Comparative Analysis and Predictors of 10-year Tumor Necrosis Factor Inhibitors Drug Survival in Patients with Spondyloarthritis: First-year Response Predicts Longterm Drug Persistence

Irini D Flouri; Theodora E Markatseli; Kyriaki A Boki; Ioannis Papadopoulos; Fotini N Skopouli; Paraskevi V Voulgari; Loukas Settas; Dimitrios Zisopoulos; Alexios Iliopoulos; Pierre Geborek; Alexandros A Drosos; Dimitrios T Boumpas; Prodromos Sidiropoulos

doi:10.3899/jrheum.170477

Comparative Analysis and Predictors of 10-year Tumor Necrosis Factor Inhibitors Drug Survival in Patients with Spondyloarthritis: First-year Response Predicts Longterm Drug Persistence

J Rheumatol. 2018 Jun;45(6):785-794. doi: 10.3899/jrheum.170477. Epub 2018 Apr 1.

Authors

Irini D Flouri^{1

2}, Theodora E Markatseli^{1

2}, Kyriaki A Boki^{1

2}, Ioannis Papadopoulos^{1

2}, Fotini N Skopouli^{1

2}, Paraskevi V Voulgari^{1

2}, Loukas Settas^{1

2}, Dimitrios Zisopoulos^{1

2}, Alexios Iliopoulos^{1

2}, Pierre Geborek^{1

2}, Alexandros A Drosos^{1

2}, Dimitrios T Boumpas^{1

2}, Prodromos Sidiropoulos^{3

4}

Affiliations

¹ From the Rheumatology, Clinical Immunology and Allergy Department, Medical School, University of Crete, Heraklion; Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina; Rheumatology Department, Sismanoglio Hospital; Department of Nutrition and Dietetics, Harokopio University of Athens; Department of Rheumatology, Veterans Administration Hospital; Joint Academic Rheumatology Program, Faculty of Medicine, National and Kapodestrian University of Athens; Fourth Internal Medicine Department, Attikon University Hospital of Athens, Athens; Rheumatology Clinic, General Hospital of Kavala, Kavala; First Department of Internal Medicine, Rheumatology Section, AHEPA Hospital of the Aristotle University Medical School; Rheumatology Department, 424 General Army Hospital, Thessaloniki, Greece; Department of Rheumatology, Skȧne University Hospital, Lund, Sweden.
² I.D. Flouri, MD, Rheumatology, Clinical Immunology and Allergy Department, Medical School, University of Crete; T.E. Markatseli, MD, PhD, Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina; K.A. Boki, MD, PhD, Rheumatology Department, Sismanoglio Hospital; I. Papadopoulos, MD, PhD, Rheumatology Clinic, General Hospital of Kavala; F.N. Skopouli, MD, PhD, Department of Nutrition and Dietetics, Harokopio University of Athens; P.V. Voulgari, MD, PhD, Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina; L. Settas, MD, PhD, First Department of Internal Medicine, Rheumatology Section, AHEPA Hospital of the Aristotle University Medical School; D. Zisopoulos, MD, First Department of Internal Medicine, Rheumatology Section, AHEPA Hospital of the Aristotle University Medical School, and Rheumatology Department, 424 General Army Hospital; A. Iliopoulos, MD, PhD, Department of Rheumatology, Veterans Administration Hospital; P. Geborek, MD, PhD, Department of Rheumatology, Skȧne University Hospital; A.A. Drosos, MD, PhD, Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina; D.T. Boumpas, MD, PhD, Joint Academic Rheumatology Program, Faculty of Medicine, National and Kapodestrian University of Athens, and Fourth Internal Medicine Department, Attikon University Hospital of Athens; P. Sidiropoulos, MD, PhD, Rheumatology, Clinical Immunology and Allergy Department, Medical School, University of Crete.
³ From the Rheumatology, Clinical Immunology and Allergy Department, Medical School, University of Crete, Heraklion; Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina; Rheumatology Department, Sismanoglio Hospital; Department of Nutrition and Dietetics, Harokopio University of Athens; Department of Rheumatology, Veterans Administration Hospital; Joint Academic Rheumatology Program, Faculty of Medicine, National and Kapodestrian University of Athens; Fourth Internal Medicine Department, Attikon University Hospital of Athens, Athens; Rheumatology Clinic, General Hospital of Kavala, Kavala; First Department of Internal Medicine, Rheumatology Section, AHEPA Hospital of the Aristotle University Medical School; Rheumatology Department, 424 General Army Hospital, Thessaloniki, Greece; Department of Rheumatology, Skȧne University Hospital, Lund, Sweden. sidiropp@med.uoc.gr.
⁴ I.D. Flouri, MD, Rheumatology, Clinical Immunology and Allergy Department, Medical School, University of Crete; T.E. Markatseli, MD, PhD, Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina; K.A. Boki, MD, PhD, Rheumatology Department, Sismanoglio Hospital; I. Papadopoulos, MD, PhD, Rheumatology Clinic, General Hospital of Kavala; F.N. Skopouli, MD, PhD, Department of Nutrition and Dietetics, Harokopio University of Athens; P.V. Voulgari, MD, PhD, Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina; L. Settas, MD, PhD, First Department of Internal Medicine, Rheumatology Section, AHEPA Hospital of the Aristotle University Medical School; D. Zisopoulos, MD, First Department of Internal Medicine, Rheumatology Section, AHEPA Hospital of the Aristotle University Medical School, and Rheumatology Department, 424 General Army Hospital; A. Iliopoulos, MD, PhD, Department of Rheumatology, Veterans Administration Hospital; P. Geborek, MD, PhD, Department of Rheumatology, Skȧne University Hospital; A.A. Drosos, MD, PhD, Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina; D.T. Boumpas, MD, PhD, Joint Academic Rheumatology Program, Faculty of Medicine, National and Kapodestrian University of Athens, and Fourth Internal Medicine Department, Attikon University Hospital of Athens; P. Sidiropoulos, MD, PhD, Rheumatology, Clinical Immunology and Allergy Department, Medical School, University of Crete. sidiropp@med.uoc.gr.

PMID: 29606666
DOI: 10.3899/jrheum.170477

Abstract

Objective: To evaluate the 10-year drug survival of the first tumor necrosis factor inhibitor (TNFi) administered to patients with spondyloarthritis (SpA) overall and comparatively between SpA subsets, and to identify predictors of drug retention.

Methods: Patients with SpA in the Hellenic Registry of Biologic Therapies, a prospective multicenter observational cohort, starting their first TNFi between 2004-2014 were analyzed. Kaplan-Meier curves and Cox regression models were used.

Results: Overall, 404 out of 1077 patients (37.5%) discontinued treatment (followup: 4288 patient-yrs). Ten-year drug survival was 49%. In the unadjusted analyses, higher TNFi survival was observed in patients with ankylosing spondylitis (AS) compared to undifferentiated SpA and psoriatic arthritis [PsA; significant beyond the first 2.5 (p = 0.003) years and 7 years (p < 0.001), respectively], and in patients treated for isolated axial versus peripheral arthritis (p = 0.001). In all multivariable analyses, male sex was a predictor for longer TNFi survival. Use of methotrexate (MTX) was a predictor in PsA and in patients with peripheral arthritis. Absence of peripheral arthritis and use of a monoclonal antibody (as opposed to non-antibody TNFi) independently predicted longer TNFi survival in axial disease because of lower rates of inefficacy. Achievement of major responses during the first year in either axial or peripheral arthritis was the strongest predictor of longer therapy retention (HR 0.33, 95% CI 0.26-0.41 for Ankylosing Spondylitis Disease Activity Score inactive disease, and HR 0.35, 95% CI 0.24-0.50 for 28-joint Disease Activity Score remission).

Conclusion: The longterm retention of the first TNFi administered to patients with SpA is high, especially for males with axial disease. The strongest predictor of longterm TNFi survival is a major response within the first year of treatment.

Keywords: ANKYLOSING SPONDYLITIS; PSORIATIC ARTHRITIS; REGISTRY; SPONDYLOARTHRITIS; TUMOR NECROSIS FACTOR INHIBITORS.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Adalimumab / therapeutic use
Adult
Antirheumatic Agents / therapeutic use*
Arthritis, Psoriatic / drug therapy*
Biological Products / therapeutic use*
Female
Humans
Infliximab / therapeutic use
Male
Middle Aged
Prospective Studies
Registries
Spondylarthritis / drug therapy*
Treatment Outcome
Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

Antirheumatic Agents
Biological Products
Tumor Necrosis Factor-alpha
Infliximab
Adalimumab