OP0140 BIOLOGIC REFRACTORY DISEASE IN AXIAL SPONDYLOARTHRITIS - DEFINITION, PREVALENCE AND PATIENT CHARACTERISTICS. A COLLABORATION BETWEEN FIVE NORDIC BIOLOGIC REGISTRIES
Authors: D. DI Giuseppe, U. Lindström, K. Aaltonen, H. Relas, S. Aarrestad Provan, B. Gudbjornsson, M. L. Hetland, J. Askling, T. Schjødt Jørgensen, L. Dreyer, D. Nordström, B. Michelsen, A. J. Geirsson, L. T. H. Jacobsson, B. Glintborg
Journal: Annals of the Rheumatic Diseases (2021)

Background: In clinical practice, some patients with axial spondyloarthritis (axSpA) fail several consecutive biological treatments (bDMARDs). How this group of ”refractory” patients should best be defined, how common they are, and what their characteristics are, is poorly understood. Objectives: To explore the point prevalence of bDMARD refractory disease in axSpA over time, according to different definitions, and to describe the characteristics of refractory vs. not-refractory patients upon start of their first bDMARD. Methods: Observational prospective cohort study. Patients with axSpA (ankylosing spondylitis/non-radiographic axial SpA) starting a first bDMARD 2009-2018 were identified in biologic registries in Denmark, Sweden, Finland, Norway and Iceland. Clinical characteristics and treatments were retrieved, and data were pooled for analysis. Refractory disease was defined based on the number of different bDMARD treatments started in individual patients: mild (≥3 bDMARDs), moderate (≥4), and strict (5 or more). Restart of same bDMARD with another bDMARD in between counted as separate courses whereas switch from originator to corresponding biosimilar was ignored. Proportions of patients fulfilling each definition of refractory disease at 2 and 5 years after the start of 1st bDMARD were calculated. Point-prevalence per calendar-year was calculated as the number of patients with refractory disease at the end of each year, divided by the total number of patients ever having starting a first bDMARD before that time-point, and who were still alive and resident in the country. Results: The point prevalence of refractory axSpA increased with calendar-time (Figure). Among 12,037 included axSpA patients (64% male), the point-prevalence of bDMARD refractory disease in 2018 was 16%/7%/3% according to mild/moderate/strict definitions (Table). Table 1. Biologic refractory axSpA according to three definitions A. Baseline characteristics upon start 1st bDMARD Refractory definition Overall cohort MILD MODERATE STRICT N 12037 1969 832 351 Age, years 42 (13) 41 (12) 41 (12) 41 (12) Male, % 64% 57% 54% 56% Disease duration, years 7 (10) 6 (9) 6 (8) 5 (8) BASDAI, 0-100 53 (28) 60 (29) 63 (27) 66 (35) ASDAS 3.3 (1.1) 3.5 (1.2) 3.6 (1.0) 3.7 (1.1) CRP, mg/L 16 (23) 18 (26) 21 (28) 23 (32) Patient global, VAS, 0-100 59 (25) 65 (22) 66 (22) 67 (23) Patient Pain, VAS, 0-100 57 (24) 62 (22) 63 (22) 63 (22) Fatigue, VAS, 0-100 59 (27) 66 (26) 66 (26) 68 (25) B. Proportions of patients having refractory disease 2 and 5 years after start of their first bDMARD 2 years, % 5% 1% 0% 5 years, % 13% 4% 1% Numbers are means (SD) unless otherwise stated Upon start of their 1 st bDMARD, patients later fulfilling the definitions for refractory axSpA were more frequently women, had shorter disease duration, higher C-reactive protein and higher patient reported outcomes. Overall, 5%/1%/0% had mild/moderate/strict refractory disease 2 years after start of first bDMARD, after 5 years it was 13%/4%/1% (Table). Conclusion: In this large Nordic observational cohort of axSpA patients treated in routine care, we could demonstrate that a substantial proportion of all patients had used multiple bDMARDs. In 2018, one in six patients had received ≥3 bDMARDs, indicating a bDMARD refractory disease. Multiple switching was more frequent during later years, probably due to more bDMARDs becoming available. The characteristics of refractory axSpA, including sex and disease activity, will have to be further explored, as will the impact of refractory disease on long-term outcomes. Acknowledgements: the DANBIO, SRQ, ICEBIO, ROB-FIN and NOR-DMARD registries. Partly sponsored by Nordforsk and Foreum. Disclosure of Interests: Daniela Di Giuseppe: None declared, Ulf Lindström: None declared, Kalle Aaltonen: None declared, Heikki Relas Speakers bureau: Abbvie, Celgene, MSD, Roche, Sella Aarrestad Provan: None declared, Björn Gudbjornsson Speakers bureau: Amgen and Novartis, Merete L. Hetland Grant/research support from: AbbVie, Biogen, BMS, Celtrion, Eli Lilly Denmark A/S, Janssen Biologics B.V, Lundbeck Fonden, MSD, Pfizer, Roche, Samsung Biopis, Sandoz. MLH chairs the steering committee of the Danish Rheumatology Quality Registry (DANBIO), which receives public funding from the hospital owners and funding from pharmaceutical companies. MLH co-chairs the EuroSpA research collaboration, which generates real-world evidence of treatment of psoriatic arthritis and axial spondyloarthritis based on secondary use of quality data and is partly funded by Novartis., Johan Askling: None declared, Tanja Schjødt Jørgensen: None declared, Lene Dreyer Speakers bureau: Eli-Lilly and Galderma, Grant/research support from: BMS, Dan Nordström: None declared, Brigitte Michelsen: None declared, Arni Jon Geirsson: None declared, Lennart T.H. Jacobsson: None declared, Bente Glintborg Grant/research support from: Abbvie, BMS, Pfizer, Lundbeck foundation