Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose:
Predicting response to anti-TNF alpha inhibitors (TNFi) in rheumatoid arthritis (RA) patients is challenging. Therefore there is a high need for identification of biomarkers of clinical outcome to guide therapeutical decisions. A number of studies have suggested that the differential response to TNFi may partly be explained by modulation of synovial ectopic lymphocytic aggregates (ELN) within the synovial tissue.
Certolizumab pegol is a pegylated fully humanized TNFi and at present data regarding in vivo effects on pathobiological responses within the synovial membrane of patients with RA are limited. In particular whether specific synovial pathotypes predict response to treatment is unknown.
The main aim of this study is to investigate whether the presence of synovial ELN at baseline predicts clinical response to treatment with certolizumab pegol in RA patients.
Methods:
A cohort of biologic-naïve RA patients who qualified for treatment with TNFi according to NICE guidance (National Institute for Health and Clinical Excellence, http://guidance.nice.org.uk/TA186) were recruited to the study at Barts and the London Hospital. Patients underwent ultrasound guided synovial biopsy of an active joint prior to commencing therapy with certolizumab pegol. Following 3 months of therapy, response to treatment was assessed according to EULAR response criteria and a repeat ultrasound guided synovial biopsy of the same joint obtained for 20 patients.
Paraffin embedding sequentially cut sections of synovial tissue underwent routine H&E staining and immunohistochemical staining for CD20 to detect B cells. Sections were graded as either a diffuse or aggregate infiltrate as previously described [Manzo, Eur J Immunol 2005]. The study received local ethics approval.
Results:
25 patients were recruited, 72% female, median age 54 years old (IQR: 45 -59), with a median disease duration of 4 years (IQR: 2 – 8.5). Median DAS28 was 6.2 (IQR: 5.7 – 6.8), 10 pts (40%) had an erosive disease and 17 (68%) were seropositive for RF or CCP, with 16 (64%) CCP positive. ELN was found in 11 patients (44%). 18 patients (72%) responded to the drug according to EULAR response criteria (32% were good responders and 40% moderate responders). The clinical response was maintained at 48 weeks. All patients with lymphocytic aggregates had a good or moderate response, while patients with negative ELN were equally either responders (50%) or non responders (50%) [p=0,01]. 9 of the 11 patients who resulted ELN positive at baseline had a second biopsy, and 4 (44%) reversed into a ELN negative status. Univariate analysis showed that ELN was the only independent predictor of good or moderate clinical response [p<0.05].
Conclusion:
To the authors’ knowledge, this is the first time that clinical response to certolizumab pegol has been evaluated in association with synovial ELN.
Our work shows that the presence of ELN is an independent predictor of clinical response to certolizumab pegol treatment, in line with previous data observed for other TNFi [Klaasen, Arthritis & Rheum 2009], suggesting that histopathology could be considered in the future as a potential key tool to guide therapeutic decisions for RA patients.
Disclosure:
M. Di Cicco,
None;
S. Kelly,
None;
F. Humby,
None;
N. Ng,
None;
S. Dadoun,
None;
R. Hands,
None;
V. Rocher,
None;
A. Nerviani,
None;
M. Bombardieri,
None;
C. Pitzalis,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/synovial-ectopic-lymphoneogenesis-predicts-clinical-response-to-certolizumab-pegol-in-patients-with-rheumatoid-arthritis/