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.


Effect of Belimumab, a B-Lymphocyte StimulatorSpecific Inhibitor, on Functional Antibodies to Pneumococcal, Tetanus, and Influenza Vaccines.

Chatham6,  W. W., Wallace1,  D. J., Stohl11,  W., Latinis8,  K., Manzi10,  S., McCune9,  J., Tegzova3,  D.

Cedars-Sinai/UCLA, Los Angeles, CA
University of Pittsburgh School of Medicine, PA
USC Keck School of Medicine, Los Angeles, CA
Human Genome Sciences, Inc, Rockville, MD
Institute of Rheumatology and Rheumatological Clinic, Prague, Czech Republic
Instituto Jalisciense de Investigacion Clinica, Guadalajara, Mexico
Oklahoma Center for Arthritis Therapy & Research, Tulsa, OK
UAB Arthritis Clinical Intervention Program, Birmingham, AL
University of Chicago, IL
University of Kansas Medical Center, Kansas City, KS
University of Michigan Health System, Ann Arbor, MI

Purpose:

To evaluate the effect of belimumab plus standard of care (SOC) on antibodies against pneumonia, tetanus, and influenza in SLE patients with history of vaccination against these pathogens prior to study entry.

Methods:

The phase 3, multicenter, randomized, double-blind, placebo-controlled, 76-wk BLISS-76 study evaluated the efficacy and safety of belimumab 1 or 10 mg/kg (IV infusion over 1 h on d 0, 14, and 28, and every 28 d thereafter through 72 wk) plus SOC vs placebo plus SOC in patients with seropositive SLE (ANA >=1:80 and/or anti-dsDNA >=30 IU/mL; NCT00410384). History of receiving pneumococcal, tetanus, and influenza vaccines was obtained at screening. Patients receiving a pneumococcal (n=73) or tetanus (n=81) vaccine within 5 y prior to d 0, or an influenza vaccine (n=146) within 1 y prior to d 0, were tested for vaccine antibody levels on d 0 and at wk 52. Immunoglobulin-G antibodies were measured for each vaccine (multi-analyte immune detection for pneumonia, enzyme-linked immunosorbent assay for tetanus, and hemagglutination inhibition test for influenza). Endpoints used to determine the impact of belimumab on vaccine responses included % change in antibody levels from baseline to wk 52 in patients with pre-existing antibodies, and proportion of patients with protective antibodies at baseline who maintained protective levels at wk 52.

Results:

Consistent with the preservation of the memory B-cell compartment (CD20+/27+ B cells), belimumab did not cause a statistically significant decrease in pre-existing antibodies to pneumococcal and tetanus vaccines; most patients were able to maintain protective titers to these vaccines, and changes were similar across treatment groups (table). Pre-existing antibody responses to seasonal influenza vaccines were generally not affected by treatment with belimumab, although a statistical, but not clinically relevant, difference (<1-fold median change in titers) between treatment groups was observed for some antigens; the percentages of patients that maintained protective specific titers at the end of 52 wk were similar in the belimumab and placebo treatment groups.

Conclusion:

In this study, treatment with belimumab did not significantly affect the ability of SLE patients to maintain a protective immune response to prior immunizations.

Table.% Immunoglobulin-G Change in Response From Wk 0 to 52

Antipneumococcala SOC + Placebo, n = 24SOC + Belimumab 1 mg/kg, n = 27SOC + Belimumab 10 mg/kg, n = 22
9 (9N)Mean ± SE-10.3 ± 6.9-1.5 ± 7.5-11.9 ± 3.3
 Median0.00.00.0
 %Protectiveb100.0%100.0%92.3%
14 (14)Mean ± SE-8.3 ± 7.0-1.2 ± 4.0-10.1 ± 5.1
 Median-8.60.0-10.3
 %Protectiveb100.0%95.2%94.7%
19 (19F)Mean ± SE-5.3 ± 7.2-3.5 ± 5.8-10.3 ± 5.1
 Median-3.3-2.6-7.9
 %Protectiveb100.0%100.0%93.8%
23 (23F)Mean ± SE-8.1 ± 8.5-2.4 ± 6.4-6.6 ± 3.9
 Median-2.30.00.0
 %Protectiveb94.4%95.2%100.0%
Antitetanus SOC + Placebo, n = 29SOC + Belimumab 1 mg/kg, n = 29SOC + Belimumab 10 mg/kg, n = 23
 Mean ± SE-12.0 ± 5.118.5 ± 36.2-11.4 ± 7.1
 Median-16.7-17.5-14.3
 %Protectiveb81.8%95.8%78.6%
Anti-influenza (2006–7) SOC + Placebo, n = 15SOC + Belimumab 1 mg/kg, n = 22SOC + Belimumab 10 mg/kg, n = 12
New CaledoniaMean ± SE38.9 ± 18.726.6 ± 21.21.2 ± 19.0
 Median0.00.0-18.3
 %Protectiveb93.3%95.2%100.0%
WisconsinMean ± SE916.4 ± 842.43.8 ± 17.6-11.4 ± 12.3
 Median0.00.00.0
 %Protectiveb100.0%100.0%100.0%
MalaysiaMean ± SE43.0 ± 18.5-11.4 ± 7.8a520.8 ± 525.6
 Median0.00.00.0
 %Protectiveb100.0%100.0%100.0%
Anti-influenza (2007–8) SOC + Placebo, n = 29SOC + Belimumab 1 mg/kg, n = 41SOC + Belimumab 10 mg/kg, n = 27
Soloman Island 1_2_3Mean ± SE2.6 ± 26.3-4.8 ± 11.2-8.8 ± 16.5
 Median-20.6-10.0-37.5
 %Protectiveb100.0%100.0%100.0%
Wisconsin 1_2_3Mean ± SE63.1 ± 36.925.5 ± 19.8-4.9 ± 15.1c
 Median0.00.0-20.6
 %Protectiveb100.0%100.0%100.0%
Malaysia 1_2_3Mean ± SE-7.8 ± 11.3-2.1 ± 7.8-32.0 ± 5.5
 Median0.00.0-50.0
 %Protectiveb100.0%97.1%92.6%
aIncludes several representative antigen serotype results;bpercentage of patients maintaining protective antibody level at wk 52;c1 patient did not have data available at wk 52 (n = 26).
* p < 0.05 for the comparison between active and placebo.
SE, standard error.

To cite this abstract, please use the following information:
Chatham, W. W., Wallace, D. J., Stohl, W., Latinis, K., Manzi, S., McCune, J., et al; Effect of Belimumab, a B-Lymphocyte StimulatorSpecific Inhibitor, on Functional Antibodies to Pneumococcal, Tetanus, and Influenza Vaccines. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :457
DOI: 10.1002/art.28226

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