Does the reason for discontinuation of a first TNF inhibitor influence the effectiveness of a second TNF inhibitor in axial spondyloarthritis? Results from the Swiss Clinical Quality Management Cohort.

Beate Steininger,Rudolf O Kissling,Pascale Exer, ,Adrian Ciurea,Ulrich Weber,Almut Scherer,Jürg Bernhard,Giorgio Tamborrini

doi:10.1186/s13075-016-0969-2

Abstract

BackgroundWith regard to switching tumor necrosis factor inhibitors (TNFi) in axial spondyloarthritis (axSpA), conflicting results have been reported as to whether the effectiveness of a second TNFi depends on the reason for discontinuation of the first TNFi.MethodsPatients with a clinical diagnosis of axSpA starting a second TNFi in the Swiss Clinical Quality Management cohort were included. Effectiveness of treatment at 1 year, as well as drug survival, was compared between subgroups having discontinued the first TNFi because of lack of response, adverse events (AEs), or other reasons. Lack of response was further divided into primary or secondary lack of response (PLR or SLR, respectively), depending on whether the first TNFi was stopped before or after 6 months of treatment.ResultsAmong 632 patients with axSpA, median survival of a second TNFi was 1.1 years after PLR and 3.8 years after SLR (p = 0.003). At least moderate disease activity as defined by an Ankylosing Spondylitis Disease Activity Score using the erythrocyte sedimentation rate (ASDAS-ESR) <2.1 was achieved after 12 months by 11 %, 39 %, 26 %, and 39 % of patients who discontinued their first TNFi because of PLR, SLR, AEs, and other reasons, respectively (p = 0.01). Only 4 % of patients achieved an ASDAS-ESR inactive disease state after PLR, in comparison to 22 % of those after SLR. Similar results were demonstrated in patients fulfilling the Assessment of SpondyloArthritis international Society classification criteria for axSpA (n = 488): ASDAS-ESR <2.1 was achieved after 12 months by 9 %, 41 %, 29 %, and 39 % of patients who discontinued their first TNFi because of PLR, SLR, AEs, and other reasons, respectively (p = 0.01).ConclusionsThe effectiveness of a second TNFi is significantly impaired in patients with axSpA after PLR to a first TNFi compared with SLR.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-0969-2) contains supplementary material, which is available to authorized users.

Highlights

With regard to switching tumor necrosis factor inhibitors (TNFi) in axial spondyloarthritis, conflicting results have been reported as to whether the effectiveness of a second TNFi depends on the reason for discontinuation of the first TNFi
Male sex, high baseline Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), low baseline Bath Ankylosing Spondylitis Functional Index (BASFI), high baseline C-reactive protein (CRP), human leukocyte antigen B27 (HLA-B27) positivity, and the absence of enthesitis have been described as predictors of good response to TNFi [6, 7]
A total of 54 patients lost to follow-up after the start of a second TNFi were excluded from the analyses

Summary

Introduction

With regard to switching tumor necrosis factor inhibitors (TNFi) in axial spondyloarthritis (axSpA), conflicting results have been reported as to whether the effectiveness of a second TNFi depends on the reason for discontinuation of the first TNFi. the use of tumor necrosis factor-α inhibitors (TNFi) has revolutionized the treatment of axial spondyloarthritis (axSpA), a significant proportion of patients do not adequately respond [1,2,3,4,5]. No evidence for a differential response to a second TNFi in dependence on the reason for discontinuation of the first TNFi has been observed in axSpA. As new compounds with different modes of action are currently being tested in axSpA as potential alternatives to TNFi switching [27,28,29], we explored the effectiveness of switching TNFi in a large real-life observational axSpA cohort

Methods

Results

Discussion

Conclusion