K Gandhi

OP0113 No Increased Incidence of Inflammatory Bowel Disease among Secukinumab-Treated Patients with Moderate To Severe Psoriasis, Psoriatic Arthritis, or Ankylosing Spondylitis: Data from 14 Phase 2 and Phase 3 Clinical Studies

Background Secukinumab (SEC), a fully human anti–interleukin-17A monoclonal antibody, has been evaluated and approved for the treatment of moderate to severe psoriasis (PsO), active psoriatic arthritis (PsA) and active ankylosing spondylitis (AS). Inflammatory bowel disease (IBD), including Crohns disease (CD) and ulcerative colitis (UC), is commonly associated with PsO, PsA and AS.1,2 The risk of CD in PsO pts is ∼4-fold higher than that in the general population; this risk is even higher among PsO pts with PsA, reported at a rate of 0.05 cases per 100 pt-years.1 The rate of CD among placebo (Pbo) treated pts in AS trials has been reported as 0.7 cases per 100 pt-years.3 Endoscopic subclinical inflammation occurs in up to 50% of AS patients.2 Objectives To assess the incidence of CD and ulcerative colitis (UC) among SEC-treated pts in the PsO, PsA, and AS clinical trial programs. Methods This analysis included data from 10 Phase 2 and Phase 3 studies in moderate to severe PsO, 2 Phase 3 studies in active PsA, and 2 Phase 3 studies in active AS, pooled per indication. Most studies included short-term, Pbo treatment arms; 1 PsO study included an etanercept (ETN) active comparator arm. Pts with prior history of, but not active, IBD could be enrolled. Study durations varied; data from all pts receiving ≥1 SEC dose up to Week (Wk) 52 (PsO studies) or Wk 112 visit were included. Data are reported as crude frequency rates (%) in the short-term (Wk 12 in PsO studies and Wk 16 in the PsA/AS studies) and exposure adjusted incidence rates (EAIR; per 100 pt-years) over the entire treatment period. Results Overall, 3430, 974, and 571 pts received ≥1 SEC dose in the PsO, PsA, and AS studies, respectively. AEs of CD or UC were reported infrequently amongst SEC-treated pts in both the short- and long-term treatment periods (Table). Rates of CD and UC were similar across the PsO and PsA cohort, and rates with SEC were similar to those seen with ETN in PsO pts. Across all indications, there was no dose dependency with respect to the incidence of CD or UC with SEC, and no pattern in time-to-onset (data not shown). Conclusions Events of CD and UC in the 14 clinical studies were reported infrequently in SEC-treated pts with PsO, PsA, or AS; rates were similar across the PsO and PsA cohorts. EAIR rates of CD and UC observed in SEC-treated patients are consistent with those reported in the literature in PsO, PsA, and AS pts. References Li et al. Ann Rheum Dis 2013;72:1200–5; Rudwaleit et al. Best Pract Res Clin Rheumatol 2006;20:451–71; Braun et al. Arthritis Rheum 2007;57:639–47; Ward et al. AAD 2014. Poster presentation #8233; Secukinumab US Prescribing Information Acknowledgement The study was sponsored by Novartis Pharma AG. Disclosure of Interest S. Schreiber Grant/research support from: Abbvie, AstraZeneca/Medimmune, Boehringer, Celltrion, Ferring, Jansen, Novartis, MSD, Pfizer, Sanofi, Takeda, UCB, Consultant for: Abbvie, Celltrion, Ferring, MSD, Takeda, B. Sands: None declared, A. Deodhar Grant/research support from: AbbVie, Amgen, Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Consultant for: AbbVie, Amgen, Boehringer Ingelheim, Janssen, Novartis, Pfizer, UCB, D. Baeten Grant/research support from: Boehringer Ingelheim, Janssen, MSD, Novartis, Pfizer, Consultant for: AbbVie, Boehringer Ingelheim, BMS, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, UCB, J. Huang Shareholder of: Novartis, Employee of: Novartis, K. Gandhi Shareholder of: Novartis, Employee of: Novartis, C. Karyekar Shareholder of: Novartis, Employee of: Novartis, T. Fox Shareholder of: Novartis, Employee of: Novartis, C. Gaillez Shareholder of: Novartis, Employee of: Novartis

THU0437 Secukinumab for The Treatment of Psoriatic Arthritis: Comparative Effectiveness Results versus Licensed Biologics and Apremilast from A Network Meta-Analysis

Background Secukinumab (SEC) is approved for the treatment of active PsA in adults who have responded inadequately to DMARD therapy. The FUTURE 1 and 2 RCTs which included biologic-naïve and biologic-experienced patients, demonstrated superiority of SEC 150 mg and 300 mg over placebo. As no direct trial comparisons are yet available there is a need for comparative effectiveness assessment. Objectives Comparative assessment of SEC via network meta-analysis (NMA) vs. licensed biologics and apremilast in adults with active PsA who had failed conventional DMARD therapy. Methods A systematic review of the literature (November 2015) identified 20 relevant RCTs. NMAs were conducted following health technology assessment guidance using Bayesian fixed-effects models. PASI and ACR responses and their credible intervals (CrIs), which can be interpreted similarly to CIs, were modelled using a conditional binomial likelihood NMA with probit link function. The results of pairwise comparisons are presented for SEC using relative risks (RRs) [95%CrI]. Non-responder imputation data were used for all comparators except golimumab QM (GOL) and infliximab 5 mg/kg Q2M (INF) for which only last observation carried forward data were available. Analyses were performed in biologic-naïve, biologic-experienced, and mixed populations at week 16 for ACR and at weeks 12–16 for PASI. Results At week 16 in the biologic-naïve population, ACR20 responses were statistically significantly higher for SEC 150 mg (61%) and 300 mg (58%) than for ustekinumab QM (UST) 45 mg (RR 1.95 [1.29–2.86] and RR 1.84 [1.21–2.74], respectively), and for SEC 150 mg vs UST 90 mg (RR 1.52 [1.03–2.16]). ACR20 responses were statistically significantly higher for SEC 150 and 300 mg vs. apremilast BID (APR) 20 mg (RR 2.51 [1.52–4.29] and RR 2.37 [1.39–4.12] respectively), and for SEC 150 mg vs. APR 30 mg (RR 1.72 [1.09–2.71]). Comparisons between SEC and anti-TNFs did not show statisticall significance. For ACR50 and 70, both SEC doses showed the same pattern of significance as for ACR20. Sensitivity analyses using the mixed population were in general agreement with these observations. For PASI50, 75, and 90 at weeks 12–16 in the biologic-naïve population, only a small evidence network with SEC, GOL 50/100mg, adalimumab 40 mg (ADA) and INF was available and there were no statistically significant differences between SEC and these comparators. In the mixed population, SEC was statistically significantly superior to ADA, APR 20/30 mg, certolizumab pegol (CZP) 200/400 mg, etanercept (ETN) 25/50 mg BIW and 50 mg QW, and (SEC 300 mg only) GOL 50 mg. Conclusions SEC shows statistically significantly higher results vs. UST and APR in ACR20, 50 and 70, with at least comparable response rates across all ACR and PASI endpoints vs. all therapies included in this NMA. For PASI50, 75, and 90 responses, SEC had high response rates with statistically significant results vs. ADA, APR, CZP, ETN, and (SEC 300 mg only) GOL 50 mg. Disclosure of Interest I. McInnes Consultant for: Novartis, Janssen, Abbvie, Pfizer and UCB, P. Nash Grant/research support from: Novartis, Consultant for: Novartis, C. Ritchlin Grant/research support from: Abbvie, Amgen, UCB, Consultant for: Amgen, Abbvie, Jannsen, Novartis, Sun Pharma, Sanofi, UCB, Boeringer Ingelheim, H. Thom Consultant for: Novartis Pharma AG and for a short time in 2015 for Eli Lilly, S. Kanters Consultant for: Novartis, E. Palaka Employee of: Novartis employee, K. Gandhi Shareholder of: Novartis, Employee of: Novartis, S. Mpofu Shareholder of: Novartis, Employee of: Novartis, S. Jugl Shareholder of: Novartis, Employee of: Novartis

Minimal Disease Activity Among Active Psoriatic Arthritis Patients Treated With Secukinumab: 2‐Year Results From a Multicenter, Randomized, Double‐Blind, Parallel‐Group, Placebo‐Controlled Phase III Study

Objective: To evaluate minimal disease activity (MDA) among psoriatic arthritis (PsA) patients receiving secukinumab through 2 years in the FUTURE 2 study (NCT01752634). Methods: Patients with active PsA were randomized to receive subcutaneous secukinumab 300, 150, or 75 mg or placebo. MDA was assessed in the overall population (anti-tumor necrosis factor [TNF]-naïve and inadequate responders [antiTNF-IR]) and in patients stratified by prior anti-TNF exposure and by time since diagnosis at Weeks 16, 24, 52, and 104. Function, patient-reported outcomes (PROs) including health-related quality of life (QoL), and work productivity were assessed in MDA responders versus non-responders. Results: Overall, 28% (27/98) and 23% (23/100) of patients achieved MDA at Week 16 with secukinumab 300 and 150 mg, respectively, versus 10% (9/94) with placebo. In the anti–TNF-naïve cohort, a higher proportion of patients achieved MDA at Week A cc ep te d A rt ic le This article is protected by copyright. All rights reserved. 16 with secukinumab 300 and 150 mg (34% and 32%, respectively) versus placebo (13%). The corresponding value in the anti-TNF-IR cohort was 15% and 8% with secukinumab 300 and 150 mg, respectively, versus placebo (3%). At Week 16, 27.1% (16/59) of MDA responders achieved a very low disease activity (VLDA) response, with the percentage being numerically greater with secukinumab 300 and 150 mg (30% [8/27] and 26% [6/23], respectively) versus placebo (22% [2/9]). The MDA and VLDA responses with secukinumab 300 and 150 mg were sustained through 2 years. MDA responders showed greater improvements in QoL outcomes compared to non-responders through 2 years. Conclusion: A greater proportion of patients achieved MDA with secukinumab versus placebo at Week 16, with response rates sustained through 2 years. MDA was associated with improved PROs, including QoL, through 2 years.To evaluate minimal disease activity (MDA) among psoriatic arthritis (PsA) patients receiving secukinumab through 2 years in the FUTURE 2 study.

SAT0288 Secukinumab demonstrates rapid and sustained efficacy in ankylosing spondylitis patients with normal or elevated baseline crp levels: pooled analysis of two phase 3 studies

Background Elevated baseline (BL) CRP levels is one of the predictors of treatment response in patients (pts) with active AS.1 The relationship between BL CRP levels and the treatment response to IL-17A inhibition has not been assessed in AS pts thus far. Objectives This post-hoc analysis assessed the response to secukinumab (SEC) treatment in AS pts with normal or elevated BL CRP from the phase 3 MEASURE 1 and MEASURE 2 studies over 3 years. Methods The study designs of MEASURE 1 and 2 have been reported.2 This analysis pooled data from all pts with available BL CRP levels who received subcutaneous (s.c.) SEC 150 mg (approved dose; n=197) or placebo (PBO; n=195). Efficacy endpoints included ASAS20/40, BASDAI, BASDAI50, ASDAS inactive disease, and ASAS partial remission (PR) stratified by normal (<5 mg/L) and elevated (≥5 mg/L) BL CRP; elevated BL CRP group was further subdivided into a range of elevated CRP levels:>5–10,>10–15,>15 mg/L. Data are presented as non-responder imputation (NRI) at Week (Wk)16 and multiple imputation (MI) at Wk156 for binary variables and mixed-effect model repeated measure (MMRM) at Wks 16 and 156 for continuous variables. Results Overall, 36.5% (143/392) of pts with normal CRP and 63.5% (249/392) of pts with elevated BL CRP were included in the pooled analysis. BL characteristics were balanced across normal and elevated BL CRP groups.3 At Wk16, efficacy endpoints were improved with SEC 150 mg vs PBO in pts with normal or elevated BL CRP.3 Results were consistent across all levels of elevated BL CRP with a trend for greater improvement in pts with more elevated CRP (Table). Improvements were sustained or further improved at Wk156 in all groups (Table).Abstract SAT0288 – Table 1 Summary of Clinical Efficacy Conclusions SEC 150 mg demonstrated sustained efficacy through 3 years in AS patients with both normal and elevated CRP levels, with an increased effect in elevated CRP patients. References [1] Davis JC Jr, et al. J Rheumatol. 2005;32:1751–4. [2] Baeten D, et al. N Engl J Med 2015;373:2534–48. [3] et al. Arthritis Rheumatol 2017;69 [4] Braun J, et al. Arthritis Rheumatol 2017;69(suppl 10). Acknowledgements The study was sponsored by Novartis Pharma AG 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, 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, 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, UCB, J. Sieper Grant/research support from: AbbVie Inc., Pfizer Inc., and Merck, Consultant for: AbbVie Inc., Pfizer Inc., Merck, UCB, and Novartis, Speakers bureau: AbbVie Inc., Pfier Inc., Merck, and UCB, R. Landewé Grant/research support from: Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB, Wyeth, Consultant for: Abbott/AbbVie, Ablynx, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Centocor, GlaxoSmithKline, Novartis, Merck, Pfizer, Roche, Schering-Plough, UCB, Wyeth, Speakers bureau: Abbott, Amgen, Bristol-Myers Squibb, Centocor, Merck, Pfizer, Roche, Schering-Plough, UCB, Wyeth, X. Baraliakos Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB, Werfen, Consultant for: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB, Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB, Werfen, C. Miceli-Richard Grant/research support from: Abbott/AbbVie, Bristol-Myers Squibb, Novartis, Merck, Pfizer, Wyeth, Consultant for: Pfizer, Roche, UCB, Wyeth, Merck, Speakers bureau: Abbott, Bristol-Myers Squibb, Merck, Pfizer, Roche, Schering-Plough, Wyeth, E. Quebe-Fehling Employee of: Novartis, B. Porter Shareholder of: Novartis Pharmaceutical Corporation, Employee of: Novartis Pharmaceutical Corporation, K. Gandhi Shareholder of: Novartis Pharmaceutical Corporation, Employee of: Novartis Pharmaceutical Corporation, D. van der Heijde Consultant for: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB

AB0685 Secukinumab provides sustained improvements in work productivity and health related quality of life in patients with ankylosing spondylitis: long-term results from measure 1 and measure 2

Background Patients (pts) with ankylosing spondylitis (AS) experience significant restrictions in work productivity and health-related quality of life (HRQoL). Secukinumab (SEC) demonstrated rapid improvements in signs, symptoms and physical functioning in pts with AS.1 Objectives To assess whether the beneficial effects of SEC on AS signs and symptoms were reflected in improvements in work productivity and HRQoL in the overall population and in TNF inhibitor (TNF)-naïve pts and pts with an inadequate response or intolerance to TNF inhibitors (TNF-IR) for up to 52 weeks (wks) in MEASURE 2 and 104 wks in MEASURE 1. Methods 371 and 219 pts were randomized to SEC or placebo (PBO) in MEASURE 1 (10 mg/kg IV followed by 150 or 75 mg SC) and MEASURE 2 (150 or 75 mg SC), respectively. At Wk 16, PBO pts were re-randomized to SEC 150 or 75 mg SC (PBO pts with ASAS20 response at Wk 16 were switched to SEC at Wk 24 in MEASURE 1). Productivity was measured using the Work Productivity and Activity Impairment-General Health (WPAI-GH) questionnaire, which includes questions to assess absenteeism, presenteeism and overall work productivity impairment in employed pts, and general activity impairment in all pts during the preceding 7 days (0–100%). HRQoL was assessed with the ASQoL questionnaire (0–18 points). Across both studies, approximately 69% of pts were TNF-naïve and 31% were TNF-IR. Observed data are presented from the full analysis set and in subgroups stratified by prior TNF exposure. Only data with the approved dose (SEC 150 mg) are shown. Results At baseline (BL), 77 of 125 and 45 of 72 randomized pts were employed and working in the SEC groups in MEASURE 1 and 2, respectively. Improvements in all WPAI domains were observed with SEC in the overall, TNF-naïve and TNF-IR populations at Wk 16 in both studies, and effects were generally sustained through Wks 52 and 104 (Table). In MEASURE 1, activity impairment in the total group improved by 49% and overall work productivity in those employed improved by 45% from BL at Wk 104. Improvements were 51%/49% in TNF-naïve and 42%/19% in TNF-IR pts, respectively. In MEASURE 2, activity impairment and work productivity improved by 43% and 40% vs BL, respectively at Wk 52; improvements in activity impairment/work productivity in TNF-naïve and TNF-IR pts were 49%/54% and 32%/16%, respectively. Similar responses were seen in the other WPAI scores across both studies. Early improvements in ASQoL were sustained through Wk 104 in MEASURE 1 and Wk 52 in MEASURE 2. At Wk 104 of MEASURE 1, ASQoL scores had improved by 48% vs. BL with SEC; improvements were 50% and 39% in TNF-naïve and TNF-IR pts, respectively. Conclusions SEC provides sustained improvements in work productivity and ASQoL for up to 104 wks among AS pts, regardless of prior TNF exposure. References Baeten. NEJM 2015;373:2534–48. Disclosure of Interest A. Deodhar Grant/research support from: Amgen, Abbvie, GSK, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Speakers bureau: Eli Lilly, Janssen, Novartis, Pfizer, UCB, P. Conaghan Consultant for: Abbvie, BMS, Lilly, Novartis, Pfizer, Roche, Speakers bureau: Abbvie, BMS, Lilly, Novartis, Pfizer, Roche, V. Strand Consultant for: AbbVie, Amgen, BMS, Celgene, Celltrion, CORRONA, Genentech/Roche, GSK, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Samsung, Sanofi, and UCB, A. Boonen Grant/research support from: Merck, Pfizer, Abbvie and Amgen, Speakers bureau: Sandoz, Janssen, Lilly, G. Ferraccioli Grant/research support from: BMS, Roche, MSD, Speakers bureau: AbbVie, Pfizer, UCB.Roche, MSD, Eli Lilly, GSK, Novartis, F. Van den Bosch Consultant for: Abbvie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, UCB, Speakers bureau: Abbvie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, UCB, V. Bhosekar Employee of: Novartis, B. Porter Shareholder of: Novartis, Employee of: Novartis, K. Gandhi Shareholder of: Novartis, Employee of: Novartis, S. Jugl Shareholder of: Novartis, Employee of: Novartis

FRI0494 Secukinumab provides rapid and sustained pain relief in psoriatic arthritis: 2-year results from the future 2 study

Background Pain remains a major clinical challenge in the treatment of psoriatic arthritis (PsA). Secukinumab (SEC) has demonstrated significant efficacy in PsA patients (pts), across a range of quality of life related outcome measures.1,2 Objectives This post-hoc analysis evaluated change in pain scores from baseline (BL) to Week (Wk) 104 in PsA pts receiving SEC in the FUTURE 2 study. Methods FUTURE 2 study design has been reported.2 Mean change from BL in pain VAS and SF-36 bodily pain domain scores were evaluated using mixed-effect model for repeated measures (MMRM) through Wk 16 and as observed through Wk 104. Proportion of pts reporting improvements ≥clinically meaningful differences in pain VAS (mean change from BL ≥20%) was assessed. Results are reported for SEC 300 and 150mg in overall population and stratified by prior use of TNF inhibitor (TNFi; TNFi-naïve vs. inadequate responder/intolerant [TNFi-IR]). EQ–5D-3L pain item scores (no-, moderate- or extreme-pain/discomfort) were assessed as proportions. Results Mean changes from BL in pain VAS were greater with SEC vs. placebo (PBO) by Wk 3 (least squares mean [LSM]: -16.9, -12.6 with SEC 300 and 150mg, respectively vs. -5.75 with PBO; P<0.05), and Wk 16 (LSM: -24.0 and -23.0 for SEC 300 and 150mg, respectively vs. -8.41 with PBO; P<0.05). Mean changes were sustained through Wk 104 (-26.1 and -25.9 with SEC 300 and 150mg, respectively). In both SEC groups, >50% pts reported improvements of ≥20% by Wk 3 and this increased through Wk 104. Similarly, SF-36 bodily pain domain scores improved from BL by Wk 4 and 16 with SEC vs. PBO, exceeding minimum clinically important differences of 5.0 (Wk 4: LSM: 16.2 and 16.3 for SEC 300 and 150mg, respectively vs. 5.9 with PBO; P<0.05 and Wk 16: LSM: 21.1 and 22.0 for SEC 300 and 150mg, respectively vs. 6.9 with PBO; P<0.05). Improvements in pain were consistent in TNFi-naïve and TNFi-IR pts; and of greater magnitude in the naïve subgroup (table). Based on the EQ–5D-3L pain/discomfort item, 99% pts reported moderate to extreme pain or discomfort at BL. At Wk 4, the proportion of pts with no pain or discomfort was greater for the SEC 300mg (15%) and 150mg (10%) vs. PBO (5%) and increased through Wk 104 to 28% and 16% with SEC 300 and 150mg, respectively.Table 1. Summary of results by TNFi status at baseline TNFi-naïve TNFi-IR SEC 300mg SEC 150mg PBO SEC 300mg SEC 150mg PBO N 67 63 63 33 37 35 Pain VAS  Wk 16 -27.8* -25.1† -11.3 -18.2‡ -21.1§ -4.4  Wk 104 -29.6 -28.3 – -19.3 -20.4 – SF-36 bodily pain  Wk 16 23.8* 25.4* 8.6 18.3§ 17.9§ 5.2  Wk 104 24.2 22.2 – 24.5 14.0¶ – *P<0.0001; †P<0.001; §P<0.01; ‡P<0.05 vs. PBO. P-values and LS mean change at Wk 16 from MMRM analysis. Mean change at Wk 104 from observed data in n=57 (300mg) and 53 (150mg) for TNFi-naïve and n=29 (300mg) and 24 (150mg) for TNFi-IR; ¶n=26. Conclusions SEC provides rapid and sustained pain relief through 104 wks in pts with PsA as assessed by multiple clinically relevant patient-reported measures of pain. Improvements were reported by pts regardless of their prior TNFi therapy status. References Strand V, et al. Ann Rheum Dis 2017;76:203–7. McInnes IB, et al. Lancet 2015;386:1137–46. Disclosure of Interest 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, P. Mease Grant/research support from: Abbvie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, and UCB, Consultant for: Abbvie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, and UCB, Speakers bureau: Abbvie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer and UCB, G. Schett: None declared, B. Kirkham Grant/research support from: AbbVie, Eli Lilly, Novartis, Roche and UCB, Consultant for: Abbott, Eli Lilly and Novartis, Speakers bureau: Abbott, Janssen, Novartis and Pfizer, V. Strand Consultant for: AbbVie, Amgen, BMS, Celgene, Celltrion, Corrona, Genentech/Roche, GSK, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Sanofi and UCB, N. Williams Consultant for: Novartis through employment at RTI, Employee of: RTI Health Solutions, T. Fox Shareholder of: Novartis, Employee of: Novartis, L. Pricop Shareholder of: Novartis, Employee of: Novartis, S. Jugl Shareholder of: Novartis, Employee of: Novartis, K. Gandhi Shareholder of: Novartis, Employee of: Novartis

THU0393 Secukinumab provides sustained reduction in fatigue in patients with ankylosing spondylitis through 3 years: long-term results of two randomised double-blind placebo-controlled phase 3 studies

Background In patients (pts) with ankylosing spondylitis (AS), fatigue is a common symptom negatively affecting health-related quality of life (HRQoL) and social functioning. Secukinumab (SEC), a fully human anti–IL-17A mAb, rapidly improved signs and symptoms, physical functioning, and HRQoL in pts with AS.1,2 Objectives To assess the long-term effects of SEC on fatigue in TNF inhibitor (TNF)-naïve and TNF inhibitor inadequate responder/intolerant (TNF-IR) AS pts in MEASURE 1 and MEASURE 2. Methods 371 and 219 pts were randomized to SEC or placebo (PBO) in MEASURE 1 (10 mg/kg IV followed by 150 or 75 mg SC) and MEASURE 2 (150 or 75 mg SC), respectively. At Week (Wk) 16, non-responder PBO pts were re-randomized to SEC 150 or 75 mg SC (in MEASURE 1, PBO pts achieving ASAS20 response at Wk 16 were switched to SEC at Wk 24). Fatigue was measured at baseline (BL) and Wks 4, 8, 12, 16, 24, 52, 104 and 156 using FACIT-F, which assesses fatigue in the previous 7 days using 13 questions graded on a 0–4 scale (higher scores=less fatigue). An increase from BL in FACIT-F score of ≥4 points (based on MCID) was used to define “response”. Approximately 69% of pts were TNF-naïve and 31% were TNF-IR across both trials. Analyses were based on the full analysis set and subgroups stratified by prior TNF therapy. Correlations between BL characteristics and improvements in fatigue were investigated using a logistical regression model. Only data from the approved dose (SEC 150 mg) are presented. Results FACIT-F was 24.5–25.6 and 22.6–24.3 at BL across groups in MEASURE 1 and 2, respectively. Improvements in FACIT-F with SEC at Wk 16 were sustained through Wk 156 in MEASURE 1 and Wk 104 in MEASURE 2 (Table). Rapid and sustained fatigue responses were also seen in subgroups stratified by prior TNF use. In the overall population, LS mean changes (±SEM) from BL in FACIT-F scores were significantly greater with SEC vs PBO at Wk 16 in both MEASURE 1 (7.60±0.99 vs 3.34±1.00, P=0.002) and MEASURE 2 (8.10±1.09 vs 3.27±1.09, P=0.018); reductions in fatigue were sustained throughout the entire follow up in both trials (MEASURE 1 Wk 156: 9.81±0.95; MEASURE 2 Wk 104: 9.27±1.13). Similar results were reported in both TNF-naïve and TNF-IR pts. Correlational analyses based on pooled data from both trials did not identify any BL factors that consistently predicted improvement in fatigue response at Wks 16, 52, and 104. A one-unit increase in BL BASDAI score (i.e. worsening) was a significant factor for achieving FACIT-F response at Wk 104 (P=0.02). Conclusions SEC provided sustained improvements in fatigue for up to 156 wks in both TNF-naïve and TNF-IR pts with AS. Fatigue response was generally higher in TNF-naïve pts. References Baeten. NEJM 2015;373:2534–48. Kvien. ARD 2016;75(Suppl2):823. Disclosure of Interest T. Kvien Consultant for: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celltrion, Eli Lilly, Epirus, Janssen, Merck-Serono, MSD, Mundipharma, Novartis, Oktal, Orion Pharma, Hospira/Pfizer, Roche, Sandoz and UCB, Speakers bureau: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celltrion, Eli Lilly, Epirus, Janssen, Merck-Serono, MSD, Mundipharma, Novartis, Oktal, Orion Pharma, Hospira/Pfizer, Roche, Sandoz and UCB, A. Deodhar Grant/research support from: Eli Lilly, Janssen, Novartis, Pfizer, UCB, Abbvie, Amgen, GSK, L. Gossec Grant/research support from: BMS, Lippy, Pfizer, Consultant for: Abbvie, BMS, Celgene, Janssen, MSD, Novartis, Pfizer, Roche and UCB, P. Conaghan Consultant for: Abbvie, BMS, Lilly, Novartis, Pfizer, Roche, Speakers bureau: Abbvie, BMS, Lilly, Novartis, Pfizer, Roche, V. Strand Consultant for: AbbVie, Amgen, BMS, Celgene, Celltrion, CORRONA, Genentech/Roche, GSK, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Samsung, Sanofi, and UCB, M. Østergaard Consultant for: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Janssen, Merck, Novartis, Orion, Pfizer, Regeneron, Roche, UCB, Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Janssen, Merck, Novartis, Orion, Pfizer, Regeneron, Roche, UCB, N. Williams Employee of: RTI Health Solutions, B. Porter Shareholder of: Novartis, Employee of: Novartis, K. Gandhi Shareholder of: Novartis, Employee of: Novartis, S. Jugl Shareholder of: Novartis, Employee of: Novartis

OP0114 Secukinumab for The Treatment of Ankylosing Spondylitis: Comparative Effectiveness Results versus Adalimumab Using A Matching-Adjusted Indirect Comparison

Background Secukinumab 150 mg (SEC) is approved for the treatment of active AS in adults with inadequate response to conventional therapy. The MEASURE 2 (M2) trial showed superiority for SEC over placebo for the primary outcome measure, ASAS20 response, at week 16 and for multiple secondary outcomes. Efficacy was sustained up to 2 years. The ATLAS trial compared adalimumab 40 mg (ADA) with placebo, but there is no head-to-head trial of SEC vs. ADA. Placebo patients could switch to active treatment as early as week 12 in ATLAS and at week 16 in M2. Matching-adjusted indirect comparison (MAIC) can assess comparative effectiveness by re-weighting patient level data (PLD) resulting in a reduced effective sample size (ESS), to match the baseline patient characteristics of another trial. Thus, MAIC is able to simulate head-to-head comparisons. Objectives To assess the relative efficacy of SEC vs. ADA using adjusted PLD from M2 and published ATLAS data. Methods PLD from the SEC arm in M2 (n=72) was re-weighted to match baseline characteristics of the ADA arm in ATLAS (n=208). Logistic regression was used to determine weights for age, sex, mean BASFI score, mean CRP level, and prior biologic use. Sensitivity analyses including adjustment for BASDAI score were performed. Correlation analyses of baseline characteristics with ASAS20/40 responses were not available before the regression analyses. Both trials reported non-responder imputation (NRI) results until week 24; beyond which ATLAS used LOCF with n=311, including placebo switchers. Weighted outcomes from M2 (ESS n=34) were compared with outcomes from ATLAS. Pairwise comparisons using relative risks (RR) were performed. Results are presented as probability of response (95% CI) and RR (95% CI). Results SEC treatment led to statistical significantly higher ASAS responses at week 24 vs. ADA for ASAS20 (72.3% [62–83]; RR 1.43 [1.12–1.84] p=0.004) and ASAS40 (61.4% [50–73]; RR 1.56 [1.14–2.14] p=0.006). The ASAS20 and 40 response rates for ADA were 50.5% (44–57) and 39.4% (33–46) respectively. At week 52, SEC led to higher ASAS responses vs. ADA. The ASAS20 and 40 response rates for SEC were 78.9% (69–89) and 57.6% (46–69) respectively, and for ADA were 65.4% (60–71) and 47.1% (42–53). The SEC vs. ADA comparison at ASAS20 approached significance (RR 1.21 [0.996–1.461] p=0.055). No significant differences were observed at week 12 and 16. Sensitivity analyses support these findings. Conclusions SEC demonstrated statistically significant higher symptomatic improvement in terms of ASAS20 and 40 responses vs. ADA at week 24 in this first MAIC in AS. A similar trend was noted up to week 52, even though SEC NRI data was compared with ADA LOCF data at week 52. Differences in study designs, such as the early-escape criteria and disease duration together with the small ESS (n=34) for SEC may result in potential limitations, warranting further MAIC analyses in AS. Disclosure of Interest W. Maksymowych Grant/research support from: Abbvie, Pfizer, Sanofi, Consultant for: Abbvie, Amgen, Boehringer, Eli-Lilly, Janssen, Merck, Pfizer, Sanofi, UCB, V. Strand Consultant for: Abbvie, Amgen Corporation, AstraZeneca, BMS, Celgene, Celltrion, CORRONA, Genentech/Roche, GlaxoSmithKline, Janssen, Jazz Pharmaceuticals, Lilly, Novartis, Pfizer, Regeneron, Sandoz, Sanofi and UCB, D. Baeten Grant/research support from: Pfizer, MSD, AbbVie, UCB, Novartis, Janssen and Boehringer Ingelheim, Consultant for: Pfizer, MSD, AbbVie, UCB, Novartis, Janssen, Boehringer Ingelheim, Eli Lilly, Roche, BMS and Glenmark, P. Nash Grant/research support from: Novartis, Consultant for: Novartis, H. Thom Consultant for: Novartis Pharma AG and for a short time in 2015 for Eli Lilly, S. Cure: None declared, E. Palaka Employee of: Novartis, K. Gandhi Shareholder of: Novartis, Employee of: Novartis, H. Richards Shareholder of: Novartis, Employee of: Novartis, S. Jugl Shareholder of: Novartis, Employee of: Novartis

THU0448 Secukinumab for The Treatment of Psoriatic Arthritis: Comparative Effectiveness Results versus Adalimumab Up To 48 Weeks Using A Matching-Adjusted Indirect Comparison

Background Secukinumab (SEC) is approved for the treatment of active PsA in adults with inadequate response to DMARDs. The FUTURE 2 (F2) trial showed superiority of SEC 150 mg and 300 mg over placebo for the primary outcome of ACR20 response at week 24 and for multiple secondary outcomes, with efficacy sustained to week 52. The ADEPT trial compared adalimumab 40 mg (ADA) with placebo in biologic-naïve patients. In F2, patients could switch from placebo (from week 16); for both trials all had switched after week 24. In the absence of direct comparison or a continuous common placebo arm, matching-adjusted indirect comparison (MAIC) can assess relative efficacy. MAIC adjusts for differences in patient characteristics at baseline, reducing the effective sample size (ESS) for the therapy arm in one trial, but matching this with the population of the therapy arm from another trial, thus simulating head-to-head comparison. Objectives To assess the relative efficacy of SEC 150 mg and 300 mg vs. ADA using F2 and the published ADEPT trial. Methods Patient-level data from the SEC arms of the F2 trial (n=200 across SEC doses) were weighted to match patient baseline characteristics for the ADA arm of ADEPT (n=151). Logistic regression was used to determine weights for age, body weight, sex, race, methotrexate use, presence of psoriasis (≥3% body surface area), mean PASI score, dactylitis, enthesitis, mean HAQ-DI and previous biologic therapy. Weighted outcomes from F2 (ESS: n=36 for SEC 150 mg; n=38 for SEC 300 mg) were compared with data from ADEPT (both trials used non-responder imputation). Pairwise comparisons using relative risks (RRs) were performed and results are presented as RR (95% CI) and probability of response (95% CI) for ACR20, 50 and 70 at week 48. For PASI75 and 90, ADA week 48 results are compared with SEC week 52 data (the nearest data point). Results In the MAIC, both SEC doses had higher mean ACR20, 50 and 70 responses than ADA, with statistical significance for SEC 150 mg (RR: 1.41 [1.14–1.76], p=0.002) and SEC 300 mg (RR: 1.31 [1.03–1.66], p=0.027) at ACR20 and for SEC 300 mg (RR: 1.41 [1.03–1.92], p=0.032) at ACR50. The ACR20, 50 and 70 response rates were 79.6% (72–88), 57.1% (47–67) and 32.4% (23–42) respectively for SEC 150 mg; 73.5% (64–83), 61.4% (51–71) and 42.9% (33–53) for SEC 300 mg; and 56.3% (48–64), 43.7% (36–52) and 29.8% (23–37) for ADA. Findings were consistent across sensitivity analyses which also showed significance for SEC 300 mg at ACR70. PASI 75 and 90 response rates were numerically better for SEC 300 mg: 71.1% (57–86) and 52.2% (36–68) than ADA: 58.0% (46–70) and 46.4% (35–58). SEC 150 mg rates were 51.2% (38–64) and 40.8% (28–54) respectively. Conclusions When adjusted for patient baseline characteristics, SEC was associated with numerically higher response rates for joint and skin outcomes with statistically significantly higher responses vs. ADA for ACR endpoints at week 48. The next level of evidence will be a head-to-head to substantiate these findings. Disclosure of Interest P. Nash Grant/research support from: Novartis, Consultant for: Novartis, I. McInnes Consultant for: Novartis, Janssen, Abbvie, Pfizer and UCB, P. Mease Grant/research support from: Corrona, Speakers bureau: Corrona, Merck and Novartis, H. Thom Consultant for: Novartis Pharma AG and for a short time in 2015 for Eli Lilly, S. Cure: None declared, E. Palaka Employee of: Novartis, K. Gandhi Shareholder of: Novartis, Employee of: Novartis, S. Mpofu Shareholder of: Novartis, Employee of: Novartis, S. Jugl Shareholder of: Novartis, Employee of: Novartis

FRI0451 Secukinumab Provides Rapid and Sustained Reductions in Dactylitis and Enthesitis in Patients with Psoriatic Arthritis: Analysis of Data from The Phase 3 Randomised, Multicentre, Double-Blind, Placebo-Controlled Future 2 Study

Background Dactylitis and enthesitis are common debilitating manifestations of psoriatic arthritis (PsA).1 Secukinumab has previously been reported to reduce the number of dactylitic digits and enthesitis sites in patients (pts) with PsA, with a greater proportion of pts achieving complete resolution of dactylitis and enthesitis than placebo (PBO) at Week (Wk) 24.2,3 Objectives To evaluate the effects of secukinumab on dactylitis and enthesitis through Wk 52 in FUTURE 2 (NCT01752634). Methods The study design from FUTURE 2 has been reported previously.2 The proportions of pts with resolution of dactylitis and enthesitis at Wk 24 and Wk 52 were secondary and exploratory endpoints, respectively; additional measures were dactylitic digit and enthesitis counts. Post-hoc analyses included Kaplan Meier (KM) analysis to achieve resolution of enthesitis and dactylitism and proportion of pts with resolution of dactylitis and enthesitis by baseline (BL) severity. Results Of the 397 pts randomized, 138 (35%) and 253 (64%) had dactylitis and enthesitis, respectively, at BL. KM curves indicate that median time to resolution in dactylitis and enthesitis was Wk 4 for secukinumab 300 and 150 mg. At Wk 24, a greater proportion of secukinumab-treated pts achieved complete resolution of dactylitis and enthesitis than PBO (P<0.05); more secukinumab-treated pts had complete resolution of symptoms at Wk 52 than Wk 24. Improvements at Wk 24 and 52 were observed regardless of BL severity. A sustained decrease in mean changes from BL to Wk 24 and 52 in dactylitis and enthesitis count were shown in those pts with symptoms at BL (Table), with improvements versus PBO observed by Wk 4 (P<0.05).Table 1. Dactylitis and Enthesitis Data at Wks 24 and 52 Variable Secukinumab 300 mg Secukinumab 150 mg Secukinumab 75 mg PBO N=100 N=100 N=99 N=98 Dactylitis at BL, n (%) 46 (46.0) 32 (32.0) 33 (33.3) 27 (27.6) Dactylitis count at BL, mean 3.6 4.4 3.0 2.7 Dactylitis count, mean change from BL [95% CI]  Wk 24 −2.56 [−2.32, 0.89] −2.53 [−3.16, 0.04] −1.68 [−2.32, 0.89] −0.97  Wk 52 −3.08 [−1.06, 1.11] −3.11 [−2.31, −0.15] −1.85 [−2.44, −0.07] – Enthesitis at BL, n (%) 56 (56.0) 64 (64.0) 68 (68.7) 65 (66.3) Enthesitis count at BL, mean 2.82 3.19 3.16 3.06 Enthesitis count, mean change from BL [95% CI]  Wk 24 −1.68 [−1.27, 0.12] −1.83 [−1.40, −0.04] −1.38 [−0.95, 0.40] −1.11  Wk 52 −1.68 [−0.38, 0.84] −1.91 [−0.78, 0.43] −1.50 [−1.00, 0.19] – Symptoms in those patients with dactylitis/enthesitis at BL; dactylitis count from 20 digits (score of 0–20) and enthesitis count from 6 sites (score of 0–6); mixed-effect model repeated measures (MMRM) data. Conclusions Secukinumab demonstrated a rapid resolution of dactylitis and enthesitis as early as Wk 4 and this was sustained up to Wk 52. A higher proportion of pts achieved complete resolution and reduced mean counts of dactylitis and enthesitis at Wk 52 than Wk 24. References Gladman et al. Ann Rheum Dis 2005;64:14–7; McInnes et al. Lancet 2015;386:1137–46; Kirkham et al. Ann Rheum Dis 2015;74:351 Disclosure of Interest B. Kirkham Grant/research support from: Abbvie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Roche, UCB, Consultant for: Abbvie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Roche, UCB, Speakers bureau: Abbvie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Roche, UCB, P. Mease Grant/research support from: Abbvie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, Consultant for: Abbvie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, Speakers bureau: Abbvie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, I. McInnes Grant/research support from: Abbvie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB, Consultant for: Abbvie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB, Speakers bureau: Abbvie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB, V. Bhosekar: None declared, S. Mpofu Shareholder of: Novartis, Employee of: Novartis, K. Gandhi Employee of: Novartis, C. Gaillez Shareholder of: Novartis, Employee of: Novartis