Background/Purpose: B cell activating factor (BAFF) is an important modulator of B cell development and proliferation and is secreted by neutrophils, monocytes, macrophages and dendritic cells. Tabalumab, a monoclonal antibody that neutralizes both membrane-bound and soluble BAFF, has previously been shown to reduce the signs and symptoms of rheumatoid arthritis (RA)^1,2. In this open label, uncontrolled , extension study, we examined the effect of tabalumab on B cell populations,  serum immunoglobulins (Ig) and the relationship between these parameters and infections.

Methods: One hundred eighty-six patients (pts) who completed one of two 24 week phase 2 trials of tabalumab versus placebo were elligible for this study, and 182 (98%) of those pts enrolled. Pts were methotrexate  or TNF antagonist inadequate responders. All pts received open label 60 mg subcutaneous tabalumab every 4 weeks for 48 weeks. The dose could be increased to 120 mg and, if necessary, decreased to 60 mg one time at the investigators’ discretion. B cell populations and serum Igs were compared to their pre-treatment baseline from the initial phase 2 studies. Total  B cell counts were monitored during a post study follow-up period.

Results: Sixty pts (33%) received 60 mg throughout the study, and 121 pts (66%) escalated to 120 mg at different times (60/120 mg group).One pt escalated to 120 mg then returned to 60 mg. In all groups, total B cell and mature naïve B cell  counts gradually declined over time but were not depleted at week 52 (table). Memory B cells increased  ~ 100% over baseline at week 12 and returned to ~ 60-70% over baseline at week 52. Sixty-six pts had total B cell counts < 43 cells/μl and < 50% of baseline at week 52 or after and the Kaplan-Meier estimate of median time to recovery after the last injection was 40.6 weeks (CI: 39.6-51.3).  All of these pts who completed follow up (n=47) recovered by 66 weeks. Among pts whose B cells decreased below  50% of baseline at any time during the treatment period, 37% had infections compared to 53% among pts whose  B cells did not. Serum Igs (IgA, IgM, IgG) decreased for all groups at week 52 (table).  Eleven pts had treatment-emergent  serum Ig levels below the lower limit of normal (LLN) during the treatment period with no concurrent infections.

Conclusion:

Tabalumab treatment reduced total B cells, mature naïve B cells and serum Igs, while memory B cells were increased. Total B cells were only partially depleted and recovered in all pts during the post treatment follow -up period.  There was no indication that reductions in B cells or in serum Igs below the LLN were associated with an increased frequency of infections. Additional studies will help further understand the effect of tabalumab treatment on B cells, serum Igs  and adverse events.

1. Genovese et al. Ann Rheum Dis 2011;70(Suppl3):611

2. Genovese et al. Ann Rheum Dis 2011;70(Suppl3):71

Change from Baseline in B Cell Populations and Serum Immunoglobulins at Week 52†
	60 mg (N=60)	60/120 mg (N=121)	All pts* (N=182)
Total B cells         (CD20+)	(n=59) -41.1 %	(n=118) -34.7 %	(n=178) -37.1 %
Mature naïve B cells (CD19+ IgD+ CD27-)	(n=59) -65.8 %	(n=118) -72.0 %	(n=178) -70.1 %
Memory B cells    (CD19+ IgD- CD27+)	(n=59) 58.4 %	(n=118) 78.6 %	(n=178) 71.8 %
Serum IgA	(n=57) -14.7 %	(n=121) -13.5 %	(n=179)  -13.8 %
Serum IgG	(n=57) -10.9 %	(n=121) -11.2 %	(n=179) -11.1 %
Serum IgM	(n=57) -18.7 %	(n=121) -19.4 %	(n=179) -19.1 %
†Last observation carried forward method was used to impute missing values at week 52. Small ‘n’ indicates the number of patients with both baseline and post baseline assessments *1 pt that had dose escalated to 120 mg and decreased back to 60 mg is included in ‘all pts’ category

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/changes-in-b-cell-populations-and-serum-immunoglobulins-and-their-relationship-to-infections-in-a-one-year-uncontrolled-open-label-study-of-tabalumab/