Abstract: SA-PO103

Elevated BAFF Following Rituximab for Lupus Nephritis (LN) Is Associated with Higher Anti-dsDNA Titers in Patients with B Cell Recovery

Session Information

Category: Glomerular

  • 1005 Clinical Glomerular Disorders

Authors

  • Gomez Mendez, Liliana Michelle, UCSF, San Francisco, California, United States
  • Cascino, Matthew, Genentech, South San Francisco, California, United States
  • Rovin, Brad H., Ohio State University , Columbus, Ohio, United States
  • Brakeman, Paul R., UCSF, San Francisco, California, United States
  • Garg, Jay P., Genentech, South San Francisco, California, United States
  • Brunetta, Paul, Genentech, South San Francisco, California, United States
  • Dragone, Leonard Louis, Genentech, South San Francisco, California, United States
Background

B-cell activating factor (BAFF) increases following B cell depletion by rituximab (RTX) in lupus. This has been associated with increased anti-dsDNA titers and may contribute to lupus relapses. The relationship between treatment with RTX, changes in BAFF, and anti-dsDNA titers at time of B cell recovery has not been previously assessed using clinical trial data.

Methods

We analyzed data from LUNAR (NCT00282347), a randomized trial that compared the addition of RTX or placebo (PBO) to background therapy of mycophenolate mofetil and steroids for the treatment of LN. At 78 weeks (12 months after final RTX infusion), linear regression was used to estimate the association between treatment, change in BAFF, B cell recovery, and anti-dsDNA titers. B cell recovery was defined as CD19 counts ≥ 50 cells/µL.

Results

Complete data was available for 99 patients. At baseline, median BAFF did not differ by treatment arm (3145 vs 3150 pg/mL) but was higher in patients who were anti-dsDNA positive (3540 vs 2380 pg/mL, p=0.002). BAFF increased in both arms at week 28 vs baseline (PBO 1674 pg/mL, p<0.001; RTX 4940 pg/ml, p<0.001). Between weeks 28 and 78, BAFF fell in both treatment arms but did not return to baseline. At week 78, 25 RTX patients had B cell recovery. In this subgroup, every increment of 1000 pg/mL in BAFF predicted a 9% higher anti-dsDNA at week 78 (p=0.019). This association was not seen among patients without B cell recovery or in PBO arm. However, absolute anti-dsDNA levels at week 78 were similar in the B cell recovery group vs patients without recovery (42 vs 24 IU/mL, p=0.8). Furthermore, anti-dsDNA levels were significantly lower in RTX-treated patients than PBO patients at week 78 (37 vs 66 IU/mL p=0.03).

Conclusion

BAFF increased in both treatment arms of the LUNAR trial, but with a larger increase in the RTX arm. In patients with B cell recovery at week 78, increased BAFF levels correlated with increased anti-dsDNA levels. Despite higher BAFF, anti-dsDNA levels remained significantly lower in the RTX group compared to the PBO group throughout 78 weeks. Therefore, the overall effect RTX has on lowering antibody titers may offset the effects of RTX-induced increases in BAFF.

Funding

  • Commercial Support