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Exploring sub-optimal response to tumour necrosis factor inhibitors in axial spondyloarthritis

Fariz Yahya^1,2, Karl Gaffney³, Raj Sengupta^1,4

¹Department of Rheumatology, Royal National Hospital for Rheumatic Diseases, RUH NHS Foundation Trust, Bath, UK.

Rheumatology Advances in Practice

|August 22, 2019

Abstract

Objectives:

The aim was to define sub-optimal response to TNF inhibitors (TNFi), compare long-term drug survival rates and identify predictors of sub-optimal response in axial spondyloarthritis (axSpA) patients in a UK cohort.

Methods:

All axSpA patients attending two centres who commenced TNFi between 2002 and 2016 were included. Routinely recorded patient data were reviewed retrospectively. Patients with paired BASDAI at baseline, 3 and/or 6 months were included for analysis. Sub-optimal response was defined as achieving a ≥ 2-point reduction in BASDAI but not BASDAI50, post-treatment BASDAI remaining at ≥4, and in the opinion of the treating physician these patients demonstrated a meaningful clinical response.

Results:

Four hundred and ninety-nine patients were included: 82 (16.4%) patients were classified as having a sub-optimal response; 64 (78%) males, 78 (95.1%) AS and 55/67 (82.1%) HLA-B27 positive. Results are reported as the mean (s.d.). Time to diagnosis was 10 (8.6) years, age at diagnosis was 37 (11.7) years, and age at initiating index TNFi was 48 (11.1) years. Individual index TNFi were Humira (adalimumab, n = 41, 50%), Enbrel (etanercept, n = 27, 32.9%), Remicade (infliximab, n = 5, 6.1%), Simponi (golimumab, n = 3, 3.7%) and Cimzia (certolizumab pegol, n = 6, 7.3%). The rate of attrition was greater among sub-optimal responders at 2 and 5 years (P < 0.05), but not at 10 years (P = 0.06), compared with responders. Older age at initiation of TNFi was a predictor of sub-optimal response (odds ratio 1.04, 95% CI 1.01, 1.09, P < 0.05).

Conclusion:

A significant proportion of patients continued TNFi despite demonstrated sub-optimal response. Further research needs to be undertaken in order to understand this group.

Insights

A significant proportion of axial spondyloarthritis patients show a sub-optimal response to TNF inhibitors (TNFi) but continue treatment. Older age at TNFi initiation predicts this sub-optimal response.

Area of Science:

Rheumatology
Immunology
Clinical Medicine

Background:

Tumor Necrosis Factor inhibitors (TNFi) are a cornerstone therapy for axial spondyloarthritis (axSpA).
Defining and understanding sub-optimal response to TNFi is crucial for optimizing patient outcomes.
Predictors of sub-optimal response require further elucidation in real-world cohorts.

Purpose of the Study:

To define sub-optimal response to TNFi in axSpA patients.
To compare long-term drug survival rates between responders and sub-optimal responders.
To identify predictors of sub-optimal response within a UK axSpA cohort.

Main Methods:

Retrospective review of routinely recorded patient data from two UK centers (2002-2016).
Inclusion of axSpA patients initiating TNFi with paired BASDAI scores at baseline and 3/6 months.
Definition of sub-optimal response: ≥2-point BASDAI reduction (not BASDAI50), post-treatment BASDAI ≥4, and physician-judged meaningful clinical response.

Main Results:

82% of 499 axSpA patients exhibited sub-optimal response to TNFi.
Sub-optimal responders had higher attrition rates at 2 and 5 years compared to responders (P<0.05).
Older age at TNFi initiation was a significant predictor of sub-optimal response (OR 1.04, P<0.05).

Conclusions:

A notable percentage of axSpA patients continue TNFi despite demonstrating sub-optimal response.
Further research is warranted to understand the reasons behind continued TNFi use in this patient group.
Identifying predictors like age can aid in personalized treatment strategies for axSpA.

Read full analysis

Keywords:

TNF inhibitors axial spondyloarthritis predictors sub-optimal response survival rates

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