Session Information
Date: Wednesday, October 24, 2018
Title: 6W021 ACR Abstract: Misc Rheumatic & Inflam DZ II (2970–2975)
Session Type: ACR Concurrent Abstract Session
Session Time: 11:00AM-12:30PM
Background/Purpose:
Despite a low incidence of hypogammaglobulinemia (HG) in clinical trials using rituximab (RTX), HG occurs in follow-up of patients with autoimmune disease.
Immunoglobulin replacement therapy (IRT) has been used to reduce infection rates but there is a paucity of data on its efficacy and impact on longer-term outcomes.
We examined the characteristics of patients with RTX associated HG in autoimmune disease, and their long-term outcomes with and without IRT.
Methods:
Patients attending a Vasculitis and Lupus clinic, who received RTX for autoimmune disease between 2004 and 2012, with an immunoglobulin G (IgG) <7 g/L on at least 2 occasions were included in this retrospective case note review. Patients were categorized into nadir IgG subgroups of <3 g/L, 3 to <5 g/L and 5 to <7 g/L. Categorical variables are summarised as proportions, and continuous variables as mean ± standard deviation or median [interquartile range (IQR)]. Differences between nadir IgG subgroups were assessed by Chi squared tests and trends across subgroups confirmed by Somer’s D tests. Continuous variables were compared using analysis of variance (ANOVA), Kruskall-Wallis and Wilcoxon sign ranked tests as appropriate. Analyses were performed in SPSS.
Results:
Of 142 patients, 101 (71.1%) had ANCA associated vasculitis, 18 (12.7%) systemic lupus erythematosus and 23 (16.2%) other diagnoses. Most received RTX for relapsing (69.3%) or refractory (25.0%) disease. Mean follow-up was 97.2 months from first RTX.
Progressive HG was observed. Median time to IgG <5 g/L was 22.5 months [IQR 3.0 to 61.5] and to IgG <3 g/L was 24.5 months [IQR 4.0 to 80.75].
Mycophenolate use prior to RTX and prednisolone use following RTX were associated with a lower nadir of IgG (Table 1). These associations were confirmed by Somer’s D tests.
IRT was commenced in 29 patients, the majority (65.5%) with IgG <3 g/L. It was well tolerated, with 2 discontinuing due to adverse effects. IRT was withdrawn without excess recurrent infections in 5 patients.
IRT was associated with a reduction in annual infection rates (Table 2). Severe infections (requiring intravenous antibiotics or hospital admission) were uncommon, with no change with the use of IRT.
Conclusion:
RTX associated HG is progressively identified with longer term follow-up. Although annual infection rates were low, in patients with recurrent infection, use of IRT was associated with a reduction in infection burden.
Table 1
|
|
All (n = 142) |
nadir IgG 5 – 7 g/L (n = 40) |
nadir IgG 3 – 5 g/L (n = 66) |
nadir IgG < 3 g/L (n = 36) |
p |
|
|
|||||
|
Pre-RTX immunosuppression |
|||||
|
Cyclophosphamide |
107/142 (75.4) |
29/40 (75.0) |
49/66 (74.2) |
28/36 (77.8) |
0.92 |
|
cum CYC |
12.0 [6.0 – 26.0] |
12.0 [5.8 – 27.8] |
11.5 [6.0 – 17.3] |
11.0 [5.7 – 27.0] |
0.91 |
|
Azathioprine |
88/141 (62.4) |
27/40 (67.5) |
39/65 (60.0) |
22/36 (61.1) |
0.73 |
|
Mycophenolate |
94/141 (66.7) |
25/40 (62.5) |
39/65 (60.0) |
30/36 (83.3) |
0.05* |
|
Methotrexate |
36/141 (25.5) |
10/40 (25.0) |
20/65 (30.8) |
6/36 (16.7) |
0.30 |
|
PLEX |
16/141 (11.3) |
4/40 (10.0) |
5/65 (7.7) |
7/36 (19.4) |
0.19 |
|
Number of prior IS medications |
2.9 ± 1.7 |
2.9 ± 1.3 |
2.8 ± 1.8 |
3.2 ± 1.7 |
0.57 |
|
|
|||||
|
Cumulative RTX |
9.0 ± 5.1 |
8.5 ± 4.7 |
9.8 ± 5.6 |
8.1 ± 4.4 |
0.23 |
|
|
|||||
|
Glucocorticoid use (prednisolone) |
|||||
|
Baseline |
115/121 (95.0) |
36/38 (94.7) |
53/55 (96.4) |
26/28 (92.9) |
0.78 |
|
6 months |
120/133 (90.2) |
31/39 (79.5) |
61/63 (96.8) |
28/31 (90.3) |
0.02 |
|
12 months |
113/137 (82.5) |
27/39 (69.2) |
56/64 (87.5) |
30/34 (88.2) |
0.04* |
|
24 months |
98/133 (73.7) |
22/37 (59.5) |
48/62 (77.4) |
28/34 (82.4) |
0.06* |
|
|
|||||
|
CYC: cyclophosphamide, PLEX: plasma exchange, IS: immunosuppressive mean ± standard deviation, median [IQR], proportion (%) Chi squared test p-values presented for proportions; * Somer’s D test p-value ≤0.05 |
|||||
Table 2
|
|
All (n = 142) |
nadir IgG 5 – 7 g/L (n = 40) |
nadir IgG 3 – 5 g/L (n = 66) |
nadir IgG < 3 g/L (n = 36) |
p |
|
|
|||||
|
No IRT |
113/142 (79.6) |
39/40 (97.5) |
57/66 (86.4) |
17/36 (47.2) |
<0.001* |
|
Infections/yr |
0.44 [0.15 – 0.99] |
0.38 [0.14 – 0.94] |
0.48 [0.15 – 1.04] |
0.50 [0.00 – 1.12] |
0.34 |
|
Severe inf/yr |
0.00 [0.00 – 0.24] |
0.12 [0.00 – 0.24] |
0.00 [0.00 – 0.26] |
0.00 [0.00 – 0.09] |
0.39 |
|
|
|||||
|
IRT |
29/142 (20.4) |
1/40 (2.5) |
9/66 (13.6) |
19/36 (52.8) |
<0.001* |
|
Infections/yr (no IRT) |
1.02 [0.54 – 1.88] |
2.49 |
1.02 [0.57 – 1.98] |
0.89 [0.44 – 1.85] |
– |
|
Infections/yr (IRT) |
0.13 [0.00 – 0.35] |
|
|
|
<0.001 α |
|
Severe inf/yr (no IRT) |
0.19 [0.00 – 0.45] |
1.17 |
0.28 [0.00 – 0.66] |
0.07 [0.00 – 0.41] |
– |
|
Severe inf/yr (IRT) |
0.00 [0.00 – 0.89] |
|
|
|
0.97 α |
|
|
|||||
|
median [IQR], proportion (%) α IRT vs no IRT; Wilcoxon sign ranked tests Chi squared test p-values presented for proportions; * Somer’s D test p-value ≤0.05 |
|||||
To cite this abstract in AMA style:
Tieu J, Gopaluni S, Smith R, Jayne D. Rituximab Associated Hypogammaglobulinemia in Autoimmune Disease: Long Term Outcomes [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/rituximab-associated-hypogammaglobulinemia-in-autoimmune-disease-long-term-outcomes/. Accessed .« Back to 2018 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/rituximab-associated-hypogammaglobulinemia-in-autoimmune-disease-long-term-outcomes/