Background/Purpose: MAINRITSAN trial (NCT 00748644) results demonstrated that 500 mg of rituximab (RTX) every 6 months was superior to azathioprine (AZA) to maintain ANCA-associated–vasculitis (AAV) remission. Infection frequencies were comparable in the 2 arms, and other SAE were infrequent and resolved in most patients. This study aimed to determine whether globulin levels could be associated with infectious side effects .
Methods: Once remission was obtained with a conventional regimen, patients with newly diagnosed or relapsing AAV were randomly assigned to receive a 500-mg RTX infusion on D1, D15, 5.5 months later, then every 6 months for a total of 5 infusions over 18 months, or AZA (initial dose 2 mg/kg/d) for 22 months. The primary endpoint was the major relapse rate (EULAR/ACR criteria) at 28 months. Other outcome measures were the severe adverse event (SAE) rate (WHO definition) associated with each maintenance regimen. Infectious SAE occurring in both groups were one of the study’s secondary endpoints, as were gammaglobulin, IgG and IgM levels (1/3 missing data for valid reasons).
Results:
Among the 115 patients (50 men/65 women; mean age, 55±13 years; 92 newly diagnosed and 23 relapsers) study participants (57 RTX arm, 58 AZA arm): 87 had granulomatosis with polyangiitis, 23 microscopic polyangiitis and 5 kidney-limited diseases. The main clinical involvements at diagnosis or last relapse were: 89 (77.4%) ENT, 71 (61.7%) lung and 81 (70.4%) kidney. Major relapses occurred in 20 (17.3%) patients: 3 (3.5%) in the RTX arm and 17 (29.3%) in the AZA arm, with 3 AZA-arm deaths (1 sepsis, 1 pancreatic cancer, 1 mesenteric ischemia). Seven infectious SAE (12.2%) were recorded in the RTX arm and 8 (13.7%) in the AZA arm (Table). Respective RTX- and AZA-arm mean levels (g) of gammaglobulin were: 8.04 (±6.05) and 7.21 (±2.18) at M0, and 7.41 (±2.16) and 8.1 (±2.89) at M28; IgG were 6.06 (±2.66) and 5.44 (±1.58) at M0, and 6.87 (±2.50) in the RTX arm and 6.71 (±1.05) at M28; IgM were 0.64 (± 0.5) and 0.58 (± 0.51) at M0, and 0.44 (±0.62) and 0.6 (±0.32) at M28.
|
Infection |
RTX 57 patients |
AZA 58 patients |
|
Bronchitis |
2 |
0 |
|
Tuberculosis |
1 |
0 |
|
Bacterial pneumonia |
0 |
1 |
|
Pneumocystis jiroveci pneumonia |
1 |
0 |
|
Bacterial endocarditis |
0 |
1 |
|
Mycobacterial infection |
0 |
1 |
|
Prostatitis |
0 |
1 |
|
Herpes zoster |
1 |
1 |
|
Angiocholitis |
0 |
1 |
|
Septicemia |
0 |
1 (died) |
|
Esophageal candidiasis |
1 |
0 |
|
Campylobacter jejuni diarrhea |
1 |
1 |
Conclusion: These trial results demonstrated that 500 mg of RTX every 6 months was not only superior to AZA to maintain AAV remission but as safe as AZA. At the chosen dose, RTX did not significantly decrease gammaglobulin, IgG and IgM levels. The rare infections, observed in both groups, were reflected causes and mechanisms other than Ig levels.
Disclosure:
L. Guillevin,
Roche Pharmaceuticals,
9;
C. Pagnoux,
Roche Pharmaceuticals,
9;
A. Karras,
None;
C. Khouatra,
None;
O. Aumaître,
None;
P. Cohen,
None;
O. Decaux,
None;
H. Desmurs-Clavel,
None;
P. Gobert,
None;
T. Quemeneur,
None;
C. Blanchard-Delaunay,
None;
P. Godmer,
None;
X. Puechal,
None;
P. L. Carron,
None;
P. Y. Hatron,
None;
N. Limal,
None;
M. Hamidou,
None;
F. Maurier,
None;
T. Papo,
None;
M. Büchler,
None;
B. Bonnotte,
None;
P. Ravaud,
None;
L. Mouthon,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/relationship-between-infectious-side-effects-and-immunoglobulin-levels-in-the-maintenance-rituximab-vs-azathioprine-for-anca-associated-vasculitides-trial/