LAUSR

Background: Elevated levels of the B cell activating cytokine BAFF (also known as BLyS) have been associated with active systemic lupus erythematosus (SLE), and the anti-BAFF monoclonal antibody belimumab has been approved as an add-on to standard-of-care SLE treatment, the latter mainly comprising glucocorticoids, antimalarial agents (AMA) and other immunosuppressive treatments. Objectives: To investigate the effect of AMA and three other commonly used in SLE immunosuppressive agents (methotrexate, azathioprine, mycophenolate mofetil/sodium) on serum BAFF levels. Methods: Access to data from the phase III clinical trials of belimumab BLISS-52 (n=865; NCT00424476) and BLISS-76 (n=819; NCT00410384) was granted by GlaxoSmithKline (Uxbridge, UK); a total of 1684 SLE patients were analysed. Serum samples obtained prior to belimumab initiation were stored at -80°C until BAFF level determination by ELISA. The non-parametric Mann-Whitney U test was used to compare BAFF level distributions between treatment groups. Linear regression models were applied to determine independence. Results: BAFF levels (mean, SD; pg/mL) were higher in patients receiving methotrexate (1835, 1617; n=212; P=0.001), azathioprine (1901, 1472; n=364; P<0.001) or mycophenolate mofetil/sodium (1994, 1544; n=175; P<0.001) and no immunosuppressive treatment other than the one investigated compared with patients receiving no immunosuppressive treatment (1593, 1929; n=860); AMA were allowed in both groups, in all comparisons. In contrast, patients on AMA displayed lower BAFF levels (1654, 1318; n=1085) compared with patients who did not use AMA (1942, 2408; n=580; P=0.002). In linear regression, AMA use showed a consistent and independent association with lower BAFF levels in all models, whereas use of each one of methotrexate, azathioprine and mycophenolic acid was associated with higher BAFF levels. All models were adjusted for the use of immunosuppressive agents other than the one investigated. Conclusion: Our data imply differential effects of antimalarial agents and other immunosuppressive treatments on BAFF levels; AMA diminished while methotrexate, azathioprine and mycophenolic acid increased BAFF levels. It is worth noting that methotrexate and mycophenolic acid are not approved for the treatment of SLE. Considering the importance of BAFF in B cell homeostasis and SLE pathogenesis, exploration of the biological significance of the differential effects of different immunosuppressive agents on BAFF levels is anticipated. Acknowledgement: The authors would like to thank GlaxoSmithKline (Uxbridge, UK) for granting access to the data from the BLISS-52 and BLISS-76 trials (ClinicalTrials.gov identifiers NCT00424476 and NCT00410384, respectively) through the Clinical Study Data Request (CSDR) consortium. Disclosure of Interests: None declared