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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

Dose escalation of infliximab in both primary and secondary nonresponders is widely reported; however, the usefulness of dose escalation has been disputed. The objective of this analysis is to evaluate trends in clinical efficacy following multiple infliximab dose escalations in patients with rheumatoid arthritis (RA). Patients enrolled in a US RA registry were included if they initiated infliximab at 3 mg/kg every 8 weeks, received ≥ 1 infliximab dose escalation within 12 months of initiation, and had ≥ 1 visit following dose escalation. Trends in mean Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire (HAQ) scores from visits following dose escalations were evaluated. In patients who received 2 or 3 dose escalations, the initial (1 or 2) dose escalations resulted in reduced mean CDAI scores, but subsequent escalations did not further reduce disease activity. In patients who received ≥ 4 dose escalations, mean CDAI scores did not further reduce disease activity over time. Mean HAQ scores were stable over time in patients who received 2 or 3 dose escalations. In patients who received ≥ 4 dose escalations, mean HAQ scores decreased following 1 dose escalation but progressively increased following subsequent dose escalations. Initial dose escalations (from 3 mg/kg to the equivalent of approximately 5 to 7 mg/kg) may be useful in controlling disease activity; however, there may be diminishing clinical benefit of further escalations, which can also increase the potential risk for infection and increase incremental drug costs. • Initial infliximab dose escalations (1 to 2) may be useful in lowering disease activity in patients with rheumatoid arthritis. • There does not appear to be a clinical benefit in infliximab dose escalations above the equivalent of 5 to 7 mg/kg.

OBJECTIVE To evaluate whether intravenous (IV) golimumab produces improvements in skin and nail symptoms that are concomitant with improvements in quality of life (QoL) and joint symptoms in patients with psoriatic arthritis. METHODS Patients were randomized to either IV golimumab 2 mg/kg at weeks 0, 4, then every 8 weeks (q8w) through week 52 or placebo at weeks 0, 4, then q8w, with crossover to IV golimumab 2 mg/kg at weeks 24, 28, and then q8w through week 52. Assessments included Psoriasis Area and Severity Index (PASI), modified Nail Psoriasis Severity Index (mNAPSI), Dermatology Life Quality Index (DLQI), and American College of Rheumatology (ACR) rheumatoid arthritis response criteria. RESULTS Through week 24, achievement of PASI 75/90/100 responses (P ≤ .0098) and mean improvements in mNAPSI (-11.4 vs -3.7; P < .0001) and DLQI (-9.8 vs -2.9; P < .0001) were significantly greater with golimumab versus placebo. Responses were maintained in patients treated with golimumab through week 52. In placebo-crossover patients, increases in the proportion of patients achieving PASI 75/90/100 responses were observed from weeks 24 to 52, and mean improvements in mNAPSI (from -3.7 to -12.9) and DLQI (from -2.9 to -7.8) increased from weeks 24 to 52. Simultaneous achievement of PASI and DLQI responses, PASI and ACR responses, and mNAPSI and DLQI responses were also observed. Similar responses were observed for all assessments regardless of concomitant methotrexate use. CONCLUSION Improvements in skin and nail psoriasis symptoms with IV golimumab in patients with psoriatic arthritis were concomitant with improvements in QoL and arthritis disease activity through 1 year.

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

s / Osteoarthritis and Cartilage 22 (2014) S57–S489 S399 were younger and had higher levels of hip-related pain and disability. The LBP group also had a higher number of painful spinal levels and pelvic pain provocation tests. Results should be interpreted with caution due to the low sample size. Further research is warranted to explore the cause and effect relationship and underlying pain mechanisms associated with co-existing hip OA and LBP. DSPCC 35 mg TID (n [ 98) DSPCC 35 mg BID (n [ 104) Placebo (n [ 103) (n [ 96) (n [ 102) (n [ 96) Subjects with 30% reduction from baseline to week 12 75 (78.1 %) 70 (68.6%) 58 (60.4%) P value 0.0078 0.2271 Subjects with 50% reduction from baseline to week 12 60 (62.5%) 57 (55.9%) 44 (45.8%) P value 0.0205 0.1575 P-values are compared with placebo. 712 LOWER-DOSE DICLOFENAC CAPSULES DEVELOPED USING SOLUMATRIX FINE PARTICLE TECHNOLOGY RESULT IN CLINICALLY MEANINGFUL IMPROVEMENTS IN PAIN IN A PHASE 3 STUDY OF PATIENTS WITH OSTEOARTHRITIS C. Young y, D. Parenti y, M. Hochberg z. y Iroko Pharmaceuticals, LLC, Philadelphia, PA, USA; zUniv. of Maryland, Baltimore, MD, USA Purpose: Osteoarthritis (OA) is characterized by acute and chronic pain and reduced physical function. Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed for the management of OA pain. As a class, NSAIDs are associated with dose-related serious gastrointestinal, cardiovascular, and renal adverse events which has prompted international health authorities and the United States Food and Drug Administration to recommend that NSAIDs be used at the lowest effective dose for the shortest possible duration. Diclofenac submicron particle containing capsules (DSPCC) consisting of submicron drug particles and a proprietary combination of excipients were developed using SoluMatrix Fine Particle Technology to provide efficacy at lower doses than commercially available diclofenac drug products and are licensed for treatment of mild-to-moderate acute pain in adults. As previously reported, DSPCC 35 mg three times daily (TID) significantly reduced the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain subscale score compared with placebo (P 1⁄4 0.0024) in a phase 3 study in adults with OA pain of the hip or knee. Therewas some evidence of improvement in theWOMAC pain subscale score compared with placebo for DSPCC 35 mg twice daily (BID), although this did not achieve statistical significance (P 1⁄4 0.08). We report the results for measures of clinically meaningful pain relief following treatment with low-dose DSPCC in the phase 3 study. Methods: This multicenter, randomized, double-blind, placebo-controlled study enrolled patients 40 years with clinically and radiologically confirmed (Kellgren-Lawrence grade II-III) hip or knee OA pain. Eligible patients were chronic NSAID and/or acetaminophen users with baseline WOMAC pain subscale scores 40 mm (based on 100-mm Visual Analog Scale) and a documented OA flare ( 15-mm increase in WOMAC pain subscale score from screening). Patients were randomized to receive DSPCC 35 mg TID, DSPCC 35 mg BID, or placebo for 12 weeks. Efficacy parameters included responder rates for patients who achieved a reduction of 10 mm in pain intensity from baseline based on theWOMAC pain subscale score at week 2, 6, and 12; the proportion of patients with a reduction (0%-100%) in WOMAC pain subscale score at week 12 (continuous responder analysis); and the proportion of patients who discontinued from the study due to lack of efficacy. Results: Overall, 305 patients were randomized. The mean (SD) age of patients was 61.6 (8.9) years and 66.6% were female. Both DSPCC 35 mg TID (86/96, 89.6% [P 1⁄4 0.007]) and BID (86/102, 84.3% [P 1⁄4 0.0148]) resulted in significantly more patients achieving 10-mm reductions in the WOMAC pain subscale score from baseline compared with placebo (67/96, 69.8%) at week 12. Similar effects were noted at week 2 (DSPCC 35 mg TID: 73/94, 77.7% [P 1⁄4 0.0130]; DSPCC 35 mg BID: 78/100, 78.0% [P 1⁄4 0.0098]; placebo: 56/92, 60.9%) and week 6 (DSPCC 35 mg TID: 76/ 86, 88.4% [P 1⁄4 0.0031]; DSPCC 35 mg BID: 76/91, 83.5% [P 1⁄4 0.0338]; placebo: 61/87, 70.1%). The DSPCC 35 mg TID and BID groups experienced greater reductions in pain intensity compared with placebo. More than two-thirds of patients in the DSPCC 35 mg TID and BID groups achieved a reduction of 30% in theWOMAC pain subscale score from baseline and amajority of patients achieved a reduction of 50% at week 12 based on continuous responder analysis (Table). No patients in the DSPCC 35 mg TID group and 2 patients (1.9%) in the DSPCC 35 mg BID group withdrew from the study due to lack of efficacy compared with 6 patients (5.8%) in the placebo group. Conclusions: Treatment with DSPCC 35 mg TID and BID resulted in clinically meaningful improvements in pain in this study in patients with OA of the hip or knee. 713 INTRA-ARTICULAR INFILTRATION THERAPY FOR PATIENTS WITH GLENOHUMERAL OSTEOARTHRITIS. A SYSTEMATIC REVIEW OF THE LITERATURE. S. Colen y, P. Geervliet z, D. Haverkamp x, M. van den Bekerom k. yUniv. Hosp. Leuven, Leuven, Belgium; zGemini Hosp., Dept. of Orthopaedic Surgery, Den Helder, Netherlands; x Slotervaart Hosp., Dept. of Orthopaedic Surgery, Amsterdam, Netherlands; kOnze Lieve Vrouwe Gasthuis, Dept. of Orthopaedic Surgery, Amsterdam, Netherlands Purpose: Conservative treatments are especially in patients with GHOA important, since shoulder arthroplasty has its limitations. In this systematic review we will evaluate the current evidence regarding the efficacy of intra-articular infiltration treatment options in patients with glenohumeral osteoarthritis (GH-OA). Methods: The following databases are searched: Pubmed/Medline, Cochrane Clinical Trial Register, Embase and the WHO clinical trial register. All intra-articular injection products used for the treatment of shoulder OA in humans are included. Results: A total of 8 studies could be included in this review. Hyaluronic acid (HA) showed effect sizes of 2.07, 2.02 and 2.11 at 6,12 and 26weeks follow-up, respectively. Placebo (1.60 , 1.82 and 1.68) also showed stable effect sizes at the same time points. The efficacy of corticosteroids (CS) decreased rapidly at follow-up (1.08, 0.43 and 0.19). Although statistical significant, the maximum difference in effect sizes between HA and placebo was only 0.43 with absolute values between 2.0 and 6.4 on a 100-point VAS for pain. Conclusion: Intra-articular treatment with HA has a good efficacy at follow-up compared to baseline. However, the difference in efficacy between HA and placebo never reaches the minimal clinically important difference at any of the follow-up points. We are not able to give clear recommendations for the use of intra-articular CS injections in patients with GH-OA. In future research we recommend to focus on sufficiently powered randomized trials to compare the efficacies of HA, CS, placebo and other intra-articular treatment options in patients with GH-OA. 714 IMPROVEMENT IN CARTILAGE FOLLOWING INTRA-ARTICULAR INJECTION OF TG-C, A CELL MEDIATED GENE THERAPY FOR OSTEOARTHRITIS B. Lee y, S. Totterman z, D. Gale z, A. Schreyer z, J. Cho y, T. Kim y, Y. Park y, E. Jeong y. yKolon Life Sci., Inc., Gwacheon-si, Republic of Korea; zQmetrics Tech., Rochester, NY, United States Purpose: A randomized single-blind phase IIa trial was conducted in 28 patients with knee OA to determine both safety and efficacy of TG-C. TG-C is a cell mediated gene therapy that contains non-transduced (hChonJ) and transduced (hChonJb#7) human allogeneic chondrocytes. hChonJb#7 cells were transduced with TGF-b1 gene using retroviral vector, while hChonJ cells were not modified. The hChonJb#7 cells were

Background Clinical studies demonstrated that baseline disease activity including C-reactive protein (CRP) level was a predictor variable for radiographic joint damage in patients with rheumatoid arthritis (RA). Objectives To identify variables associated with radiographic joint damage in patients with RA treated with intravenously administered golimumab (GLM) + Methotrexate (MTX) or MTX + placebo (PBO). Methods GO-FURTHER was a multicenter, randomized, placebo-controlled study. Adult patients with active RA despite MTX therapy (≥6 tender and swollen joints, CRP ≥1.0 mg/dL, and RF and/or anti-CCP positive) were randomized to placebo (PBO) + MTX or GLM (2mg/kg) plus MTX at week 0, 2, and every 8 week thereafter (GLM group). Patients in PBO group with Sharp score (TSS). The correlations of TSS with hemoglobin, disease activity score (DAS28-CRP)and physical function evaluated with Health Assessment Questionnaire (HAQ) were assessed using Spearman9s correlation or multivariable liner regression model. Anemia was defined based on World Health Organization (WHO) criteria as Hgb Results Moderate to severe RA was demonstrated by a mean DAS28 score of 5.9 with TSS of 48.5 in all patients group at baseline. In linear regression models, baseline DAS28, HAQ score, and Hgb level was correlated with baseline TSS with Spearman9s correlation coefficient (r) of 0.148 (p Conclusions Hemoglobin level is an independent variable predicting radiographic progression in MTX refractory RA patients. Disclosure of Interest R. Westhovens Grant/research support from: Janssen R & D, LLC, C. Han Employee of: Johnson & Johnson Pharmaceutical Services, LLC, M. Weinblatt Grant/research support from: Janssen R & D, LLC, L. Kim Employee of: Janssen R & D, LLC, E. Hsia Employee of: Janssen R & D, LLC, D. Parenti Employee of: Janssen Scientific Affairs, LLC, S. Kafka Employee of: Janssen Scientific Affairs, LLC, C. Bingham III Grant/research support from: Janssen R & D, LLC

Background Little is known about the influence of specific comorbidities on response to biologic therapy. Objectives To examine the impact of comorbidities on anti-TNF therapy efficacy in rheumatoid arthritis (RA) patients (pts) within the US CORRONA RA registry. Methods A retrospective cohort of adult RA pts with moderate-to-severe RA (CDAI>10) who initiated anti-TNF biologics after June 1, 2009 and had a 6 month follow up (in a window of 3–9 months) were included. Comorbidity assessments included a modified Charlson comorbidity index (CCI) [HIV status was not assessed]) and diagnoses of diabetes, cardiovascular disease (CV) and history of depression. Propensity score (PS) method was employed to match pts with and without select comorbidities. Variables used for PS matching were selected if standardized differences were ≥0.1 between groups. PS were stratified by line of therapy. The primary outcome was achievement of low disease activity (LDA) at 6 months (CDAI ≤10). Secondary outcomes included DAS28(ESR) LDA (DAS Results A total of 4064 anti-TNF initiations were included. For CCI, diabetes and CV, there were no significant differences in response in the matched populations. For patients with a history of reported depression (hxdep), LDA rates were significantly lower (29% for hxdep vs 39% for no hxdep, p Conclusions Of the comorbidities examined, a history of reported depression in RA patients is an indicator of lower response rates to TNFi. CDAI was primarily influenced by patient responses. Patient fatigue may be a manifestation of depression and explained response rate differences. Further analyses are needed to explore this relationship. Acknowledgement This study is sponsored by Corrona, LLC. The Corrona RA registry has been supported through contracted subscriptions in the last two years by AbbVie, Amgen, BMS, Crescendo, Genentech, Horizon Pharma USA, Janssen, Eli Lilly, Novartis, Pfizer, and UCB. Disclosure of Interest D. Parenti Employee of: Janssen Scientific Affairs, LLC, G. Reed Shareholder of: Corrona, LLC, Employee of: Corrona, LLC, S. Kafka Employee of: Janssen Scientific Affairs, LLC, L. Ellis Employee of: Janssen Scientific Affairs, LLC, J. Greenberg Shareholder of: Corrona, LLC, Consultant for: Janssen Scientific Affairs, LLC, AstraZeneca, Celgene, Genentech, Novartis, Pfizer, Employee of: Corrona, LLC, R. DeHoratius Employee of: Janssen Scientific Affairs, LLC

Background Clinical studies demonstrated that patients with rheumatoid arthritis (RA) experience lower hemoglobin level and higher prevalence of anemia than general population. Objectives This study was to examine the treatment effect of intravenously administered golimumab on improving hemoglobin (Hgb) level, and relieving anemia and anemia-related outcomes among patients with RA using data from the phase III clinical trial GO-FURTHER. Methods In the GO-FURTHER trial, adult patients with active RA were randomized to placebo + MTX (PBO group) or GLM (2mg/kg) plus MTX at week 0, 2, and every 8 weeks thereafter (GLM group). Patients in placebo group with Results At baseline, mean (SD) of Hgb was 12.1 (1.39) g/dl in female and 13.8 (1.29) g/dl in male, and 40.8% female patients and 23.4% male patients had anemia. Significantly greater improvement in hemoglobin in the GLM-treated patients than patients in the placebo group was observed as early as Week 4. At Week 12, mean improvement in Hgb was 0.34g/dl in male and 0.69g/dl in female in the GLM group, compared to an improvement of 0.01g/dl in male (p Conclusions Intravenously administered golimumab therapy improves Hgb, resulting in reduced anemia, improved physical function and fatigue in patients with moderate to severe active RA despite MTX. Disclosure of Interest C. Han Employee of: Johnson & Johnson Pharmaceutical Services, M. Weinblatt Grant/research support from: Janssen R & D, LLC, R. Westhovens Grant/research support from: Janssen R & D, LLC, L. Kim Employee of: Janssen R & D, LLC, E. Hsia Employee of: Janssen R & D, LLC, D. Parenti Employee of: Janssen Scientific Affairs, LLC, S. Kafka Employee of: Janssen Scientific Affairs, LLC, C. Bingham III Grant/research support from: Janssen R & D, LLC

Background Limited data are available about infliximab (IFX) dose escalation. Objectives This analysis examines the frequency of dose escalation among IFX patients using data from the US CORRONA RA registry and describes the characteristics of patients who dose escalate vs those who do not. Methods RA patients initiating IFX at a dose of ≤5 mg/kg on or after 6/1/2009 with at least 1 follow-up visit with dose information were eligible for analysis. Subgroup analysis was performed among patients with follow-up at 1yr to compare characteristics between those who dose escalated vs those who did not. Dose escalation was defined as an increase of >1mg/kg in dose and/or a decrease in the frequency of dosing by at least 1 wk (e.g. q 8 wks to q7 wks). Censoring occurred if patients switched to another biologic or left the registry. Descriptive statistics were used to compare baseline characteristics of infliximab patients stratified by number of biologics, and also comparing those who dose escalated vs those who did not within the 1st yr after initiating therapy. Results A total of 716 patients initiated IFX after June 2009. Common characteristics included mean age (61yrs), women (78%), mean weight (83 kg), RF+ (70%) and CCP+ (67%), baseline CDAI (22.5), and insurance status (Medicare 46%, Medicaid 6%). Differences between those who initiated IFX as their 1st, 2nd, or 3rd biologic included RA duration (7.0, 9.6, 11.0 yrs, respectively, p Over 3 yrs follow-up, the proportions of patients escalating IFX significantly differed, ranging from a low of 21% at 1 yr for patients using IFX as 1st line to a high of 81% at 3yrs for patients using it as 3rd line (Table, p=0.0024 for between-group differences). In patients with follow-up data at 12mo (n=608), there were some baseline characteristics associated with dose escalating vs not in the 1st yr of therapy including shorter RA duration (p=0.03), greater number of prior biologics (p=0.04), monotherapy (p=0.03), greater prednisone use (p=0.01), and higher CDAI (p=0.04) and related disease activity measures. Conclusions Dose escalation of IFX is relatively frequent over time. Patients with more severe RA undergo dose escalation more commonly than those with less severe disease. Understanding long term benefits and persistence and related factors following dose escalation may help optimize dose escalation as a treatment strategy compared to switching. Acknowledgement This study is sponsored by Corrona, LLC. The Corrona RA registry has been supported through contracted subscriptions in the last two years by AbbVie, Amgen, Astra Zeneca, BMS, Genentech, Horizon Pharma USA, Janssen, Eli Lilly, Novartis, Pfizer, and UCB. Disclosure of Interest J. Curtis Grant/research support from: Janssen Scientific Affairs, LLC, Consultant for: Roche, Genentech, UCB, CORRONA, AMGEN, PFIZER, BMS, Crescendo, ABB VIE, Y. Shan Grant/research support from: Janssen Scientific Affairs, LLC, Employee of: CORRONA, LLC, K. Saunders Grant/research support from: Janssen Scientific Affairs, LLC, Employee of: CORRONA, LLC, D. Parenti Employee of: Janssen Scientific Affairs, LLC, S. Kafka Employee of: Janssen Scientific Affairs, LLC, J. Kremer Grant/research support from: Janssen Scientific Affairs, LLC, Consultant for: CORRONA, LLC

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

Background Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended for the management of pain associated with rheumatoid arthritis and osteoarthritis. As a class, NSAIDs are associated with dose-related serious gastrointestinal, cardiovascular, and renal adverse events (AEs), prompting the European Medicines Agency, the US Food and Drug Administration, and others to recommend that NSAIDs be used at the lowest effective dose for the shortest possible duration. 1 To deliver effective pain relief with lower systemic exposure than commercially available drug products, Iroko Pharmaceuticals is developing investigational, lower-dose SoluMatrix® meloxicam manufactured using SoluMatrix Fine Particle Technology™ and containing submicron particles of meloxicam with enhanced dissolution properties. Objectives To evaluate the pharmacokinetic (PK) properties and safety of lower-dose submicron meloxicam in healthy adult volunteers. Methods In this 4-period, 4-sequence crossover study, healthy adults aged 18 to 55 years were randomized to receive single doses of lower-dose submicron meloxicam 5 mg (under fasted conditions), lower-dose submicron meloxicam 10 mg (under fasted and fed conditions), and conventional meloxicam 15-mg tablets (Mobic®); Boehringer Ingelheim; under fasted conditions). Blood samples for PK assessment were collected pre dose through 96 h post dose and were analyzed using a validated LC-MS/MS method. Safety was also evaluated. Results Twenty-eight participants were enrolled and 25 participants completed the study. Lower-dose submicron meloxicam 10 mg (1.25±0.25 μg/mL) attained similar mean peak plasma meloxicam levels ± SD compared with conventional meloxicam 15-mg tablets (1.29±0.42 μg/mL; Table) under fasting conditions. Lower-dose submicron meloxicam 5 mg (2.0 h) and 10 mg (2.0 h) achieved more rapid time to peak plasma meloxicam levels under fasting conditions compared with conventional meloxicam 15-mg tablets (4.0 h). Lower-dose submicron meloxicam 10 mg demonstrated approximately 29% lower overall systemic exposure compared with conventional meloxicam 15-mg tablets (Table). As described for other NSAIDs, food decreased the rate but not the overall extent of meloxicam absorption from lower-dose submicron meloxicam (Table). Lower-dose submicron meloxicam 5 and 10 mg and conventional meloxicam 15-mg tablets demonstrated similar drug clearance based on half-life and the terminal elimination rate constant (Table). Treatment-related AEs included 1 case each of mild abdominal pain and mild diarrhea in the lower-dose submicron meloxicam 10 mg (fed) group and 1 report of mild somnolence in the lower-dose submicron meloxicam 5 mg group. Conclusions Lower-dose submicron meloxicam 10 mg demonstrated comparable peak plasma levels, earlier time to peak plasma levels, and lower overall systemic exposure compared with conventional meloxicam 15-mg tablets under fasting conditions. Trials are underway to assess the clinical impact of this investigational, lower-dose meloxicam drug product. References McCarberg BH, et al. Clin Ther. 2012;34(9):1954-1963. Disclosure of Interest K. Olugemo Employee of: PAREXEL, D. Parenti Employee of: Iroko Pharmaceuticals, LLC, C. Young Employee of: Iroko Pharmaceuticals, LLC DOI 10.1136/annrheumdis-2014-eular.5403

Background Indomethacin is used to treat acute gouty arthritis and other acute pain conditions, but similar to other NSAIDs, is associated with dose-related gastrointestinal, cardiovascular, and renal complications. International health authorities recommend that NSAIDs be used at the lowest effective dose. To deliver effective pain relief with lower systemic exposure than commercially available NSAIDs, Iroko Pharmaceuticals, LLC is developing an investigational, lower-dose SoluMatrix® indomethacin drug product manufactured using SoluMatrix Fine Particle Technology™ that contains submicron indomethacin drug particles allowing for faster dissolution. In a phase 1 pharmacokinetic study, lower dose submicron indomethacin 40 mg demonstrated faster absorption (tmax), comparable maximum plasma concentrations (Cmax), and lower overall extent of exposure (AUC0–∞) compared with conventional indomethacin immediate-release capsules 50 mg under fasting conditions. Objectives To evaluate the efficacy of lower-dose submicron indomethacin compared with placebo in two phase 3 studies in postsurgical patients. Methods Two phase 3, multicenter, double-blind studies enrolled patients aged 18–68 years with moderate-to-severe acute pain (≥40 mm/100 mm by Visual Analog Scale) following bunionectomy. Patients were randomized to receive lower-dose submicron indomethacin 40 mg TID, 40 mg BID, 20 mg TID, or placebo. One study included a treatment group of celecoxib 400-mg loading dose followed by 200 mg BID. The efficacy parameters for both studies included the overall (summed) pain intensity difference over 0-48 h (SPID-48) following the first dose of study medication and pain intensity differences (PID) at each scheduled assessment. Results In total, 835 patients were enrolled: 462 in study 1 and 373 in study 2. In study 1, the lower-dose submicron indomethacin 40 mg TID (509.6±91.9;P Conclusions Lower-dose submicron indomethacin provided effective analgesia in two phase 3 studies in patients with acute pain following bunionectomy and represents a potentially promising treatment option for patients with acute pain. Disclosure of Interest : R. Altman Consultant for: Pfizer, Teva Pharmaceutical Industries Ltd., Petah Tikva, Oletec, Novartis, Johnson & Johnson, Iroko Pharmaceuticals, LLC, Ferring Pharmaceuticals, Speakers bureau: Ferring Pharmaceuticals, A. Gibofsky Shareholder of: GlaxoSmithKline plc, Bristol-Myers Squibb, Amgen, Pfizer, AbbVie, and Johnson & Johnson, Consultant for: Takeda, Amgen, AbbVie, Genentech, Horizon, UCB, and Iroko Pharmaceuticals, LLC, D. Parenti Employee of: Iroko Pharmaceuticals, LLC, C. Young Employee of: Iroko Pharmaceuticals, LLC DOI 10.1136/annrheumdis-2014-eular.5286

Background Indomethacin, a potent non-steroidal anti-inflammatory drug (NSAID) used to treat acute pain, is, like other NSAIDs, associated with dose-dependent gastrointestinal (GI), cardiovascular (CV), and renal adverse events (AEs). US and EU health authorities recommend NSAIDs be used at the lowest effective dose.1 To deliver effective pain relief with lower systemic exposure than commercially available drug products, Iroko Pharmaceuticals is developing investigational, lower-dose SoluMatrix® indomethacin using SoluMatrix Fine Particle Technology™, containing submicron particles of indomethacin with enhanced dissolution properties. We present safety and tolerability data from two phase 3 studies evaluating the efficacy of lower-dose submicron indomethacin in patients with acute pain following elective surgery. Objectives Evaluate safety of lower-dose submicron indomethacin in postsurgical patients. Methods Two phase 3, randomized, multicenter, double-blind studies enrolled patients 18–68 years old undergoing bunionectomy. Patients with moderate-to-severe pain (≥40 mm/100-mm Visual Analog Scale) received lower-dose submicron indomethacin (40 mg TID, n=187, or BID, n=184, or 20 mg TID, n=183), placebo (n=188), or, in 1 study, celecoxib (400 mg loading dose followed by 200 mg BID, n=93). AEs, vital signs, pain intensity, and rescue medication use were monitored for 48 hours. Treatment-emergent AEs (TEAEs) were summarized by severity and seriousness. Results TEAEs were similar across treatment groups. The most common TEAEs (≥5% of patients in any treatment group) were nausea, post-procedural edema, headache, dizziness, vomiting, post-procedural hemorrhage, and constipation (Table). Seven (0.8%) patients withdrew due to a TEAE, including 2 cases of urticaria and 1 case each of uvulitis, angioedema, and nausea among recipients of lower-dose submicron indomethacin, and 1 case each of pyrexia and anxiety in the placebo group. A serious TEAE, a single report of deep vein thrombosis, in the lower-dose submicron indomethacin 40 mg BID group was determined to be unrelated to the study drug. Conclusions Lower-dose submicron indomethacin was generally well tolerated in two phase 3 studies in patients with postsurgical pain. There were no serious CV, GI, or renal AEs associated with NSAID use. Based on available efficacy data, the investigational lower-dose submicron indomethacin represents a potentially promising lower-dose option for treating acute pain. References Langford RM. Clin Rheumatol. 2006;25 Suppl 1:S2-8. Acknowledgements The authors would like to thank Jennifer Nezzer, MS, and Daniel Solorio, whose contributions and individual efforts helped make these studies possible. Disclosure of Interest : R. Altman Consultant for: Pfizer, Teva Pharmaceutical Industries Ltd, and Iroko Pharmaceuticals, LLC, A. Gibofsky Shareholder of: GlaxoSmithKline, Amgen, Bristol-Meyers Squibb, Pfizer, Abbvie, and Johnson & Johnson, Consultant for: Takeda, Amgen, AbbVie, Genentech, Horizon, UCB, and Iroko Pharmaceuticals, LLC, D. Parenti Employee of: Iroko Pharmaceuticals, LLC, C. Young Employee of: Iroko Pharmaceuticals, LLC DOI 10.1136/annrheumdis-2014-eular.5355

Background Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed for the management of osteoarthritis (OA) pain. As a class, NSAIDs are associated with dose-related, serious gastrointestinal, cardiovascular, and renal adverse events (AEs), which has prompted the European Medicines Agency, the US Food and Drug Administration, and other organizations to recommend that NSAIDs be used at the lowest effective dose for the shortest possible duration [1]. To deliver effective pain relief with lower systemic exposure than commercially available drug products, Iroko Pharmaceuticals is developing investigational, lower-dose SoluMatrix® meloxicam manufactured using SoluMatrix Fine Particle Technology™ and containing submicron particles of meloxicam with enhanced dissolution properties. Objectives To evaluate the efficacy and safety of lower-dose submicron meloxicam in patients with OA pain. Methods This randomized, double-blind, placebo-controlled, pivotal phase 3 study enrolled adults ≥40 years of age with radiographically confirmed (Kellgren-Lawrence grade II–III) hip or knee OA. Eligible patients were chronic NSAID and/or acetaminophen users with a baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale score ≥40 mm (based on 100-mm Visual Analog Scale) and a documented OA pain flare (≥15-mm increase in WOMAC pain subscale score following washout of prior analgesics). Patients (N=403) were randomized 1:1:1 to receive once-daily treatment with lower-dose submicron meloxicam 5 mg (n=139), lower-dose submicron meloxicam 10 mg (n=130), or placebo (n=134). The primary efficacy endpoint was the mean change from baseline in WOMAC pain subscale score at week 12. Safety was also evaluated. Results Overall, 350 patients (86.8%) completed the study. At week 12, lower-dose submicron meloxicam 5 mg (least squares [LS] mean [SE]: -36.36 [2.485]; P =0.0005) and 10 mg (-34.23 [2.677]; P =0.0059) provided significantly greater pain relief as measured by the primary endpoint compared with placebo (-25.49 [2.635]). In addition, pain was significantly improved based on the patient global impression of change with lower-dose submicron meloxicam 5 mg ( P =0.0049) and 10 mg ( P =0.0012) compared with placebo. Furthermore, patients in the lower-dose submicron meloxicam 5 mg (LS mean [SE]: 52.4 [6.61] doses; P =0.006) and 10 mg (48.4 [7.13] doses; P =0.0013) treatment groups used significantly less rescue medication compared with patients in the placebo group (73.2 [7.03] doses). Across all treatment groups, the most common AEs (occurring in ≥2% of patients) were diarrhea, headache, and urinary tract infection. No deaths or serious AEs were reported. Conclusions Lower-dose submicron meloxicam 5 and 10 mg once daily provided significantly greater relief from OA pain compared with placebo and were generally well tolerated. These data suggest that lower-dose submicron meloxicam may represent a promising treatment option for adults with OA pain. References McCarberg BH, et al.Clin Ther. 2012;34(9):1954-1963. Disclosure of Interest : R. Altman Consultant for: Ferring Pharmaceuticals; Iroko Pharmaceuticals, LLC; Johnson & Johnson; Novartis; Oletec; Petah Tikva; Pfizer; and Teva Pharmaceutical Industries Ltd, Speakers bureau: Ferring Pharmaceuticals, M. Hochberg Consultant for: AbbVie; Bioiberica SA; Eli Lilly; EMD Serono; Genentech/Roche; Iroko Pharmaceuticals, LLC; Merck & Co, Inc; Novartis Pharma AG; Pfizer; Pozen; and UCB, Inc, A. Gibofsky Shareholder of: AbbVie; Amgen; Bristol-Myers Squibb; GlaxoSmithKline plc; Johnson & Johnson; and Pfizer, Consultant for: AbbVie; Amgen; Genentech; Iroko Pharmaceuticals, LLC; Horizon; Takeda; and UCB, D. Parenti Employee of: Iroko Pharmaceuticals, LLC, C. Young Employee of: Iroko Pharmaceuticals, LLC DOI 10.1136/annrheumdis-2014-eular.5445