OBJECTIVES:Peripheral and axial manifestations of psoriatic arthritis (PsA) can lead to irreversible structural damage and chronic disability. Our objective was to explore predictors of radiographic progression and to increase our understanding of treatment effects in subgroups of patients with different rates of structural damage progression.METHODS:We analysed data from two large Phase-3 trials of secukinumab in PsA patients, FUTURE-1 (NCT01392326, n=606) and FUTURE-5 (NCT02404350, n=996), where different posologies ranging from 75 mg to 300 mg were used. We applied a longitudinal Bayesian mixture model with random effects to account for the variability in the repeated radiographic assessments. "Fast progressors" were defined post hoc as patients with a 50% model-estimated probability to progress at least 0.5 mTSS/year faster than an average patient.RESULTS:Higher baseline inflammation and higher body weight were identified as significant predictors of radiographic progression (multivariate model). Model-estimated structural damage progression in an average patient treated with secukinumab 150 mg subcutaneous (s.c.) was slower (0.04 mTSS/year; 95% CI -0.28, 0.34) compared to a patient treated with placebo (0.94 mTSS/year; 95% CI 0.45, 1.45). According to the model, the subgroup of "fast progressors" (hsCRP ≥26 mg/L, body weigth ≥94 kg, inadequate response to prior anti-TNF-alpha, structural damage ≥42 mTSS) treated with secukinumab 150 mg s.c. progressed at 0.56 mTSS/year (95% CI 0.02, 1.09) and 1.46 mTSS/year (95% CI 0.81, 2.11) when treated with placebo.CONCLUSIONS:Greater systemic inflammation and higher body weight at baseline were identified as significant predictors of progression. Even patients with fast radiographic progression could experience a beneficial effect with secukinumab that holds promise to prevent further mobility loss.

ObjectiveTo assess the efficacy of secukinumab on axial and peripheral enthesitis in patients with ankylosing spondylitis (AS) using pooled data from randomized controlled phase III studies.MethodsIn this posthoc analysis, data were pooled from patients originally randomized to secukinumab 150 mg, 300 mg, or placebo (PBO) from phase III MEASURE 1–4 studies (ClinicalTrials.gov: NCT01358175, NCT01649375, NCT02008916, and NCT02159053). Maastricht AS Enthesitis Score (MASES) was used for assessments of enthesitis through Week 52. Efficacy outcomes were mean change in MASES score and complete resolution (MASES = 0) of enthesitis in patients with baseline MASES > 0.ResultsA total of 693 (71.5%) patients had enthesitis at baseline in secukinumab 300 mg, 150 mg, and PBO groups (58 [76.3%], 355 [70.4%], and 280 [72%], respectively) out of 969 patients pooled in this analysis. At Week 16, mean changes from baseline for overall MASES and enthesitis at axial MASES sites, respectively, were as follows: –2.9 (P < 0.01) and –2.9 (P < 0.01) for secukinumab 300 mg; –2.4 (P < 0.015) and –2.3 (P < 0.05) for secukinumab 150 mg; and –1.9 and –1.8 for PBO, with improvements seen through Week 52. More than one-third of secukinumab-treated patients (300 mg: 36.2%; 150 mg: 40.8%) achieved complete resolution of enthesitis at Week 16.ConclusionSecukinumab improved enthesitis at overall MASES and axial sites in patients with AS.

Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease of the axial skeleton associated with pain, stiffness, and disability. 1 Up to 66% of patients (pts) with AS may also have peripheral involvement, including swollen and tender joints (STJs), 2,3 which are associated with worse overall disease activity. 4 A previous analysis showed that secukinumab, a selective inhibitor of interleukin 17A, led to significant improvements in efficacy outcomes vs placebo, regardless of peripheral joint involvement. 3 However, the effect of secukinumab on symptoms of peripheral arthritis in pts with AS was not assessed. Objectives: The objective of this analysis was to assess changes in peripheral symptoms in pts with AS treated with secukinumab vs placebo. Methods: Data from pts with active AS and peripheral symptoms who were enrolled in MEASURE 1 ( NCT01358175 ), 2 ( NCT01649375 ), 3 ( NCT02008916 ), and 4 ( NCT02159053 ) were pooled in this post hoc, hypothesis-generating analysis. No adjustments for multiple comparisons were made. Pts with peripheral symptoms were identified by the presence of STJs, based on 44-joint counts at baseline (BL). Pts received subcutaneous (SC) secukinumab every 4 weeks at doses of 300 mg with an intravenous (IV) loading dose (MEASURE 3 only), 150 mg with an IV or SC loading dose, or placebo. Treatment response through Week 16 was assessed based on the proportions of pts who achieved improvements of 20%, 50%, 70%, or 100% in the number of swollen and number of tender joints and improvements in the BASDAI score for question 3 and Patient Global Assessment (PGA). Changes in the number of swollen and number of tender joints were assessed in pts with swollen or tender joints at BL, respectively. Results: This pooled analysis included 560 pts with AS and STJs at BL (Table). At Week 16, treatment with secukinumab led to significantly greater proportions of pts achieving reductions in the number of swollen (Fig 1A) or tender (Fig 1B) joints compared with placebo; the treatment effect was more pronounced in reduction of swollen joints. Furthermore, a greater proportion of secukinumab-treated pts achieved complete resolution of swollen or tender joints vs placebo (Fig 1). Secukinumab also led to significant improvements in peripheral pain/swelling (Fig 2A) and disease activity (Fig 2B) vs placebo, as assessed using BASDAI question 3 and the PGA, respectively. Table. Patient Characteristics at Baseline Secukinumab Placebo (n = 252 ) 300 mg (n = 52 ) 150 mg (n = 256 ) Age, mean, y 43.6 43.7 44.9 Time since diagnosis, mean, y 5.6 7.2 7.3 Male, % 63.5 62.1 57.5 PGA of Disease Activity, mean, mm 73.4 71.7 70.1 BASDAI question 3, mean 6.3 6.6 6.4 Swollen 44-joint count, mean 1.9 2.6 2.5 Tender 44-joint count, mean 7.1 7.8 7.9 Conclusion: In parallel with its previously reported efficacy in axial symptoms, 3 secukinumab led to significant improvements in symptoms of peripheral arthritis in pts with AS. Significant improvements were seen in both tender and swollen joints. References: [1]Braun J, Sieper J. Lancet . 2007;369:1379-1390. [2]de Winter JJ, et al. Arthritis Res Ther . 2016;18:196. [3]Mease P, et al. Arthritis Rheumatol . 2019;71(suppl 10):1553. [4]de Winter JJ, et al. RMD Open . 2019;5:e000802. Acknowledgments: This study was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ. The authors thank Amos Race, PhD, of ArticulateScience LLC, Hamilton, NJ, USA, for providing medical writing/editorial support, which was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, in accordance with Good Publication Practice (GPP3) guidelines ( http://www.ismpp.org/gpp3 ). Disclosure of Interests: Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau, Atul Deodhar Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Renato Calheiros Shareholder of: Novartis, Employee of: Novartis, Xiangyi Meng Shareholder of: Novartis, Employee of: Novartis, Todd Fox Shareholder of: Novartis, Employee of: Novartis, Xenofon Baraliakos Grant/research support from: Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Consultant of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen

Background: Evaluation of long-term efficacy and safety for treatments for ankylosing spondylitis (AS) is important.Secukinumab, a fully human monoclonal antibody that directly inhibits interleukin-17A, has shown significant and sustained improvement in the signs and symptoms of AS through 3 years in the MEASURE 2 study (NCT01649375).We report the 5-year end-of-study results of subcutaneous (SC) secukinumab 150 mg in MEASURE 2. Methods: AS patients (N ¼ 219) were randomised to receive SC secukinumab 150 mg, 75 mg or placebo at baseline, Weeks 1, 2 and 3 and every 4 weeks from Week 4. At Week 16, placebo-treated patients were re-randomised to receive secukinumab 150/75 mg.Efficacy results are reported for patients initially randomised to secukinumab 150 mg and those who switched from placebo to secukinumab 150 mg at Week 16 (N ¼ 106).An optional dose escalation from secukinumab 75 mg to 150 mg was initiated beginning Week 140.Outcome measures at Week 260 included ASAS20/40, BASDAI50, BASMI, BASFI, SF-36 PCS[JB1] and ASAS partial remission.Analyses stratified by TNF inhibitor (TNFi) status (TNFi-naive and TNFi inadequate response [IR]) were performed.Safety analysis included all patients who received !1 dose of secukinumab.Results are reported as observed.Results: The retention rate to Week 260 was 77% (82/106) for secukinumab 150 mg.Sustained efficacy was observed with secukinumab 150 mg across all endpoints through 5 years.Improvements were maintained regardless of prior exposure to TNFi therapy with greater responses in TNFi-naive patients.A total of 49 patients on secukinumab 75 mg (46.7%) escalated dose to 150 mg after Week 140; efficacy responses improved in patients whose dose was escalated.Over the entire study period, the mean exposure (AESD) to secukinumab was 1459.1 AE 597.8 days.Exposure-adjusted incidence rates (per 100 patient-years) with any secukinumab dose for selected adverse events were: Candida infections (1.0), Crohn's disease (0.5), major adverse cardiovascular events (0.7), uveitis (0.5), and malignant/ unspecified tumours (0.5). Conclusion: Conclusion:Secukinumab 150 mg provided sustained improvement in the signs, symptoms, and physical function in patients with AS through 5 years of treatment.The safety profile of secukinumab remained consistent with previous reports.

TNF-α- as well as non-TNF-α-targeting biologics are prescribed to treat a variety of immune-mediated inflammatory disorders. The well-documented risk of tuberculosis progression associated with anti-TNF-α treatment highlighted the central role of TNF-α for the maintenance of protective immunity, although the rate of tuberculosis detected among patients varies with the nature of the drug. Using a human, in-vitro granuloma model, we reproduce the increased reactivation rate of tuberculosis following exposure to Adalimumab compared to Etanercept, two TNF-α-neutralizing biologics. We show that Adalimumab, because of its bivalence, specifically induces TGF-β1-dependent Mycobacterium tuberculosis (Mtb) resuscitation which can be prevented by concomitant TGF-β1 neutralization. Moreover, our data suggest an additional role of lymphotoxin-α-neutralized by Etanercept but not Adalimumab-in the control of latent tuberculosis infection. Furthermore, we show that, while Secukinumab, an anti-IL-17A antibody, does not revert Mtb dormancy, the anti-IL-12-p40 antibody Ustekinumab and the recombinant IL-1RA Anakinra promote Mtb resuscitation, in line with the importance of these pathways in tuberculosis immunity.

Abstract Background Enthesitis can be a debilitating extra-articular spondyloarthritis manifestation that causes considerable pain and reduced quality of life. We evaluated the effect of secukinumab on axial and peripheral enthesitis in ankylosing spondylitis (AS) patients with baseline enthesitis (BLE) across all MASES sites (N = 13), axial MASES sites (N = 11; 13 MASES minus Achilles tendons [AT] [AxS]), peripheral sites (N = 6; AT + lateral condyles of humerus/femur [PS]) and the AT (N = 2) at Weeks 16 and 52. Methods This post-hoc analysis pooled data across four AS studies (MEASURE 1-4) from patients originally randomised to secukinumab 150 mg (approved AS dose), 300 mg (MEASURE 3 only) or placebo with BLE (MASES >0). Evaluations included mean change from baseline in MASES score, complete resolution (CR; MASES=0) and improvement from baseline in MASES score ≥5 counts. Mixed-effect model repeat measurement analysis was performed on change from baseline in MASES score and non-responder imputation for resolution of enthesitis at Week 16; data are reported as observed at Week 52. Results 355 (70.4%), 58 (76.3%) and 280 (72%) patients had BLE in the 150 mg, 300 mg and placebo groups, respectively. Baseline characteristics were comparable across groups. At Week 16, mean change from baseline for overall MASES and at AxS was greater for secukinumab 150 mg (−2.4, −2.3) and 300 mg (−2.9, −2.9) vs placebo (−1.9, −1.8; P < 0.05, P < 0.01). At Week 16, patients treated with secukinumab 150 mg (40.8%, 42.7%) and 300 mg (36.2%, 42.1%) vs placebo (28.9%, 30.1%) achieved CR of enthesitis at overall MASES and AxS. Secukinumab 150 mg and 300 mg were consistently associated with a higher mean change in MASES and CR of enthesitis at PS and AT vs placebo. More patients treated with secukinumab 150/300 mg vs placebo achieved a higher threshold of improvement (≥5 counts) in overall MASES at Week 16. Further improvements were observed for all endpoints at Week 52 (Table 1). Conclusion Secukinumab 150 mg and 300 mg were associated with a higher mean change in MASES and CR of enthesitis for overall MASES and at AxS vs placebo in AS patients at Week 16, which further improved through Week 52. Disclosures N. Barkham Grants/research support; Novartis, Eli Lilly, UCB, Celgene. G. Schett None. X. Baraliakos Consultancies; AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Janssen Biologics, Novartis, Pfizer, UCB Pharma, Galapagos. Member of speakers’ bureau; AbbVie, Chugai, Janssen, Novartis, Pfizer, UCB Pharma. Grants/research support; AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Chugai, Janssen, MSD, Novartis, Pfizer, Roche, UCB. F. van den Bosch Consultancies; AbbVie, Bristol-Myers Squibb, Galapagos, Janssen, Lilly, Merck, Novartis, Pfizer, UCB. Member of speakers’ bureau; AbbVie, Bristol-Myers Squibb, Janssen, Lilly, Merck, Novartis, Pfizer, UCB. A. Deodhar Consultancies; AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Janssen, Novartis, Pfizer, UCB. Grants/research support; AbbVie, Amgen, Eli Lilly, GSK, Janssen, Novartis, Pfizer, Bristol-Myers Squibb, Boehringer Ingelheim, UCB. L.S. Gensler Consultancies; Novartis, Lilly, Janssen. Grants/research support; AbbVie, Amgen, UCB Pharma. M. Ǿstergaard Consultancies; AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, UCB. Member of speakers’ bureau; AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, UCB. Grants/research support; AbbVie, Celgene, Centocor, Merck, Novartis. S. Agawane Other; Employee of: Novartis. A. Das Gupta Other; Employee of: Novartis. S. Mpofu Other; Employee of: Novartis. T. Fox Other; Employee of: Novartis. A. Winseck Other; Employee of: Novartis. A. Shete Shareholder/stock ownership; Novartis. Other; Employee of: Novartis. B. Porter Shareholder/stock ownership; Novartis. Other; Employee of: Novartis.

Background: Ankylosing spondylitis (AS) is an inflammatory disease resulting in progressive disability due to structural damage in the spine. The identification of predictors of progression would allow treating physicians to personalize treatments but requires an approach accounting for a relatively short follow-up of clinical studies, large between-patient variability, and low sensitivity of X-ray images which generate intra-patient variability when repeated measurements are taken. Objectives: 1) To identify patient characteristics predicting faster structural damage progression. 2) To quantify the progression over four years of secukinumab treatment, depending on dose/exposure. Methods: Data came from the phase 3 randomized placebo-controlled trial MEASURE 1 (NCT01358175)1 in which patients were treated with secukinumab (intravenous loading of 10 mg/kg at weeks 0, 2, and 4, followed by secukinumab subcutaneously at a dose of either 75 mg or 150 mg every 4 weeks) over 208 weeks. Only patients treated with secukinumab with at least two assessments of structural damage were included. We explored the effect of multiple baseline demographic traits, disease stage, severity, bone cartilage biomarkers as well as prior and current treatment on change in modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) using a longitudinal Bayesian mixture model with random effects, which accounted simultaneously for the probability of progression, magnitude of progression and inter-patient variability. Posterior predictive check was performed. Results: Out of 249 patients randomized to secukinumab, 167 had their structural damage assessed at least twice. These patients contributed in total 409 assessments of change in structural damage between weeks 0, 52, 104 and 208. Of the factors tested, a higher baseline BASMI score was associated with faster progression rate in a statistically significant way (+0.60 in mSASSS/year for each additional standard deviation of baseline BASMI (SD=1.74), 95% interval 0.03 to 1.14). Trends were also detected for association between faster mSASSS progression and younger age, prior exposure to TNFα inhibitor, HLA-B27 positivity, and higher osteocalcin levels. Increased exposure to secukinumab was associated with slower structural damage progression (-0.23 in mSASSS/year for each additional standard deviation in exposure, 95% interval -0.58 to 0.10). Model estimation suggested that secukinumab 150 mg was associated with a yearly progression of -0.2 (95% interval -1.2 to 0.8) in the first two years of treatment and 0.1 mSASSS (95% interval -0.8 to 1.0) in the third and fourth year of treatment. Analogously, secukinumab 75mg (currently not approved for clinical use) was associated with a progression of -0.2 mSASSS/year (95% interval -1.3 to 0.9) in the first two years of treatment and 0.5 mSASSS/year (95% interval -0.5 to 1.6) in the third and fourth year of treatment. Conclusion: Potential predictors of structural progression suggested by the model were higher baseline BASMI, younger age, prior exposure to TNFα inhibitor, HLA-B27 positivity, and higher osteocalcin at baseline, although only baseline BASMI showed statistical significance. Further analyses using larger, deeper and real-world data are needed to confirm these findings and to estimate progression rates in AS patients in daily practice. Reference [1] Baeten D, Sieper J, Braun J, et al. Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis. N Engl J Med. 2015;373(26):2534-2548. Disclosure of Interests: Olivier Luttringer Shareholder of: Novartis, Employee of: Employee of Novartis Pharma AG, Todd Fox Employee of: Novartis, Brian Porter Shareholder of: Novartis, Employee of: Novartis, Abhijit Shete Shareholder of: Novartis Pharma AG, Employee of: Novartis Pharma AG, Hanno Richards Shareholder of: Novartis Pharma AG, Employee of: Novartis Pharma AG, Witold Wiecek Consultant for: Employee of CERTARA Strategic Consulting., Zuzanna Angehrn Shareholder of: Owns funds which might occassionaly invest in pharmaceutical companies' stocks., Consultant for: Employee of CERTARA strategic consulting., Helene Karcher Consultant for: Former employee of Analytica Laser, a Certara company. Former independent consultant. Current employee of PAREXEL., Employee of: Former employee of Novartis., Billy Amzal Consultant for: Employee of CERTARA Strategic Consulting., Employee of: Former employee of Novartis.

Objectives Here, we present the reported incidence rates of inflammatory bowel disease (IBD) in patients receiving treatment with secukinumab for psoriasis (PsO), psoriatic arthritis (PsA) or ankylosing spondylitis (AS), in a pooled analysis of 21 clinical trials. Methods Data from all patients who had received at least one dose of secukinumab were included. Safety analyses were conducted to evaluate cumulative IBD rates as well as per-year rates, by indication. Crohn’s disease (CD), ulcerative colitis (UC) and IBD unclassified (IBDU) events were analysed using exposure-adjusted incidence rates (patient incidence rates per 100 patient-years (PY)). Results A total of 7355 patients with a cumulative exposure of 16 226.9 PY were included in the pooled analysis. Among 5181 patients with PsO, there were 14 cases of UC, 5 cases of CD and 1 case of IBDU, with exposure adjusted incidence rates (EAIRs) of 0.13, 0.05 and 0.01, respectively. Of these 20 cases, 14 were new-onset. In 1380 patients with PsA, there were 3 cases of UC, 3 cases of CD and 2 cases of IBDU (EAIRs 0.08, 0.08 and 0.05); 7 of these represented new-onset cases. Among 794 patients with AS, there were 4 cases of UC, 8 cases of CD and 1 case of IBDU (EAIRs 0.2, 0.4 and 0.1); 9 were new-onset cases. In the per year analysis, the EAIRs for each indication did not increase over time with secukinumab treatment. Conclusions In this pooled secukinumab safety analysis of 7355 patients across 21 clinical trials, cases of IBD events (including CD, UC and IBDU) were uncommon.

The aim of this study was to compare radiographic progression in patients with ankylosing spondylitis (AS) treated for up to 2 years with secukinumab (MEASURE 1) with a historical cohort of biologic-naïve patients treated with NSAIDs (ENRADAS). Baseline and 2-year lateral cervical and lumbar spine radiographs were independently evaluated using mSASSS by two readers, who were blinded to the chronology and cohort of the radiographs. The primary endpoint was the proportion of patients with no radiographic progression (mSASSS change ≤ 0 from baseline to year 2). The Primary Analysis Set included patients with baseline (≤ day 30) and post-baseline day 31–743 radiographs. Sensitivity analyses were performed to assess the robustness of the comparison between the two cohorts, as follows: Sensitivity Analysis Set 1 included all patients with baseline (≤ day 30) and year 2 (days 640–819) radiographs; Sensitivity Analysis Set 2 included all patients with baseline and post-baseline (> day 30) radiographs. A total of 168 patients (84%) from the MEASURE 1 cohort and 69 (57%) from the ENRADAS cohort qualified for the Primary Analysis Set. Over 2 years, the LS (SE) mean change from baseline in mSASSS for the primary analysis was 0.55 (0.139) for MEASURE 1 vs 0.89 (0.216) for ENRADAS (p = 0.1852). Mean changes from baseline in mSASSS were lower in MEASURE 1 vs ENRADAS for the primary and sensitivity analyses. The proportion of patients with no radiographic progression was consistently higher in the MEASURE 1 vs ENRADAS cohort across all cutoffs for no radiographic progression (change in mSASSS from baseline to year 2 of ≤ 0, ≤ 0.5, ≤ 1, and ≤ 2), but the differences were not statistically significant. Secukinumab-treated patients demonstrated a numerical, but statistically non-significant, higher proportion of non-progressors and lower change in mSASSS over 2 years versus a cohort of biologic-naïve patients treated with NSAIDs.

Background: Pooled safety data from secukinumab (SEC) studies in psoriasis and psoriatic arthritis (PsA) have been reported previously. Objectives: To report updated longer-term safety data with up to 5 years of SEC treatment from psoriasis and PsA studies. Methods: The moderate-to-severe plaque psoriasis and active PsA data pool consisted of 15 Phase 2 and 3 Phase 3 studies. Different SEC doses in the studies included intravenous (up to 10 mg/kg) or subcutaneous (s.c.; 75-300 mg) loading, followed by s.c. maintenance dosing (300, 150 or 75 mg). Placebo patients were rerandomised to SEC at 12-24 weeks depending on study design. Adverse events (AEs) were reported as exposure-adjusted incident rates (EAIR) per 100 patientyears and analyses included all patients who received ≥1 dose of SEC. Results: A total of 5,181 and 1,380 patients from psoriasis and PsA studies representing an exposure of 10,416.9 and 3,866.9 patient-years, respectively, were included in this study. The most frequently reported AE was viral upper respiratory tract infection (Table 1). EAIRs for serious infections, Candida infections, inflammatory bowel disease and major adverse cardiac events were low and similar in both psoriasis and PsA indications (Table 1). No cases of tuberculosis were reported. Conclusion: SEC demonstrated a favourable safety profile during long-term treatment (up to 5 years) in patients with moderate-to-severe plaque psoriasis or PsA, hence, supporting long-term use. The safety profile of SEC was consistent with previous reports and comparable across psoriasis and PsA patients.

Secukinumab, a fully human immunoglobulin G1-kappa monoclonal antibody that directly inhibits interleukin (IL)-17A, has been shown to have robust efficacy in the treatment of moderate-to-severe psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) demonstrating a rapid onset of action and sustained long-term clinical responses with a consistently favorable safety profile in multiple Phase 2 and 3 trials. Here, we report longer-term pooled safety and tolerability data for secukinumab across three indications (up to 5 years of treatment in PsO and PsA; up to 4 years in AS). The integrated clinical trial safety dataset included data pooled from 21 randomized controlled clinical trials of secukinumab 300 or 150 or 75 mg in PsO (14 Phase 3 trials and 1 Phase 4 trial), PsA (3 Phase 3 trials), and AS (3 Phase 3 trials), along with post-marketing safety surveillance data with a cut-off date of June 25, 2017. Adverse events (AEs) were reported as exposure-adjusted incident rates (EAIRs) per 100 patient-years. Analyses included all patients who received ≥ 1 dose of secukinumab. A total of 5181, 1380, and 794 patients from PsO, PsA, and AS clinical trials representing secukinumab exposures of 10,416.9, 3866.9, and 1943.1 patient-years, respectively, and post-marketing data from patients with a cumulative exposure to secukinumab of ~ 96,054 patient-years were included in the analysis. The most frequent AE was upper respiratory tract infection. EAIRs across PsO, PsA, and AS indications were generally low for serious infections (1.4, 1.9, and 1.2, respectively), Candida infections (2.2, 1.5, and 0.7, respectively), inflammatory bowel disease (0.01, 0.05, and 0.1, respectively), and major adverse cardiac events (0.3, 0.4, and 0.6, respectively). No cases of tuberculosis reactivation were reported. The incidence of treatment-emergent anti-drug antibodies was low with secukinumab across all studies, with no discernible loss of efficacy, unexpected alterations in pharmacokinetics, or association with immunogenicity-related AEs. Secukinumab demonstrated a favorable safety profile over long-term treatment in patients with PsO, PsA, and AS. This comprehensive assessment demonstrated that the safety profile of secukinumab was consistent with previous reports in patients with PsO, PsA, and AS, supporting its long-term use in these chronic conditions.

Outcome measures at Week 16 in APR treated patients Outcome measure Week 0 Week 16 ACR 20 -71% ACR 50 -47% ACR 70 -35% Mean TJC (68 joints) 16.6 6.0 Mean SJC (66 joints) 10.2 4.2 Mean DAS28 5.74 3.95 Mean Patient assessment of pain (0-10) 8.2 3.8 Mean Physician assessment of pain (0-10) 8.0 3.7 CRP 12.35 6.88

Background Secukinumab, a fully human interleukin 17A (IL-17A) inhibitor, improved signs and symptoms of ankylosing spondylitis (AS) in patients (pts) in the MEASURE 1 core trial at 2 years and through 4 years in the extension study.1,2 A low radiographic progression rate was reported for the modified Stoke Ankylosing Spondylitis Spinal Score (Δ mSASSS at Yr 2=0.3).1 Comparison of anti-TNF agents with historical NSAID-treated cohorts have not shown a significant benefit at 2 years in reducing radiographic progression.3,4 Objectives This retrospective analysis compared spinal radiographic progression over 2 years in the MEASURE 1 cohort of secukinumab-treated AS patients (C1; NCT01358175) vs a historical cohort of biologic-naïve AS pts (ENRADAS [C2; NCT00715091]).5 Methods Baseline (BL) and 2 year X-ray data from the 2 cohorts were compared. Only data from pts with X-rays at BL and Yr 2 (data capture window for Yr 2 X-rays: 31–744 days) were included (n=168 [C1], n=69 [C2]). X-rays were independently re-evaluated using the mSASSS by 2 reviewers and an adjudicator blinded to the timing and cohorts; averaged values were analysed. Cases with the highest difference in Δ mSASSS between readers (top 10%) were adjudicated. The primary outcome was to compare the% pts with no radiographic progression (Δ mSASSS at Year 2≤0) in C1 vs C2. The difference between C1 and C2 was analysed using a logistic regression with cohort as a factor and BL mSASSS as a covariate. Results BL demographics were comparable across cohorts, with mean age 40.9 vs 42.6 years, and gender 72.8% vs 66.7% male in C1 vs C2, respectively. Over 2 years, least squares (LS) mean Δ mSASSS was 0.55 for C1 vs 0.89 for C2 (p=0.185) and% pts with no radiographic progression (Δ mSASSS at Year 2≤0) was slightly higher in C1 vs C2 (table 1). Conclusions Over 2 years, a numerically lower rate of progression was seen in secukinumab-treated pts vs a control cohort of biologic-naïve AS pts. Further research is needed to understand the impact of IL-17A inhibition with secukinumab on spinal disease progression in AS pts; SURPASS (NCT03259074), an ongoing H2H study powered to compare differences in spinal radiographic progression with secukinumab vs biosimilar adalimumab, will help answer these questions. References [1] Braun J, et al. Ann Rheum Dis Ann Rheum Dis2017;76:1070–77. [2] Braun J, et al. Arthritis Rheumatol2017;69(10). [3] van der Heijde D, et al. Arthritis Rheum2008;58:1324–31. [4] van der Heijde D, et al. Arthritis Res Ther2009;11:R127. [5] Sieper J, et al. Ann Rheum Dis2016;75:1438–43. Disclosure of Interest J. Braun Grant/research support from: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis and UCB, Consultant for: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis and UCB, Speakers bureau: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi- Aventis and UCB, H. Haibel: None declared, M. de Hooge Employee of: MdH Research, R. Landewé Grant/research support from: Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB and Wyeth, Consultant for: Abbott/AbbVie, Ablynx, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Centocor, GlaxoSmithKline, Novartis, Merck, Pfizer, Roche, Schering-Plough, UCB and Wyeth, Employee of: Rheumatology Consultancy BV, Speakers bureau: Abbott, Amgen, Bristol-Myers Squibb, Centocor, Merck, Pfizer, Roche, Schering-Plough, UCB and Wyeth, M. Rudwaleit Speakers bureau: Abbvie, BMS, Celgene, Chugai, Janssen, MSD, Novartis, Pfizer, UCB, T. Fox Shareholder of: Novartis, Employee of: Novartis Pharma AG, A. Readie Shareholder of: Novartis, Employee of: Novartis Pharmaceuticals Corporation, H. Richards Shareholder of: Novartis, Employee of: Novartis Pharma AG, B. Porter Shareholder of: Novartis, Employee of: Novartis Pharmaceuticals Corporation, R. Martin Shareholder of: Novartis, Employee of: Novartis Pharmaceuticals Corporation, D. Poddubny Grant/research support from: Abbvie, Janssen, MSD, Novartis and Pfizer, Consultant for: AbbVie, Bristol-Myers Squibb, MSD, Novartis, Pfizer and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Janssen, MSD, Novartis, Pfizer, Roche and UCB, J. Sieper Grant/research support from: AbbVie, Boehringer Ingelheim, Janssen, Novartis, Merck, Lilly, Pfizer, and UCB, Consultant for: AbbVie, Janssen, Novartis, Merck, Lilly, Pfizer, Sun and UCB, Speakers bureau: AbbVie, Janssen, Novartis, Merck, Pfizer, Roche and UCB, D. van der Heijde Consultant for: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boeringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi and UCB, Employee of: Imaging Rheumatology BV

BackgroundPooled safety data from secukinumab (SEC) studies in psoriasis and psoriatic arthritis (PsA) have been reported previously.1ObjectivesTo report updated longer-term safety data with up to 5 years of SEC treatment from psoriasis and PsA studies.MethodsThe moderate to severe plaque psoriasis and active PsA data pool consisted of 15 and 3 Phase III studies, respectively. Different SEC doses in the studies included intravenous (up to 10 mg/kg) or subcutaneous (s.c.; 75–300 mg) loading, followed by s.c. maintenance dosing (300, 150 or 75 mg). Placebo patients were re-randomised to SEC at 12–24 weeks depending on study design. Adverse events (AEs) were reported as exposure adjusted incident rates (EAIR) per 100 patient-years and analyses included all patients who received ≥1 dose of SEC.ResultsA total of 5181 and 1380 patients from psoriasis and PsA studies representing an exposure of 10416.9 and 3866.9 patient years, respectively, were included in this study. The most frequently reported AE was viral upper respiratory tract infection (table 1). EAIRs for serious infections, Candida infections, inflammatory bowel disease (IBD) and major adverse cardiac events (MACE) were low and similar in both psoriasis and PsA indications (table 1). No cases of tuberculosis were reported.ConclusionsSEC demonstrated a favourable safety profile during long-term treatment (up to 5 years) in patients with moderate to severe plaque psoriasis or PsA, hence, supporting long-term use. The safety profile was consistent with previous reports and comparable across psoriasis and PsA patients.Reference[1] Mease, et al. Arthritis Rheumatol2017; 69(suppl 10):A606.Disclosure of InterestP. Mease Grant/research support from: AbbVie, Amgen, BMS, Janssen, Lilly, Novartis, Pfizer, and UCB, Consultant for: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, SUN Pharma, UCB,, Speakers bureau: AbbVie, Amgen, BMS, Janssen, Lilly, Pfizer, and UCB, I. McInnes Grant/research support from: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, and UCB, Consultant for: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, and UCB, Speakers bureau: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, and UCB, K. Reich Consultant for: Abbvie, Affibody, Amgen, Biogen, Boehringer Ingelheim Pharma, Celgene, Centocor, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, Leo, Lilly, Medac, Merck Sharp and Dohme Corp., Novartis, Ocean Pharma, Pfizer, Regeneron, Sanofi, Takeda, UCB Pharma, Xenoport, Speakers bureau: Abbvie, Affibody, Amgen, Biogen, Boehringer Ingelheim Pharma, Celgene, Centocor, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, Leo, Lilly, Medac, Merck Sharp and Dohme Corp., Novartis, Ocean Pharma, Pfizer, Regeneron, Sanofi, Takeda, UCB Pharma, Xenoport., P. Nash Grant/research support from: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Hospira, MSD, Pfizer, Janssen, UCB, Novartis, Roche, Consultant for: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Hospira, MSD, Pfizer, Janssen, UCB, Novartis, Roche, Speakers bureau: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Hospira, MSD, Pfizer, Janssen, UCB, Novartis, Roche, A. Widmer Shareholder of: Novartis Stock, Employee of: Novartis, K. Abrams Shareholder of: Novartis Stock, Employee of: Novartis, L. Pricop Shareholder of: Novartis Stock, Employee of: Novartis, T. Fox Shareholder of: Novartis Stock, Employee of: Novartis

Background: Disease Activity Index for Psoriatic Arthritis (DAPSA) is a validated tool to measure disease activity states in psoriatic arthritis (PsA) and can be used to assess treatment targets such as remission or low-disease activity (LDA).Secukinumab has shown sustained improvements in PsA disease activity as assessed by Disease Activity Score 28-joint count (DAS28)-C-reactive protein (CRP), physical function and patient-reported outcomes (PROs) over 104 weeks in the FUTURE 2 study.This post-hoc exploratory analysis assessed the relationship between DAPSA states and function, health-related quality of life (QoL) and PROs, and the individual DAPSA components in the different states in secukinumab-treated patients.Methods: DAPSA was derived as the sum of five variables: tender joint and swollen joint counts (TJC68 and SJC66), patient global assessment and pain assessed on a 10-cm visual analogue scale, and C-reactive protein levels (mg/dL) with validated cut-offs to indicate remission ( 4), LDA (>4 and 14), moderate-disease activity (MODA; >14 and 28) and high-disease activity (HDA; >28).MeanAESD of each DAPSA core component was analysed at Weeks 16, 24, 52 and 104 using observed data.The relationship between HAQ-DI, SF-36 PCS and MCS, PsAQoL, DLQI, FACIT-Fatigue and DAPSA states was assessed in the pooled treatment arms at each time-point using a mixed-effect model for repeated measures (MMRM) analyses.Results: Baseline characteristics were similar across treatment groups.DAPSA scores at baseline (meanAESD) were 42.0AE17.4,46.8AE24.3 and 44.9AE25.3 in the secukinumab 300 mg, 150 mg and placebo groups, respectively.Mean scores of each component by DAPSA state at week 16 are shown in the table; these were sustained through week 104.Significant differences were observed among secukinumab-treated patients between remission vs. HDA and LDA vs. HDA states for PRO scores through Week 104. Conclusion:In patients treated with secukinumab 300 mg or 150 mg who achieved DAPSA remission, mean scores for the five individual components were all <1, in contrast with other disease states, and were sustained through week 104.DAPSA remission was associated with significantly greater improvement in physical function, health-related QoL and fatigue, indicating that it is an important target to be achieved and sustained in PsA patients.

and 14/16 (both placebo-adjusted).At week 24, non-placebo-adjusted ASAS 20 and ASAS 40 responses using NRI were higher with secukinumab than golimumab (OR [95% CI]: 1.58 [0.93, 2.69], p ¼ 0.089 and 1.58 [0.94, 2.64], p ¼ 0.084, respectively).There was no evidence of differences in ASAS PR responses between secukinumab and golimumab at weeks 12/14, 14/16, and 24.A sensitivity analysis conducted after adding Bath AS Disease Activity Index score to the matching parameters yielded similar results.Conclusion: There was no evidence of differences in ASAS responses between secukinumab and golimumab in placebo-adjusted analyses.In non-placebo-adjusted analyses, secukinumab showed higher ASAS 20 and ASAS 40 responses than golimumab at week 24.

Background Pooled safety data from secukinumab psoriasis (PsO) and psoriatic arthritis (PsA) clinical trial programs after ∼1 year of exposure have been reported.1,2 Objectives To report updated longer-term secukinumab exposure safety data from PsO and PsA studies (data cut-off: 25 June 2016). Methods The PsO data pool consisted of 9 Phase III studies in moderate-to-severe plaque PsO and PsA pool consisted of 3 Phase III studies in active PsA. Secukinumab doses differed in the studies and included intravenous (up to 10 mg/kg) or subcutaneous (s.c.; 75–300 mg) loading, followed by s.c. maintenance dosing (300, 150 or 75 mg). Placebo patients were re-randomised to secukinumab at 12–24 weeks depending on study design. Only data for approved secukinumab 300 and 150mg doses were included in analysis. Exposure adjusted incident rates (EAIR) were used to adjust for differences in exposure. Results In both PsO and PsA, the most frequently reported adverse events (AEs) with secukinumab were non-serious infections of the upper respiratory tract, headache and arthralgia (Table). The EAIRs of AEs of special interest with secukinumab including Crohn9s disease, Candida infections, serious infections, inflammatory bowel disease, major adverse cardiac events and neutropenia (reported in the Table) were similar in both PSO and PsA indications, and comparable to those reported previously.1,2 No cases of tuberculosis (new onset or reactivation) were reported. Conclusions The safety profile of secukinumab was similar for PsO and PsA patients supporting its long-term use in these chronic conditions. Secukinumab long-term exposure safety data is consistent with that previously reported with shorter-term exposure, including being well tolerated, and without any new safety signals identified. References Van de Kerkhof PC, et al. J Am Acad Dermatol 2016;75:83–98. Mease PJ, et al. Arthritis Rheumatol 2015; 67:A2886. Disclosure of Interest P. Mease Grant/research support from: AbbVie, Amgen, Biogen Idec, BMS, Celgene, Crescendo, Janssen, Lilly, Merck, Novartis, Pfizer, and UCB, Consultant for: AbbVie, Amgen, Biogen Idec, BMS, Celgene, Covagen, Crescendo, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Biogen Idec, BMS, Crescendo, Janssen, Lilly, Pfizer, and UCB, I. McInnes Grant/research support from: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, and UCB, Consultant for: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, and UCB, Speakers bureau: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, and UCB, K. Reich Grant/research support from: AbbVie, Amgen, Biogen, Boehringer Ingelheim Pharma, Celgene, Centocor, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cliag, Leo, Lilly, Medac, Merck Sharp and Dohme Corp., Novartis, Ocean Pharma, Pfizer, Regeneron, Takeda, UCB Pharma, Xenoport, Speakers bureau: AbbVie, Amgen, Biogen, Boehringer Ingelheim Pharma, Celgene, Centocor, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cliag, Leo, Lilly, Medac, Merck Sharp and Dohme Corp., Novartis, Ocean Pharma, Pfizer, Regeneron, Takeda, UCB Pharma, Xenoport, P. Nash Grant/research support from: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Hospira, MSD, Pfizer, Janssen, UCB, Novartis, Roche; Consultancy fees: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Hospira, MSD, Pfizer, Janssen, UCB, Novartis, Roche, Speakers bureau: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Hospira, MSD, Pfizer, Janssen, UCB, Novartis, Roche, M. Andersson Employee of: Novartis, K. Abrams Shareholder of: Novartis, Employee of: Novartis, L. Pricorp Shareholder of: Novartis, Employee of: Novartis, T. Fox Shareholder of: Novartis, Employee of: Novartis