P246 Predicting non-response to biologic therapy amongst patients with axSpA: results from the British Society for Rheumatology Biologics Register

• Published in: Rheumatology (Oxford, England) Vol. 59; no. Supplement_2
• Main Authors: Dean, Linda E, Pathan, Ejaz, Jones, Gareth T, Macfarlane, Gary J
• Format: Journal Article
• Language: English
• Published: Oxford University Press 01-04-2020
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/keaa111.240

Abstract
Background
Biologic therapies have transformed treatment for axial spondyloarthritis (axSpA). However, although studies report overall benefits, these are average effects. There remains a subset of patients in whom response is not achieved. Here, we aimed to identify characteristics of patients who may need additional therapeutic approaches to optimise outcome.
Methods
The British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS) is a prospective cohort of axSpA patients recruited from 83 centres across Great Britain. All patients were biologic-naïve at recruitment, however those in the “biologic” cohort commenced a biologic therapy shortly thereafter, or during follow-up. Clinical data was collected from medical records, and socio-economic/patient reported outcomes via questionnaires. Response was assessed at first follow-up, between 10 weeks and 9 months from therapy commencement, and defined in four ways: ASAS20 and ASAS40 criteria, ≥1.1 reduction in ASDAS, and achieving moderate/inactive ASDAS (<2.1). Factors associated with non-response were assessed by logistic regression and parsimonious models identified using stepwise methods. The ability to predict non-response was assessed by positive predictive value (PPV).
Results
335 biologic participants provided information at a median follow-up of 14 weeks (inter-quartile range (IQR) 12-17). Median age was 47 years (IQR 36-56), 69% were male and 61% met AS modified New York criteria. The proportion meeting response varied by criteria: ASAS20 52%, ASAS40 33%, ASDAS reduction 47% and ASDAS <2.1 35%. Socio-economic circumstances predicted non-response, specifically (in all models) work status and (in some models) fewer years of education (Table 1). Poorer mental health and high number of co-morbidities was associated with non-response across multiple (but not all) outcomes, while body mass index, enthesitis and gender were included in models for a single outcome. Disease-specific factors were largely not associated with non-response. All models demonstrated a good level of fit and were effective at predicting non-response (PPV 65%-77%).
P246 Table 1
Baseline factors associated with non-response at follow-up (stepwise logistic regression models)
ASAS 20
ASAS 40
ASDAS reduction
ASDAS <2.1
Baseline variables
OR (95% CI)
OR (95% CI)
OR (95% CI)
OR (95% CI)
Employment (ref. full-time)
part-time
2.07 (0.97, 4.40)
2.64 (1.19, 5.84)
2.54 (0.98, 6.60)
3.52 (1.36, 9.13)
unpaid/seeking
0.55 (0.16, 1.88)
0.86 (0.28, 2.60)
4.26 (0.79, 22.92)
4.16 (0.78, 22.09)
retired
1.49 (0.68, 3.27)
0.66 (0.29, 1.48)
0.93 (0.32, 2.72)
1.11 (0.40, 3.07)
retired/unemployed (ill-health)
2.70 (1.32, 5.50)
3.84 (1.58, 9.35)
3.49 (1.31, 9.27)
22.88 (2.95, 177.66)
student
low N.
1.001 (0.13, 7.74)
0.47 (0.03, 8.38)
0.37 (0.04, 3.80)
Body Mass Index
per unit increase
1.05 (1.00, 1.10)
Education (ref. secondary school)
apprenticeship
0.50 (0.22, 1.18)
0.70 (0.25, 1.99)
college
0.71 (0.36, 1.39)
0.99 (0.42, 2.32)
university degree
0.36 (0.18, 0.71)
0.58 (0.24, 1.38)
further degree
0.79 (0.29, 2.12)
0.38 (0.12, 1.21)
Enthesitis (ref. absent)
present
0.26 (0.09, 0.75)
SF-12 - MCS
per unit increase
0.95 (0.92, 0.98)
0.96 (0.93, 0.99)
ASDAS
per unit increase
0.23 (0.14, 0.35)
Gender
female vs. male
1.69 (0.83, 3.46)
Comorbidity Count
per unit increase
1.55 (1.09, 2.23)
1.75 (1.14, 2.67)
1.66 (1.05, 2.61)
HADs anxiety
per unit increase
1.07 (1.0, 1.14)
PPV/NPV
64.9/62.7
72.2/58.3
76.6/75.9
77.3/63.2
OR - Odds ratio; CI - Confidence Interval; ref - reference category; ASAS - Assessment in Ankylosing Spondylitis; ASDAS - Ankylosing Spondylitis Disease Activity Score; SF-12 MCS - Short Form 12 Mental Component Score; SF-12 PCS - Short Form 12 Physical Component Score; HADS - Hospital Anxiety and Depression Scale; ROC - Receiver Operating Characteristic; PPV - Positive Predictive Value; NPV - Negative Predictive Value.
Conclusion
We have identified factors which predict non-response to biologic therapy, some of which may be modifiable and others which identify patients who are unlikely to benefit from biologic therapy alone. In such patients additional/alternative treatment strategies should be considered to maximise the benefits which others gain from biologic therapy.
Disclosures
L.E. Dean None. E. Pathan Other; E.P. has recieved salary funding from Jansen (2019) and Merck (2018). G.T. Jones None. G.J. Macfarlane None.