Session Information
Date: Sunday, November 5, 2017
Session Title: Epidemiology and Public Health Poster I: Rheumatoid Arthritis
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Biologic therapy has revolutionised treatment pathways and improved outcomes for patients with Rheumatoid Arthritis (RA) who do not tolerate or respond to conventional synthetic therapies. However, for some patients on biologics, disease control remains elusive with so-called refractory disease. The aim was to quantify the frequency of biologic resistant disease and identify factors, measured at the start of first biologic, associated with resistant disease.
Methods: Patients with RA starting first-line TNFi (previously failed ≥2 DMARDs) in the BSRBR-RA were included if they had a full 10 years of study follow-up (N=5755). Patients were classified as “refractory” if they had used ≥3 classes of biologic, and were compared with “persistent” patients who remained on first TNFi for 10 years. Stop reasons were investigated. HAQ was assessed at 3 years (end of patient follow-up) and DAS28 at 10 years. Associations with age, gender, disease duration, baseline DAS28 and components, comorbidities, HAQ and refractory disease were analysed in a multivariable logistic analysis. Multiple imputation was used to account for missing data.
Results: Of the whole cohort, 2147 (37%) were classed as persistent TNFi patients, and 272 (5%) as refractory (Table 1). Refractory patients remained on their first TNFi for a mean of 2.9 years, and 51% stopped for inefficacy. Refractory patients had also used rituximab (94%), tocilizumab (77%), and other classes (48%), whilst 74% had also used >1 TNFi. In the refractory cohort, 34% reported recurrent drug inefficacy only, 8% recurrent adverse events only and 50% a combination of reasons for repeated drug failures (with reasons missing in 8%). Disease activity was higher among patients with refractory disease (DAS28 5.0 vs 3.7; HAQ 2.0 vs 1.6). In multivariable analysis, older patients (>50 years, OR 0.5 (95% CI 0.4, 0.7)) and those with longer disease duration (>10 years, OR 0.7 (95% CI 0.6, 0.95)) had reduced odds of refractory disease. In addition, greater baseline HAQ (OR 1.8 (95% CI 1.4, 2.4)), and patient global assessment (OR 1.1 (95% CI 1.0, 1.2)) had increased odds of refractory disease (Table 2).
Conclusion: In this real-world cohort of patients with RA, followed for 10 years, approximately 5% had biologic resistant disease, with 2/3 reporting lack of response to any biologic. This may be an under-estimate as many patients in this study may have died before alternative non-TNFi biologics became available. Higher disability at the start of first TNFi predicted resistant disease but in general persistent and resistant patients were similar at the outset of therapy.
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Table 1: Baseline Characteristics. |
Multiple Failures [N=272] |
Persistent First Users [N=2147] |
p-value |
|
First TNFi, n (%) |
Etanercept: 115 (42%) Infliximab: 74 (27%) Adalimumab: 83 (31%) |
Etanercept: 1045 (49%) Infliximab: 511 (24%) Adalimumab: 591 (28%) |
P=0.1 |
|
Females, n (%) |
222 (82%) |
1612 (75%) |
P=0.02 |
|
Age (years), median (IQR) |
51 (43, 58) |
55 (47, 62) |
P<0.001 |
|
Disease Duration (years), median (IQR) |
9 (4, 17) |
11 (6, 18) N=2125 |
P=0.01 |
|
Rheumatoid Factor Positive, n (%) |
175 (64%) |
1331 (62%) N=2143 |
P=0.5 |
|
Fulfilled RA ACR criteria at baseline, n (%) |
272 (100%) |
2147 (100%) |
– |
|
On concurrent methotrexate, n (%) |
165 (61%) |
1377 (64%) |
P=0.3 |
|
On steroids at baseline, n (%) |
116 (43%) |
848 (40%) |
P=0.3 |
|
Total Comorbidities* |
|
|
P=0.2 |
|
None |
128 (47%) |
1137 (53%) |
|
|
1 comorbidity |
95 (35%) |
711 (33%) |
|
|
2 comorbidities |
38 (14%) |
241 (11%) |
|
|
3+ comorbidities |
11 (4%) |
58 (3%) |
|
|
SF-36 scores [range 0 (worse) to 100], median (IQR) |
N=221 |
N=1707 |
|
|
Physical Component Score |
14 (9, 19) |
16 (11, 23) |
P<0.001 |
|
Mental Component Score |
40 (33, 49) |
43 (35, 53) |
P=0.007 |
|
Disease Activity, median (IQR) |
|
|
|
|
Tender Joint Count (range 0 – 28) |
17 (12, 24) N=265 |
15 (10, 21) N=2095 |
P=0.002 |
|
Swollen Joint Count (range 0 – 28) |
12 (7, 17) N=265 |
11 (7, 15) N=2096 |
P=0.05 |
|
Patient Global Assessment, cms (range 0 – 10) |
8.0 (6.9, 9.0) N=264 |
7.5 (6.0, 8.5) N=2091 |
P<0.001 |
|
ESR (mm/hr) |
38 (23, 69) N=253 |
38 (22, 59) N=2011 |
P=0.8 |
|
DAS28 (range 0 – 10) |
6.8 (6.0, 7.5) |
6.5 (5.8, 7.2) N=2124 |
P<0.001 |
|
HAQ (range 0 – 3) |
2.1 (1.9, 2.5) N=266 |
2.0 (1.5, 2.4) N=2034 |
P<0.001 |
|
*Total comorbidities = hypertension, ischemic heart disease, stroke, lung disease, renal disease, diabetes, depression, liver disease. Tumour Necrosis Factor inhibitor (TNFi), interquartile range (IQR), Rheumatoid Arthritis (RA), American College of Rheumatology (ACR), 36-item Short Form Survey for quality of life (SF-36), erythrocyte sedimentation rate (ESR), 28-joint Disease Activity Score (DAS28), Health Assessment Questionnaire (HAQ) |
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Table 2: Multivariable analysis (imputed data, 71 datasets), odds ratios for having refractory disease compared with persistent first users. |
Odds Ratio |
P-value [mean] |
|
Females |
1.3 (0.95, 1.8) |
P=0.1 |
|
Age Groups (>50 years vs ≤ 50 years) |
0.5 (0.4, 0.7) |
P<0.001 |
|
Disease Duration Groups (>10 years vs ≤ 10 years) |
0.7 (0.6, 0.95) |
P=0.02 |
|
Tender Joint Count |
1.0 (1.0, 1.1) |
P=0.07 |
|
Swollen Joint Count |
1.0 (1.0, 1.0) |
P=0.6 |
|
Patient Global Assessment (cms) |
1.1 (1.0, 1.2) |
P<0.05 |
|
ESR (mm/hr) |
1.0 (1.0, 1.0) |
P=0.4 |
|
DAS28 (whole unit) |
0.9 (0.5, 1.5) |
P=0.6 |
|
HAQ (whole unit) |
1.8 (1.4, 2.4) |
P<0.001 |
|
Total Comorbidities* (vs none) |
|
|
|
1 comorbidity |
1.2 (0.9, 1.6) |
P=0.3 |
|
2 comorbidities |
1.3 (0.9, 2.0) |
P=0.2 |
|
3+ comorbidities |
1.6 (0.8, 3.1) |
P=0.2 |
|
*Total comorbidities = hypertension, ischemic heart disease, stroke, lung disease, renal disease, diabetes, depression, liver disease. Erythrocyte sedimentation rate (ESR), 28-joint Disease Activity Score (DAS28), Health Assessment Questionnaire (HAQ) |
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To cite this abstract in AMA style:
Kearsley-Fleet L, De Cock D, Watson K, Buch MH, Isaacs JD, Hyrich KL. Refractory Disease in Rheumatoid Arthritis: Results from the British Society of Rheumatology Biologics Register for Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/refractory-disease-in-rheumatoid-arthritis-results-from-the-british-society-of-rheumatology-biologics-register-for-rheumatoid-arthritis/. Accessed January 25, 2020.« Back to 2017 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/refractory-disease-in-rheumatoid-arthritis-results-from-the-british-society-of-rheumatology-biologics-register-for-rheumatoid-arthritis/