Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Serum Cytokine Profile Predicts Response to Rituximab Therapy in Rheumatoid Arthritis.

Vital4,  Edward M., Cuthbert4,  Richard J., Dass1,  Shouvik, Parmar4,  Rekha, Rawstron3,  Andrew C., Ponchel1,  Frederique C., Emery2,  Paul

Leeds, West Yorkshire, United Kingdom
Chapel Allerton Hospital, Leeds, United Kingdom
Leeds Teaching Hospitals NHS Trust, Leeds, West Yorkshire, United Kingdom
University of Leeds, Leeds, West Yorkshire, United Kingdom

Background:

Response to B-cell depletion with rituximab in rheumatoid arthritis is variable. Several factors have been shown to have predictive value at baseline: RF and CCP status, IgG titre, circulating memory B cell numbers, synovial expression of CD79a, as well as persistence of circulating plasmablasts and synovial plasma cells after treatment. These data suggest it may be possible to select patients for therapy based on parameters indicating greater active B-cell involvement. However, parameters identified to date are not accurate and many are not suitable for routine clinical practice. We therefore studied serum cytokines that have a hypothetical role in B-cell function in RA to better understand the determinants of response, and as convenient biomarkers.

Patients and Methods:

85 patients were treated with rituximab and clinical response was evaluated at 6 months by EULAR criteria. Relapse was determined by rise in DAS28 >= 0.6. Serum was tested for BAFF (n=85 at baseline, 29 serial samples), IL6 (n=46) and IL10 (n=26) by ELISA (R&D Systems). B cell subsets were measured by 6-parameter flow cytometry using CD19, CD20, CD3, CD14, CD27 and CD38. The strength of correlations was tested by Spearman's log rank test and relationships between cytokine titres and categorical variables by either Mann Whitney U test or log transformation and Student's t test, as appropriate.

Results: Baseline Cytokines and disease activity:

IL6 was correlated with CRP at baseline as expected (R = 0.591, p < 0.001) but there was no relationship of BAFF or IL-10 with DAS28 or CRP, nor any interrelationship between cytokines.

Cytokine changes after therapy:

6 months after B-cell depletion, BAFF significantly increased (p<0.001) and IL-6 significantly reduced (p=0.001) but there was no substantive or significant change in IL10. As expected, IL-6 was higher in non-responders at 6 months (p<0.001). Levels of each cytokine correlated between baseline and 6 months after therapy (BAFF, R=0.735, p<0.001; IL-6, R=0.541, p<0.001; IL-10, R=0.675, p=0.008).

Predictive value of baseline cytokines:

Baseline DAS28, its components, and CRP/ESR did not differ between responders and non-responders. Most importantly, levels of IL-6 and BAFF were predictive of response at baseline: in responders BAFF was higher (p=0.03) and IL-6 was lower (p=0.014).

No relationship of serum cytokines with B cell depletion or repopulation:

No relationship was identified between IL6, IL10 or BAFF levels at baseline or follow up and baseline B-cell number, degree of depletion at 2 or 6 weeks or rate of repopulation of any subset.

Conclusions:

Serum BAFF and IL-6 titres are predictive of response to rituximab in rheumatoid arthritis and may have utility as biomarkers. However, this effect appears to be independent of B cell depletion, and the hypothesis that BAFF inhibits B cell depletion, as suggested by animal models, is not supported by these results. These relationships may differ in the synovium or other tissues.

To cite this abstract, please use the following information:
Vital, Edward M., Cuthbert, Richard J., Dass, Shouvik, Parmar, Rekha, Rawstron, Andrew C., Ponchel, Frederique C., et al; Serum Cytokine Profile Predicts Response to Rituximab Therapy in Rheumatoid Arthritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1126
DOI: 10.1002/art.28893

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