The impact of seropositivity on the effectiveness of biologic anti-rheumatic agents: results from a collaboration of 16 registries

Author:

Courvoisier Delphine S1ORCID,Chatzidionysiou Katarina2,Mongin Denis1,Lauper Kim13ORCID,Mariette Xavier4,Morel Jacques5,Gottenberg Jacques-Eric6,Bergstra Sytske Anne7ORCID,Suarez Manuel Pombo8,Codreanu Catalin9,Kvien Tore K10,Santos Maria Jose11ORCID,Pavelka Karel12,Hetland Merete L1314,Askling Johan15,Turesson Carl16ORCID,Kubo Satoshi17,Tanaka Yoshiya17ORCID,Iannone Florenzo18ORCID,Choquette Denis19,Nordström Dan C20,Rotar Ziga21,Lukina Galina22,Gabay Cem1,Van Vollenhoven Ronald23,Finckh Axel1

Affiliation:

1. Rheumatology, University Hospitals of Geneva, Geneva, Switzerland

2. Rheumatology, Karolinska Institutet, Stockholm, Sweden

3. Centre for Epidemiology Versus Arthritis, Centre for Musculoskeletal Research, University of Manchester, Manchester, UK

4. Rheumatology, Université Paris Sud, AP-HP, Paris, France

5. Rheumatology, CHU and University of Montpellier, Montpellier, France

6. Rheumatology, University Hospital of Strasbourg, Strasbourg, France

7. Rheumatology, Leiden University Medical Center, Leiden, The Netherlands

8. Rheumatology, Clinical University Hospital, Santiago de Compostela, Spain

9. Center of Rheumatic Diseases, University of Medicine and Pharmacy, Bucharest, Romania

10. Rheumatology, Diakonhjemmet Hospital, Oslo, Norway

11. Rheumatology, Hospital Garcia de Orta, Almada, Portugal

12. Rheumatology, Charles University, Prague, Czech Republic

13. DANBIO Registry and Copenhagen Center for Arthritis Research, Rigshospitalet, Glostrup, Denmark

14. Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

15. Clinical Epidemiology, Karolinska Institutet, Stockholm, Sweden

16. Rheumatology, Skåne University Hospital, Malmö, Sweden

17. First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan

18. Italian Group for the Study of Early Arthritis, University Hospital of Bari, Bari, Italy

19. Institut de Recherche en Rhumatologie de Montréal, Centre hospitalier de l'Université de Montréal and Université de Montréal, Montréal, Canada

20. ROB-FIN Registry, Helsinki University Hospital and Helsinki University, Helsinki, Finland

21. Rheumatology, University Medical Centre Ljubljana, Ljubljana, Slovenia

22. Rheumatology, V. A. Nasonova Research Institute of Rheumatology, Moscow, Russia

23. Rheumatology and Clinical Immunology, Amsterdam University Medical Centers, Amsterdam, The Netherlands

Abstract

Abstract Objectives RF and ACPA are used as diagnostic tools and their presence has been associated with clinical response to some biologic DMARDs (bDMARDs) in RA. This study compared the impact of seropositivity on drug discontinuation and effectiveness of bDMARDs in patients with RA, using head-to-head comparisons in a real-world setting. Methods We conducted a pooled analysis of 16 observational RA registries. Inclusion criteria were a diagnosis of RA, initiation of treatment with rituximab (RTX), abatacept (ABA), tocilizumab (TCZ) or TNF inhibitors (TNFis) and available information on RF and/or ACPA status. Drug discontinuation was analysed using Cox regression, including drug, seropositivity, their interaction, adjusting for concomitant and past treatments and patient and disease characteristics and accounting for country and calendar year of bDMARD initiation. Effectiveness was analysed using the Clinical Disease Activity Index evolution over time. Results Among the 27 583 eligible patients, the association of seropositivity with drug discontinuation differed across bDMARDs (P for interaction <0.001). The adjusted hazard ratios for seropositive compared with seronegative patients were 1.01 (95% CI 0.95, 1.07) for TNFis, 0.89 (0.78, 1.02)] for TCZ, 0.80 (0.72, 0.88) for ABA and 0.70 (0.59, 0.84) for RTX. Adjusted differences in remission and low disease activity rates between seropositive and seronegative patients followed the same pattern, with no difference in TNFis, a small difference in TCZ, a larger difference in ABA and the largest difference in RTX (Lundex remission difference +5.9%, low disease activity difference +11.6%). Conclusion Seropositivity was associated with increased effectiveness of non-TNFi bDMARDs, especially RTX and ABA, but not TNFis.

Publisher

Oxford University Press (OUP)

Subject

Pharmacology (medical),Rheumatology

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