Abstract

Background:Axial spondylarthritis (axSpA) patients treated with a tumour necrosis factor inhibitor (TNFi) may receive a concomitant conventional synthetic disease-modifying anti-rheumatic drug (csDMARD), although the value of combination therapy remains unclear.Objectives:Describe the proportion and phenotype of patients with axSpA initiating their first TNFi as monotherapy compared to TNFi+csDMARD combination therapy, and to compare the 1-year TNFi retention between the two groups.Methods:Data from 13 European registries was collected. Two exposure treatment groups were defined: TNFi monotherapy at baseline (=TNFi start date) and TNFi+csDMARD combination therapy. TNFi retention rates were assessed with Kaplan-Meier curves for each country and combined. Hazard ratios (HR, 95% CI) for discontinuing the TNFi were obtained with Cox models: (i) crude; adjusted for (ii) country, and (iii) country, sex, age, calendar year, disease duration and BASDAI. Participating countries were dichotomized into two strata, depending on their 1-year retention rate being above (stratum A) or below (stratum B) the average retention rate across all countries.Results:22,196 axSpA patients were included with 34% on TNFi+csDMARD combination therapy. Baseline characteristics are presented in table 1. Overall, the crude TNFi retention rate was marginally longer in the combination therapy group (80% (79-81%)) compared to the monotherapy group (78% (77-79%)) and was primarily driven by differences in stratum B (fig. 1). TNFi retention rates varied significantly across countries (range:-11.0% to +11.3%), with a clear distinction between the 2 strata. The HRs for discontinuation over 1-year (reference=TNFi monotherapy) in the 3 models were: (i) 0.88 (0.82-0.93), (ii) 0.87 (0.82-0.92), (iii) 0.88 (0.82-0.93).Table 1Baseline characteristicsAll patients(n=22196)Country stratum ACountry stratum BTNFi mono(n=4940)csDMARD + TNFi(n=2547)TNFi mono(n=9693)csDMARD + TNFi(n=5016)Age (years), mean (SD)42.6 (12.5)43.4 (12.0)42.8 (12.2)41.6 (12.7)43.7 (12.7)Females, %41.137.738.242.044.2Disease duration (yrs), mean (SD)5.7 (8.0)6.2 (7.7)6.7 (7.4)4.9 (8.2)6.1 (8.2)Enthesitis, %50.316.733.957.859.7SJC-28, median (IQR)0 (0-1)0 (0-0)0 (0-2)0 (0-0)0 (0-2)VAS pain (0-100), mean (SD)60.9 (24.5)63.3 (26.5)67.8 (23.3)60.2 (23.4)57.2 (24.3)CRP (mg/L), median (IQR)8 (3-20)7.8 (2-20)18 (6.7-32.6)6.0 (2.7-15)8.0 (3-22)BASDAI (0-10), mean (SD)5.7 (2.1)5.7 (2.2)6.2 (2.1)5.6 (2.0)5.4 (2.2)BASFI (0-10), mean (SD)4.4 (2.5)4.4 (2.6)4.9 (2.5)4.3 (2.4)4.2 (2.9)ASDAS, mean (SD)3.5 (1.1)3.7 (1.0)4.0 (1.0)3.3 (1.0)3.3 (1.1)On Infliximab, %25.721222436Baseline csDMARD use, %-Methotrexate045063-Sulfasalazine068033-Leflunomide0801Conclusion:Considerable differences were observed across countries in the use of combination therapy and TNFi retention in axSpA patients. The overall 1-year TNFi retention was higher with csDMARD co-therapy compared to TNFi monotherapy. TNFi monotherapy had a 12-13% higher risk of treatment discontinuation.Acknowledgments:Novartis Pharma AG and IQVIAMN and BD participated equallyDisclosure of Interests:Michael Nissen Grant/research support from: Abbvie, Consultant of: Novartis, Lilly, Abbvie, Celgene and Pfizer, Speakers bureau: Novartis, Lilly, Abbvie, Celgene and Pfizer, Bénédicte Delcoigne: None declared, Daniela Di Giuseppe: None declared, Lennart T.H. Jacobsson Consultant of: AbbVie, Eli Lilly, Janssen, Novartis and Pfizer, Karen Fagerli: None declared, Anne Gitte Loft Grant/research support from: Novartis, Consultant of: AbbVie, MSD, Novartis, Pfizer and UCB, Speakers bureau: AbbVie, MSD, Novartis, Pfizer and UCB, Adrian Ciurea Consultant of: Consulting and/or speaking fees from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Merck Sharp & Dohme, Novartis and Pfizer., Dan Nordström Consultant of: Abbvie, Celgene, Lilly, Novartis, Pfizer, Roche and UCB., Speakers bureau: Abbvie, Celgene, Lilly, Novartis, Pfizer, Roche and UCB., Ziga Rotar Consultant of: Speaker and consulting fees from Abbvie, Amgen, Biogen, Eli Lilly, Medis, MSD, Novartis, Pfizer, Roche, Sanofi., Speakers bureau: Speaker and consulting fees from Abbvie, Amgen, Biogen, Eli Lilly, Medis, MSD, Novartis, Pfizer, Roche, Sanofi., Florenzo Iannone Consultant of: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Speakers bureau: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Maria Jose Santos Speakers bureau: Novartis and Pfizer, Manuel Pombo-Suarez Consultant of: Janssen, Lilly, MSD and Sanofi., Speakers bureau: Janssen, Lilly, MSD and Sanofi., Björn Gudbjornsson Speakers bureau: Novartis and Amgen, Heřman Mann: None declared, Nurullah Akkoc: None declared, Catalin Codreanu Consultant of: Speaker and consulting fees from AbbVie, Accord Healthcare, Alfasigma, Egis, Eli Lilly, Ewopharma, Genesis, Mylan, Novartis, Pfizer, Roche, Sandoz, UCB, Speakers bureau: Speaker and consulting fees from AbbVie, Accord Healthcare, Alfasigma, Egis, Eli Lilly, Ewopharma, Genesis, Mylan, Novartis, Pfizer, Roche, Sandoz, UCB, Irene van der Horst-Bruinsma Grant/research support from: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Consultant of: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Brigitte Michelsen: None declared, Gary Macfarlane: None declared, Merete L. Hetland Grant/research support from: BMS, MSD, AbbVie, Roche, Novartis, Biogen and Pfizer, Consultant of: Eli Lilly, Speakers bureau: Orion Pharma, Biogen, Pfizer, CellTrion, Merck and Samsung Bioepis, Matija Tomsic: None declared, Burkhard Moeller: None declared, Pedro Ávila-Ribeiro Grant/research support from: Novartis, Carlos Sánchez-Piedra: None declared, Heikki Relas Grant/research support from: Abbvie., Consultant of: Abbvie, Celgene, and Pfizer., Speakers bureau: Abbvie, Celgene, and Pfizer., Arni Jon Geirsson: None declared, Lucie Nekvindova: None declared, Gozde Yildirim Cetin Speakers bureau: AbbVie, Novartis, Pfizer, Roche, UCB, MSD, Ruxandra Ionescu Consultant of: Consulting fees from Abbvie, Eli-Lilly, Novartis, Pfizer, Roche, Sandoz, Speakers bureau: Consulting and speaker fees from Abbvie, Eli-Lilly, Novartis, Pfizer, Roche, Sandoz, Niels Steen Krogh: None declared, Johan Askling Grant/research support from: JA acts or has acted as PI for agreements between Karolinska Institutet and the following entities, mainly in the context of the ARTIS national safety monitoring programme of immunomodulators in rheumatology: Abbvie, BMS, Eli Lilly, Merck, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB Pharma, Bente Glintborg Grant/research support from: Grants from Pfizer, Biogen and Abbvie, Ulf Lindström: None declared

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