Clarence W. Legerton

Impact of T-cell costimulation modulation in patients with undifferentiated inflammatory arthritis or very early rheumatoid arthritis: a clinical and imaging study of abatacept (the ADJUST trial)

Background Several agents provide treatment for established rheumatoid arthritis (RA), but a crucial therapeutic goal is to delay/prevent progression of undifferentiated arthritis (UA) or very early RA. Objective To determine the impact of T-cell costimulation modulation in patients with UA or very early RA. Methods In this double-blind, phase II, placebocontrolled, 2-year study, anti-cyclic citrullinated peptide (CCP)2-positive patients with UA (not fulfilling the ACR criteria for RA) and clinical synovitis of two or more joints were randomised to abatacept (∼10 mg/kg) or placebo for 6 months; the study drug was then terminated. The primary end point was development of RA (by ACR criteria) at year 1. Patients were monitored by radiography, MRI, CCP2, rheumatoid factor and 28 joint count Disease Activity Score (DAS28) over 2 years. Results At year 1, 12/26 (46%) abatacept-treated versus 16/24 (67%) placebo-treated patients developed RA (difference (95% CI) −20.5% (−47.4% to 7.8%)). Adjusted mean changes from baseline to year 1 in Genant-modified Sharp radiographic scores for abatacepttreated versus placebo-treated patients, respectively, were 0 versus 1.1 for total score, and 0 versus 0.9 for erosion score. Mean changes from baseline to year 1 in MRI erosion, osteitis and synovitis scores were 0, 0.2 and 0.2, respectively, versus 5.0, 6.7 and 2.3 in the abatacept versus placebo groups. Safety was comparable between groups; serious adverse events occurred in one patient (3.6%) in each group. Conclusion Abatacept delayed progression of UA/very early RA in some patients. An impact on radiographic and MRI inhibition was seen, which was maintained for 6 months after treatment stopped. This suggests that it is possible to alter the progression of RA by modulating T-cell responses at a very early stage of disease. Trial registration number NCT00124449.

Subcutaneous abatacept versus intravenous abatacept : a phase IIIb noninferiority study in patients with an inadequate response to methotrexate.

Objective To compare the efficacy and safety of subcutaneous (SC) and intravenous (IV) abatacept. Methods In this phase IIIb double-blind, double-dummy, 6-month study, patients with rheumatoid arthritis (RA) and inadequate responses to methotrexate were randomized to receive 125 mg SC abatacept on days 1 and 8 and weekly thereafter (plus an IV loading dose [∼10 mg/kg] on day 1) or IV abatacept (∼10 mg/kg) on days 1, 15, and 29 and every 4 weeks thereafter. The primary end point for determining the noninferiority of SC abatacept to IV abatacept was the proportion of patients in each group meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at month 6. Other efficacy end points, immunogenicity, and safety were also assessed. Results Of 1,457 patients, 693 of 736 (94.2%) treated with SC abatacept and 676 of 721 (93.8%) treated with IV abatacept completed 6 months. At month 6, 76.0% (95% confidence interval 72.9, 79.2) of SC abatacept–treated patients versus 75.8% (95% confidence interval 72.6, 79.0) of IV abatacept–treated patients achieved an ACR20 response (estimated difference between groups 0.3% [95% confidence interval –4.2, 4.8]), confirming noninferiority of SC abatacept to IV abatacept. Onset and magnitude of ACR responses and disease activity and physical function improvements were comparable between the SC and IV abatacept–treated groups. The proportions of adverse events (AEs) and serious AEs over 6 months were 67.0% and 4.2%, respectively, in the SC abatacept–treated group and 65.2% and 4.9%, respectively, in the IV abatacept–treated group, with comparable frequencies of serious infections, malignancies, and autoimmune events between groups. SC injection site reactions (mostly mild) occurred in 19 SC abatacept (IV placebo)–treated patients (2.6%) and 18 IV abatacept (SC placebo)–treated patients (2.5%). Abatacept-induced antibodies occurred in 1.1% of SC abatacept–treated patients and 2.3% of IV abatacept–treated patients. Conclusion SC abatacept provides efficacy and safety comparable with that of IV abatacept, with low immunogenicity and high retention rates, consistent with the established IV abatacept profile. Rates of injection site reactions were low. SC abatacept will provide additional treatment options, such as an alternative route of administration, for patients with RA.

Subcutaneous abatacept for the treatment of rheumatoid arthritis: longterm data from the ACQUIRE trial.

Objective. Assess longterm tolerability, safety, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate-refractory patients with rheumatoid arthritis (RA). Methods. The phase III, multinational Abatacept Comparison of Sub[QU]cutaneous Versus Intravenous in Inadequate Responders to MethotrexatE (ACQUIRE) trial comprised a 6-month, randomized, double-blind (DB) period, in which patients received intravenous (IV) or SC ABA, plus MTX, followed by an open-label, longterm extension (LTE), in which patients received SC ABA, 125 mg/week. Safety and efficacy from the LTE (∼3.5 yrs of exposure) are reported. Results. Patients who completed the DB period (1372/1385, 99.1%) entered the LTE; 1134 patients (82.7%) kept taking the treatment at time of reporting. Mean (SD) was 31.9 months (6.8); median (range) exposure was 33.0 (8–44) months. Patients entering the LTE had longstanding, moderate-to-severe disease [mean 7.6 (7.9) yrs and DAS28 (C-reactive protein) 6.2 (0.9)]. Incidence rates (events/100 patient-yrs) were reported for serious adverse events (8.76, 95% CI 7.71, 9.95), infections (44.80, 95% CI 41.76, 48.01), serious infections (1.72, 95% CI 1.30, 2.27), malignancies (1.19, 95% CI 0.86, 1.66), and autoimmune events (1.31, 95% CI 0.95, 1.79). Twenty-seven patients (2%) experienced injection-site reactions; all except 1 were mild. American College of Rheumatology 20, 50, and 70 responses achieved during the DB period were maintained through the LTE, and on Day 981 were 80.2% (95% CI 77.2, 83.2), 63.5% (95% CI 58.2, 68.9), and 39.5% (95% CI 34.0, 44.9) for patients who kept taking SC ABA, and 80.0% (95% CI 77.0, 83.0), 63.2% (95% CI 57.8, 68.7), and 39.2% (95% CI 33.7, 44.7) for those who switched from IV to SC ABA. Conclusion. These findings support SC ABA as a well-tolerated and efficacious longterm treatment for patients with RA and inadequate response to MTX (ClinicalTrials.gov identifier NCT00559585).

Subcutaneous abatacept: long-term data from the Acquire Trial

Background/Purpose: MicroRNAs (miRs) are a novel class of posttranscriptional regulators. A single miR can have profound effects on cell activation due to its ability to modulate multiple pathways at once. We have previously shown that miR-155 is upregulated in rheumatoid arthritis (RA) synovial macrophages and promotes the development of autoimmunity and joint inflammation. Pre-clinical arthritis may be associated with lung changes e.g. bronchial wall thickening, thus the aim of this study was to investigate the contribution of miR-155 regulated pathways to lung homeostasis. Methods: Normal human lung tissue was tested by in situ hybridisation with miR-155 and control probes. To model the fibrotic response, WT and miR-155 / mice were given bleomycin (0.06 unit/mouse) intranasally. Intervention included intraperitoneal injections of the Liver X Receptor (LXR) agonist (GW3965 daily; 40 mg/kg). End-points included bronchial lavage (BAL) cytology, lung tissue histology, evaluation of the expression of inflammatory and fibrotic genes by qPCR and concentrations of soluble mediators in serum and BAL fluid by multiplex assays. The validation of miR-155 binding to LXR, and the LXR response element in collagen gene promoters were performed with reporter assays. Results: In situ hybridisation showed an abundant expression of miR-155 in the normal human lung suggesting that this miR may contribute to normal lung homeostasis. miR-155 / mice developed more severe bleomycininduced lung fibrosis compared to WT mice, as seen by increased collagen 1a/3a mRNA expression and protein deposition in the lungs, as well as accumulation of macrophages and lymphocytes in BAL. Gene expression analysis of lung extracts revealed an increase in the M2 pro-fibrotic macrophage markers Arginase 2, IL-13R and Ym1. In addition, the levels of pro-fibrotic cytokines such as VEGF and bFGF were significantly higher in BAL and serum of miR-155 / mice. Primary lung fibroblast lines derived from miR-155 / mice showed higher proliferation rates and motility compared to WT cells in wound healing assays. Computational analysis followed by functional luciferase assays revealed that the transcription activator LXR alpha is a direct target of miR-155 in the lungs. Expression of LXR alpha was significantly upregulated in the lungs of naive miR-155 / mice and was further increased in mice given bleomycin compared to similarly treated WT controls. Injection of the LXR agonist to WT mice increased LXR expression and mirrored the same phenotypic response to bleomycin as the miR-155 deficient mice; shown by increased collagen deposition and M2 macrophage and fibroblast activation. Promoter analysis revealed that LXRs could directly induce collagen production by binding to col1a and col3a promoters. / Conclusion: miR-155 appears important for lung homeostasis, likely by fine tuning levels of LXR thereby protecting from excessive remodelling. Given this and the emerging contribution of miR-155 to development of autoimmunity, this miR may act as a master-switch determining the duration of inflammation and the initiation of remodelling, as well as the balance between the immune and auto-immune responses.Background/Purpose: High mobility group box 1 (HMGB1) is a non-histone DNA binding protein that is passively released by dying cells or actively secreted by immunocompetent cells and the receptor for advanced glycation end-products (RAGE) is one of its receptors. Higher levels of HMGB1 have been found in patients with granulomatosis with polyangiitis (GPA) with active disease whereas higher HMGB1 and lower soluble (sRAGE) levels have been found in patients with acute atherosclerotic events suggesting sRAGE acts as a decoy receptor. This study aims to evaluate HMGB1 levels in relation to subclinical carotid atherosclerosis in GPA, and the impact of therapy on HMGB1 levels. Methods: A cross-sectional study was performed on 23 GPA patients during a quiescent phase of the disease in comparison to 20 matched controls. All study participants underwent carotid ultrasound to assess atherosclerotic plaques and intima-media thickness (IMT) and were tested for traditional risk factors for atherosclerosis, serum HMGB1 levels (ELISA-Shino Test, Kanagawa, Japan), and sRAGE levels (ELISA RD P = 0.978), HDLcholesterol (1.41 ± 0.37 vs. 1.51±0.33 mmol/L; P = 0.359), LDLcholesterol (3.01±0.79 vs. 3.29±0.82 mmol/L; P = 0.267), and a similar frequency of smoking (8.7% vs. 5.0%; P = 0.635), family history of premature coronary artery disease (CAD) (39.1% vs. 40.0%; P = 0.954), and obesity (4.3% vs. 10.0%; P = 0.446). Hypertension was only found in GPA patients (39.1% vs. 0.0%; P = 0.002) while no study participants had diabetes. Overt cardiovascular disease was found only in 13.0% of GPA patients. Statins were prescribed for 21.7% of GPA patients and 5.0% of controls (P = 0.127). Among GPA patients, prednisolone was being used by 34.8% with a median daily dose of 5.0mg (2.5-15.0) and azathioprine by 34.8%. Only two GPA patients used statins and prednisolone concomitantly. Carotid plaques were found in 30.4% of GPA patients and in 15.0% of controls (P = 0.203) and the overall IMT was similar in GPA patients and in controls (0.833±0.256 vs. 0.765±0.133mm; P = 0.861). Median serum HMGB1 levels were similar between GPA patients and controls [2.13ng/mL (1.11-7.22) vs. 2.42ng/mL (0.38-6.75); P = 0.827] as well as mean sRAGE levels (1256.1±559.6 vs. 1483.3±399.8pg/mL; P = 0.155). No correlations were found between HMGB1 and sRAGE ( = 0.068; P = 0.681) and between HMGB1 and maximum IMT in carotid arteries ( = -0.067; P = 0.720). GPA patients on prednisolone (1.77±0.76 vs. 3.53±2.06ng/ mL; P = 0.017) and statins (1.39±0.28 vs. 3.34±1.94ng/mL; P = 0.001) presented significantly lower serum HMGB1 levels whereas no difference in mean HMGB1 levels was found regarding azathioprine use (2.89±2.28 vs. 2.93±1.75; P = 0.970). Conclusion: No association was found between subclinical atherosclerosis in carotid arteries and HMGB1 levels in GPA patients. Furthermore, the use of either prednisone or statins was associated with lower HMGB1 levels in GPA patients. These findings suggest that the anti-inflammatory properties of statins include effects on serum HMGB1 levels in GPA.

FRI0193 SC vs IV abatacept in RA: post-hoc efficacy analysis of long-term acquire (SC) data with aim (IV) data

Background ACQUIRE was a Ph IIIb study demonstrating comparability of SC and IV abatacept (ABA) over a 6-mth DB period. At 6 mths, all patients (pts) entered an open-label (OL) period in which they received SC ABA. AIM was a Ph III 12-mth, DB, placebo-controlled study of IV ABA, also with an OL extension. Pts in both trials had moderate-to-severe RA, inadequate response to MTX and similar BL demographics and disease activity. Objectives To provide a long-term (LT) comparison of SC and IV ABA, we performed a post-hoc efficacy analysis of LT data from the OL periods of ACQUIRE and AIM. Methods In ACQUIRE, pts received 125 mg SC ABA weekly (after 10 mg/kg IV load on Day 1) +MTX. In AIM, pts received ∼10 mg/kg IV ABA every 4 weeks (after loading doses on Days 1, 15 & 29) +MTX; only pts who received ABA in DB and OL periods were included in this analysis. LT analysis began at Day 253 for ACQUIRE; Day 225 was selected as a comparison starting point for AIM. The most recent LT data lock for ACQUIRE (Day 897) was then used as the comparison end date for AIM as well. At the time of analysis, however, not all ACQUIRE pts had reached this later time point. As-observed data were used to assess both response to treatment (ACR 20, 50 and 70) and disease status (DAS28[CRP], SDAI and CDAI). No safety analyses were performed on this subset as larger pooled safety analyses are presented elsewhere. Results In the OL period of ACQUIRE, 1372 pts received SC ABA compared with 378 pts who received IV ABA in AIM. ACR 20, 50 and 70 rates, and DAS remission rates were sustained from Days 253/225 through Day 897 for ACQUIRE/AIM, respectively (Table). SDAI and CDAI remission rates at Day 253 (13.3%; 179/1341 and 15.6%; 211/1349) were maintained up to Day 897 (20.2%; 123/608 and 22.1%; 143/646) in ACQUIRE; in AIM, corresponding rates at Day 225 (9.9%; 36/365 and 12.2%; 45/369) were similarly maintained up to Day 897 (15.0%; 45/300 and 16.7%; 52/311). Table 1 Efficacy Parameter Study Day ACQUIRE SC ABA AIM IV ABA ACR 20  Subjects, n/m (%) Start of Comparison 968/1080 (89.6) 250/269 (92.9)  (95% CI) (87.8, 91.4) (89.9, 96.0)  Subjects, n/m (%) Day 897 493/544 (90.6) 215/236 (91.1)  (95% CI) (88.2, 93.1) (87.5, 94.7) ACR 50  Subjects, n/m (%) Start of Comparison 563/719 (78.3) 134/161 (83.2)  (95% CI) (75.3, 81.3) (77.5, 89.0)  Subjects, n/m (%) Day 897 285/371 (76.8) 107/145 (73.8)  (95% CI) (72.5, 81.1) (66.6, 81.0) ACR 70  Subjects, n/m (%) Start of Comparison 284/369 (77.0) 58/81 (71.6)  (95% CI) (72.7, 81.3) (61.8, 81.4)  Subjects, n/m (%) Day 897 130/196 (66.3) 45/72 (62.5)  (95% CI) (59.7, 72.9) (51.3, 73.7) DAS Remission  Subjects, n/m (%) Start of Comparison 210/331 (63.4) 37/61 (60.7)  (95% CI) (58.3, 68.6) (48.4, 72.9)  Subjects, n/m (%) Day 897 104/166 (62.7) 37/54 (68.5)  (95% CI) (55.3, 70.0) (56.1, 80.9) Conclusions SC abatacept provided similar efficacy to IV abatacept when compared across these 2 trials; overall, efficacy achieved in the short term was maintained in the LT. Disclosure of Interest M. Genovese Consultant for: Bristol-Myers Squibb, C. Pacheco Tena: None Declared, A. Covarrubias Cobos Grant/Research support from: Bristol-Myers Squibb, G. Leon: None Declared, E. Mysler Grant/Research support from: Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, Speakers Bureau: Bristol-Myers Squibb, M. Keiserman Grant/Research support from: Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, Speakers Bureau: Bristol-Myers Squibb, R. Valente Grant/Research support from: Pfizer, UCB, BMS, Roche, Takeda, and Lilly, P. Nash Grant/Research support from: Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, Speakers Bureau: Bristol-Myers Squibb, J. Simon Campos Speakers Bureau: Bristol-Myers Squibb, J. Box Consultant for: Bristol-Myers Squibb, Speakers Bureau: Bristol-Myers Squibb, C. Legerton III: None Declared, E. Nasonov Speakers Bureau: Roche; Bristol-Myers Squibb Company; Abbott Laboratories; Merck Sharp & Dohme Corp; UCB Pharma, Inc, P. Durez Speakers Bureau: Bristol-Myers Squibb, I. Delaet Employee of: Bristol-Myers Squibb, A. Elegbe Employee of: Bristol-Myers Squibb, R. Alten Grant/Research support from: BMS, Merck Pharma GmbH, Wyeth Pharmaceuticals, Pfizer, Consultant for: Abbott Laboratories, Horizon Pharma, Merck Pharma GmbH, Nitec Pharma GmbH, Novartis Pharmaceuticals Corporation, Roche, Speakers Bureau: Abbott Laboratories, BMS, Horizon Pharma, Merck Pharma GmbH, Novartis

Longterm Safety and Efficacy of Subcutaneous Abatacept in Patients with Rheumatoid Arthritis: 5-year Results from a Phase IIIb Trial

Objective. To assess 5-year safety, tolerability, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate (MTX)-refractory patients with rheumatoid arthritis (RA). Methods. The Abatacept Comparison of sub[QU]cutaneous versus intravenous in Inadequate Responders to methotrexatE (ACQUIRE) phase IIIb, randomized, double-dummy, multinational trial compared efficacy and safety of SC and intravenous (IV) ABA in patients with RA. In the initial 6-month double-blind (DB) period, patients received IV or SC ABA, plus MTX, and in the subsequent open-label longterm extension (LTE) period, all patients received SC ABA (125 mg/wk). The final 5-year safety, tolerability, and efficacy analyses are reported. Results. Of 1385 patients who completed the DB period, 1372 entered LTE and 945 (68.8%) completed ≥ 5 years of treatment. During LTE, 97 (7.1%) patients discontinued treatment because of an adverse event (AE). Incidence rate (IR; event/100 patient-yrs of exposure; based on LTE data, 95% CI) for AE of interest were the following: serious AE 7.73 (6.96–8.58), infection 38.60 (36.24–41.12), serious infection 1.68 (1.35–2.07), malignancies 1.09 (0.84–1.42), and autoimmune disorders 1.33 (1.05–1.69), and were stable over time. No association between immunogenicity and either worsening of ABA safety or loss of efficacy was noted. Efficacy in the LTE was consistent with the DB period and was maintained to the end of the study. Conclusion. These 5-year data establish that SC ABA (125 mg/wk) has a consistent safety profile and durable efficacy for longterm treatment of patients with RA who had an inadequate response to MTX.

SAT0396 Secukinumab Provides Sustained Improvements in The Signs and Symptoms of Active Ankylosing Spondylitis: 2-Year Results from A Phase 3 Trial with Subcutaneous Loading and Maintenance Dosing (Measure 2)

Background Secukinumab, an anti–interleukin-17A monoclonal antibody, improved the signs and symptoms of ankylosing spondylitis (AS) over 52 weeks (wks) in the randomised, double-blind, placebo (PBO)-controlled, Phase 3 MEASURE 2 study (NCT01649375).1 Objectives To evaluate the long-term (104 wks) efficacy and safety of secukinumab in MEASURE 2 study. Methods 219 subjects with active AS, classified by modified New York criteria, despite therapy with NSAIDs, were randomised to subcutaneous (s.c.) secukinumab 150 or 75 mg or PBO at baseline (BL), Wks 1, 2 and 3, and every 4 wks (q4w) from Wk 4. At Wk 16, PBO-treated subjects were re-randomised to secukinumab 150 or 75 mg s.c. q4w. At BL, 39% of subjects had an inadequate response/intolerance to prior anti-TNF therapy (anti–TNF-IR). Primary endpoint was ASAS20 response rates at Wk 16. Secondary endpoints included ASAS40, hsCRP, ASAS5/6, BASDAI, SF-36 PCS and ASAS partial remission. Endpoints were assessed through Wk 104, with multiple imputation for binary variables and a mixed-model repeated measures for continuous variables. Analyses stratified by anti-TNF history were pre-specified and are reported as observed. Results 60/72 (83.3%), 57/73 (78.1%) and 57/74 (77%) subjects completed 104 wks of treatment with secukinumab 150 mg, 75 mg and PBO, respectively. As reported previously, secukinumab 150 mg significantly improved all pre-specified endpoints at Wk 16 vs. PBO, except ASAS partial remission; the 75 mg dose did not reach statistical significance at Wk 16 based on hierarchical testing.1 ASAS20/40 response rates at Wk 104 were 71.5/47.5% with both secukinumab doses. Clinical improvements with secukinumab were sustained through Wk 104 across all secondary endpoints (Table). In the subgroup of anti–TNF-naïve subjects, ASAS20/40 response rates at Wk 104 (observed data) were 76.9/56.4% and 80.0/60.0% with secukinumab 150 mg and 75 mg, respectively; corresponding rates in anti–TNF-IR subjects were 85.0/50.0% and 68.8/43.8%. Across the treatment period (mean secukinumab exposure: 735.6 days), exposure-adjusted incidence rates for serious infections/infestations, IBD, malignant/unspecified tumours and MACE with secukinumab were 1.2, 1.4, 0.5 and 0.7 per 100 subject-years, respectively. No cases of TB, opportunistic infections or suicidality-related AEs were reported. Conclusions Secukinumab provided sustained improvement through 2 years in the signs and symptoms of AS with improved physical function, regardless of anti-TNF status. Safety was consistent with previous reports. References Baeten D et al. N Engl J Med 2015;373:2534–48 Disclosure of Interest H. Marzo-Ortega Grant/research support from: Janssen and Pfizer, Consultant for: Abbvie, Celgene, Janssen, Novartis and UCB, Speakers bureau: Abbvie, Celgene, Janssen and UCB, C. Legerton Grant/research support from: AbbVie, Ablynx, Acerta, Amgen, AstraZeneca, Celgene, GSK, Janssen, E. Lilly, BMS, Pfizer, Novartis, Sandoz, UCB, Daiichi Sankyo, ChemoCentryx, Boehringer Ingelheim, Speakers bureau: Celgene and Amgen, J. Sieper Grant/research support from: AbbVie, Pfizer and Merck, Consultant for: AbbVie, Pfizer, Merck, UCB and Novartis, Speakers bureau: AbbVie, Pfizer, Merck and UCB, A. Kivitz Consultant for: AbbVie, Pfizer, Genentech, UCB and Celgene, Speakers bureau: Celgene, Pfizer, and Genentech, R. Blanco: None declared, M. Cohen Consultant for: Abbvie, Amgen, BMS, Celgene, Hospira, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi and UCB, Speakers bureau: Abbvie, Amgen, BMS, Celgene, Hospira, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi and UCB, J. Zuazo Employee of: Novartis, A. Readie Shareholder of: Novartis, Employee of: Novartis, B. Porter Shareholder of: Novartis, Employee of: Novartis, H. Richards Employee of: Novartis

THU0369 Secukinumab 150mg provides sustained improvements in the signs and symptoms of active ankylosing spondylitis with high retention rate: 3-year results from phase iii trial, measure 2

Background Secukinumab improved signs and symptoms of ankylosing spondylitis (AS) over 2 years in the MEASURE 2 study (NCT01649375).1,2 Objectives To report the efficacy and safety of secukinumab over 3 years from the MEASURE 2 study. Methods 219 patients (pts) with active AS were randomised to subcutaneous secukinumab 150mg (72 pts), 75mg (73 pts) or placebo (PBO, 74 pts). At Week (Wk) 16, PBO treated pts were re-randomised 1:1 to secukinumab 150mg or 75mg, irrespective of clinical response. Pts initially randomised to secukinumab and those who switched from PBO to secukinumab at Wk 16 were included in the analysis (secukinumab 150mg, N=106 and secukinumab 75mg, N=105). Outcome measures at Wk 156 included ASAS20 and 40, ASDAS-CRP inactive disease, ASAS5/6, BASDAI, SF-36 PCS and ASAS partial remission. Data are reported as observed. Safety analyses included all pts who received ≥1 dose of secukinumab. Results At 156 wks, the completion rates for secukinumab 150mg was 81.1% (86/106) and 72.4% (76/105) for 75mg. Higher discontinuation rates for 75mg were in part due to lack of efficacy or patient/guardian decision. Efficacy observed across endpoints from Wks 52 to 156 are summarised in the Table. Higher responses were observed in the 150mg group (Table and Figure). Over the entire study period, the mean exposure [±SD] to secukinumab was 914.3±315.5 days. The exposure-adjusted incidence rates with Any secukinumab for infections/infestations, Crohns disease, malignant/unspecified tumours and major adverse cardiovascular events were 1.5, 0.6, 0.6 and 0.6 per 100 pt-years, respectively.Table 1. Summary of Efficacy Results at Wks 52 and 156 Variable Wk Secukinumab 150mg 75mg ASAS20, % responders (n/N) 52 74.2 (69/93) 62.5 (55/88) 156 70.1 (61/87) 53.9 (41/76) ASAS40, % responders (n/N) 52 57.0 (53/93) 43.2 (38/88) 156 60.9 (53/87) 38.2 (29/76) ASDAS-CRP Inactive Disease, % pts (n/N) 52 19.4 (18/93) 17.2 (15/87) 156 25.6 (22/86) 12.0 (9/75) ASAS 5/6, % responders (n/N) 52 61.3 (57/93) 49.4 (44/89) 156 58.6 (51/87) 40.8 (31/76) ±SD (N) 52 -3.2±2.3 (93) -2.5±2.2 (89) 156 -3.3±2.5 (87) -2.5±2.3 (76) ±SD (N) 52 7.6±7.7 (94) 6.4±7.3 (85) 156 6.3±9.8 (84) 4.5±9.7 (72) ASAS partial remission, % pts (n/N) 52 24.7 (23/93) 18.0 (16/89) 156 32.2 (28/87) 11.8 (9/76) ASAS, Assessment of Spondyloarthritis International Society criteria; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; hsCRP, high sensitivity C-reactive protein; n, number of responders; N, number of pts in the treatment group with evaluation SD, standard deviation; SF-36 PCS, Short Form-36 physical component summary. Conclusions Secukinumab 150mg provided sustained improvement in the signs & symptoms along with physical functions with over 80% retention rate through 3 years in pts with AS. Safety profile remained favourable and was consistent with previous reports.1,2 References Baeten et al. N Engl J Med. 2015;373:2534–48. Marzo-Ortega et al. Ann Rheum Dis. 2016;75:812–3. Disclosure of Interest H. Marzo-Ortega Grant/research support from: Janssen and Pfizer, Consultant for: Abbvie, Celgene, Janssen, Novartis and UCB, Speakers bureau: Abbvie, Celgene, Janssen and UCB, C. Legerton Grant/research support from: AbbVie, Ablynx, Acerta, Amgen, AstraZeneca, Celgene, GSK, Janssen, E. Lilly, BMS, Pfizer, Novartis, Sandoz, UCB, Daiichi Sankyo, ChemoCentryx, Boehringer Ingelheim, Speakers bureau: Novartis, Celgene and Amgen, J. Sieper Grant/research support from: AbbVie, Pfizer and Merck, Consultant for: AbbVie, Pfizer, Merck, UCB and Novartis, Speakers bureau: AbbVie, Pfizer, Merck and UCB, A. Kivitz Consultant for: AbbVie, Pfizer, Genentech, UCB and Celgene, Speakers bureau: AbbVie, Pfizer, Genentech, UCB and Celgene, R. Blanco: None declared, M. Cohen Consultant for: Abbvie, Amgen, BMS, Celgene, Hospira, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi and UCB, Speakers bureau: Abbvie, Amgen, BMS, Celgene, Hospira, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi and UCB, E. M. Delicha Employee of: Novartis, S. Rohrer Shareholder of: Novartis, Employee of: Novartis, H. Richards Shareholder of: Novartis, Employee of: Novartis

THU0246 Subcutaneous Abatacept: Long-Term Data From the Acquire Trial

Background The Abatacept (ABA) Comparison of Sub[QU]cutaneous (SC) versus Intravenous (IV) in Inadequate Responders to MethotrexatE (MTX) (ACQUIRE) study showed comparable efficacy and safety of SC vs IV ABA over 6 mths.1 Objectives To present 32-mth safety and efficacy data from the long-term extension (LTE) of ACQUIRE, during which all patients (pts) received SC ABA. Methods ACQUIRE was a Phase IIIb, 6-mth, double-blind (DB) study in which pts with active RA (³10 swollen and ³12 tender joint count [SJC and TJC], C-reactive protein (CRP) ≥0.8 mg/dL) refractory to MTX received IV or SC ABA, plus MTX, followed by an open-label LTE when pts received SC ABA 125 mg/wk. Not all pts had reached later time points at time of analysis, as a result of differential enrolment in the trial. Results Of 1372 pts entering the LTE, 1134 (82.7%) remained on therapy at time of reporting. Mean baseline RA duration was 8 yrs, TJC and SJC were 30 and 20, respectively, and HAQ-DI was 1.7. Median (range) ABA exposure was 33 (8–44) mths. The incidence rate (IR; events/100 pt-yrs) of serious adverse events for pts treated with SC ABA in the LTE (8.76 [95% CI: 7.71–9.95]) was comparable with that for SC ABA in the DB period (9.02 [6.31–12.90]) and did not increase with increasing exposure. The IR of overall and serious infections in the LTE (44.80 [41.81–48.01] and 1.72 [1.30–2.27], respectively) did not increase vs the DB period (84.62 [74.50–96.11] and 1.48 [0.62–3.56], respectively). Bacterial, viral and hospitalised infections occurred at IRs of 27.28 (25.16–29.57), 18.25 (16.61–20.06) and 1.55 (1.16–2.07) during the LTE. The IR of malignancy did not increase in the LTE (1.19 [0.86–1.66]) vs the DB period (0.59 [0.15–2.36]). Injection-site reactions occurred in 27 (2.0%) pts in the LTE (none serious) and 19 (2.6%) pts in the DB period. Overall, 139/1365 (10.2%) and 1/153 (0.7%) pts experienced immunogenicity during the LTE and DB periods, respectively. ACR responses were maintained and comparable with original SC and IV groups: at Day 169, ACR 20 response rates were 80.2% (95% CI: 77.2, 83.2) and 80.0% (77.0, 83.0) and at Day 981 were 84.8% (80.8, 88.8) and 84.7% (80.7, 88.8). DAS28 (CRP) <2.6 rates (95% CI) were 24% (21–27; n=685) and 25% (22–28; n=667) at Day 169, and 39% (33–44; n=288) and 35% (29–40; n=275) at Day 981 for the original SC and IV groups, respectively. HAQ-DI responses (change from baseline ≥0.3) were 73% (95% CI: 69–76; n=691) and 68% (65–72; n=672) at Day 169, and 74% (69–79; n=313) and 70% (65–75; n=303) at Day 981 for the original SC and IV groups, respectively. Conclusions Over 32 mths, SC abatacept showed consistent safety with high patient retention. ACR, HAQ-DI response and DAS28 remission rates were maintained through the LTE. References Genovese MC, et al. Arthritis Rheum 2011;63:2854–64 Disclosure of Interest R. Alten Grant/research support from: BMS, Merck Pharma GmbH, Wyeth Pharmaceuticals, Pfizer, Consultant for: Abbott Laboratories, Horizon Pharma, Merck Pharma GmbH, Nitec Pharma GmbH, Novartis Pharmaceuticals Corporation, Roche, Speakers bureau: Abbott Laboratories, BMS, Horizon Pharma, Merck Pharma GmbH, Novartis Pharmaceuticals Corporation, Roche, C. Pacheco-Tena: None Declared, A. Covarrubias Shareholder of: UNIDAD REUMATOLOGICA LAS AMERICAS SCP, Grant/research support from: BMS, Pfizer, Lilly ICOS, G. Leon: None Declared, E. Mysler Grant/research support from: BMS, Consultant for: BMS, Speakers bureau: BMS, M. Keiserman Grant/research support from: Abbott Laboratories, Biogen Idec, Bristol-Myers Squibb, Eli Lilly and Company, Human Genome Sciences, Inc., MSD, Pfizer Inc, Roche, UCB, Inc, Novartis, Consultant for: Abbott Laboratories, Bristol-Myers Squibb, MSD, Speakers bureau: Bristol-Myers Squibb, MSD, R. Valente Grant/research support from: Pfizer, UCB, BMS, Roche, Takeda, Lilly, P. Nash Grant/research support from: BMS, Consultant for: BMS, Speakers bureau: BMS, J. Simon-Campos: None Declared, J. Box Shareholder of: Box Arthritis and Rheumatology of the Carolinas PLLC, Consultant for: BMS, Speakers bureau: BMS, C. Legerton III Consultant for: BMS, E. Nasonov Speakers bureau: Roche; Bristol-Myers Squibb Company; Abbott Laboratories; Merck Sharp & Dohme Corp; UCB Pharma, Inc, P. Durez Speakers bureau: BMS, I. Delaet Shareholder of: BMS, Employee of: BMS, M. Genovese Consultant for: Bristol-Myers Squibb