Search

Summary Background Secukinumab, a fully human monoclonal antibody that directly inhibits interleukin 17A, has shown significant and sustained improvement in the signs and symptoms of ankylosing spondylitis over 3 years in the MEASURE 2 study. We report the 5-year (end-of-study) results of subcutaneous secukinumab 150 mg in the MEASURE 2 study. Methods MEASURE 2 was a phase 3, double-blind, randomised, placebo-controlled, study done in 13 countries and 53 centres. Patients with ankylosing spondylitis who were 18 years of age or older and fulfilled the modified New York criteria were randomly assigned to receive secukinumab (150 mg or 75 mg) or placebo subcutaneously at baseline and weeks 1, 2, and 3, and then every 4 weeks from week 4. At week 16, patients initially given placebo were randomly assigned again (placebo switchers) to receive secukinumab 150 mg or 75 mg. Efficacy results are reported for patients initially randomised to secukinumab 150 mg and those who switched from placebo to secukinumab 150 mg at week 16. An optional dose escalation from secukinumab 75 mg to 150 mg was initiated beginning week 140. We assessed efficacy endpoints at week 260 (5 years), including Assessment of Spondyloarthritis International Society (ASAS) 20 and ASAS 40, inactive disease according to ankylosing spondylitis disease activity score with C-reactive protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BASDAI50, Bath Ankylosing Spondylitis Metrology Index, Bath Ankylosing Spondylitis Functional Index, Short Form-36 Physical Component Summary, and ASAS partial remission. Analyses were stratified by anti-tumour necrosis factor (TNF) status (anti-TNF-naive and anti-TNF inadequate response). The safety analysis included all patients who received one dose or more of secukinumab. We report data as observed without accounting for missing data. The MEASURE 2 study was registered with ClinicalTrials.gov , NCT01649375 . Findings 219 patients were randomly assigned during the trial and 150 (68%) completed 5 years of treatment, including 82 (77%) of 106 patients in the secukinumab 150 mg group and 68 (65%) of 105 in the secukinumab 75 mg group. Efficacy analysis in the secukinumab 150 mg group included 53 patients who completed the study and one additional patient who was assessed in the treatment period weeks 212–260, but did not complete the study. 134 (61%) of 219 patients were anti-TNF-naive and 85 (39%) were anti-TNF inadequate responders. ASAS responses at 5 years with secukinumab 150 mg were 36 (67%) of 54 patients (ASA20) and 27 (50%) patients (ASAS40). Sustained improvement was observed across other efficacy endpoints with secukinumab 150 mg at 5 years. At 5 years, the proportion of patients achieving efficacy endpoints of BASDAI 50 response was 53% (44/83); ASAS 5/6 response was 51% (42/83); ASDAS-CRP inactive disease was 21% (17/81); and ASAS partial remission was 25% (21/83). Exposure-adjusted incidence rates with any secukinumab dose for selected adverse events were 1·0 per 100 patient-years (95% CI 0·4–1·9) for Candida infections, 0·5 (0·1–1·2) for Crohn's disease, 0·4 (0·1–1·1) for ulcerative colitis, 0·6 (0·2–1·4) for major adverse cardiovascular events, 0·5 (0·1–1·2) for uveitis, and 0·6 (0·2–1·4) for malignant or unspecified tumours. Interpretation Secukinumab 150 mg provided sustained improvement in the signs, symptoms, and physical function in patients with ankylosing spondylitis after 5 years of treatment. The safety profile of secukinumab remained consistent with previous reports. Funding Novartis Pharma.

OBJECTIVE: To report the 5-year efficacy and safety of secukinumab in the treatment of patients with psoriatic arthritis (PsA) in the FUTURE 1 study (NCT01392326).METHODS: Following the 2-year core trial, eligible patients receiving subcutaneous secukinumab entered a 3-year extension phase. Results are presented for key efficacy endpoints for the secukinumab 150-mg group (n = 236), including patients who escalated from 150 to 300 mg (approved doses) starting at week 156. Safety is reported for all patients (n = 587) who received 1 dose or more of study treatment.RESULTS: Overall, 81.8%% (193 of 236) of patients in the secukinumab 150-mg group completed 5 years of treatment, of which 36.4% (86 of 236) had dose escalation from 150 to 300 mg. Sustained improvements were achieved with secukinumab across all key efficacy endpoints through 5 years. Overall, 71.0%/51.8%/36.3% of patients achieved American College of Rheumatology (ACR) 20/50/70 responses at 5 years. Efficacy improved in patients requiring dose escalation from 150 to 300 mg and was comparable with those who did not require dose escalation. Exposure-adjusted incidence rates for selected adverse events per 100 patient-years for any secukinumab dose were serious infections (1.8), Crohn's disease (0.2), Candida infection (0.9), and major adverse cardiac events (0.5).CONCLUSION: Secukinumab provided sustained improvements in the signs and symptoms in the major clinical domains of PsA. Efficacy improved for patients requiring dose escalation from 150 to 300 mg during the study. Secukinumab was well tolerated with no new safety signals.

Background Secukinumab demonstrated sustained efficacy, inhibition of radiographic progression and a stable safety profile over 52 weeks in patients with psoriatic arthritis (PsA) in FUTURE 5. We report the end-of-study (2-year) results on the effect of secukinumab on radiographic progression in PsA patients in FUTURE 5. Methods Adults (N = 996) with active PsA were randomised to subcutaneous secukinumab 300 mg load, 150 mg load, 150 mg no load or placebo at baseline, Weeks 1, 2, 3 and 4, and every 4 weeks thereafter. The secukinumab dose could be escalated from 150 to 300 mg from Week 52 onwards, based on physician judgement. Radiographic progression (mean change in vdH-mTSS) was based on hand/wrist/foot radiographs obtained at baseline, and Weeks 16 (nonresponders), 24, 52 and 104, assessed by two blinded readers (plus an adjudicator if required). Radiographic data were analysed using a linear mixed-effects model (random intercept, random slopes) at Weeks 24 and 52, and as observed at Week 104. Data are presented for patients originally randomised to secukinumab (300 and 150 mg); the 150 mg groups also included patients who had dose escalation to 300 mg. Analyses by prior TNF inhibitor (TNFi) status (naive vs inadequate response) were also performed. Results Overall, 85% (300 mg), 82% (150 mg) and 75% (150 mg no load) of patients completed 2 years of treatment. A total of 86 (39%) and 92 (41%) patients had their dose escalated to 300 mg in the 150 mg and 150 mg no load groups, respectively. In the overall population, the proportions of patients with no radiographic progression (change from baseline in vdH-mTSS≤0.5) with secukinumab were 89.5% (300 mg), 82.3% (150 mg) and 81.1% (150 mg no load) at 2 years; the corresponding proportions of patients with changes from baseline in vdH-mTSS≤0.0 were: 81.2%, 69.1% and 73.4%, respectively. Radiographic progression was low in secukinumab-treated patients in the overall population and by prior TNFi use over 2 years (Table 1). Clinical responses were sustained through 2 years of secukinumab treatment. Conclusion Low radiographic progression was observed over 2 years of treatment with secukinumab 300 and 150 mg in PsA patients. Disclosures H. Tahir: Member of speakers’ bureau; AbbVie, Janssen, Eli Lilly, Novartis. Grants/research support; Novartis, Eli Lilly. P. Mease: Consultancies; AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Galapagos, Gilead, GlaxoSmithKline, Janssen, Leo, Eli Lilly, Merck, Novartis, Pfizer, Sun Pharmaceutical Industries, INC pharma, UCB, Crescendo Bioscience. Member of speakers’ bureau; AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Leo, Merck, Novartis, Pfizer, UCB, Crescendo Bioscience. Grants/research support; AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Leo, Eli Lilly, Merck, Novartis, Pfizer, Sun Pharmaceutical Industries, INC pharma, UCB, Crescendo Bioscience. R. Landewé: None. P. Rahman: Consultancies; AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, UCB. Member of speakers’ bureau; AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis. Grants/research support; Janssen, Novartis. A. Singhal: Grants/research support; AbbVie, Gilead, Sanofi, Regeneron, Amgen, Roche, Bristol-Myers Squibb, Janssen, Lilly, Novartis, Pfizer, UCB, Astra Zeneca, MedImmune, FujiFilm, Nichi-Iko, Mallinckrodt. E. Böttcher: Consultancies; Amgen, Roche, Eli Lilly, Pfizer, MSD, Novartis. Member of speakers’ bureau; Amgen, Roche, Eli Lilly, Pfizer, MSD, Novartis. S. Navarra: Member of speakers’ bureau; Astellas, Johnson & Johnson, Novartis, Pfizer. A. Readie: Shareholder/stock ownership; Novartis. Other; Employee of: Novartis. S. Mpofu: Shareholder/stock ownership; Novartis. Other; Employee of: Novartis. E. Delicha: Consultancies; Novartis. L. Pricop: Shareholder/stock ownership; Novartis. Other; Employee of: Novartis. D. van der Heijde: Corporate appointments; Imaging Rheumatology BV. Consultancies; AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma.

Objectives. To assess long-term efficacy, safety and tolerability of secukinumab up to 104 weeks in\ud patients with active PsA.\ud Methods. Patients with PsA (n = 397) were randomized to s.c. secukinumab 300, 150 or 75 mg or placebo at\ud baseline, weeks 1, 2, 3 and 4 and every 4 weeks thereafter. Placebo-treated patients were re-randomized to\ud receive secukinumab 300 or 150 mg s.c. from week 16 (placebo non-responders) or week 24 (placebo\ud responders). Exploratory endpoints at week 104 included 20, 50 and 70% improvement in ACR criteria\ud (ACR20, 50, 70); 75 and 90% improvement in the Psoriasis Area Severity Index, 28-joint DAS with CRP,\ud presence of dactylitis and enthesitis and other patient-reported outcomes. For binary variables, missing\ud values were imputed; continuous variables were analysed by a mixed-effects model for repeated measures.\ud Results. A total of 86/100 (86%), 76/100 (76%) and 65/99 (66%) patients in the secukinumab 300, 150\ud and 75 mg groups, respectively, completed 104 weeks. At week 104, ACR20 response rates after multiple\ud imputation in the 300, 150 and 75 mg groups were 69.4, 64.4 and 50.3%, respectively. Sustained clinical\ud improvements were observed through week 104 with secukinumab across other clinically important domains\ud of PsA. Responses were sustained through week 104 regardless of prior anti-TNF-a use. Over the\ud entire treatment period the incidence, type and severity of adverse events were consistent with those\ud reported previously.\ud Conclusion. Secukinumab provided sustained improvements in signs and symptoms and multiple clinical\ud domains in patients of active PsA through 2 years of therapy. Secukinumab was well tolerated, with a\ud safety profile consistent with that reported previously.\ud Trial registration: ClinicalTrials.gov (https://clinicaltrials.gov), NCT01752634

Background Evaluation of long-term efficacy and safety for treatments for ankylosing spondylitis (AS) is important. Secukinumab, a fully human monoclonal antibody that directly inhibits interleukin-17A, has shown significant and sustained improvement in the signs and symptoms of AS through 3 years in the MEASURE 2 study (NCT01649375).1 Objectives We report the 5-year end-of-study results of subcutaneous (s.c.) secukinumab 150 mg in the MEASURE 2 study. Methods AS patients (pts; N = 219) were randomised to receive s.c. secukinumab 150 mg, 75 mg or placebo at baseline, Weeks (Wks) 1, 2 and 3 and every 4 wks from Wk 4. At Wk 16, placebo-treated pts were re–randomised to receive secukinumab 150/75 mg. Efficacy results are reported for pts initially randomised to secukinumab 150 mg and those who switched from placebo to secukinumab 150 mg at Wk 16 (N = 106). An optional dose escalation from secukinumab 75 mg to 150 mg was initiated beginning Wk 140. Outcome measures at Wk 260 included ASAS20/40, BASDAI50, BASMI, BASFI, SF-36 PCS and ASAS partial remission. Analyses stratified by anti-TNF status (anti–TNF-naive and anti-TNF inadequate response [IR]) were performed. Safety analysis included all pts who received ≥1 dose of secukinumab. Results are reported as observed. Results The retention rate to Wk 260 was 77% (82/106) for secukinumab 150 mg. Sustained efficacy was observed with secukinumab 150 mg across all endpoints through 5 years (Table). Improvements were maintained regardless of prior exposure to anti–TNF therapy with greater responses in anti–TNF-naive pts. A total of 49 pts on secukinumab 75 mg (46.7%) escalated dose to 150 mg after Wk 140; efficacy responses improved in pts whose dose was escalated. Over the entire study period, the mean exposure (±SD) to secukinumab was 1459.1 ± 597.8 days. Exposure-adjusted incidence rates (per 100 pt-years) with any secukinumab dose for selected adverse events were: Candida infections (1.0), Crohn’s disease (0.5), major adverse cardiovascular events (0.7), uveitis (0.5), and malignant/unspecified tumours (0.5). Conclusion Secukinumab 150 mg provided sustained improvement in the signs, symptoms, and physical function in pts with AS through 5 years of treatment. The safety profile of secukinumab remained consistent with previous reports.1–3 References [1] Marzo-Ortega, et al. RMD Open. 2017;3:e000592; 2. Marzo-Ortega, et al. Ann Rheum Dis. 2016;75:812–3; 3. Baraliakos X,et al. Clin Exp Rheumatol2017. Disclosure of Interests Helena Marzo-Ortega Grant/research support from: Janssen, Novartis and Pfizer, Consultant for: AbbVie, Celgene, Janssen, Eli-Lilly, Novartis and UCB, Speakers bureau: AbbVie, Celgene, Janssen, Eli-Lilly, Novartis and UCB, Joachim Sieper Consultant for: Abbvie, Bohringer Ingelheim, Janssen, Lilly, Merck, Mylan, Novartis, Pfizer, UCB., Speakers bureau: Abbvie, Bohringer Ingelheim, Janssen, Lilly, Merck, Mylan, Novartis, Pfizer, UCB., Alan Kivitz Shareholder of: Novartis, Consultant for: Abbvie, Janssen, Pfizer, UCB, Genzyme, Sanofi, Regeneron, Boehringer Ingelheim, Sun Pharma Advanced Research, Flexion., Paid instructor for: Celgene, Horizon, Merck, Novartis, Pfizer, Genzyme, Sanofi, Regeneron, Speakers bureau: Celgene, Horizon, Merck and Genetech, Flexion, Ricardo Blanco Grant/research support from: Abbvie, MSD and Roche, Consultant for: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Martin Cohen Consultant for: AbbVie, Amgen, Celgene, Lilly, Novartis, Pfizer, Sandoz, Sanofi and UCB, Speakers bureau: AbbVie, Amgen, Celgene, Janssen, Merck, Novartis and Pfizer, Karel Pavelka: None declared, Eumorphia Maria Delicha Employee of: Novartis, Anna Stefanska Shareholder of: Novartis, Employee of: Novartis, Hanno Richards Shareholder of: Novartis Pharma AG, Employee of: Novartis Pharma AG, Susanne Rohrer Shareholder of: Novartis, Employee of: Novartis

Background The primary treatment goal in patient with axial Spondyloarthritis (axSpA) is to optimize health-related quality of life through control of signs and symptoms, no structural damage progression and preservation of function.1 The 2017 Treat to Target recommendations (T2T) outlined Ankylosing Spondylitis Disease Activity Score (ASDAS) -inactive disease (ID) as an optimal treatment target for axSpA patients.1 ASDAS states were shown to correlate with syndesmophyte formation as assessed with X-Ray and MRI changes.2 Secukinumab, a fully human monoclonal antibody that directly inhibits IL-17A, demonstrated sustained efficacy and low radiographic progression through 4 years in patient with ankylosing spondylitis (AS) in MEASURE 1 study (NCT01863732).3 Objectives To investigate the relationship between ASDAS states and inhibition of radiographic structural progression in patient with AS treated with secukinumab 150 mg from the MEASURE 1 study over 4-years using post hoc analysis. Methods Lateral radiographs of the cervical and lumbar spine were assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS: range 0-72). Images were scored twice at baseline/Week (Wk) 104 and baseline/Wk 208 by 2 central readers blinded to treatment/visit; mean change from baseline to Wk 104 or 208 in mSASSS scores were used. The ASDAS-CRP was used to define the disease activity states at Wks 16, 52, 104, and 208: ID (ASDAS-CRP Results The proportion of patients achieving each ASDAS state are shown in Table. Patients with ASDAS-ID were associated with numerically lower mSASSS mean change from baseline to Wks 104/208 compared to other ASDAS states (Figure). Conclusion In this post hoc analysis, patients with ASDAS-ID state and sustained ASDAS-ID state had lower radiographic progression than patients with higher disease activity at 2 and 4-years suggesting a potential relationship between ASDAS state and structural progression in patients with AS. Further confirmation is needed in larger prospective studies. References [1] Smolen JS, et al. Ann Rheum Dis. 2018;77:3-17. [2] Poddubnyy D, et al. Ann Rheum Dis. 2014;73:422. [3] Braun J, et al. Rheumatology (Oxford)2018. Doi: 10.1093/rheumatology/key375. Disclosure of Interests Xenofon Baraliakos Grant/research support from: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Chugai, Janssen, MSD, Novartis, Pfizer Inc, Roche and UCB, Grant/research support from: AbbVie, Pfizer, Merck Sharp & Dohme, UCB Pharma, Novartis, Consultant for: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Janssen Biologics, Novartis, Pfizer, UCB Pharma, Galapagos, Speakers bureau: AbbVie, Chugai, Janssen, Novartis, Pfizer, UCB Pharma, Helena Marzo-Ortega Grant/research support from: Janssen, Novartis and Pfizer, Consultant for: AbbVie, Celgene, Janssen, Eli-Lilly, Novartis and UCB, Speakers bureau: AbbVie, Celgene, Janssen, Eli-Lilly, Novartis and UCB, Filip van den Bosch Consultant for: AbbVie, BMS, Galapagos, Janssen, Lilly, Merck, Novartis, Pfizer and UCB, Speakers bureau: AbbVie, BMS, Janssen, Lilly, Merck, Novartis, Pfizer and UCB., Atul Deodhar Grant/research support from: AbbVie, Amgen, Eli Lilly, GSK, Janssen, Novartis, Pfizer, and UCB, Consultant for: AbbVie, Amgen, BMS, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Erhard Quebe-Fehling Shareholder of: Novartis, Employee of: Novartis, Eumorphia Maria Delicha Employee of: Novartis, Zsolts Talloczy Shareholder of: Novartis, Employee of: Novartis, Corine Gaillez Shareholder of: Novartis, BMS, Employee of: Novartis

Background Secukinumab (SEC) provided sustained clinical efficacy, and inhibition of radiographic progression over 52 Weeks (Wks) in patients (pts) with psoriatic arthritis (PsA) in the FUTURE 5 study1. Objectives To report the effect of SEC on radiographic progression at Wk 104 (2 years) in PsA pts in the FUTURE 5 study. Methods Adults (N=996) with active PsA, stratified by prior anti-TNF therapy (naive and inadequate response/intolerance [IR]) were randomised 2:2:2:3 to subcutaneous SEC 300mg with loading dose (LD; 300mg), 150mg LD (150mg), 150mg no LD, or placebo at baseline (BL), Wks 1, 2, 3, 4, and every 4 wks thereafter. Pts could have SEC dose escalated from 150 to 300 mg starting from Wk 52, based on physicians9 judgement. Data are shown for pts originally randomised to SEC; 150mg groups include pts who had dose escalated to 300mg. Concomitant MTX (≤25 mg/week) was allowed. Radiographic progression (mean change in van der Heijde-modified total Sharp score [vdH-mTSS] and its components: erosion and joint space narrowing [JSN] scores, was based on hand/wrist/foot X-rays obtained at BL and Wk 104, and assessed by two blinded readers (plus an adjudicator if required). Other efficacy endpoints included ACR20/50, PASI90 and resolution of dactylitis and enthesitis. Results Overall, 84.7% (300mg), 82.3% (150mg) and 75.2% (150mg no LD) pts completed 2 years of treatment. A total of 86 (39%) and 92 (41%) pts had their dose escalated to 300mg in the 150mg and 150mg no LD groups, respectively. Inhibition of radiographic progression was sustained with SEC through 2 years (Table 1). Proportions of pts with no radiographic progression (change from BL in mTSS ≤0.5) with SEC were 89.5% (300 mg), 82.3% (150 mg), and 81.1% (150 mg no LD) at 2 years; corresponding proportion of pts for change from BL in mTSS ≤0.0 were: 81.2%, 69.1% and 73.4%, respectively. Clinical responses were also sustained through 2 years (Table 1). Conclusion Subcutaneous secukinumab provided sustained inhibition of radiographic progression and sustained clinical responses through 2 years of treatment in pts with active PsA. Reference [1] Mease PJ et al. Arthritis Rheumatol 2018;70(suppl 10). Disclosure of Interests Philip J Mease Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Leo, Eli Lilly, Merck, Novartis, Pfizer, Sun Pharmaceutical Industries, Inc., and UCB., Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Galapagos, Gilead, Janssen, Leo, Eli Lilly, Merck, Novartis, Pfizer, Sun Pharmaceutical Industries, Inc., and UCB., Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Leo, Merck, Novartis, Pfizer and UCB.., Robert B.M. Landewe: None declared, Proton Rahman Grant/research support from: Investigator for Janssen Research & Development, LLC and Novartis, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly,Novartis, and UCB, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, and Novartis, Hasan Tahir Grant/research support from: Novartis, Eli-Lilly, Speakers bureau: AbbVie, Janssen, Eli Lilly, and Novartis, Atul Singhal Grant/research support from: AAbbVie, Gilead, Sanofi, Regeneron, Amgen, Roche, BMS, Janssen, Lilly, Novartis, Pfizer, UCB, Astra Zeneca, MedImmune, FujiFilm, Nichi-Iko, Mallinckrodt, Speakers bureau: AbbVie, Elke Boettcher Consultant for: Amgen, Roche, Eli Lilly, Pfizer, MSD, Novartis, Speakers bureau: Amgen, Roche, Eli Lilly, Pfizer, MSD, Novartis, Sandra Navarra Speakers bureau: Astellas, Johnson & Johnson, Novartis, Pfizer, Aimee Readie Shareholder of: Novartis, Employee of: Novartis, Shephard Mpofu Shareholder of: Novartis, Employee of: Novartis, Eumorphia Maria Delicha Consultant for: Novartis, Luminita Pricop Shareholder of: Novartis, Employee of: Novartis, Desiree van der Heijde Consultant for: AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, Union Chimique Belge

[Tahir, Hasan] Barts Hlth NHS Trust, Rheumatol, London, England. [Mease, Philip J.] Swedish Med Ctr, Dermatol, Seattle, WA USA. [Mease, Philip J.] Univ Washington, Seattle, WA 98195 USA. [Kavanaugh, Arthur] Univ Calif La Jolla, San Diego Sch Med, La Jolla, CA USA. [Reimold, Andreas] Dallas Vet Affairs Med Ctr, Dallas, TX USA. [Reimold, Andreas] Univ Texas Southwestern Med Ctr Dallas, Dallas, TX 75390 USA. [Rech, Juergen] Friedrich Alexander Univ Erlangen Nurnberg, Univ Klinikum Erlangen, Dept Internal Med Rheumatol & Immunol, Erlangen, Germany. [Hall, Stephen] Emeritus Res, Rheumatol, Camberwell, Australia. [Geusens, Piet] Univ Hasselt, Rheumatol, Hasselt, Belgium. [Pellet, Pascale; Mpofu, Shephard] Novartis Pharma AG, Immunol & Dermatol, Basel, Switzerland. [Delicha, Eumorphia Maria] Novartis Pharma AG, Biostat, Basel, Switzerland. [Pricop, Luminita] Novartis Pharmaceut, Immunol Hepatol & Dermatol Franchise, E Hanover, NJ USA.

Objective To evaluate the effect of secukinumab, a fully human anti-interleukin-17A monoclonal antibody, on efficacy, imaging outcomes, and safety through 4 years (208 weeks) in patients with ankylosing spondylitis. Methods Patients opting to enrol had completed 2 years’ treatment in the MEASURE 1 core study with subcutaneous secukinumab 150 or 75 mg every 4 weeks (q4Wk), following intravenous loading to Week (Wk) 4, or placebo treatment to Wk16/24. Up-titration from secukinumab 75–150 mg q4Wk was permitted following a protocol amendment. Efficacy is reported for patients originally randomized to secukinumab. Radiographic changes were assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and changes in MRI measures of inflammation using the Berlin scoring method. Safety and tolerability were evaluated. Results Among 274 extension study participants, 89.7% (78/87) and 93.0% (93/100) originally randomized to secukinumab 150 and 75 mg, respectively, completed 208Wk. Through Wk208, Assessment of Spondyloarthritis International Society 20/40 (observed) were 79.7%/60.8% (150 mg), 71.0%/43.5% (75 mg) and 80.0%/76% (up-titrators; n = 25). Mean (s.d.) changes in mSASSS were 1.2 (3.91) (150 mg), 1.8 (4.32) (75 mg) and 1.6 (5.67) (up-titrators). No radiographic progression (mSASSS change from Baseline < 2) was observed in 79% of patients receiving either secukinumab dose. Exposure-adjusted incidence rates per 100 patient-years were: serious infections (1.0), Candida infections (0.4), Crohn’s disease (0.6), ulcerative colitis (0.2), and malignant/unspecified tumours (0.5), with no new safety signals. Conclusion Through 4 years, secukinumab provided sustained efficacy on signs and symptoms, and MRI outcomes, a low rate of radiographic progression and a consistent safety profile. Trial registration NCT01863732.