Background: Psoriatic arthritis (PsA) is a chronic, systemic, immune-mediated, inflammatory musculoskeletal disease in which dysregulated interleukin (IL)-17A activity plays a pivotal role in disease pathogenesis. Izokibep (IZO) is a small protein therapeutic (18.6 kDa) designed to selectively inhibit IL-17A with high potency through tight binding affinity [1]. IZO demonstrated efficacy across multiple PsA measures through week (wk) 46 in a phase 2 study. Objectives: To evaluate the efficacy and safety of IZO through wk 16 in a phase 2b/3 study in patients (pts) with active PsA. Methods: Study 22104 (NCT05623345) included a 16-wk, randomized, double-blind, placebo (PBO)-controlled treatment period. Eligible pts had adult-onset, active PsA (duration ≥6 months and ≥3 tender/swollen joints) and an inadequate response, intolerance, or contraindication to an NSAID, csDMARD, and/or TNFi. Pts reported here were equally randomized to IZO 160 mg every 2 wks (Q2W), IZO 160 mg every wk (QW), or PBO QW. The primary endpoint was ACR50 at wk 16. Results: A total of 343 pts were included (IZO 160 mg Q2W, n=113; IZO 160 mg QW, n=112; PBO, n=118). The mean age was 51 years, BMI was 30 kg/m2, time since diagnosis was 7 years, and 53% were male. Baseline (BL) disease characteristics were generally balanced across groups. The primary endpoint of ACR50 at wk 16 was met; a higher percentage of pts receiving IZO Q2W (43%, P<0.0001) and QW (40%, P<0.0001) achieved ACR50 vs PBO (15%), with improvement as early as wk 4 (Figure 1). Higher percentages of pts receiving either dose of IZO vs PBO achieved the high-hurdle endpoints of ACR70, PASI100, and MDA (Table 1). Higher percentages of pts receiving IZO also achieved HAQ-DI minimal clinically important difference (≥0.35) vs PBO (Table 1). Subgroup summaries showed clinically meaningful enthesitis resolution rates with IZO vs PBO in pts with high BL enthesitis burden (Table 1). Treatment-emergent adverse events (AEs) occurred in 66%, 72%, and 41% of pts receiving IZO Q2W, IZO QW, and PBO, respectively. The most common AEs were injection site-related events, the majority of which were mild to moderate in severity and infrequently led to discontinuation (1%, 4%, and 0% of pts receiving IZO Q2W, IZO QW, and PBO, respectively). Serious AEs were reported at low rates (2%, 3%, and 1%). Rates of ulcerative colitis (1%, 1%, and 0%) and candidiasis (0%, 1%, and 1%) were also low. No deaths, uveitis cases, or suicidal ideation were reported. Conclusion: IL-17A selective inhibition by IZO in pts with active PsA resulted in rapid improvement in disease activity across multiple disease domains. In addition to meeting the primary endpoint of ACR50, a substantial portion of IZO-treated pts achieved responses for the high-hurdle endpoints of ACR70, PASI90, PASI100, and MDA. These findings are consistent with the hypothesis that the IZO molecular construct allows optimal efficacy by IL-17A inhibition, without requiring blockade of IL-17F. IZO treatment was well tolerated, with a safety profile generally consistent with that of other IL-17A inhibitors. REFERENCES: [1] Klint S, et al. MAbs. 2023;15(1):2209920. Acknowledgements: NIL. Disclosure of Interests: Philip J. Mease AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, AbbVie, ACELYRIN, INC., Aclaris, Alumis, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Immagene, Janssen, Moonlake, Novartis, Pfizer, Takeda, UCB, and Ventyx, AbbVie, ACELYRIN, INC., Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Frank Behrens Abbvie, Affibody, Amgen, Boehringer Ingelheim, Galapagos, GSK, Janssen Cilag, Lilly, MoonLake, MSD, Novartis, Pfizer, Sandoz, Sanofi, and UCB, Abbvie, Affibody, Amgen, Boehringer Ingelheim, Galapagos, GSK, Janssen Cilag, Lilly, MoonLake, MSD, Novartis, Pfizer, Sandoz, Sanofi, and UCB, Bionorica, BMS, Chugai, Iron4u, Janssen-Cilag, LEO, Novartis, Pfizer, and Roche, Alan Kivitz AbbVie, Amgen, Flexion, GSK, Lilly, Pfizer, Sanofi - Regeneron, and UCB, Amgen, Gilead, GSK, Novartis, and Pfizer, AbbVie, Coval, Ecor1, Fresenius Kabi, Gilead, Grunenthal, GSK, Halia, Horizon, Janssen, Prime, Prometheus, Selecta, Synact, Takeda – Nimbus, UCB, and XBiotech, Edit Drescher: None declared, Piotr Adrian Klimiuk: None declared, Howard Sofen ACELYRIN, INC., Nehad Soloman AbbVie, Amgen, AstraZeneca, GSK, Scifer Medical, and UCB, Anne M. Stevens ACELYRIN, INC., ACELYRIN, INC., Myreen E. Tomas ACELYRIN, INC., ACELYRIN, INC., Brian Wiens ACELYRIN, INC. and Horizon, ACELYRIN, INC., Shephard Mpofu ACELYRIN, INC., ACELYRIN, INC., Peter C. Taylor AbbVie, ACELYRIN, INC., Aqtual, Inc., Biogen, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Nordic Pharma, Pfizer, Sanofi, UCB, Galapagos.Figure 1ACR50 Response Over 16 Weeks. Full analysis set; nonresponse imputation. Nominal significance: *P<0.05; ***P<0.0001. Table 1Week 16 Efficacy ResultsIZO 160 mg Q2W(n=113)IZO 160 mg QW(n=112)PBO QW(n=118)ACR5043%***40%***15%ACR2064%***59%**35%ACR7023%***25%***5%PASI90a58%***64%***12%PASI100a47%***51%***12%MDA42%***41%***14%PsAID9b42%***38%***12%HAQ-DIc50%47%37%LEI=0BL LEI>056%45%47%BL LEI=3-6d52%41%37%BL LEI=5-6d50%22%8%Data are reported using NRI analysis unless otherwise indicated. Despite the previously disclosed dose-sequencing error that occurred in the Q2W arm, all pts received correct aggregate amounts of drug. Nominal significance: **P<0.01, ***P<0.0001 vs PBO.aBL Psoriasis Body Surface Area ≥3%. b≥3-unit improvement in pts with BL PsAID ≥3. c≥0.35-unit improvement in pts with BL HAQ-DI >0.35. dData reported as observed.BL, baseline; HAQ-DI, Health Assessment Questionnaire–Disability Index; MDA, minimal disease activity; PsAID, Psoriatic Arthritis Impact of Disease.

Background: Secukinumab (SEC), an interleukin-17A inhibitor, has demonstrated improvements on multiple domains of psoriatic arthritis (PsA). 1 Adalimumab (ADA), a TNF inhibitor, is widely used as a first–line biologic in PsA. Objectives: To report efficacy and safety outcomes from the head-to-head EXCEED trial ( NCT02745080 ) that compares SEC vs. ADA as first–line biologic monotherapy through 52-weeks (wks), with a musculoskeletal primary endpoint in pts with active PsA. Methods: Head-to-head, phase-3b, randomised, double-blind trial: biologic naïve active PsA pts were randomised to receive SEC 300mg subcutaneous at baseline, Wk1-4, and then every 4wks (q4w) until Wk48 or ADA 40mg subcutaneous at baseline and then q2w until Wk50. The primary endpoint was superiority of SEC vs. ADA on ACR20 response at Wk52. Binary and continuous variables were analysed using logistic-regression model and MMRM, respectively. Safety analysis included patients who received ≥1 dose of study-drug. Results: 853 pts were randomised to receive SEC (n=426) or ADA (n=427). Baseline demographics and disease characteristics were comparable between treatment-groups except higher proportion of female pts and pts without enthesitis in the SEC group. ACR20 response at Wk52 for SEC vs. ADA were 67·4% vs. 61·5%, respectively (p=0·0719) (Figure). Higher clinical responses were observed with SEC vs. ADA for a range of musculoskeletal, skin, and higher-hurdle outcomes (Table). A higher retention rate was observed for SEC (85.7%) vs. ADA (76.3%). Safety profiles of SEC and ADA were consistent with previous reports. 2,3 Conclusion: Results suggest that SEC is at least as efficacious as ADA on musculoskeletal endpoints whilst providing higher responses on skin endpoints, and is associated with a higher retention rate. No new safety signals were reported. References: [1]van der Heijde, et al. Rheumatol. (Oxford).2019; DOI10.1093/rheumatology/kez420. [2]Deodhar A, et al. Arthritis Res Ther. 2019;21:111. [3]Burmester GR, et al. Ann Rheum Dis.2013; 72:517-24. Figure. ACR20 Response through Wk 52 Table. Efficacy Outcomes at Wk 52 Endpoints, % response unless specified otherwise SEC 300 mg (N=426) ADA 40 mg (N=427) P-value (unadjusted)* ACR20 67·4 61·5 0·0719 a ACR20 66·9 59·5 0·0239 Key Secondary b PASI 90 65·4 43·2 <0·0001 ACR50 49·0 44·8 0·2251 HAQ-DI mean change from baseline ± SE -0·58 ± 0.03 -0·56 ± 0.03 0·5465 c Resolution of enthesitis (based on LEI) 60·5 54·2 0·1498 Exploratory MDA 43·0 37·9 0·1498 VLDA 18·1 16·6 0·6107 DAPSA LDA+Remission 61·7 53·1 0·0178 PASDAS LDA+Remission 51·1 44·1 0·0557 *Unadjusted P-values vs ADA Binary variables were analysed using logistic regression. Pts who discontinued study treatment prematurely or took csDMARDs after week-36 were considered non-responders. Multiple imputation was used for all other missing data. HAQ-DI mean change from baseline was analysed using mixed-effect model repeated measures a Non-responder imputation was used for pre-specified sensitivity analysis b N=215 in SEC and N=202 in ADA in psoriasis subset c N=234 in SEC and N=264 in ADA in enthesitis subset Disclosure of Interests: Iain McInnes Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB, Frank Behrens Grant/research support from: Pfizer, Janssen, Chugai, Celgene, Lilly and Roche, Consultant of: Pfizer, AbbVie, Sanofi, Lilly, Novartis, Genzyme, Boehringer, Janssen, MSD, Celgene, Roche and Chugai, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau, Arthur Kavanaugh Grant/research support from: Abbott, Amgen, AstraZeneca, BMS, Celgene Corporation, Centocor-Janssen, Pfizer, Roche, UCB – grant/research support, Christopher T. Ritchlin Grant/research support from: UCB Pharma, AbbVie, Amgen, Consultant of: UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, Peter Nash Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Jordi Gratacos-Masmitja Grant/research support from: a grant from Pfizzer to study implementation of multidisciplinary units to manage PSA in SPAIN, Consultant of: Pfizzer, MSD, ABBVIE, Janssen, Amgen, BMS, Novartis, Lilly, Speakers bureau: Pfizzer, MSD, ABBVIE, Janssen, Amgen, BMS, Novartis, Lilly, Philippe Goupille Grant/research support from: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Lilly, Janssen, Medac, MSD France, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Consultant of: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Lilly, Janssen, Medac, MSD France, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Speakers bureau: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Lilly, Janssen, Medac, MSD France, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Tatiana Korotaeva Grant/research support from: Pfizer, Consultant of: Abbvie, BIOCAD, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, UCB, Speakers bureau: Abbvie, BIOCAD, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, UCB, Alice B Gottlieb Grant/research support from:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Consultant of:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Speakers bureau:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Ruvie Martin Shareholder of: Novartis, Employee of: Novartis, Kevin Ding Employee of: Novartis, Pascale Pellet Shareholder of: Novartis, Employee of: Novartis, Shephard Mpofu Shareholder of: Novartis, Employee of: Novartis, Luminita Pricop Shareholder of: Novartis, Employee of: Novartis

Background:Magnetic resonance imaging (MRI) offers a non-invasive and objective method of early diagnosis and classification, monitoring disease burden and treatment response for patients (pts) with axial spondyloarthritis (axSpA) including ankylosing spondylitis (AS).1Numerous scoring schemes such as the AS Spine MRI Activity (ASspiMRIa) score are available for the quantitative assessment of MRI, but are subject to intra- and inter-rater variability, labor intensive and costly. Nevertheless, quantification of MRI changes has become an important tool to demonstrate treatment success of biologic drugs in axSpA.Objectives:To evaluate the performance of machine learning (ML) based software for automated Berlin grading of spinal MRI bone marrow oedema in pts with AS and compare with expert scoring.Methods:Fully automated ML software (Figure) was developed to detect and label 23 vertebrae, define vertebral units (VU) as per the Berlin modification of the ASspiMRIa score, and score each VU as either 0 (score of 0) or 1 (score of 1, 2 or 3). The ML algorithm was based on the previously developed SpineNet software.2Analysis included 108 pts from the secukinumab MEASURE 1 study3, in which imaging was done using T1 and STIR sagittal MRI at baseline and Weeks 16, 52, 104, 156 and 208. Two expert readers, blinded to treatment and visit, evaluated all images by ASspiMRIa score. The scores from Reader 2 (R2) were binned into two groups: 0 vs 1, 2, or 3. As a result of multiple pt time points and expert reading sessions, the complete dataset comprised of 10,988 VU. Ten-way cross-validation at per-VU was used to train and validate the ML software. The dataset was split into 10 randomly selected subsets, ensuring that each pt appears in only one subset, after which 8 subsets were used for training the ML software, 1 was used to check for correct training and 1 was used for validation. The process was repeated ten times such that all 10 subsets were used for validation. Accuracy weighted for the frequency of each category, sensitivity and specificity were calculated using scores from R2 as reference. Intra-reader accuracy was also calculated.Results:Accuracy of the software in relation to expert reader scores was 67% with a sensitivity of 0.63 and specificity of 0.70. The intra-reader accuracy was 71% and 77% for R1 and R2, respectively. Individual VU scoring of the Software vs. R2 are presented in the Table as a confusion matrix.Conclusion:Automated scoring of MR images in AS pts provided moderate agreement to that of expert reader-based assessments. ML software has potential to provide an automated guided-reading approach to scoring MR images, which may enable further clinical insights.References:[1]Lukas C, et al. J Rheumatol. 2007;34:862-70.[2]Jamaludin A, et al. Eur Spine J. 2017;26:1374-83.[3]Baeten D, et al. N Engl J Med. 2015;373,2534-48.Figure.Processing pipeline of automated Berlin scoring softwareTable.Confusion matrix between the software and R2SoftwareScore = 0SoftwareScore = 1, 2 or 3Total VU scoredR2 Score = 07199 (70%)3068 (30%)10,267R2 Score = 1, 2 or 3251 (35%)475 (65%)7267,4503,54310,993Percentages calculated as a fraction over the total in each row. Overall accuracy is the average of the highlighted percentages.Disclosure of Interests:Amir Jamaludin: None declared, Rhydian Windsor: None declared, Sarim Ather: None declared, Timor Kadir: None declared, Andrew Zisserman: None declared, Juergen Braun Grant/research support from: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, Eli Lilly and Company, Medac, MSD (Schering Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi- Aventis, and UCB Pharma, Consultant of: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Eli Lilly and Company, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB Pharma, Speakers bureau: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Eli Lilly and Company, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB Pharma, Lianne S. Gensler Grant/research support from: Pfizer, Novartis, UCB, Consultant of: AbbVie, Eli Lilly, GSK, Novartis, UCB, Pedro Machado Consultant of: Abbvie, Celgene, Janssen, Lilly, MSD, BMS, Novartis, Pfizer, Roche and UCB, Speakers bureau: AbbVie, Centocor, Eli Lilly, Janssen, MSD, Novartis, Pfizer and UCB Pharma, Mikkel Ǿstergaard Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Merck, and Novartis, Consultant of: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Denis Poddubnyy Grant/research support from: AbbVie, MSD, Novartis, and Pfizer, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Thibaud Coroller Shareholder of: Novartis, Employee of: Novartis, Brian Porter Shareholder of: Novartis, Employee of: Novartis, Shephard Mpofu Shareholder of: Novartis, Employee of: Novartis, Aimee Readie Shareholder of: Novartis, Employee of: Novartis

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 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 significantly improved the signs and symptoms of psoriatic arthritis (PsA) over 2 years (yrs) in the FUTURE 1 study.1 Objectives To report efficacy and safety of secukinumab through 3 yrs in an extension of the FUTURE 1 study (NCT01892436). Methods After 2-yr core trial, patients (pts) receiving secukinumab 150/75mg s.c. entered the 3-yr extension phase. Efficacy results at Week (Wk) 156 are presented for those pts originally randomised to secukinumab (n=308) and included ACR20/50/70, PASI 75, DAS28-CRP, SF-36 PCS, HAQ-DI, dactylitis and enthesitis. Multiple imputation was used for analysis of binary variables while continuous variables are reported as observed. Analyses by anti-TNF status (naïve/inadequate response) were prespecified and reported as observed. Safety analysis included all pts (n=587) who received ≥1 dose of secukinumab. Results Overall, 457 of the original 606 pts entered the extension study of which 435 (95.2%) pts completed 156 wks (151 [93.8%] pts in IV→150 mg group; 142 [96.6%] in IV→75 mg group; 142 [95.3%] in PBO→ secukinumab groups). Sustained clinical improvements through Wk 156 were observed across all endpoints and were seen regardless of prior anti-TNF use (Table 1). Over the entire study period (mean [±SD] exposure to secukinumab of 1025.1±372.7 days), the exposure-adjusted incidence rate with secukinumab for serious infections/infestations, candida infections, Crohn9s disease, and malignant/unspecified tumors was 1.7 (27), 1.2 (17), 0.1 (2), and 0.9 (14) per 100 pt-yrs, respectively. Conclusions Secukinumab provided sustained improvements in signs/symptoms and across multiple clinical domains of active PsA in pts who completed 3 yrs of therapy. Secukinumab was well tolerated with a favorable safety profile consistent with that previously reported.1 References Kavanaugh A, et al. Arthritis Care Res. (Hoboken) 2016. Disclosure of Interest 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, A. Kavanaugh Consultant for: Novartis, A. Reimold Grant/research support from: AbbVie, H. Tahir Speakers bureau: Novartis, Eli Lilly, and Abbvie, J. Rech Speakers bureau: Abbvie, BMS, Celgene, Fresenius, medicap, MSD, Novartis, Pfizer, and Roche, S. Hall: None declared, P. Geusens Grant/research support from: Pfizer, Abbott, Lilly, Amgen, MSD, Will, Bio Minerals and Roche, Speakers bureau: Pfizer, Abbott, Lilly, Amgen, MSD, Will, Bio Minerals and Roche, P. Pascale Shareholder of: Novartis, Employee of: Novartis, E. M. Delicha Employee of: Novartis, L. Pricop Shareholder of: Novartis, Employee of: Novartis, S. Mpofu Shareholder of: Novartis, Employee of: Novartis

Background Minimal disease activity (MDA), a validated composite measure in PsA, is gaining acceptance as a target for achieving substantial disease control. Objectives Secukinumab (SEC), an anti–IL-17A monoclonal antibody, significantly improved the signs and symptoms of PsA over 52 wks in the FUTURE 2 study. This post-hoc exploratory analysis assessed MDA response rates through 52 wks. Methods 397 patients (pts) with active PsA were randomized to subcutaneous (SC) SEC (300 mg, 150 mg, or 75 mg) or placebo (PBO) at baseline (BL), Wks 1, 2, and 3, and every 4 wks (q4w) from Wk 4. PBO pts were re-randomized to SEC 300 or 150 mg SC q4w from Wk 16 or 24, depending upon clinical response. Pts were considered in MDA when they met at least 5 of the following 7 criteria: 1) tender joint count ≤1; 2) swollen joint count ≤1; 3) Psoriasis Activity and Severity Index ≤1 or psoriasis affecting <3% body surface area at BL; 4) pt pain VAS ≤15; 5) pt global disease activity VAS ≤20; 6) HAQ-DI ≤0.5; 7) tender entheseal points ≤1. MDA was assessed in the overall population and in pts stratified by prior anti-tumor necrosis factor (anti-TNF) therapy use (anti–TNF-naïve and inadequate response/intolerance to these agents [anti–TNF-IR]) and disease duration (≤2 yrs vs >2 yrs since diagnosis). Observed data are shown. 75 mg data are not reported as this was not considered an effective dose (no secondary endpoints were met). Results In the overall population, 23/100 (23%) and 27/97 (28%) pts achieved MDA at Wk 16 with SEC 150 mg and 300 mg, respectively, vs 9/88 (10%) pts with PBO; these response rates were sustained through Wk 52 (150 mg: 29/88 [33%]; 300 mg: 33/93 [35%]). In the anti–TNF-naïve cohort, a higher proportion of pts achieved MDA at Wk 16 with SEC 150 mg (20/63 [32%]) or 300 mg (22/65 [34%]) vs PBO (8/58 [14%]), with response rates sustained through Wk 52 (150 mg: 23/59 [39%]; 300 mg: 26/63 [41%]). Lower rates were observed in anti–TNF-IR pts (SEC vs PBO at Wk 16: 150 mg, 3/37 [8%]; 300 mg, 5/32 [16%]; PBO, 1/30 [3%]; Wk 52: 150 mg, 6/29 [21%]; 300 mg, 7/30 [23%]). The proportion of pts achieving MDA at Wk 16 and Wk 52 in the overall population was greater for those ≤2 yrs since diagnosis vs those >2 yrs since diagnosis for both SEC 150 mg and 300 mg. The proportion of pts achieving MDA with SEC at Wk 16 was higher in anti–TNF-naïve pts with low disease duration vs pts with longer disease duration, and higher in the anti–TNF-naïve cohort than the anti–TNF-IR cohort at all times (Figure). Conclusions SEC pts had higher MDA response rates vs PBO pts at Wk 16, with response rates sustained through Wk 52. Response rates were consistent with those previously reported with anti-TNF therapies in comparable pt populations.1 This study is the first to report MDA in anti–TNF-IR pts. The finding that greater MDA can be achieved in early anti–TNF-naive PsA pts warrants further research. References Mease et al. J Rheumatol 2013;40:647–52 Acknowledgement The study was sponsored by Novartis Pharma AG. Disclosure of Interest L. Coates Grant/research support from: Abbvie, Pfizer, Janssen, Consultant for: Abbvie, Celgene, Pfizer, UCB, MSD, Boehringer Ingelheim, Novartis, Lilly, 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, B. Kirkham Grant/research support from: Abbvie, Novartis and Roche, Consultant for: Abbott, BMS, Chugai, MSD, Novartis, Pfizer, Roche and UCB, Speakers bureau: Abbott, BMS, Chugai, MSD, Novartis, Pfizer, Roche and UCB, L. McLeod Consultant for: Novartis through employment at RTI Health Solutions, Employee of: RTI Health Solutions, S. Mpofu Shareholder of: Novartis, Employee of: Novartis, C. Karyekar Shareholder of: Novartis, Employee of: Novartis, K. Gandhi Shareholder of: Novartis, Employee of: Novartis

Background Secukinumab, an anti–interleukin-17A monoclonal antibody, provided rapid and significant improvements in multiple clinical domains of psoriatic arthritis (PsA) including, signs and symptoms, joint structural damage, physical function, and quality of life, through 52 weeks (wks) in the Phase 3 FUTURE 1 study (NCT01392326).1 Objectives To assess the long-term efficacy and safety of secukinumab in patients (pts) with PsA treated for up to 104 wks in FUTURE 1. Methods 606 adults with active PsA were randomised to secukinumab or placebo (PBO). Secukinumab pts received a 10 mg/kg i.v. loading dose at baseline (BL), Wks 2 and 4, followed by 150 mg s.c. (IV→150 mg) or 75 mg s.c. (IV→75 mg) every 4 wks from Wk 8. PBO was given on the same dosing schedule. At Wk 16, PBO-treated pts were re-randomised to receive secukinumab 150 or 75 mg s.c. from either Wk 16 or Wk 24, based on clinical response. Clinical assessments at Wk 104 included: ACR 20/50/70, PASI 75/90, DAS28-CRP, SF-36 PCS, HAQ-DI, mTSS, dactylitis, and enthesitis. Efficacy variables are presented from those pts originally randomised to secukinumab. Multiple imputation (binary variables) and a mixed-effect model repeated measures (continuous variables) were used for analyses at Wk 104. mTSS data are as observed. Results Overall, 476 pts (78.5%) completed 104 wks of study (167 [82.7%] pts in IV→150 mg group; 155 [76.7%] in IV→75 mg group). At Wk 104, ACR 20/50/70 response rates were 66.8/39.0/22.4% with IV→150 mg and 58.6/29.7/17.6% with IV→75 mg, respectively. Sustained clinical improvements with secukinumab through Wk 104 were observed across other clinically important domains of PsA (Table). Responses were sustained through Wk 104 in pts naïve to anti-TNF therapy and in those with an inadequate response or intolerance to these agents (anti-TNF-IR). ACR20 response rates at Wk 104 in anti-TNF-naïve pts were 75.2% and 63.7% with IV→150 mg and IV→75 mg, respectively; corresponding rates in anti-TNF-IR pts were 48.0% and 46.9%. No radiographic disease progression (≤0.5 change in mTSS) was observed between BL and Wk 104 in 84.6% of x-ray completers in the IV→150 mg and 83.9% in the IV→75 mg groups. Over the entire study period (mean exposure to secukinumab of 627.1 days) the type, incidence and severity of AEs were consistent with that reported previously. Infections and infestations were the most common AEs observed with secukinumab (67.9 per 100 pt-years). No cases of TB were reported. Malignant/unspecified tumours and major adverse cardiac events occurred at a rate of 0.6 and 0.7 per 100 pt-years, respectively with secukinumab. No suicides were recorded in secukinumab-treated patients. Conclusions Secukinumab provided sustained improvements in signs and symptoms and multiple clinical domains of active PsA in pts who completed 2 years of therapy. Secukinumab was well tolerated with a safety profile consistent with that previously reported. References Mease P et al. N Engl J Med 2015; 373:1329–39 Disclosure of Interest A. Kavanaugh Consultant for: Novartis, 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, A. Reimold Grant/research support from: AbbVie, H. Tahir Speakers bureau: Novartis, Eli Lilly, and Abbvie, J. Rech Speakers bureau: Abbvie, BMS, Celgene, Fresenius, medicap, MSD, Novartis, Pfizer, and Roche, S. Hall: None declared, P. Geusens Grant/research support from: Pfizer, Abbott, Lilly, Amgen, MSD, Will, Bio Minerals and Roche, Speakers bureau: Pfizer, Abbott, Lilly, Amgen, MSD, Will, Bio Minerals and Roche, Z. Wang Employee of: Novartis, S. Mpofu Shareholder of: Novartis, Employee of: Novartis

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). 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

Background Fatigue is an important symptom associated with active psoriatic arthritis (PsA) and can impact on health-related quality of life (HRQoL) and social functioning. Secukinumab (SEC) has resulted in rapid improvements in signs and symptoms, physical functioning and HRQoL in patients with active PsA vs placebo (PBO) in the FUTURE 1 (F1) and FUTURE 2 (F2) studies. Rapid improvements in fatigue were reported in F2. Objectives To assess 1- and 2-year data on the effects of SEC on fatigue in patients with PsA, including both biologic-naïve patients and those with an inadequate response to TNF therapy (TNF-IR) and to investigate correlations between fatigue and baseline characteristics or clinical endpoints. Methods Patients with active PsA (F1, N=606; F2, N=397) received SEC or PBO every 4 weeks. Patients receiving PBO who did not meet predefined response criteria at week 16 were re-randomized at week 24 to active treatment. Fatigue was assessed at baseline and weeks 4, 8, 12, 16, 24, 52 and 104 using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale. A change in FACIT-F score of ≥4 from baseline was used to define fatigue response. Logistic regression was used to explore the relationship between fatigue response (weeks 16 and 52) and baseline characteristics and clinical response criteria. The FACIT-F response analyses were based on observed data with no imputation; the FACIT-F score analyses used mixed-effect model repeated measure imputation. Results Improvements in fatigue compared with PBO were observed for all SEC doses in from week 4 onwards. A fatigue response at week 16 was achieved by 58.4% (F1) and 70.0% (F2) of patients receiving SEC 150 mg, compared with 51.6% (F1) and 43.2% (F2) of those receiving PBO (see figure for F1 data). For SEC 300 mg, a 16 week response was achieved by 50.5% (F2). Responses were sustained at week 52 for 150 mg (F1, 67.2%; F2, 68.5%) and 300 mg (F2, 60.2%) and at week 104 for 150 mg (F1, 63.8%). Sustained responses were also seen in both biologic-naïve (F1, n=425; F2, n=258) and TNF-IR patients (F1, n=181; F2, n=104). Logistic regression analyses of pooled data from F1 and F2 found age and baseline HAQ-DI scores were associated with fatigue response (weeks 16 and 52). Achieving a fatigue response was moderately to strongly correlated with clinical response criteria (including ACR, HAQ-DI and PASI scores at weeks 16 and 52). Conclusions SEC provided rapid and sustained improvements in fatigue for up to 104 weeks in patients with active PsA, regardless of prior biologic exposure. Achieving a fatigue response was moderately to strongly correlated with improvement in clinical response criteria, indicating a relationship between fatigue and PsA disease activity. SEC-induced sustained improvements in fatigue may be important for improving HRQoL in patients with PsA. Analysis of factors predictive of fatigue response may help to clarify the drivers of fatigue; this study highlights the importance of age and physical functioning. Disclosure of Interest L. Gossec Consultant for: Abbvie, Celgene, Janssen, Novartis, Pfizer, Roche and UCB, T. K. Kvien Grant/research support from: AbbVie, BMS, MSD, Pfizer, Roche and UCB, Consultant for: AbbVie, BMS, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Hospira, Merck-Serono, MSD, Novartis, Orion Pharma, Pfizer, Roche, Sandoz and UCB, P. Conaghan Speakers bureau: Abbvie, Janssen, Lilly, Novartis, Pfizer, Roche, M. Østergaard Grant/research support from: Abbvie, BMS, Janssen, Merck, Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Centocor, GSK, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer, Regeneron, Schering-Plough, Roche, Takeda, UCB, and Wyeth, J. Cañete Consultant for: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Biogen, Janssen, Merck, Novartis, Pfizer and UCB, Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Biogen, Janssen, Merck, Novartis, Pfizer and UCB, C. Gaillez Shareholder of: Novartis, Employee of: Novartis, S. Mpofu Shareholder of: Novartis, Employee of: Novartis, E. Davenport Consultant for: Novartis, S. Jugl Shareholder of: Novartis, Employee of: Novartis

Secukinumab (SEC) has European approval for the treatment of active psoriatic arthritis (PsA) in adults who had inadequate response to previous disease-modifying anti-rheumatic drug (DMARD) therapy. Psoriatic Arthritis Response Criteria (PsARC) responses are useful for economic modelling, although clinical utility is limited. As no trials directly compare SEC against biologics, we used network meta-analysis (NMA) to compare short-term differences in PsARC response. A systematic literature review (November 2015) identified randomised controlled trials of licensed biologics in adults with active PsA who had failed conventional DMARD therapy. Twelve trials were identified for the PsARC network. An NMA was developed in accordance with health technology assessment guidance using a Bayesian random effects model. Because of differences in placebo response across trials, which could bias the NMA, placebo adjustments were considered. Deviance information criteria were similar but leverage plots suggested a better fit with placebo adjustment. Results at 12–16 weeks are presented as probability of response (95% credible interval [CrI]) and relative risk (RR) (CrI) from pairwise comparison for the placebo-adjusted model. In the mixed population of biologic-naïve and experienced patients, SEC 150 mg QM (79.6% [52–94], RR, 1.81 [1.18–2.38]) and SEC 300 mg QM (82.8% [47–97], RR, 1.88 [1.07–2.48]) were statistically significantly superior to apremilast (APR) 20 mg BID, and SEC 150 mg was statistically significantly superior to APR 30 mg BID (RR, 1.50 [1.04–1.97]). There was no statistically significant difference between either SEC dose and APR 40 mg BID, adalimumab 40 mg Q2W, etanercept 25 mg BIW, golimumab 50/100 mg QM or infliximab 5 mg/kg Q2M. This placebo-response adjusted NMA showed that SEC has at least comparable efficacy against all licensed biologics in PsARC and superiority over APR at some doses.

Background: Rheumatoid arthritis (RA), a chronic inflammatory polyarthritis, should be treated promptly to improve clinical outcomes and prevent further joint destruction. Reaching the optimal control of RA requires regular evaluation of inflammatory activity with the aim of defined indices, such as the Disease Activity Score in 28 joints (DAS28) (1, 2). Objective: To evaluate the reliability of DAS28 in RA, with focus on a subgroup of patients with DAS28 > 3.2. Method: All RA patients with DAS28 > 3.2 who were registered in the local part of the DANBIO registry were categorized into two groups: (i) patients with at least one swollen joint (SJ) or elevated C-reactive protein (CRP) (the ‘objective group’) and (ii) patients with no swollen joints and normal CRP values (the ‘subjective group’). We defined a new score, the subjective DAS28 (DAS28s), to focus on subjective parameters. Results: Of the 230 included patients, 198 (86.1%) and 32 (13.9%) were in the objective and subjective groups, respectively. Patients in the subjective group had lower mean values of DAS28 (p < 0.001) and evaluator global assessment (p < 0.001), with less frequent IgM RF (p < 0.001) and anti-cyclic citrullinated peptide (anti-CCP) antibody positivity (p = 0.02), but higher mean values of tender joints (p = 0.04) and DAS28s (p = 0.003) compared to the objective group (Table 1). Conclusions: DAS28 should be used cautiously in patients who are considered for treatment intensification.

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

Background Secukinumab, a human anti–IL-17A monoclonal antibody, demonstrated significant efficacy in the randomized, double-blind, placebo (PBO)-controlled phase 3 FUTURE 2 study (NCT01752634).1 Objectives To evaluate secukinumab efficacy by prior tumor necrosis factor inhibitor (anti-TNF) therapy status. Methods 397 adults with active PsA were randomized to subcutaneous (s.c.) secukinumab (300, 150 or 75 mg) or PBO at baseline, Week (Wk) 1, 2, 3, 4 and every 4 wks thereafter. Pts were stratified according to inadequate response or intolerance to prior anti-TNF therapy (anti-TNF-IR), or no prior exposure (anti-TNF-naive). The primary endpoint was American College of Rheumatology 20 (ACR20) response at Wk 24. Secondary endpoints were Psoriasis Area-and-Severity Index (PASI) 75/90 response, Disease Activity Score 28 using C-reactive protein (DAS28-CRP), Short Form-36 Physical Component Summary (SF-36 PCS), Health Assessment Questionnaire-Disability Index (HAQ-DI), ACR50, dactylitis and enthesitis. Results 35% of pts enrolled were anti-TNF-IR and 65% were anti-TNF-naive. At Wk 24, ACR20 responses were greater with secukinumab vs PBO regardless of anti-TNF status. The highest responses were generally observed among anti-TNF-naive pts (Table). Improvements were observed with secukinumab vs PBO for secondary endpoints of ACR50, PASI 75/90, DAS28-CRP, dactylitis, enthesitis, SF-36 PCS and HAQ-DI in both anti-TNF-IR and anti-TNF-naive pts. Greatest improvements in the anti-TNF-IR group were generally observed with secukinumab 300 mg (Table). Conclusions Efficacy was demonstrated with secukinumab 300 mg and 150 mg in both anti-TNF-naive and anti-TNF-IR pts, with secukinumab 300 mg being associated with the highest responses in anti-TNF-IR pts. References McInnes IB, et al. Presented at ACR 2014; L1 Acknowledgements Medical writing support was provided by Rachel Mason at Seren Communications (Tytherington, UK), and was funded by Novartis. Disclosure of Interest A. Kavanaugh Consultant for: Novartis, I. McInnes Consultant for: Novartis, Amgen, Janssen, BMS, Pfizer, UCB, Abbvie, Celgene, and Lilly, S. Hall: None declared, H. Chinoy Grant/research support from: Novartis, Janssen, Pfizer, UCB, Abbvie, Celgene, Servier, Roche, MSD, and aTyr, Consultant for: Novartis, Janssen, Pfizer, UCB, Abbvie, Celgene, Servier, Roche, MSD, and aTyr, A. Kivitz Grant/research support from: Novartis, S. Kandala Employee of: Novartis, M. Patekar Employee of: Novartis, S. Mpofu Shareholder of: Novartis, Employee of: Novartis