted into a standardized T-score with a mean of 50 and SD of 10.Results:At baseline, treatment groups were balanced on demographics & medical characteristics. Most pts were white (87.0% GLM, 86.2% IFX) & female (83.4% GLM, 82.4% IFX). Mean ages were 58.5 ±12.96 years for GLM & 59.6 ±13.24 years for IFX. Overall, 35.3% GLM & 42.9% IFX pts were bio-naïve. The proportion of GLM & IFX pts with prior exposure to 1 or 2 biologics was similar; however, 20.1% GLM pts vs 10.8% IFX pts had exposure to ≥3 biologics. Methotrexate use was similar between GLM (76.4%) & IFX pts (75.0%). Based on mean PROMIS T-scores at baseline (Table 1), Fatigue, Pain Interference, & Physical Function domains approached or exceeded 1 SD worse than those of general US population. Through the 8th infusion, GLM- & IFX-treated pts achieved meaningful improvement based on mean changes from baseline in most PROMIS-29 domains & respective SFs with no significant difference between GLM and IFX. The percentage of GLM or IFX pts with improvements of ≥3, ≥5, or ≥10 units change in T-scores increased from infusion 2 through infusion 8.Conclusion:RA pts treated with GLM or IFX achieved comparable improvements across PROMIS-assessed social, mental, & physical health. PROMIS-29 was able to detect change to subsequent anti-tumor necrosis factor-α therapies.Table 1.Mean (SD) Change from Baseline PROMIS-29 Domain and Short Form T-Scores: 52 Week Analysis SetGLMIFXLSM difference (95% CI)*Anxiety (4-item)N=6N=570Baseline53.4 (10.13)54.6 (10.53)Change from baseline at infusion 8N=223 -2.6 (8.10)N=286-3.7 (7.86)-0.29 (-1.54, 0.97)Depression (4-item)BaselineN=67451.9 (9.83)N=57452.5 (10.21)Change from baseline at infusion 8N=225-2.1 (7.56)N=287-2.3 (7.89)0.49 (-0.72, 1.70)Fatigue (4-item)BaselineN=67158.4 (9.91)N=57459.4 (9.99)Change from baseline at infusion 8N=225-3.4 (8.72)N=281-3.1 (7.77)0.69 (-0.64, 2.03)Short form Fatigue 7aBaselineN=68159.1 (8.51)N=57659.7 (8.25)Change from baseline at infusion 8N=228-3.2 (7.40)N=287-2.4 (6.35)1.01 (-0.11, 2.14)Pain interference (4-item)BaselineN=67963.0 (7.56)N=57463.9 (7.80)Change from baseline at infusion 8N=227-4.2 (8.23)N=284-3.1 (7.77)1.84 (0.55, 3.13)Short form Pain interference 6bBaselineN=68061.9 (7.45)N=57662.8 (7.54)Change from baseline at infusion 8N=228-3.8 (7.88)N=287-3.2 (6.67)1.31 (0.15, 2.48)Physical function (4-item)BaselineN=67838.2 (6.79)N=57138.0 (6.90)Change from baseline at infusion 8N=2242.2 (5.64)N=2831.9 (5.85)-0.76 (-1.73, 0.21)Sleep disturbance (4-item)BaselineN=67154.6 (8.72)N=569N=55.5 (8.61)Change from baseline at infusion 8N=221-1.4 (7.45)N=281-1.7 (7.61)0.23 (-0.96, 1.42)Social participation (4-item)BaselineN=67343.7 (8.40)N=57442.9 (8.77)Change from baseline at infusion 8N=2253.2 (8.15)N=2833.4 (7.48)-0.10 (-1.36, 1.16)*Least squares mean (LSM) difference & confidence interval (CI) are based on analysis of covariance controlling for baseline PROMIS score using inverse probability of treatment weighted propensity score.Disclosure of Interests:Clifton Bingham Consultant of: AbbVie, BMS, Eli Lilly, Gilead, Janssen, Pfizer, Regeneron/Sanofi, Grant/research support from: Bristol-Myers Squibb, Shelly Kafka Employee of: Janssen Research & Development, LLC, Shawn Black Employee of: Janssen Research & Development, LLC, Stephen Xu Employee of: Janssen Research & Development, LLC, Wayne Langholff Employee of: Janssen Research & Development, LLC, Jeffrey Curtis Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, UCB

A series of potent and receptor-selective cannabinoid-1 (CB1) receptor inverse agonists has been discovered. Peripheral selectivity of the compounds was assessed by a mouse tissue distribution study, in which the concentrations of a test compound in both plasma and brain were measured. A number of peripherally selective compounds have been identified through this process. Compound 2p was further evaluated in a 3-week efficacy study in the diet-induced obesity (DIO) mouse model. Beneficial effects on plasma glucose were observed from the compound-treated mice.

Background:AWARE (Comparative and Pragmatic Study of Golimumab IV Versus Infliximab in Rheumatoid Arthritis) is an ongoing Phase 4 comparator study designed to provide a real-world assessment of intravenous golimumab (GLM) and intravenous infliximab (IFX) in patients (pts) with rheumatoid arthritis (RA). The study recently reached its primary endpoint (comparison of overall incidence of infusion reactions in GLM- vs IFX-treated pts after 52 weeks) with the last patient reaching 52 weeks of treatment or discontinuation from the study. AWARE also records prior use of biologic medications and concomitant use of methotrexate (MTX).Objectives:To assess the incidence of infusion reactions among GLM and IFX pts reported at baseline by examining the influence of prior biologic exposure or concurrent use of MTX.Methods:AWARE is a prospective, noninterventional, observational, multicenter, 3-year study conducted in the US. RA patients (1,270 adults) were enrolled at the time of initiating treatment with GLM or IFX. All treatment decisions were made at the discretion of the treating rheumatologist. An infusion reaction was any adverse event that occurred during an infusion or within 1 hour after the infusion of either GLM or IFX. Imputations were not performed on these AWARE data. Data shown are mean ± standard deviation.Results:Demographics are shown in Table 1 and the incidence of infusion reactions in different AWARE cohorts is shown in Table 2. GLM and IFX pts were comparable in sex and utilization of MTX at baseline. Both age and disease duration of GLM pts was greater than IFX pts by ~2 years. There was a higher proportion of bionaïve pts in IFX-treated group compared to GLM-treated group. Overall, infusion reactions occurred more frequently among IFX-treated pts compared to GLM-treated pts. The difference in infusion reaction rates between IFX- and GLM-treated pts was also evident among subgroups of bionaïve vs non-bionaïve pts, and among MTX non-users vs MTX users (characteristics reported at baseline). GLM pts did not report any serious or severe infusion reactions. These were reported rarely (3/585 pts) in IFX-treated pts. Among GLM and IFX pts with an infusion reaction, 55.6% of GLM and 77.1% of IFX pts had at least one medication for infusion reaction. Infusion reactions accounted for 9.7% and 35.1% of discontinuations due to adverse events in GLM and IFX pts, respectively.Table 1.Baseline Characteristics in the AWARE StudyGLM (n=685)IFX (n=585)Age (years)60.9 ± 13.4358.0 ± 12.85Sex (% female)85.0 %79.5 %Disease Duration (years)9.16 ± 9.9757.20 ± 9.716Bionaïve (%)33.0%48.6%MTX plus (%)75.4%75.1%MTX=methotrexateTable 2.Infusion Reactions in AWARE in Subsets of Patients ± Prior Biologic Use or ± Concurrent MTXGLM (n=685)IFX (n=585)GLM (n=685)IFX (n=585)BionaïveNon-BionaïveBionaïveNon-BionaïveNo MTX UseMTXUseNo MTX UseMTX UseInfusion Reactions6/242(2.5%)21/443(4.7%)36/251(14.3%)47/334(14.1%)15/265(5.7%)12/420(2.9%)44/229(19.2%)39/356(11.0%)Medication for Infusion Reactions33.3%59.1%78.9%73.6%50.%58.3%73.6%77.6%MTX=methotrexateConclusion:Whether bionaïve, non-bionaïve, MTX non-user or MTX user at baseline, the incidence of infusion reactions was notably lower among GLM- vs IFX-treated pts. Serious and/or severe infusion reactions did not occur among GLM pts and were rare among IFX pts. IFX was more commonly administered mediation for an infusion reaction compared to GLM. Infusion reactions accounted for almost four times the number of discontinuations related to adverse events in IFX pts compared to GLM pts.Disclosure of Interests: :Sergio Schwartzman Grant/research support from: Janssen Research & Development, LLC, Consultant of: AbbVie, Crescendo Bioscience, Dermtech, Eli Lilly and Company, Gilead Sciences, Janssen Pharmaceutica, Myriad Genetics, Novartis, Regeneron, Samsung, Sanofi, UCB, Speakers bureau: AbbVie, Eli Lilly and Company, Genentech, Janssen Pharmaceutica, Novartis, Pfizer, Regeneron, Sanofi, UCB, Aaron Broadwell Grant/research support from: Janssen Research & Development, LLC, Janssen, Eli Lilly, Consultant of: AbbVie, Amgen, AstraZeneca, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Sandoz, Speakers bureau: AbbVie, Amgen, Celgene, GSK, Horizon, Janssen, Mallinckrodt, Novartis, Pfizer, Radius, Sanofi-Regeneron, UCB, Alan Kivitz Shareholder of: AbbVie, Amgen, Gilead, GSK, Pfizer Inc, Sanofi, Consultant of: AbbVie, Boehringer Ingelheim,,Flexion, Genzyme, Gilead, Janssen, Novartis, Pfizer Inc, Regeneron, Sanofi, SUN Pharma Advanced Research, UCB, Paid instructor for: Celgene, Genzyme, Horizon, Merck, Novartis, Pfizer, Regeneron, Sanofi, Speakers bureau: AbbVie, Celgene, Flexion, Genzyme, Horizon, Merck, Novartis, Pfizer Inc, Regeneron, Sanofi, Shawn Black Employee of: Janssen Research & Development, LLC, Janssen Scientific Affairs, LLC, Stephen Xu Employee of: Janssen Research & Development, LLC, Wayne Langholff Employee of: Janssen Research & Development, LLC, Shelly Kafka Employee of: Janssen Scientific Affairs, LLC

Background:Use of patient-reported outcomes (PROs) to assess health-related quality of life in clinical practice, research studies, and clinical trials in rheumatoid arthritis (RA) remains an ongoing area of research. SF-36 is commonly used in RA trials but is not feasible for routine use in clinical practice settings. ThePatientReportedOutcomesMeasurementInformationSystem (PROMIS) may address this gap but has not been widely assessed in RA patients starting therapy in a real-world comparative effectiveness study, nor examined in that setting in relation to the SF36 and Clinical Disease Activity Index (CDAI).Objectives:To assess validity of PROMIS based on Comparative and Pragmatic Study of Golimumab Intravenous (IV) Versus Infliximab in Rheumatoid Arthritis (AWARE), an ongoing Phase 4 study providing real-world assessment of IV tumor necrosis factor inhibitor (TNFi) medications in RA patients.Methods:AWARE is a prospective, non-interventional, 3-year study conducted at 88 US sites. RA patients were enrolled when initiating TNFi treatment. Treatment decisions were made by treating rheumatologists. We report baseline PROMIS-29 (7 domains and pain intensity), PROMIS Pain Interference (PI) Short Form (SF) 6b (PI6b) and PROMIS Fatigue (F) Short Form 7a (F7a), domain T-Scores, and SF-36 subdomain and Component Scores (CS) in AWARE patients. Here we report baseline data obtained from the final 1-year AWARE dataset. Correlations between PROMIS measures and comparable SF-36 component scores were calculated using Pearson correlations. Data is shown as mean ± standard deviation (SD).Results:At baseline, mean CDAI of all patients (n=1262) was 32.3±15.6, with 70.4% in high disease activity (HDA, CDAI>22), 22.8% in moderate disease activity (MDA, CDAI: >10 and ≤22), 6.1% in low disease activity (LDA, CDAI: >2.8 and ≤10), and 0.7% in remission (CDAI ≤2.8). Mean PROMIS scores were >0.5 SD worse than population means for Physical Function (PF, 38.1±6.84), PI (63.4±7.68), F (58.8±9.95), Sleep Disturbance (55.1±8.68); and Ability to Participate in Social Roles/Activities (PSRA, 43.4±8.58). Baseline Depression and Anxiety were within 0.5 SD of population T-scores. PI6b, F7a, and P29 domain T-scores correlated with the comparable SF-36 subdomain and component scores (r’s >0.58), except sleep for which no comparable SF-36 element was applicable. Examples include: P6b (r=-0.80) and P29-PI (0.81) with SF-36 Bodily Pain; F7a (-0.77) and P29-F (-0.77) with SF-36 Vitality; P29-PF with SF-36 PF (0.77), Role-Physical (0.69), and Physical CS (0.73); P29 Anxiety with SF-36 Mental Health (-0.72), Role-Emotional (-0.56), Mental CS (-0.70); and P29-PRSA with SF-36-Social Functioning (0.71). Mean PROMIS-29 T-scores (except Anxiety and Sleep Disturbance) among patients with HDA were significantly different from patients with MDA, LDA or remission (p < 0.001 for all). Further, mean PROMIS T-scores of PF, F, PSRA, PI, Pain Intensity, PI6b and P7a among patients with MDA were significantly different from patients with more or less active RA (by CDAI category).Conclusion:Analysis of baseline results from a large cohort of RA patients indicates high correlations between individual P29 domain T-scores and SF-36 component scores, as well as categorical CDAI, providing strong evidence of PROMIS construct validity in a real-world population of RA patients.Disclosure of Interests:Clifton Bingham Grant/research support from: Bristol-Myers Squibb, Consultant of: Bristol-Myers Squibb, Shelly Kafka Employee of: Janssen Scientific Affairs, LLC, Shawn Black Employee of: Janssen Research & Development, LLC, Janssen Scientific Affairs, LLC, Stephen Xu Employee of: Janssen Research & Development, LLC, Wayne Langholff Employee of: Janssen Research & Development, LLC, Jeffrey Curtis Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, UCB, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, UCB

Purpose For patients with rheumatoid arthritis (RA) who do not respond or lose response to anti-tumor necrosis factor (TNF) biologics, switching to a different anti-TNF can be an effective means to manage symptoms and disease progression. This study examined the utilization and effectiveness of intravenous golimumab within a real-world population of patients with RA switching directly from infliximab, a potent anti-TNF. Methods Patient charts (n = 113) were collected from five US-based rheumatology practices. Patient demographics, treatment characteristics, infliximab and intravenous golimumab utilization data, and Clinical Disease Activity Index (CDAI), Patient Global Assessment (PtGA), Physician Global Assessment (PhGA), and Routine Assessment of Patient Index Data (RAPID3) scores were extracted from charts. The effectiveness of intravenous golimumab was assessed by comparing disease activity status pre- and post-initiation of intravenous golimumab therapy. Findings Significant decreases in patient disease activity were observed following treatment with intravenous golimumab. Mean CDAI and PhGA scores significantly decreased, and a significantly increased proportion of the population exhibited low disease activity or remission in the post intravenous golimumab period (p

Background Pt reported outcomes (PROs) play a role in disease evaluation, therapeutic assessment and care of RA pts. The Pt Reported Outcomes Measurement Information System (PROMIS [P]) questionnaires developed by NIH have been used in RA clinical practice and studies.Bartlett 2015 AWARE (Comparative and Pragmatic Study of Golimumab Intravenous [IV] Versus Infliximab in RA) is a noninterventional, multi-centre US-based, study of golimumab IV (GLM) vs. infliximab (IFX) in RA and will assess disease activity (DA) and use PROs. Objectives 1. PRO assessments of Pt response to treatment using PROMIS-29 Profile v2.0 (P29v2), P Pain Interference Short Form-6b (PISF) and P Fatigue Short Form-7a (FSF), and Clinical DA Index (CDAI), and 2. assess relationship between PROMIS T-score and CDAI category. Methods AWARE is a 1200 adult pt study enrolling pts on initiation of treatment w/GLM or IFX. We report an interim analysis (IA) of 747 pts’ baseline PROMIS questionnaire and CDAI scores. PROMIS results are normalised to the US population, reported as a “T-score” (mean=50, SD=10) w/higher scores indicating more of the trait measured. PROMIS T–scores were compared between High DA (HDA) w/Moderate DA (MDA), low DA (LDA) and remission. Data shown are mean ±SD. Statistical testing compared T-scores across CDAI categories using ANOVA for these data (before drug admin). Data from GLM and IFX pts are combined. Results Mean baseline CDAI score was 32.5±15.4, w/71.7% of pts in HDA, 22.5% in moderate MDA, 5.2% in LDA and 0.7% in remission. PROMIS T-scores were compared to 4 CDAI categories. HDA Pt T-scores were (*, p Conclusions Our interim findings demonstrate the feasibility of using PROMIS short forms and profiles to evaluate RA Pts in clinical trials. These results confirm the domain validity of PROMIS measures according to CDAI DA category. PROMIS measures show the range of impact across multiple domains of physical, emotional, and social health experienced by RA Pts. Disclosure of Interest J. Curtis Grant/research support from: Janssen Scientific Affairs, LLC, S. Schwartzman Grant/research support from: Janssen Scientific Affairs, LLC, S. Kafka Employee of: Janssen Scientific Affairs, LLC, D. Parenti Employee of: Janssen Scientific Affairs, LLC, S. Black Employee of: Janssen Scientific Affairs, LLC, S. Xu Employee of: Janssen Research and Development, LLC, W. Langholff Employee of: Janssen Research and Development, LLC, C. Bingham III Grant/research support from: Janssen Scientific Affairs, LLC

Norman B Gaylis,1 Joanne Sagliani,1 Shawn Black,2 Kezhen L Tang,3 Raphael DeHoratius,2,4 Wesley A Kafka,2 Dennis Parenti2 1Arthritis & Rheumatic Disease Specialties, Aventura, FL, USA; 2Medical Affairs Rheumatology, Janssen Scientific Affairs, LLC, Horsham, PA, USA; 3Quantitative Sciences, Janssen Research & Development, LLC, Spring House, PA, USA; 4Department of Medicine and Pharmacology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA Objective: To evaluate patient perspectives regarding utilization of intravenous (IV) therapy for inflammatory arthritis (IA).Methods: This was a single-center, noninterventional, patient questionnaire-based study of adult IA patients currently receiving IV biologics. At a single visit, patients completed the questionnaire comprising 30 questions centered on their experience receiving an intravenously administered therapy to treat their IA. The questionnaire included questions on patient demographics, disease characteristics, and previous biologic treatment for IA (subcutaneous [SC] and IV). Patients rated their level of agreement with statements regarding satisfaction with current IV biologic therapy and potential advantages and disadvantages of IV biologic therapy using a 5-point Likert scale (1=strongly disagree, 5=strongly agree).Results: One hundred patients were enrolled and completed the survey; 66% were female and the mean age was 58 years. Before IV treatment, 97% of patients received information regarding therapy options. Ninety patients ranked their satisfaction with current IV therapy as 4 or 5. The proportion of patients with an “extremely favorable” perception of IV therapy increased from 33% to 71% following initiation of their current medication. Thirty-one patients had previously received SC therapies to treat their IA.Conclusion: These results demonstrated an overall favorable perception of IV therapy among this patient population. Patients previously treated with SC therapy also had a positive shift in the perception of IV therapy after initiating IV therapy. Patients’ perception and preference for treatment options should be highly considered by the treating physician during or as part of a shared decision-making process. Keywords: intravenous, patient satisfaction, arthritis, biologic therapy

Background Patient (Pt) reported outcomes (PROs) play a role in overall disease evaluation, therapeutic response assessment and care of rheumatoid arthritis (RA) patients (Pts). The Pt Reported Outcomes Measurement Information System (PROMIS [P]) questionnaires developed by the NIH have been validated and are a feasible assessment tool in RA (Bartlett 2015). Objectives AWARE (Comparative and Pragmatic Study of Golimumab Intravenous (IV) Versus Infliximab in RA) is a real-world study of golimumab IV (G-IV) vs. infliximab (IFX) in RA and will assess infusion reactions, disease activity and multiple PROs as outcomes measures. Methods AWARE is a prospective, noninterventional, ongoing US-based study in which 1,200 adult Pts will be enrolled on initiation of treatment with G-IV or IFX. Objectives include PRO assessments of Pt response to treatment using the PROMIS-29 Profile v2.0 (P29v2), P Pain Interference Short Form-6b (PISF) and P Fatigue Short Form-7a (FSF), 36-Item Short Form Health Survey (SF-36v2) and the Clinical Disease Activity Index (CDAI). We report an interim analysis from the first 353 Pts of baseline PROMIS questionnaire and CDAI scores, and their inter-relationships. PROMIS questionnaire results are scored on a 0 to 100 scale, normed to the US population and reported as a “T-score” (mean of 50 and standard deviation (SD) of 10). PROMIS T scores were compared across CDAI disease activity (DA) categories. Results Baseline mean (SD) CDAI score was 33.46 (±15.79), with 73.4% of pts with high DA (HDA), 22.1% with moderate disease activity (MDA), 3.7% with low disease activity (LDA) and 0.8% pts in remission. PROMIS scores are shown below. All P29v2 domains, PISF and FSF scores were significantly worse in pts with CDAI>22 vs. CDAI≤22 (p Conclusions These interim data further support the viability of using PROMIS questionnaires to evaluate RA pts, and indicate in this predominantly HDA population of RA pts correlations between PROMIS and CDAI disease activity category. Confirmation of the baseline interim analysis findings with the fully enrolled AWARE study, as well as inclusion of longitudinal and subset analyses based on disease activity levels, will further define the role of PROMIS relative to CDAI in RA patients in a real world setting. Disclosure of Interest J. Curtis Consultant for: Janssen, AbbVie, Roche/Genentech, BMS, UCB, Myriad, Lilly, Amgen, Pfizer, Corrona, S. Kafka Employee of: Janssen Scientific Affairs, LLC, D. Parenti Employee of: Janssen Scientific Affairs, LLC, S. Black Employee of: Janssen Scientific Affairs, LLC, S. Xu Employee of: Janssen Research & Development, LLC, Y. Wang Employee of: Janssen Research & Development, LLC, C. Bingham III Grant/research support from: Janssen, PCORI, NIH, Pfizer, Consultant for: Janssen, AbbVie, Amgen, BMS, Celgene, Genentech/Roche, Lilly, Macrogenics, Meoblast, Novartis, NovoNordisk, Pfizer, Regeneron, UCB

Monitoring infliximab (IFX) concentrations and antibodies-to-IFX (ATI) titers during inflammatory bowel disease treatment may allow more informed decisions in assessing exposure/response and determining appropriate dosing. To aid in interpreting results from different commercial tests in the context of Janssen’s published Remicade® results, the reliability of Janssen’s IFX and ATI assays was compared with commercial assays from KU Leuven, Sanquin, Dynacare, and LabCorp. Test results were independently reported to Janssen. All assays were tested for specificity, selectivity, and precision. ATI assays were evaluated for sensitivity, drug interference, and potential interference of tumor necrosis factor-alpha (TNF-α). IFX assays were specific, accurate, and reproducible. Intra-class correlation of Janssen IFX assay results with those from KU Leuven, Sanquin, Dynacare, and LabCorp were 0.960, 0.895, 0.931, and 0.971, respectively. ATI titers >10 interfered with IFX assessment in all IFX assays, whereas TNF-α (≤50 ng/mL) did not interfere with IFX detection in any assay. ATI assays specifically and reproducibly detected ATI. Janssen, Sanquin, and LabCorp ATI methods were more resistant to IFX interference than Dynacare and KU Leuven, which were affected by IFX concentrations at ≥2 μg/mL. TNF-α (

Peripherally restricted CB1 receptor inverse agonists hold potential as useful therapeutics to treat obesity and related metabolic diseases without causing undesired CNS-mediated adverse effects. We identified a series of tetrahydropyrazolo[4,3-c]pyridine derivatives as potent and highly peripherally selective CB1 receptor inverse agonists. This discovery was achieved by introducing polar functional groups into the molecule, which increase the topological polar surface area and reduce its brain-penetrating ability.

INTRODUCTION AND OBJECTIVES: Phase 1 and 2 trials of single dose Lu-J591 are published. We conducted two phase 1 dose escalation studies of fractionated dose Lu-J591 to test hypothesis that higher cumulative radiation doses can be safely administered. METHODS: Initially, phase 1 dose escalation study of LuJ591 administered 2 doses 2 wks apart to determine recommended phase 2 dose (RP2D). Expansion cohorts at RP2Ds were enrolled and 2 trial of escalating fractionated doses of Lu-J591 in combination with docetaxel 75 mg/m q3 wks performed to determine RP2D of the combo. Men with progressive mCRPC and normal neutrophil and platelet counts were included and Lu-J591 planar imaging performed. CTC (CellSearch) counts assessed before and after treatment in expansion cohorts and docetaxel combo study. RESULTS: In single agent fractionated dose escalation LuJ591 study, 48 pts. median age 73.05 (52.5-93.8), median PSA 45.38 (1.93-766.5), 52% elevated LDH, 47.9% elevated alk phos, 35.4% with prior chemo were treated. RP2Ds were 40 mCi/m or 45 mCi/m x2 with option for GCSF. Of 25 with available CTC counts, 14 declined, 8 remained stably favorable, and 3 increased. Of 12 with unfavorable counts, 8 converted at follow up, 2 decreased by 30 and 88% but remained 5, and 2 increased. 79.2% had accurate targeting of known disease sites on Lu-J591 imaging. Predictable, reversible myelosuppression with 19 Gr 4 thrombocytopenia [15 received transfusions], 9 (18.75%) Gr 4 neutropenia without fever. In combination with docetaxel, 15 men with median age 69.1 (49.3-80.8) were enrolled. RP2D was 40 mCi/m x2 doses (delivered with cycle 3). All 14 with baseline and post Lu-J591 CTC counts had decline or persistently favorable counts, with 7 of 10 with unfavorable counts converting to favorable. Of 11 scans analyzed to date, all had targeting. CONCLUSIONS: Fractionated Lu-J591 well tolerated with subsequent PSA declines and predictable, reversible myelosuppression. Dose fractionation allows delivery of higher cumulative dose and also combination with docetaxel, with all subjects able to continue docetaxel with a 3-6 wk delay during temporary myelosuppression from RIT. Source of Funding: Prostate Cancer Foundation; DOD PC040566; NIH 1-KL2-RR024997-01, ULI RR024996, PTBF5405; David H. Koch Foundation

Background Pt-reported outcomes (PRO) are used to assess pt-related benefit in clinical trials. Inflammatory arthritis (IA) pts are equally receptive to intravenous (IV) or subcutaneous (SC) biologic treatment 1 . Objectives We obtained PRO data to understand characteristics of pts who receive IV biologic agents for IA. Methods This was a questionnaire-based study conducted at a rheumatology practice with extensive clinical trial experience. A total of 100 pts enrolled & are included in this final analysis. Inclusion criteria: a diagnosis of IA with IV biologic use for ≥3 mo; ≥18 yrs age; able to read, write & speak English, willing to complete the questionnaire & a signed informed consent form. IV biologic treatment was per clinical practice; there were no treatment assignments & study drug was not supplied. The questionnaire had 30 questions which pts completed prior to receiving a regularly scheduled dose of IV biologic. Results Mean (±SD) age of pts was 58.35 (±14.64) yrs with mean disease duration of 10.1 (±8.13) yrs (range 0.7–45 years). Pts were Caucasian (38%), African American (28%), Latino/Hispanic (22%), Asian/Pacific Islander (1%) & 11% not identified. IV biologics used were infliximab [IFX](71%), rituximab [RTX](12%), tocilizumab [TCZ](10%), abatacept [ABT](6%) & golimumab [GLM](1%). The mean duration of current IV therapy was 4.07 (±3.27) yrs (range 0.1 to 16.0 yrs). Pts9 favorability perception of IV therapy BEFORE & AFTER starting IV therapy is shown in the Figure. Amongst all pts, “Extremely favorable” increased (p Conclusions These results suggest that among IA pts receiving IV biologic therapy for treatment of IA, there is a high degree of pt satisfaction, including a similar favorability perception of IV therapy among pts who switched from a SC to an IV biologic. Our results support the concept that when there is a shared decision making discussion with pts regarding biologic treatments, the option of IV therapy should be an essential part of that discussion & that the IA pts9 perspective should be given meaningful consideration. References Bolge SC et al Arthritis Rheum 2013;65 Suppl 10:1023 Disclosure of Interest N. Gaylis Grant/research support from: Janssen Scientific Affairs, LLC, J. Sagliani Grant/research support from: Janssen Scientific Affairs, LLC, S. Black Employee of: Janssen R & D, LLC, K. Tang Employee of: Janssen R & D, LLC, R. Dehoratius Employee of: Janssen Scientific Affairs, LLC, D. Parenti Employee of: Janssen Scientific Affairs, LLC

5053 Background: Abiraterone acetate (AA) 1000mg, in combination with prednisone (P), 10mg daily is indicated for the treatment of patients (pts) with metastatic castration-resistant prostate cance...

Background—Broad inhibition of matrix metalloproteinases (MMPs) attenuates left ventricular remodeling after myocardial infarction (MI). However, it is not clear if selective MMP inhibition strategies will be effective or if MMP inhibition will impair angiogenesis after MI.Methods and Results—We used a selective MMP inhibitor (MMPi) that does not inhibit MMP-1 in rabbits, which, like humans but unlike rodents, express MMP-1 as a major collagenase. On day 1 after MI, rabbits were randomized to receive either inhibitor (n=10) or vehicle (n=8). At 4 weeks after MI, there were no differences in infarct size or collagen fractional area. However, MMPi reduced ventricular dilation. The increase in end-diastolic dimension from day 1 to week 4 was 3.1±0.5 mm for vehicle versus 1.3±0.3 mm for MMPi (PPPPPConclusions—MMP inhibition attenuates left ventricular remodeling even when the dominant collagenase MMP-1 is not inhibited; furthermore, this selective MMP inhibition appears to increase rather than decrease neovascularization in the subendocardium.