Session Type: Abstract Submissions (ACR)
Background/Purpose: Although rituximab therapy is successful in the majority of rheumatoid arthritis (RA) patients, 30-40% of patients do not respond. The mechanism behind this is yet unknown, as B cell depletion generally takes place in all patients. This study aims to explore changes in serum cytokines during rituximab therapy in established RA patients.
Methods: Serum was collected from 18 established RA patients before and at 1, 3, 6, 9 and 12 months after start of rituximab therapy. A panel of 34 cytokines was measured by a multiplex immunoassay platform (Luminex). Rituximab responder status was determined by the change in disease activity score after 6 months; Patients with DDAS28>1.2 were considered responders.
Results: During rituximab therapy, CXCL13 showed a significant decrease in all patients (median 1.9-fold decrease (IQR 1.4-3.3)), irrespective of responder status. This pattern appeared to coincide with B cell depletion, suggesting that CXCL13 reflects B cell levels in the circulation.
No differences were observed between responders and non-responders after 1 and 3 months of therapy. However, at 6, 9 and 12 months, CXCL10 appeared to be regulated differently between responders and non-responders (R vs. NR, T6/T0 p=0.004, T9/T0 p=0.003, T12/T0 p=0.001). CXCL10 showed a relative increase compared to baseline in the non-responders and no increase or even a decrease in responders. The fold changes in CXCL10 correlated to the DDAS28 at 6 months, indicating that this reflects disease activity rather than a mechanistic effect of rituximab. Most strikingly, IL-12 was not detectable in most of the non-responders until 6 months, but showed a sudden increase after 9 months of therapy. This increase was not observed in the responders (R vs. NR T9/T6 p=0.030, Fisher’s exact p=0.049). In contrast to CXCL10, no correlation was observed between DDAS28 and the fold change in IL-12.
Conclusion: This study shows that during rituximab therapy, cytokine changes occur in the patient serum, both related and unrelated to the clinical response. CXCL13 seems to reflect B cells levels in the circulation, whereas the dynamics of CXCL10 and IL-12 during therapy are regulated differently between responders and non-responders during rituximab treatment. These findings indicate different pharmacological effects of rituximab between responders and non-responders.
This research was supported by the Center for Translational Molecular Medicine (CTMM) and the Dutch Arthritis Foundation (TRACER).
T. D. de Jong,
W. de Jager,
H. G. Raterman,
A. E. Voskuyl,
K. A. Gelderman,
C. L. Verweij,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-cytokine-changes-in-rituximab-treated-rheumatoid-arthritis-patients/