Todd Fox

Secukinumab, a fully human anti-interleukin-17a monoclonal antibody, exhibits minimal immunogenicity in patients with moderate-to-severe plaque psoriasis

The proinflammatory cytokine interleukin (IL)‐17A plays a pivotal role in psoriasis pathogenesis. Secukinumab, a fully human monoclonal antibody (mAb) that selectively targets IL‐17A, has been demonstrated to be highly efficacious for the treatment of moderate‐to‐severe psoriasis, starting at early time points, with a sustained effect and a favourable safety profile. mAb therapies may be associated with production of antidrug antibodies (ADAs) that can affect drug pharmacokinetics, diminish response or cause hypersensitivity reactions.

Inhibition of IL-17A by secukinumab shows no evidence of increased Mycobacterium tuberculosis infections

Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin‐17A (IL‐17A), has been shown to have significant efficacy in the treatment of moderate to severe psoriasis, psoriatic arthritis and ankylosing spondylitis. Blocking critical mediators of immunity may carry a risk of increased opportunistic infections. Here we present clinical and in vitro findings examining the effect of secukinumab on Mycobacterium tuberculosis infection. We re‐assessed the effect of secukinumab on the incidence of acute tuberculosis (TB) and reactivation of latent TB infection (LTBI) in pooled safety data from five randomized, double‐blind, placebo‐controlled, phase 3 clinical trials in subjects with moderate to severe plaque psoriasis. No cases of TB were observed after 1 year. Importantly, in subjects with a history of pulmonary TB (but negative for interferon‐γ release and receiving no anti‐TB medication) or positive for latent TB (screened by interferon‐γ release assay and receiving anti‐TB medication), no cases of active TB were reported. Moreover, an in vitro study examined the effect of the anti‐tumor necrosis factor‐α (TNFα) antibody adalimumab and secukinumab on dormant M. tuberculosis H37Rv in a novel human three‐dimensional microgranuloma model. Auramine‐O, Nile red staining and rifampicin resistance of M. tuberculosis were measured. In vitro, anti‐TNFα treatment showed increased staining for Auramine‐O, decreased Nile red staining and decreased rifampicin resistance, indicative of mycobacterial reactivation. In contrast, secukinumab treatment was comparable to control indicating a lack of effect on M. tuberculosis dormancy. To date, clinical and preclinical investigations with secukinumab found no evidence of increased M. tuberculosis infections.

Secukinumab sustains good efficacy and favourable safety in moderate-to-severe psoriasis after up to 3 years of treatment: results from a double-blind extension study

Secukinumab has demonstrated significant efficacy with a good safety profile through 1 year in plaque psoriasis. Given the chronic nature of this disease, long‐term follow‐up is needed to evaluate psoriasis therapies fully.

Secukinumab sustains early patient-reported outcome benefits through 1 year: Results from 2 phase III randomized placebo-controlled clinical trials comparing secukinumab with etanercept

Background Psoriasis is a chronic condition with negative impact on patients’ quality of life that most often requires lifelong effective and safe treatment. Objective This analysis focused on the effect of secukinumab treatment on patient‐reported health‐related quality of life as assessed by the Dermatology Life Quality Index (DLQI) in patients with moderate to severe psoriasis. Methods The proportion of subjects achieving DLQI score 0/1 response at week 24, time to DLQI score 0/1 response, and sustained DLQI score 0/1 response up to week 52 were compared between secukinumab and etanercept. Results Of 1470 subjects, 1144 received secukinumab and 326 received etanercept. DLQI score 0/1 response rates were significantly higher for secukinumab than for etanercept at week 24. The median time to DLQI score 0/1 response was significantly shorter for secukinumab versus etanercept (12 vs 24 weeks; P < .01). The majority of secukinumab‐treated subjects achieved DLQI score 0/1 response at week 24 and sustained it through week 52 along with a 90% to 100% reduction in the Psoriasis Area and Severity Index total score response. Limitations Placebo comparisons are limited during the maintenance period because of rerandomization at week 12. Conclusion Secukinumab treatment provided faster and greater sustained improvements in quality of life than etanercept over 52 weeks, consistent with greater clinical response.

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

Psoriasis patients with psoriasis Area and Severity Index (PASI) 90 response achieve greater health-related quality-of-life improvements than those with PASI 75–89 response: results from two phase 3 studies of secukinumab

Abstract Background: The emergence of new biological therapies showing high and sustained level of Psoriasis Area and Severity Index (PASI) 90 response has provided the possibility of both greater skin clearance and increased quality of life (QOL). Objective: To evaluate the association of greater response in skin clearance with improvements in skin-related QOL up to 52 weeks. Methods: Subjects achieving various levels of skin clearance (PASI 90–100 or PASI 75–89) and Dermatology Life Quality Index (DLQI) (0/1) response were compared using ERASURE and FIXTURE trial data. Similar analyses with IGA ratings of Clear or Almost Clear were performed. Results: Significantly more PASI 90–100 responders at week 12 had DLQI 0/1 response than PASI 75–89 (69.4% vs. 47.1%; p < .001) and sustained DLQI 0/1 response at week 52 (74.0% vs. 56.7%; p < .001). IGA results were similar. Conclusions: These results show that PASI 90–100 is a relevant therapeutic goal in moderate to severe psoriasis compared to PASI 75–89 when considering patients’ QOL.

No elevated risk for depression, anxiety or suicidality with secukinumab in a pooled analysis of data from 10 clinical studies in moderate‐to‐severe plaque psoriasis

Concerns have emerged over the potential for brodalumab, a monoclonal antibody that binds to the human interleukin (IL)-17 receptor A and blocks the activity of multiple IL-17 isoforms, to increase risk of suicidal ideation and behaviour. Although the validity of this association has been questioned,1,2 brodalumab has a boxed warning regarding suicidality in its US label and is only available through a Risk Evaluation and Mitigation Strategy. Regardless of the true association between suicidality and brodalumab, the demonstrated adverse impact of psoriasis on mental health necessitates careful assessment for possible psychiatric adverse effects of psoriasis therapies, including those that inhibit the IL-17 pathway. This article is protected by copyright. All rights reserved.

THU0359 Secukinumab demonstrates consistent safety over long-term exposure (up to 3 years) in patients with active ankylosing spondylitis: pooled analysis of three phase 3 trials

Background Safety data for secukinumab in the treatment of ankylosing spondylitis (AS) have been reported from three Phase 3 studies: MEASURE 1 (NCT01358175)1, MEASURE 2 (NCT01649375)1 and MEASURE 3 (NCT02008916).2 Objectives To report long-term (up to 3 years) pooled safety and tolerability data for secukinumab in AS (data cut-off: 25 June 2016). Methods Overall, 371, 219 and 226 patients with active AS were randomised in MEASURE 1, MEASURE 2 and MEASURE 3, respectively. Study design, efficacy and safety results of these studies have been published earlier.1,2 Secukinumab doses differed in the studies and included intravenous 10 mg/kg or subcutaneous (75–300mg) multi-dose loading, followed by subcutaneous (s.c.) maintenance dosing (75, 150, or 300mg). Data collected up to the last patient performing the Wk 156 visit in MEASURE 1, the Wk 104 visit in MEASURE 2, and the Wk 52 visit in MEASURE 3 were pooled at the patient level. Exposure-adjusted incidence rates were calculated to account for differences in treatment exposure and analyses included all patients who received ≥1 dose of secukinumab 150 or 300mg. Results A total of 510 patients were included in the analysis (968.9 patient-years of exposure). The exposure-adjusted AE and SAE rates with secukinumab across the entire safety period were 159.2 and 5.4 per 100 patient-years, respectively. Nasopharyngitis, diarrhoea and headache were the most frequently reported AEs. The incidences of Candida infections, serious infections, inflammatory bowel disease, major adverse cardiac events, neutropenia and uveitis were low and consistent with previous reports over shorter exposure periods1 (Table). No cases of suicidal ideation or depression were reported.Table 1. Summary of pooled safety across 3 AS studies (Entire safety period) Any secukinumab dose (N=510) Total exposure, patient-years 968.9 Minimum–maximum exposure (days) 1–1530 Death, n (%) 0 AEs by EAIR: AE per 100 Patient-years (95% Cl) Any AE 159.2 (144.4, 175.1) Any SAE 5.4 (4.0, 7.1) Frequent AEs1  Nasopharyngitis 13.6 (11.2, 16.5)  Diarrhoea 6.4 (4.9, 8.3)  Headache 6.7 (5.1, 8.7)  Upper respiratory tract infection 4.3 (3.1, 5.9) AEs of special interest  Candida infections 0.8 (0.4, 1.6)  Serious infections 0.7 (0.3, 1.5)  Inflammatory Bowel Disease 0.4 (0.1, 1.1)  Crohns disease 0.2 (0.0, 0.7)  Ulcerative colitis 0.2 (0.0, 0.7) MACE 0.4 (0.1, 1.1) Neutropenia 1.2 (0.6, 2.1) Uveitis 1.6 (0.9, 2.6) 1AEs that occurred in Any secukinumab group with an IR >4.0 during the entire safety period. AE, adverse event; CI, confidence interval; EAIR, exposure adjusted incidence rate per 100 patient-years; MACE, major adverse cardiac events; N, number of patients in the analysis; n, number of patients with event; SAE, serious adverse event. Conclusions This longer-term safety assessment of secukinumab in the treatment of AS was consistent with previous reports and did not identify any new safety signals. References Baeten D, et al. N Engl J Med 2015;373:2534–48. Kivitz A, et al. XIX PANLAR 2016, Panamá City, Panama. Poster No. P-081. Disclosure of Interest A. Deodhar Grant/research support from: AbbVie, Amgen, Eli Lilly, GSK, Janssen, Novartis, Pfizer, and UCB; advisory board member: Eli Lilly, Janssen, Novartis, Pfizer, and UCB., X. Baraliakos Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB, and Werfen, Consultant for: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB, and Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB, and Werfen, 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, J. Sieper Grant/research support from: for AbbVie, Boehringer Ingelheim, Janssen, Novartis, Merck, Lilly, Pfizer, and UCB, Consultant for: for AbbVie, Boehringer Ingelheim, Janssen, Novartis, Merck, Lilly, Pfizer, and UCB, M. Andersson Employee of: Novartis, B. Porter Shareholder of: Novartis, Employee of: Novartis, T. Fox 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

AB0766 Secukinumab provides sustained remission and low disease activity related to disease activity index for psoriatic arthritis (DAPSA): 2 year results from the future 2 study

Background Disease Activity Index for Psoriatic Arthritis (DAPSA) is a validated tool to measure disease activity states, focussing on peripheral joint involvement in psoriatic arthritis (PsA), and can be used to assess targets such as remission (REM) or low disease activity (LDA).1 Objectives Secukinumab, a fully human anti–interleukin-17A monoclonal antibody, significantly improved American College of Rheumatology responses vs. placebo at Week (Wk) 24 that were sustained through Wk 104 in active PsA patients (pts) in the FUTURE 2 study2. This post-hoc exploratory analysis assessed DAPSA states through Wk 104. Methods In total, 397 active PsA pts were randomised to subcutaneous (s.c) secukinumab (300, 150 or 75mg) or placebo at baseline and Wks 1, 2, 3 and 4, and every 4 wks (q4w) thereafter. Placebo pts were re-randomised to secukinumab 300 or 150mg s.c q4w from Wk 16 or 24, depending on Wk 16 clinical response. DAPSA was derived as the sum of five variables: tender joint and swollen joint counts (TJC 68 and SJC 66); pt global and pain assessed on a 10cm visual analogue scale; and C-reactive protein levels (mg/dl) with validated cut-offs to indicate REM (≤4), LDA (>4 and ≤14), moderate disease activity (MDA; >14 and ≤28) and high disease activity (HDA; >28). DAPSA was assessed in the overall population and in pts stratified by prior anti-tumour necrosis factor (anti-TNF) therapy use (anti–TNF-naïve vs. inadequate response/intolerance to these agents [anti–TNF-IR]) and time since first PsA diagnosis (≤2 vs. >2 years) using observed data. Only data for secukinumab 300 and 150mg (approved doses) are reported. Results Baseline demographics and clinical characteristics were similar across treatment groups and previously reported.3 DAPSA score at baseline (mean [SD]) was 42.0 (17.4), 46.8 (24.3) and 44.9 (25.3) in the secukinumab 300mg, 150mg and placebo groups, respectively. In the overall population, at Wk 16, REM was achieved in 14/97 (14.4%) with secukinumab 300mg and 10/100 (10%) with secukinumab 150mg vs. placebo 4/87 (4.6%); LDA in 27/97 (27.8%) and 34/100 (34%) vs. 12/87 (13.8%), respectively. REM or LDA were sustained through Wk 104 with secukinumab 300 and 150mg (55/84 [65.5%; REM + LDA] and 41/ 77 [53.2%; REM + LDA], respectively). The proportion of pts achieving each DAPSA state at Wks 16 and 104 by anti-TNF status (anti–TNF-naïve vs. anti–TNF-IR) and by time since diagnosis (≤2 vs. >2 years) for secukinumab 300 and 150mg is presented in the figure. Conclusions In the overall population, a higher proportion of pts treated with secukinumab at Wk 16 achieved DAPSA REM than those treated with placebo, with REM and LDA sustaining through Wk 104. At Wk 16, a higher proportion of anti–TNF-naïve pts treated with secukinumab achieved and sustained DAPSA REM than anti–TNF-IR pts and a higher proportion of pts with early diagnosis (≤2 years) achieved DAPSA REM vs. pts diagnosed later (>2 years). References Schoels MM, et al. Ann Rheum Dis 2016;75:811–8. McInnes IB, et al. Arthritis Rheumatol 2016;68 (suppl 10). McInnes, et al. Lancet 2015;386:1137–46. Disclosure of Interest J. Smolen Grant/research support from: AbbVie, Janssen, Eli Lilly, MSD, Pfizer, Roche, Amgen, AstraZeneca, Astro, Celgene, Celltrion, GSK, ILTOO, Medimmune, Novartis-Sandoz, Pfizer, Samsung, Sanofi and UCB., Consultant for: AbbVie, Janssen, Eli Lilly, MSD, Pfizer, Roche, Amgen, AstraZeneca, Astro, Celgene, Celltrion, GSK, ILTOO, Medimmune, Novartis-Sandoz, Pfizer, Samsung, Sanofi 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., 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., L. Pricop Shareholder of: Novartis, Employee of: Novartis, T. Fox Shareholder of: Novartis, Employee of: Novartis, L. Rasouliyan Consultant for: Novartis through employment at RTI, Employee of: RTI Health Solutions, S. Jugl Shareholder of: Novartis, Employee of: Novartis, C. Gaillez Shareholder of: Novartis and BMS, Employee of: Novartis