Bente Glintborg1,2, Inge J Sørensen3,4, Mikkel Østergaard3,4, Lene Dreyer3,4, Abdiweli A Mohamoud3,4, Niels S Krogh3,4, Oliver Hendricks3,4, Lis S Andersen3,4, Johnny L Raun3,4, Marcin R Kowalski3,4, Laura Danielsen3,4, Randi Pelck3,4, Henrik Nordin3,4, Jens K Pedersen3,4, Dorte G A Kraus3,4, Susan R Christensen3,4, Inger M J Hansen3,4, Jakob Esbesen3,4, Annette Schlemmer3,4, Anne G Loft3,4, Nabil Al Chaer3,4, Lone Salomonsen3,4, Merete L Hetland3,4. 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.
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.
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.
Authors: Delamo I Bekele; Elizabeth Cheng; Andreas Reimold; Christian Geier; Kavya Ganuthula; Jessica A Walsh; Daniel O Clegg; Maureen Dubreuil; Prashant Kaushik; Bernard Ng; Elizabeth Chang; Ryan Duong; Jina Park; Gail S Kerr Journal: Rheumatol Int Date: 2021-11-01 Impact factor: 3.580
Authors: U Kiltz; J Braun; A Becker; J-F Chenot; M Dreimann; L Hammel; A Heiligenhaus; K-G Hermann; R Klett; D Krause; K-F Kreitner; U Lange; A Lauterbach; W Mau; R Mössner; U Oberschelp; S Philipp; U Pleyer; M Rudwaleit; E Schneider; T L Schulte; J Sieper; A Stallmach; B Swoboda; M Winking Journal: Z Rheumatol Date: 2019-12 Impact factor: 1.372