FRI0271 IMPACT OF HLA-B27 STATUS ON CLINICAL OUTCOMES AMONG PATIENTS WITH ANKYLOSING SPONDYLITIS TREATED WITH SECUKINUMAB
Authors: A. Deodhar, P. J. Mease, D. Poddubnyy, R. Calheiros, X. Meng, V. Strand, M. Magrey
Journal: Annals of the Rheumatic Diseases (2020)

Background: Ankylosing spondylitis (AS) is strongly associated with the genetic marker HLA-B27. Approximately 80%-90% of white patients with AS express HLA-B27 compared with &lt; 8% of the general population. In patients with AS, negative HLA-B27 status is a predictor of worse response to TNFis. 1 The impact of HLA-B27 status on clinical efficacy of secukinumab, a fully human monoclonal antibody that selectively inhibits IL-17A, has not been studied. Objectives: To analyze the impact of HLA-B27 status on clinical outcomes at Week 16 in patients with AS treated with secukinumab vs placebo. Methods: Patients with AS were pooled from the MEASURE 1-4 studies ( NCT01358175 , NCT01649375 , NCT02008916 , and NCT02159053 ) and stratified by HLA-B27 status. All trials included patients who received secukinumab 150 mg every 4 weeks with or without an initial loading dose (10 mg/kg IV at Weeks 0, 2, 4 or 150 mg SC at Weeks 0, 1, 2, and 3) or placebo control. MEASURE 3 included patients receiving secukinumab 300 mg every 4 weeks following the initial IV loading dose. Efficacy at Week 16 was determined by the proportion of patients achieving ASAS20/40, ASAS5/6, ASAS partial remission, BASDAI50, ASDAS-CRP &lt; 2.1, ASDAS-CRP &lt; 1.3, and improvement in Patient Global Assessment (VAS) and total spinal/back pain (VAS) scores. In MEASURE 1, 2, and 4, quality of life (QOL) was assessed at Week 16 by the SF-36 PCS, SF-36 MCS, and ASQOL. ASAS, BASDAI, and ASDAS-CRP responses were analyzed by nonresponder imputation, and all other outcomes by mixed models for repeated measures. For hypothesis generation, outcomes at Week 16 with secukinumab vs placebo within HLA-B27 strata were compared by logistic regression analysis without adjustment for multiple comparisons. Results: Baseline characteristics were balanced across treatment groups, although more HLA-B27+ patients than HLA-B27− patients were male (71%-73% vs 43%-50%). HLA-B27+ patients receiving any dose of secukinumab were significantly more likely to achieve ASAS, BASDAI50, and ASDAS-CRP responses vs those receiving placebo ( P &lt; .05; Figure 1). HLA-B27− patients receiving secukinumab 300 mg were significantly more likely to achieve ASAS40, ASAS partial remission (Figure 1 A ), and BASDAI50 (Figure 1 B ) responses than those receiving placebo ( P &lt; .05). Patients receiving any dose of secukinumab were more likely to achieve ASAS5/6 and ASDAS-CRP &lt; 2.1 than those receiving placebo, regardless of HLA-B27 status ( P &lt; .05; Figure 1 B ). All secukinumab-treated patients experienced significant improvement in Patient Global Assessment at Week 16 vs placebo, regardless of HLA-B27 status, while only HLA-B27+ patients experienced significant reduction in total spinal/back pain vs placebo ( P &lt; .05; Figure 2 A ). Numerical improvements in QOL were observed in all patients receiving secukinumab 150 mg vs placebo; these reached significance for HLA-B27+ patients (Figure 2 B ). Conclusion: Secukinumab is effective in patients with AS regardless of HLA-B27 status; HLA-B27+ patients may derive increased therapeutic benefit compared with HLA-B27− patients. Reference: [1]Alazmi M, et al. Arthritis Care Res (Hoboken ). 2018;70:1393-9. Acknowledgments: This study was funded by Novartis Pharmaceuticals Corporation. The authors thank Rich Karpowicz, PhD, of Health Interactions, Inc, for providing medical writing support/editorial support, which was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ, in accordance with Good Publication Practice (GPP3) guidelines ( http://www.ismpp.org/gpp3 ). Disclosure of Interests: Atul Deodhar Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, 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, 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, Renato Calheiros Shareholder of: Novartis, Employee of: Novartis, Xiangyi Meng Shareholder of: Novartis, Employee of: Novartis, Vibeke Strand Consultant of: AbbVie, Amgen, Biogen, Celltrion, Consortium of Rheumatology Researchers of North America, Crescendo Bioscience, Eli Lilly, Genentech/Roche, GlaxoSmithKline, Hospira, Janssen, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi, UCB, Marina Magrey Grant/research support from: AbbVie, Amgen, and UCB, Consultant of: Eli Lilly and Novartis