强直性脊柱炎与非放射学轴性脊柱关节炎：肿瘤坏死因子抑制剂疗效及HLA - B27状态影响的比较。一项来自全国性DANBIO注册研究的观察性队列研究。
Ankylosing Spondylitis versus Nonradiographic Axial Spondyloarthritis: Comparison of Tumor Necrosis Factor Inhibitor Effectiveness and Effect of HLA-B27 Status. An Observational Cohort Study from the Nationwide DANBIO Registry.
作者信息
Glintborg Bente, Sørensen Inge J, Østergaard Mikkel, Dreyer Lene, Mohamoud Abdiweli A, Krogh Niels S, Hendricks Oliver, Andersen Lis S, Raun Johnny L, Kowalski Marcin R, Danielsen Laura, Pelck Randi, Nordin Henrik, Pedersen Jens K, Kraus Dorte G A, Christensen Susan R, Hansen Inger M J, Esbesen Jakob, Schlemmer Annette, Loft Anne G, Al Chaer Nabil, Salomonsen Lone, Hetland Merete L
机构信息
From the DANBIO registry and Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre of Head and Orthopedics, Rigshospitalet, Glostrup; Department of Rheumatology, Herlev and Gentofte University Hospital, Copenhagen; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen; Zitelab, Copenhagen; Kong Christian X's Gigthospital, Gråsten; The Parker Institute, Bispebjerg and Frederiksberg; Department of Internal Medicine, Rønne Hospital, Rønne; Department of Rheumatology, Sygehus Lillebælt, Fredericia; North Denmark Regional Hospital, Hjørring; Department of Rheumatology, Horsens Hospital, Horsens; Department of Rheumatology, Zealand University Hospital, Køge; Center for Rheumatology and Spine Diseases, Centre of Head and Orthopedics, Rigshospitalet, Blegdamsvej; Department of Rheumatology, Odense University Hospital (OUH), Odense; Department of Rheumatology, Silkeborg Hospital, Silkeborg; Department of Rheumatology, OUH, Svendborg Hospital, Odense; Department of Rheumatology, Vejle Hospital, Vejle; Department of Rheumatology, Aalborg University Hospital, Aalborg; Department of Rheumatology, Aarhus University Hospital, Aarhus; Department of Rheumatology, Slagelse Hospital, Slagelse, Denmark.
B. Glintborg, MD, PhD, The DANBIO registry, COPECARE, Center for Rheumatology and Spine Diseases, Centre of Head and Orthopedics, Rigshospitalet, Glostrup, and Department of Rheumatology, Gentofte and Herlev University Hospital; I.J. Sørensen, MD, PhD, COPECARE, Center for Rheumatology and Spine Diseases, Centre of Head and Orthopedics, Rigshospitalet, Glostrup, and Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen; M. Østergaard, MD, PhD, Dr. Med. Sci., Professor, COPECARE, Center for Rheumatology and Spine Diseases, Centre of Head and Orthopedics, Rigshospitalet, Glostrup, and Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen; L. Dreyer, MD, PhD, Department of Rheumatology, Gentofte and Herlev University Hospital, and The Parker Institute; A.A. Mohamoud, MD, COPECARE, Center for Rheumatology and Spine Diseases, Centre of Head and Orthopedics, Rigshospitalet, Glostrup; N.S. Krogh, MS, Zitelab; O. Hendricks, MD, Kong Christian X's Gigthospital; L.S. Andersen, MD, PhD, Department of Internal Medicine, Rønne Hospital; J.L. Raun, MD, Department of Rheumatology, Sygehus Lillebælt; M.R. Kowalski, MD, PhD, North Denmark Regional Hospital; L. Danielsen, MD, Department of Rheumatology, Horsens Hospital; R. Pelck, MD, Department of Rheumatology, Zealand University Hospital; H. Nordin, MD, Center for Rheumatology and Spine Diseases, Centre of Head and Orthopedics, Rigshospitalet, Blegdamsvej; J.K. Pedersen, MD, PhD, Department of Rheumatology, Odense University Hospital; D.G. Kraus, MD, Department of Rheumatology, Silkeborg Hospital; S.R. Christensen, MD, Department of Rheumatology, Silkeborg Hospital; I.M. Hansen, MD, Dr. Med. Sci., Associate Professor, Department of Rheumatology, OUH, Svendborg Hospital; J. Esbesen, MD, Department of Rheumatology, Vejle Hospital; A. Schlemmer, MD, MLP, Department of Rheumatology, Aalborg University Hospital; A.G. Loft, MD, Dr. Med. Sci., Associate Professor, Department of Rheumatology, Aarhus University Hospital; N. al Chaer, MD, Department of Rheumatology, Slagelse Hospital; L. Salomonsen, MD, Department of Rheumatology, Aarhus University Hospital; M.L. Hetland, MD, PhD, Dr. Med. Sci., Professor, The DANBIO registry and COPECARE, Center for Rheumatology and Spine Diseases, Centre of Head and Orthopedics, Rigshospitalet, Glostrup, and Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen.
出版信息
J Rheumatol. 2017 Jan;44(1):59-69. doi: 10.3899/jrheum.160958. Epub 2016 Dec 1.
OBJECTIVE
To compare baseline disease activity and treatment effectiveness in biologic-naive patients with nonradiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS) who initiate tumor necrosis factor inhibitor (TNFi) treatment and to study the role of potential confounders (e.g., HLA-B27 status).
METHODS
Observational cohort study based on prospectively registered data in the nationwide DANBIO registry. We used Kaplan-Meier plots, Cox, and logistic regression analyses to study the effect of diagnosis (nr-axSpA vs AS) and potential confounders (sex/age/start yr/HLA-B27/disease duration/TNFi-type/smoking/baseline disease activity) on TNFi adherence and response [e.g., Bath Ankylosing Spondylitis Activity Index (BASDAI) 50%/20 mm].
RESULTS
The study included 1250 TNFi-naive patients with axSpA (29% nr-axSpA, 50% AS, 21% lacked radiographs of sacroiliac joints). Patients with nr-axSpA were more frequently women (50%/27%) and HLA-B27-negative (85/338 = 25%), compared to AS (81/476 = 17%; p < 0.01). At TNFi start patients with nr-axSpA had higher visual analog scale scores [median (quartiles)] for pain: 72 mm (55-84)/65 mm (48-77); global: 76 mm (62-88)/68 mm (50-80); fatigue: 74 mm (55-85)/67 mm (50-80); and BASDAI: 64 (54-77)/59 (46-71); all p < 0.01. However, patients with nr-axSpA had lower C-reactive protein: 7 mg/l (3-17)/11 mg/l (5-22); and BAS Metrology Index: 20 (10-40)/40 (20-50); all p < 0.01. Median (95% CI) treatment adherence was poorer in nr-axSpA than in AS: 1.59 years (1.15-2.02) versus 3.67 years (2.86-4.49), p < 0.0001; but only in univariate and not confounder-adjusted analyses (p > 0.05). Response rates were similar in AS and nr-axSpA (p > 0.05). HLA-B27 negativity was associated with poorer treatment adherence [HLA-B27 negative/positive, nr-axSpA: HR 1.74 (1.29-2.36), AS: HR 2.04 (1.53-2.71), both p < 0.0001]; and lower response rates (nr-axSpA: 18/61 = 30% vs 93/168 = 55%; AS: 17/59 = 29% vs 157/291 = 54%, both p < 0.05).
CONCLUSION
In this nationwide cohort, patients with nr-axSpA had higher subjective disease activity at start of first TNFi treatment, but similar outcomes to patients with AS after confounder adjustment. HLA-B27 positivity was associated with better outcomes irrespective of axSpA subdiagnosis.
目的
比较初治的非放射学轴性脊柱关节炎（nr-axSpA）和强直性脊柱炎（AS）患者开始使用肿瘤坏死因子抑制剂（TNFi）治疗时的基线疾病活动度和治疗效果，并研究潜在混杂因素（如HLA-B27状态）的作用。
方法
基于全国性DANBIO注册中心前瞻性登记的数据进行观察性队列研究。我们使用Kaplan-Meier曲线、Cox回归和逻辑回归分析来研究诊断（nr-axSpA与AS）和潜在混杂因素（性别/年龄/开始年份/HLA-B27/疾病病程/TNFi类型/吸烟/基线疾病活动度）对TNFi依从性和反应[如巴斯强直性脊柱炎疾病活动指数（BASDAI）改善50%/改善20 mm]的影响。
结果
该研究纳入了1250例初治的axSpA患者（29%为nr-axSpA，50%为AS，21%缺乏骶髂关节X线片）。与AS患者相比，nr-axSpA患者女性比例更高（50%/27%），HLA-B27阴性比例更高（85/338 = 25% vs 81/476 = 17%；p < 0.01）。在开始使用TNFi时，nr-axSpA患者在疼痛的视觉模拟评分[中位数（四分位数）]方面更高：72 mm（55 - 84）/65 mm（48 - 77）；整体评分：76 mm（62 - 88）/68 mm（50 - 80）；疲劳评分：74 mm（55 - 85）/67 mm（50 - 80）；以及BASDAI评分：64（54 - 77）/59（46 - 71）；所有p < 0.01。然而，nr-axSpA患者的C反应蛋白水平更低：7 mg/l（3 - 17）/11 mg/l（5 - 22）；以及巴斯计量指数更低：20（10 - 40）/40（20 - 50）；所有p < 0.01。nr-axSpA患者的中位（95%CI）治疗依从性比AS患者差：1.59年（1.15 - 2.02）对3.67年（2.86 - 4.49），p < 0.0001；但仅在单因素分析中如此，经混杂因素调整后差异无统计学意义（p > 0.05）。AS和nr-axSpA的反应率相似（p > 0.05）。HLA-B27阴性与较差的治疗依从性相关[nr-axSpA中HLA-B27阴性/阳性，HR 1.74（1.29 - 2.36），AS中HR 2.04（1.53 - 2.71），两者p < 0.0001]；且反应率更低（nr-axSpA：18/61 = 30%对93/168 = 55%；AS：17/59 = 29%对157/291 = 54%，两者p < 0.05）。
结论
在这个全国性队列中，nr-axSpA患者在首次使用TNFi治疗开始时主观疾病活动度更高，但经混杂因素调整后与AS患者的结局相似。无论axSpA的亚诊断如何，HLA-B27阳性与更好的结局相关。
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