BACKGROUND:Using a machine learning approach, the study investigated if specific baseline characteristics could predict which psoriatic arthritis (PsA) patients may gain additional benefit from a starting dose of secukinumab 300 mg over 150 mg. We also report results from individual patient efficacy meta-analysis (IPEM) in 2049 PsA patients from the FUTURE 2 to 5 studies to evaluate the efficacy of secukinumab 300 mg, 150 mg with and without loading regimen versus placebo at week 16 on achievement of several clinically relevant difficult-to-achieve (higher hurdle) endpoints.METHODS:Machine learning employed Bayesian elastic net to analyze baseline data of 2148 PsA patients investigating 275 predictors. For IPEM, results were presented as difference in response rates versus placebo at week 16.RESULTS:Machine learning showed secukinumab 300 mg has additional benefits in patients who are anti-tumor necrosis factor-naive, treated with 1 prior anti-tumor necrosis factor agent, not receiving methotrexate, with enthesitis at baseline, and with shorter PsA disease duration. For IPEM, at week 16, all secukinumab doses had greater treatment effect (%) versus placebo for higher hurdle endpoints in the overall population and in all subgroups; 300-mg dose had greater treatment effect than 150 mg for all endpoints in overall population and most subgroups.CONCLUSIONS:Machine learning identified predictors for additional benefit of secukinumab 300 mg compared with 150 mg dose. Individual patient efficacy meta-analysis showed that secukinumab 300 mg provided greater improvements compared with 150 mg in higher hurdle efficacy endpoints in patients with active PsA in the overall population and most subgroups with various levels of baseline disease activity and psoriasis.

To evaluate the efficacy and safety of 2 canakinumab monotherapy tapering regimens in order to maintain complete clinical remission in children with systemic juvenile idiopathic arthritis (JIA).The study was designed as a 2-part phase IIIb/IV open-label, randomized trial. In the first part, patients received 4 mg/kg of canakinumab subcutaneously every 4 weeks and discontinued glucocorticoids and/or methotrexate as appropriate. Patients in whom clinical remission was achieved (inactive disease for at least 24 weeks) with canakinumab monotherapy were entered into the second part of the trial, in which they were randomized 1:1 into 1 of 2 treatment arms. In arm 1, the dose of canakinumab was reduced from 4 mg/kg to 2 mg/kg and then to 1 mg/kg, followed by discontinuation. In arm 2, the 4 mg/kg dose interval was prolonged from every 4 weeks, to every 8 weeks, and then to every 12 weeks, followed by discontinuation. In both arms, canakinumab exposure could be reduced provided systemic JIA remained in clinical remission for 24 weeks with each step. The primary objective was to assess whether >40% of randomized patients in either arm maintained clinical remission of systemic JIA for 24 weeks in the first part of the study.In part 1 of the study, 182 patients were enrolled, with 75 of those patients randomized before entering part 2 of the trial. Among the 75 randomized patients, clinical remission was maintained for 24 weeks in 27 (71%) of 38 patients in arm 1 (2 mg/kg every 4 weeks) and 31 (84%) of 37 patients in arm 2 (4 mg/kg every 8 weeks) (P ≤ 0.0001 for arm 1 versus arm 2 among those meeting the 40% threshold). Overall, 25 (33%) of 75 patients discontinued canakinumab, and clinical remission was maintained for at least 24 weeks in all 25 of these patients. No new safety signals were identified.Reduction of canakinumab exposure may be feasible in patients who have achieved clinical remission of systemic JIA, but consistent interleukin-1 inhibition appears necessary to maintain this response.

To assess the efficacy and safety of the subcutaneous (s.c.) secukinumab 150 mg with loading (150 mg) or without loading (150 mg no-load) regimen through 104 weeks in patients with active psoriatic arthritis (PsA) in the FUTURE 4 (NCT02294227) study. Patients with PsA (N = 341) were randomized to s.c. secukinumab 150 mg, 150 mg no-load or placebo at baseline, weeks 1, 2, 3 and every 4 weeks thereafter. All placebo patients were reassigned to secukinumab 150 mg no-load at either week 16 (non-responders) or week 24 (responders). The primary end point was ACR20 at week 16. Patients could have their dose escalated from 150 to 300 mg based on their physician’s decision starting at week 36. Pre- and post-escalation ACR and PASI responses were also assessed. A total of 95.6% (326/341), 84.5% (288/341) and 79.8% (272/341) patients completed 16, 52 and 104 weeks of treatment, respectively. The primary end point was met; ACR20 response rate at week 16 was 41.2% and 39.8% with the 150 mg and 150 mg no-load groups, respectively, versus placebo (18.4%; adjusted P value = 0.0003 for both treatment arms). Efficacy responses observed at week 16 in both treatment regimens were sustained up to week 52 and 104, with many patients continuing to show improvements up to week 104. After dose escalation to 300 mg, the proportion of patients with non-/low-level ACR/PASI response decreased with increasing proportions of patients having higher ACR/PASI responses. No new or unexpected safety signals were reported. The secukinumab 150 mg or 150 mg no-load regimen demonstrated significant and sustained improvements in the signs and symptoms of psoriatic arthritis through 104 weeks; the loading regimen was associated with numerically higher and earlier responses for some high-hurdle end points. Improved efficacy was observed upon dose escalation from 150 to 300 mg. The safety profile was consistent with previous reports. ClinicalTrials.gov identifier, NCT02294227. Novartis Pharma AG, Basel, Switzerland.

Background Identifying patient phenotypes using machine-learning (ML) techniques amidst the variability and heterogeneity of the clinical manifestations of psoriatic arthritis (PsA) could be the first critical step towards better understanding of the disease eventually leading to individualized medicine.1 Objectives To identify distinct clusters of patients with PsA based on patients’ tender joint (TJ) and swollen joint (SJ) counts and correlation patterns among TJ and SJ counts at baseline as captured in the secukinumab FUTURE trials program. Methods Pairwise correlations were explored among 76 SJ and 78 TJ measurements of >2,700 patients with PsA across 5 phase III studies with ≈425,000 data entries at baseline and were visualized using heatmaps. Due to high correlations between SJs and corresponding TJs, a composite variable “swollen/tender joint count” was constructed for each joint. Hierarchical clustering was then performed on the composite using “1-correlation” as the dissimilarity metric and Ward’s agglomeration method for pairwise grouping of joints. A dendrogram was used to visualize and assess the resulting joint groupings. Results The hierarchical clustering algorithm grouped the 78 individual joints into distinct and natural clusters (Figure 1A). At higher level of the dendrogram, the algorithm grouped separately all foot, larger (jaws, clavicles, ankles, hips, wrists, knees, shoulders, elbows), and hand joints. Cutting the dendrogram at 15 clusters separated all the joints into distinct groups; hand joints (distal and proximal phalanges, metacarpals and thumbs), and foot joints (distal and proximal phalanges, metatarsals and big toes). Similar clustering algorithms were explored to identify patient clusters at baseline with distinct swelling and tenderness patterns across the identified joint groups. High correlation between swelling/tenderness of the left and swelling/tenderness of the corresponding right joint was observed across all individual joints (Figure 1B); a high correlation was also observed between swelling and tenderness at all individual joints. More localized patterns showed that there is a gradual decrease in correlation (from highest to lowest) among TJs and SJs in adjacent vs non-adjacent fingers, which is evident from grey-scale patterns (Figure 1C). Specifically, a gradual decrease in correlation between the swelling of 2nd distal interphalangeal joint and the tenderness of the 2nd–5th distal phalanges was noted. Conclusion Machine learning methodology confirmed a natural grouping of joints in patients with psoriatic arthritis based on baseline swelling and tenderness and revealed complex correlation patterns. Additional cluster analyses have demonstrated distinct patient clusters across the identified joint groups. Further investigating potential associations of other disease manifestations such as skin and nail involvement to define additional phenotypes may explain differences in disease pathogenesis and treatment outcomes. Reference [1] Grys BT, et al., J Cell Biol. 2017; 216(1): 65-71. Disclosure of Interests Matthias Kormaksson Shareholder of: Novartis, Employee of: Novartis, Effie Pournara Shareholder of: Novartis, Employee of: Novartis, Gregory Ligozio Shareholder of: Novartis, Employee of: Novartis, Luminita Pricop Shareholder of: Novartis, Employee of: Novartis, Ken Abrams Shareholder of: Novartis, Employee of: Novartis, Bruce Kirkham Grant/research support from: Abbvie, Janssen, Lilly, Novartis, Roche, UCB, Consultant for: Abbvie, Janssen, Lilly, Novartis, Roche, UCB, Speakers bureau: Abbvie, Janssen, Lilly, Novartis, Roche, UCB, Kristian Reich Consultant for: Abbvie, Affibody, Amgen, Biogen, Boehringer Ingelheim Pharma, Celgene, Centocor, Covagen, Forward Pharma, Fresenius Medical Care, GlaxoSmithKline, Janssen-Cilag, Kyowa Kirin, Leo, Lilly, Medac, Merck Sharp & Dohme Corp., Novartis, Miltenyi Biotec, Ocean Pharma, Pfizer, Regeneron, Samsung Bioepis, Sanofi, Takeda, UCB Pharma, Valeant, Xenoport; Speakers bureau: Abbvie, Affibody, Amgen, Biogen, Boehringer Ingelheim Pharma, Celgene, Centocor, Covagen, Forward Pharma, Fresenius Medical Care, GlaxoSmithKline, Janssen-Cilag, Kyowa Kirin, Leo, Lilly, Medac, Merck Sharp & Dohme Corp., Novartis, Miltenyi Biotec, Ocean Pharma, Pfizer, Regeneron, Samsung Bioepis, Sanofi, Takeda, UCB Pharma, Valeant, Xenoport, Iain McInnes Grant/research support from: AstraZeneca, Celgene, Compugen, Novartis, Roche, UCB Pharma, Consultant for: AbbVie, Celgene, Galvani, Lilly, Novartis, Pfizer, UCB Pharma

BackgroundCanakinumab (CAN), a selective, human anti-IL-1β mAb, has shown sustained therapeutic effect along with corticosteroid (CS) dose reduction/discontinuation in patients (pts) with systemic juvenile idiopathic arthritis (SJIA), in a long-term extension study (NCT00891046).1ObjectivesTo evaluate the efficacy and safety of 2 different CAN tapering regimens in SJIA pts who were in clinical remission (NCT02296424).MethodsThis Phase 3b/4 study had 2 parts. Of 182 enrolled pts, 166 pts with inactive disease (ID) (cohort 1; 68pts)1 and CAN-naïve pts (cohort 2; 98pts) were administered subcutaneous CAN 4mg/kg q4w in Part I. Per protocol titration off CS and/or methotrexate (MTX) was attempted during Part I. Eligible pts (ID for 24 weeks[wks] and being CS- and MTX-free for at least 4 wks) advanced to Part II wherein, pts were randomised to either a 3-step CAN dose reduction (2mg/kg/q4w, followed by tapering to 1 mg/kg/q4w and then discontinuation) or dose interval prolongation (4mg/kg q8w, followed by tapering to 4mg/kg/q12w and then discontinuation); pts advanced to the next tapering step if ID was maintained for 24 wks. Adapted American College of Rheumatology (ACR) paediatric criteria, its individual components and Juvenile Arthritis Disease Activity Score (JADAS) were assessed.ResultsIn total, 75 pts were randomised to a dose reduction (n=38) or dose interval prolongation (n=37) CAN tapering regimen in part II. The pts who maintained ID for 24 wks exceeded the predefined threshold of 40% for the reduced CAN dose arm (71%) and prolonged dose interval (84%) treatment arm of Step 1 (primary endpoint). A total of 68.4% (26/38) and 81.1% (30/37) pts in the dose reduction and interval prolongation arms, respectively were successful in Step 2; 33% (25/75) of pts successfully discontinued CAN and maintained ID for 24 wks. ID, ACR 90/100 and JADAS 27 C-reactive protein (CRP) scores are summarised in the table. Adverse events (AEs) and serious AEs observed within the 2 cohorts and across Parts I and II were similar. The most frequent AEs were common infections (nasopharyngitis, upper respiratory tract infection, pharyngitis) followed by SJIA-related events (rash, pyrexia and arthralgia).ConclusionSJIA pts with ID for 24 wks on CAN monotherapy can successfully taper CAN by either reducing the dose or prolonging the dosing interval. However, only a minority of pts overall successfully discontinued CAN treatment and maintained ID for 24 wks. The safety profile was similar and consistent with other CAN SJIA studies. No new safety signals were identified.Reference[1] Arthritis Rheumatol.2016; 68 (S10).Disclosure of InterestsPierre Quartier Consultant for: AbbVie, Chugai-Roche, lilly, Novartis, Novimmune, Sanofi, and SOBI, Consultant for: AbbVie, Chugai-Roche, Lilly, Novartis, Novimmune, Sanofi, and SOBI, Speakers bureau: AbbVie, BMS, Chugai-Roche, Novartis, Pfizer, and SOBI, Speakers bureau: AbbVie, BMS, Chugai-Roche, Novartis, Pfizer, and SOBI, Ekaterina Alexeeva: None declared, Carine Wouters Grant/research support from: Grant/research support to Istituto Gaslini from GlaxoSmithKline immune-inflammation: unrestricted grant to study Blau syndrome; Roche: unrestricted research grant; Pfizer: grant for psychological care of patients with JIA, Grant/research support from: GSK, Roche, Pfizer, Inmaculada Calvo Grant/research support from: received research grants from Pfizer, Roche, Novartis, Clementia, Sanofi, MSD, BMS and GSK, Consultant for: Advisory boards: Novartis, AbbVie, Speakers bureau: AbbVie, Roche, Novartis, SOBI, Tilmann Kallinich Grant/research support from: Novartis, Speakers bureau: Sobi, Roche, Novartis, CLB, Nico Wulffraat: None declared, Xiaoling Wei Employee of: Novartis, Alan Slade Shareholder of: Novartis Pharmaceuticals Corporation, Employee of: Novartis Pharmaceuticals Corporation, Ken Abrams Shareholder of: Novartis, Employee of: Novartis, Alberto Martini: None declared

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.

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: Secukinumab (Sec) provided rapid, significant and sustained improvement in the signs and symptoms of psoriatic arthritis (PsA) in multiple Phase 3 studies.1‐4 Objectives: To report individual patient meta‐analysis data for Sec on achievement of high hurdle efficacy endpoints versus placebo (PBO) at Week (Wk) 16 in patients (pts) with PsA from four Phase 3 studies: FUTURE 2, 3, 4 and 5. Analyses in subgroups by baseline (BL) disease activity, BL psoriasis, prior Anti–TNF and concomitant Methotrexate (MTX) use were also evaluated. Methods: Overall, 397, 414, 341, and 996 pts with active PsA were randomized in FUTURE 2, 3, 4, and 5 studies, respectively. Sec doses included subcutaneous 300 mg and 150 mg administered at BL with loading doses (LD) at Wks 1, 2, and 3, followed by maintenance dose every 4 wks (q4w) starting at Wk 4. Data collected up to Wk 16 were pooled. Assessments included: ACR 50/70, PASI90 responses, PASDAS‐Low Disease Activity (PASDAS‐LDA), and Minimal Disease Activity (MDA) in overall population. ACR 50/70 and PASI 90 responses by BL Disease Activity Score (DAS) 28‐C‐Reactive Protein (CRP) (≤5.1 and > 5.1), BL CRP (≤10 mg/L and > 10 mg/L), BL Body Surface Area (BSA) (≥3%–<10%, and ≥ 10%) with psoriasis and prior Anti–TNF and concomitant MTX use were also assessed. Results are reported after application of non‐responder imputation. Results: 2049 pts were included in the meta‐analysis (461, 572, 335, and 681 pts received Sec 300 mg, 150 mg, 150 mg without LD and PBO, respectively). Improvements were observed with Sec (300 mg, 150 mg, and 150 mg without LD) vs PBO for all endpoints at Wk 16 in the overall population (Table) and in all subgroups (data not shown). Sec 300 mg was associated with greater improvements compared to the 150 mg dose for all endpoints in overall population and in subgroups. Conclusions: Sec provided improvements in high hurdle efficacy endpoints in pts with active PsA in the overall population and in subgroups with various levels of BL disease activity and psoriasis.

BACKGROUND: Fixed combinations are commonplace in dermatology, providing significant efficacy and tolerability benefits. In some cases, two active ingredients complement each other providing a cumulative or additive effect. In rarer cases, a synergistic effect may be seen where the sum of the two active ingredients combined action is greater than the sum of the efficacy of the constituent parts. Being able to demonstrate synergy is important in situations where the two active ingredients may be used individually to provide layering. OBJECTIVE: To determine whether a novel halobetasol propionate 0.01% and tazarotene 0.045% (HP/TAZ) fixed combination lotion provides a synergistic effect in the treatment of moderate-to-severe plaque psoriasis. MATERIALS/METHODS: Post hoc analysis of 212 patients with moderate-to-severe plaque psoriasis randomized (2:2:2:1) to HP/TAZ lotion, HP, TAZ or vehicle once-daily for 8 weeks, with a 4-week posttreatment follow-up. Treatment success was evaluated based on two outcomes: percent of patients achieving at least a 2-grade improvement in Investigator Global Assessment (IGA) and IGA score equating to ‘clear’ or ‘almost clear’; and percent change from baseline in the IGA multiplied by Body Surface Area (BSA) composite score, a simple validated alternative to assessing response to therapy that correlates well with the Psoriasis Area Severity Index (PASI). Synergy was calculated by summing up the contribution of the individual active ingredients (HP and TAZ) to overall efficacy and comparing to the efficacy achieved with HP/ TAZ lotion relative to vehicle. RESULTS: At Week 8, treatment success with HP/TAZ lotion, relative to vehicle was 42.8% compared with 23.6% and 9.0% for HP and TAZ. Percent change from baseline in IGAxBSA score, relative to vehicle was 51.6% compared with 37.3% and 3.3% for HP and TAZ. In both cases the synergy ratios were 1.3. At Week 12, treatment success with HP/TAZ lotion, relative to vehicle was 31.3% compared with 14.1% and 5.9% for HP and TAZ. Percent change from baseline in IGAxBSA score, relative to vehicle was 47.3% compared with 25.7% and 8.6% for HP and TAZ. Synergy ratios were 1.6 and 1.4 respectively. CONCLUSIONS: Halobetasol propionate 0.01% and tazarotene 0.045% (HP/TAZ) fixed combination lotion provides a synergistic effect in the treatment of moderate-to-severe plaque psoriasis. In addition, by combining two agents into one once-daily formulation, this novel formulation reduces the number of product applications and may help patient adherence. CORRESPONDENCE: brian.bulley@btinternet.com DISCLOSURES: Tina Lin, is an employee of Bausch Health; Leon Kircik: has been a consultant and investigator for Valeant Pharmaceuticals.

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

Objectives To evaluate the effect of subcutaneous (s.c.) secukinumab, an interleukin-17A inhibitor, on clinical signs and symptoms and radiographic progression in patients with psoriatic arthritis (PsA). Methods Adults (n=996) with active PsA were randomised 2:2:2:3 to s.c. secukinumab 300 mg or 150 mg with loading dose (LD), 150 mg without LD or placebo. All groups received secukinumab or placebo at baseline, weeks 1, 2 and 3 and then every 4 weeks from week 4. The primary endpoint was the proportion of patients achieving an American College of Rheumatology 20 (ACR20) response at week 16. Results Significantly more patients achieved an ACR20 response at week 16 with secukinumab 300 mg with LD (62.6%), 150 mg with LD (55.5%) or 150 mg without LD (59.5%) than placebo (27.4%) (p<0.0001 for all; non-responder imputation). Radiographic progression, as measured by van der Heijde-modified total Sharp score, was significantly inhibited at week 24 in all secukinumab arms versus placebo (p<0.01 for 300 mg with LD and 150 mg without LD and p<0.05 for 150 mg with LD; linear extrapolation). Adverse event rates at week 24 were similar across treatment arms: 63.1% (300 mg with LD), 62.7% (150 mg with LD), 61.1% (150 mg without LD) and 62.0% (placebo). No deaths or new safety signals were reported. Conclusion S.c. secukinumab 300 mg and 150 mg with and without LD significantly improved clinical signs and symptoms and inhibited radiographic structural progression versus placebo at week 24 in patients with PsA. Trial registration number NCT02404350; Results.

Background Psoriatic arthritis (PsA) is associated with joint inflammation, characterised by synovitis, presence of erosions, joint space narrowing (JSN) and new bone formation leading to structural damage, increased disability and reduced quality of life. Secukinumab (SEC) provided significant and rapid clinical efficacy, and inhibition of radiographic progression in PsA patients (pts) in the FUTURE 5 study.1 Objectives To assess the effect of subcutaneous (sc) SEC on radiographic progression by prior anti–TNF therapy or concomitant methotrexate (MTX) use in the FUTURE 5 study. Methods Adults (n=996) with active PsA, stratified by prior anti–TNF therapy (naïve and inadequate response/intolerance [IR]) were randomised 2:2:2:3 to sc SEC 300 mg with loading dose (LD), 150 mg LD, 150 mg no LD, or placebo (PBO) at baseline (BL), Wks 1, 2, 3, 4, and every 4 wks thereafter.1 At Wk 16, PBO non-responders were switched to SEC 300 or 150 mg. Concomitant MTX (≤25 mg/week) was allowed. Radiographic progression (mean change in van der Heijde-modified total Sharp score for PsA [vdH-mTSS] and its components: erosion and joint space narrowing [JSN] scores from BL to Wk 24) was based on hand/wrist/foot X-rays obtained at BL, Wks 16 (non-responders) assessed by two blinded readers (plus an adjudicator if required). Average scores were used. Statistical analyses used linear extrapolation at Wk 24 for all PBO non-responders and for all other pts with missing Wk 24 X-rays. Results At BL, 30% pts were anti–TNF-IR and 50% were on concomitant MTX. Radiographic progression was significantly inhibited at Wk 24 in the overall population with SEC vs PBO; mean change from BL in vdH-mTSS was 0.08 (300mg; p<0.01), 0.17 (150mg; p<0.05),–0.09 (150mg no LD; P<0.01) vs 0.50 (PBO). Lower radiographic progression (vdH-mTSS, erosion and JSN scores) was observed with SEC vs PBO regardless of prior anti–TNF therapy or concomitant MTX use (table 1). Conclusions Subcutaneous secukinumab 300 mg with loading dose, and 150 mg with and without loading dose, inhibited radiographic progression in patients with active PsA. Low rates of radiographic progression were observed regardless of previous anti-TNF therapy or concomitant MTX use. Reference [[1] ] ] Mease PJ, et al. Arthritis Rheumatol2017;69(suppl 10). Disclosure of Interest 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, Employee of: Director of Imaging Rheumatology, P. Mease Grant/research support from: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, SUN, and UCB, Consultant for: AbbVie, Amgen, BMS, Celgene, Covagen, Crescendo, Janssen, LEO, Lilly, Merck, Novartis, Pfizer, SUN, and UCB; speakers’ bureau for AbbVie, Amgen, BMS, Celgene, Genentech, Janssen, Lilly, Pfizer, and UCB, R. Landewé Grant/research support from: Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB, Wyeth, Employee of: Director of Rheumatology Consultancy BV, Speakers bureau: Abbott, Amgen, Bristol-Myers Squibb, Centocor, Merck, Pfizer, Roche, Schering-Plough, UCB, Wyeth, S. Mpofu Shareholder of: Novartis, Employee of: Novartis, P. Rahman Consultant for: Abbott, AbbVie, Amgen, BMS, Celgene, Janssen, Novartis, Pfizer and Roche, pharmaceutical companies dealing with biologic agents in Rheumatology, H. Tahir Grant/research support from: Novartis, Pfizer, Consultant for: Abbvie, Novartis, Pfizer, UCB, Eli-Lilly, Janssen, A. Singhal Grant/research support from: AbbVie, Gilead, Sanofi, Regeneron, Amgen, Roche, BMS, Janssen, Lilly, Novartis, Pfizer, UCB, Astra Zeneca, MedImmune, FujiFilm, Nichi-Iko, Mallinckrodt, Speakers bureau: AbbVie, E. Boettcher Consultant for: Amgen, Roche, Eli Lilly, Pfizer, MSD, Novartis, Speakers bureau: Amgen, Roche, Eli Lilly, Pfizer, MSD, Novartis, S. Navarra Consultant for: Pfizer, Novartis, Astra-Zeneca, Janssen, Astellas, Roche, Speakers bureau: Pfizer, Novartis, Astra-Zeneca, Janssen, Astellas, Roche, X. Zhu Employee of: Novartis, A. Readie Shareholder of: Novartis stock, Employee of: Novartis, L. Pricop Shareholder of: Novartis stock, Employee of: Novartis, K. Abrams Shareholder of: Novartis stock, Employee of: Novartis

Background Secukinumab has demonstrated rapid, significant and sustained improvement in the signs and symptoms of psoriatic arthritis (PsA) in multiple Phase 3 studies.1–3 Objectives To report pooled efficacy results for secukinumab versus placebo at Week (Wk) 16 in PsA patients (pts) by previous anti-TNF therapy and with or without concomitant methotrexate (MTX) use from four Phase 3 studies: FUTURE 2, FUTURE 3, FUTURE 4 and FUTURE 5. Methods Overall, 397, 414, 341, and 996 pts with active PsA were randomised in FUTURE 2, FUTURE 3, FUTURE 4 and FUTURE 5, respectively. Secukinumab doses included subcutaneous (s.c.) 300 mg and 150 mg administered at baseline (BL) with loading doses at Wks 1, 2, and 3, followed by maintenance dose every 4 wks (q4w) starting at Wk 4 and s.c. secukinumab 150 mg administered at BL without loading dose, followed by q4w starting at Wk 4. Data collected up to Wk 16 were pooled. Assessments included ACR20/50/70, DAS-28 CRP, PASI 75/90, SF-36 PCS, HAQ-DI, and resolution of dactylitis, and enthesitis. Pooled analyses examined the effect of prior anti-TNF use (naïve/inadequate response or intolerance to these agents, -IR) and with/without MTX use on clinical endpoints and are reported after application of non-responder imputation for binary variables and a mixed-effects model for repeated measures for continuous variables. Results A total of 2049 pts were included in the analysis, of which 461, 572, 335, and 681 pts received secukinumab 300 mg, 150 mg, 150 mg without load and placebo, respectively. Improvements were observed with secukinumab vs placebo for all endpoints at Wk 16 in both anti−TNF-naive and anti−TNF-IR pts and in pts with and without concomitant MTX use. Higher ACR and PASI responses and greater improvement of disease activity were observed in anti−TNF-naïve pts compared to anti−TNF-IR pts. Secukinumab 300 mg provided numerically higher ACR and PASI responses compared to the 150 mg dose particularly for anti−TNF-IR pts and in pts with no concomitant MTX use. Earlier responses were observed with secukinumab with load compared to without load primarily across ACR, DAS28-CRP and PASI endpoints. Conclusions Secukinumab provided improvements in the signs and symptoms of active PsA regardless of previous anti-TNF therapy or concomitant MTX use. Higher response rates were generally observed in anti−TNF-naïve pts compared to anti−TNF-IR pts. Secukinumab 300 mg was associated with higher responses compared to 150 mg particularly in anti−TNF-IR pts and in pts with no concomitant MTX use. References [1] Mease P, et al. Ann Rheum Dis. 2017;76:952–953 [2] McInnes IB, et al. Rheumatology (Oxford)2017;56:1993–2003 [3] Mease P, et al. Arthritis Rheumatol. 2017; 69 (suppl 10) Acknowledgements The study was sponsored by Novartis Pharma AG. Disclosure of Interest B. Kirkham Grant/research support from: Abbvie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Roche, and UCB, Consultant for: Abbvie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Roche, and UCB, Speakers bureau: Abbvie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Roche, and 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, P. Nash Grant/research support from: Novartis, Abbvie, Roche, Pfizer, BMS, Janssen, and Celgene, Consultant for: Novartis, Abbvie, Roche, Pfizer, BMS, Janssen, and Celgene, Speakers bureau: Novartis, Abbvie, Roche, Pfizer, BMS, Janssen, and Celgene, A. Balsa Grant/research support from: Pfizer, Abbvie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB, Consultant for: Pfizer, Abbvie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB, Speakers bureau: Pfizer, Abbvie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB, B. Combe Consultant for: BMS, AbbVie, Janssen, Lilly, pfizer, Msd, Novartis, roche -chugai, ucb, s’angoisse, Speakers bureau: BMS, AbbVie, Janssen, Lilly, pfizer, Msd, Novartis, roche -chugai, ucb, s’angoisse, J. Rech Grant/research support from: BMS and Celgene, Speakers bureau: Abbvie, BMS, Celgene, Fresenius, Medicap, MSD, Novartis, Pfizer, and Roche, R. Martin Shareholder of: Novartis, Employee of: Novartis, G. Ligozio Shareholder of: Novartis, Employee of: Novartis, K. Abrams Shareholder of: Novartis, Employee of: Novartis, L. Pricop Shareholder of: Novartis, Employee of: Novartis

Background Secukinumab (AIN457), a fully human anti-interleukin-17A monoclonal antibody, has demonstrated a significant clinically meaningful efficacy on signs and symptoms, structure and function in adults with ankylosing spondylitis (AS)1 and psoriatic arthritis (PsA)2, both approved indications. These data support the proposed study in children with enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA). Objectives This phase 3 study will investigate the efficacy and safety of secukinumab in children≥2 to<18 years with active JPsA or ERA. The primary objective is to demonstrate that the time to flare in a double-blind placebo control treatment withdrawal part of the trial is longer with secukinumab than placebo. Methods Eighty biologic-naïve children with active ERA or JPsA (active:≥3 active joints and >1 site of enthesitis at baseline or documented by history) will enrol into treatment period 1 and receive weekly open label s.c. secukinumab 75 or 150 mg, based on their body weight (<50 kg or ≥50 kg) to maintain secukinumab blood levels equivalent to the adult 150 mg dose, for the first month then every 4 weeks thereafter. At week 12, responders (minimum JIA ACR Pedi 30 response) enter treatment period 2 and will be randomised to receive secukinumab or a matching placebo every 4 weeks. Patients enter treatment period 3 if they experience a disease flare or when the treatment period 2 closes for the entire study because the target number of flares has been reached. Upon entering treatment period 3, patients receive open-label secukinumab every 4 weeks until week 100 and then followed until week 112. Results The primary efficacy endpoint will be time to flare in treatment period 2. Key secondary endpoints include JIA Pedi ACR 30/50/70/90/100 response rate, total dactylitis and enthesitis counts at week 12. Safety and tolerability will be assessed throughout the study. Conclusions The efficacy of Secukinumab in the approved adult indications of PsA and AS support the current study design to evaluate the efficacy and safety of secukinumab treatment in children with active JPsA or ERA. The primary efficacy endpoint will be time to flare in treatment period 2. Key secondary endpoints include JIA Pedi ACR 30/50/70/90/100 response rate, total dactylitis and enthesitis counts at week 12. Safety and tolerability will be assessed throughout the study. References [1] Baeten D, et al. Lancet. 2013;382(9906):1705–13 [] 2McInnes IB, et al. Lancet. 2015;386(9999):1137–46 Acknowledgements This research was funded by Novartis Pharma AG, Basel, Switzerland Disclosure of Interest D. Foell Consultant for: Novartis Pharma GmbH, Speakers bureau: Novartis Pharma GmbH, J. Veit Employee of: Novartis Pharma GmbH, E. Ilsley Employee of: Novartis Pharma AG, K. Abrams Shareholder of: Novartis Pharmaceuticals Corporation, Employee of: Novartis Pharmaceuticals Corporation