Abstract 261: Immunoglobulin Levels and Infection Rates in Patients with Rheumatoid Arthritis (RA) Treated With Repeated Courses of Rituximab
Authors
M Genovese, P Emery, E Ruderman, E Keystone, D Furst, R Van Vollenhoven, M Sweetser, F Magrini, E Tindall, T Shaw, D Yocum.
Purpose:
A decrease in immunoglobulins (Igs) has been reported with repeated courses of rituximab (RTX). This study associations between low Igs and infections in 1053 patients (pts) receiving RTX in clinical studies.
Methods:
RA pts who participated in any of 3 randomized controlled trials were eligible to enter open-label extensions and receive further courses of RTX (1000 mg RTX on Days 1 and 15). Repeat treatment could occur a minimum of 16 weeks after the last course. Total Ig, IgM and IgG, were measured every 8-12 weeks after each course.
Results:
1053 RA pts had received at least 1 course (C1) of RTX, for a total exposure of 2,438 pt-years. A total of 957 pts had been followed for >1y, 701 for >2, and 120 >3 yrs. 684 received C2, 400 received C3, and 142 pts received C4. Of the 1053 pts, 761 (72%) always had normal IgG and IgM, while 261 (25%) had at least one low IgM and 67 (6%) at least one low IgG. By 24 weeks following each course, 10.1% (C1) 20.4% (C2), 20.9% (C3) and 31.4% (C4) of pts treated with RTX had at least one IgM <LLN, respectively. In the same population, 1.4%, 3.5%, 4.0% and 4.3% had at least one IgG <LLN. The rate of serious infections after C1, C2, C3, and C4 remained stable at 5.36, 4.60, 6.34, and 5.41 events/100 pt-yrs. Of the 761 pts with normal IgG and IgM, the rate of serious infections overall was 4.9 (CI: 3.93-6.06) compared with 6.4 (CI: 4.74-8.68) for pts who had at least one IgM <LLN and 6.8 (CI: 4.03-11.49) for those who had at least one IgG<LLN. The types of serious infections varied and did not fall into any particular pattern. After at least one IgM or IgG<LLN, there was a trend toward a higher rate of serious infection, particularly in pts with at least one low IgG (Table). However, noting the limited exposure and wide CI, this analysis of infection rates before and after a low Ig level was unable to detect a difference in rates of infections and serious infections.
Rate of infections before and after Ig levels fell below LLN |
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Pts with IgM<LLN |
Pts with IgG<LLN |
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All Exposures (N=1053) |
Before |
After |
Before |
After |
Total pt exposure, yrs |
2438 |
252 |
403 |
81 |
125 |
Infections, n |
2040 |
289 |
344 |
88 |
109 |
Infections/100 pt-yr (95% CI) |
83.7 |
114.6 |
85.5 |
109 |
87.2 |
Serious Infections, n |
131 |
14 |
28 |
3 |
11 |
Serious Infections/100 pt-yr (95% CI) |
5.4 |
5.6 |
7.0 |
3.7 |
8.8 |
Conclusions:
In this further update on the long-term treatment of RA pts with RTX, some patients developed at least one episode of lower Ig levels, and there is a trend toward higher rates of serious infection in this population.
Editorial comment:
We have previously reported results last year from the efficacy and safety database of rituximab that showed decreasing Ig levels with repeated courses of rituximab. This study begins to evaluate whether decreases are associated with infection. While the results are not statistically significant, there is certainly a suggestion that lower Ig levels are associated with more infections as might be expected. On the basis of these results, it is probably important to monitor Ig levels over time especially in patients with repeated rituximab exposure. If Ig levels begin to drop, this may be a signal to be even more vigilant in infection surveillance.
