Rituximab associated vasculitis flare: incidence, predictors and outcome
Résumé
To report the incidence, predictor, and outcome of rituximab-associated autoimmune disease flare.
METHODS: We conducted a retrospective study in a tertiary referral centre from 2005 to 2015. Disease flare was defined as the onset of a new organ involvement or worsening of autoimmune disease, within 4 weeks following rituximab.
RESULTS: Among the 185 patients, we identified 7 (3.4%) disease flares. All were due to type II mixed cryoglobulinemia vasculitis. Vasculitis flare occurred after a median time of 8 [2; 16] days following rituximab infusion and included acute kidney insufficiency (n=7), purpura (n=7), gastrointestinal tract involvement (n=4), and myocarditis (n=1). Patients with rituximab-associated cryoglobulinemia vasculitis flare had more frequently renal involvement (p=0.008), B cell-lymphoproliferation (p=0.015), higher level of cryoglobulin (2.1 vs 0.4 g/l, p=0.004) and lower level of C4 level (0.02 vs 0.05, p=0.023) as compared to patients without flare after rituximab (n=43). Four patients (57%) died after a median time of 3.3 months. The 1-year survival rate was poorer in patients with vasculitis flare after rituximab as compared to their negative counterpart [43% (95% CI: 18-100) vs 97% (95% CI: 92-100), p<0.001]. Immunofluorescence analysis of kidney biopsy in patients with rituximab associated vasculitis worsening highlighted the presence of rituximab, IgM, and IgG1 positive staining of endomembranous deposits and thrombi within kidney lesions.
CONCLUSION: Rituximab-associated involves cryoglobulinemia vasculitis and is associated with high mortality rate. We provided evidence that kidney lesions are due to immune complex deposition and to glomerular obstruction by cryoglobulinemia and rituximab.