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

Bente Glintborg; Inge J Sørensen; Mikkel Østergaard; Lene Dreyer; Abdiweli A Mohamoud; Niels S Krogh; Oliver Hendricks; Lis S Andersen; Johnny L Raun; Marcin R Kowalski; Laura Danielsen; Randi Pelck; Henrik Nordin; Jens K Pedersen; Dorte G A Kraus; Susan R Christensen; Inger M J Hansen; Jakob Esbesen; Annette Schlemmer; Anne G Loft; Nabil Al Chaer; Lone Salomonsen; Merete L Hetland

doi:10.3899/jrheum.160958

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

J Rheumatol. 2017 Jan;44(1):59-69. doi: 10.3899/jrheum.160958. Epub 2016 Dec 1.

Authors

Bente Glintborg^{1

2}, Inge J Sørensen^{3

4}, Mikkel Østergaard^{3

4}, Lene Dreyer^{3

4}, Abdiweli A Mohamoud^{3

4}, Niels S Krogh^{3

4}, Oliver Hendricks^{3

4}, Lis S Andersen^{3

4}, Johnny L Raun^{3

4}, Marcin R Kowalski^{3

4}, Laura Danielsen^{3

4}, Randi Pelck^{3

4}, Henrik Nordin^{3

4}, Jens K Pedersen^{3

4}, Dorte G A Kraus^{3

4}, Susan R Christensen^{3

4}, Inger M J Hansen^{3

4}, Jakob Esbesen^{3

4}, Annette Schlemmer^{3

4}, Anne G Loft^{3

4}, Nabil Al Chaer^{3

4}, Lone Salomonsen^{3

4}, Merete L Hetland^{3

4}

Affiliations

¹ 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. glintborg@dadlnet.dk.
² 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. glintborg@dadlnet.dk.
³ 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.
⁴ 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.

PMID: 27909080
DOI: 10.3899/jrheum.160958

Abstract

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.

Keywords: AXIAL SPONDYLOARTHRITIS; OUTCOME; REGISTRY; TUMOR NECROSIS FACTOR-A.

Publication types

Observational Study

MeSH terms

Adult
Antirheumatic Agents / therapeutic use*
Biological Products / therapeutic use*
Cohort Studies
Female
HLA-B27 Antigen / blood*
Humans
Male
Medication Adherence
Middle Aged
Registries
Sacroiliac Joint / diagnostic imaging
Severity of Illness Index
Spondylarthritis / diagnostic imaging
Spondylarthritis / drug therapy*
Spondylarthritis / genetics
Spondylitis, Ankylosing / blood
Spondylitis, Ankylosing / diagnostic imaging
Spondylitis, Ankylosing / drug therapy*
Treatment Outcome
Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

Antirheumatic Agents
Biological Products
HLA-B27 Antigen
Tumor Necrosis Factor-alpha