Severe infections in patients with anti-neutrophil cytoplasmic antibody-associated vasculitides receiving rituximab: A meta-analysis.

INTRODUCTION: The efficacy of rituximab (RTX) for remission induction and maintenance in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) is now established, but the safety, particularly concerning severe infection risk, is not well known. OBJECTIVE: The purpose of this meta-analysis is to assess the prevalence and incidence of severe infections and the factors explaining heterogeneity in AAV patients treated with RTX. METHODS: PubMed and Embase were searched up to December 2017. Prevalence and incidence was pooled using a random-effects model in case of significant heterogeneity (I2 > 50%). Severe infection was defined as severe when it led to hospitalization, intravenous antibiotics therapy, and/or death. The heterogeneity was explored by subgroup analyses and meta-regression. RESULTS: The included studies encompassed 1434 patients with a median age of 51.9 years. The overall prevalence and incidence of severe infections was 15.4% (95% CI [8.9; 23.3], I2 = 90%, 33 studies) and 6.5 per 100 person-years (PY) (95% CI [2.9; 11.4], I2 = 76%, 18 studies), respectively. The most common infections were bacterial (9.4%, 95% CI [5.1; 14.8]). The prevalence of opportunistic infection was 1.5% (95% CI [0.5; 3.1], I2 = 58%) including pneumocytis jirovecii infections (0.2%, 95% CI [0.0; 0.6], I2 = 0), irrespective of prophylaxis administration. Mortality related to infection was estimated at 0.7% (95% CI [0.2; 1.2], I2 = 27%). The RTX cumulative dose was positively associated with prevalence of infections (13 studies, prevalence increase of 4% per 100 mg, p < .0001). The incidence of infection was negatively associated with duration of follow-up (8 studies, incidence decrease of 9% per year, p = .03). CONCLUSION: Prevalence and incidence of severe infections, mainly bacterial ones, were high in AAV patients treated with RTX. This meta-analysis highlights the need for prospective studies to stratify infectious risk and validate cumulative RTX dose and duration of follow-up as modifying factors.

Predictive factors of renal involvement in cryoglobulinaemia: a retrospective study of 153 patients.

BACKGROUND: The course of cryoglobulinaemia varies widely, from asymptomatic patients to severe vasculitis syndrome. Renal involvement (RI) is the major prognostic factor, and frequently occurs several years after diagnosis. However, predictive factors for RI are not well known. The aim of our study was to identify RI predictive factors during cryoglobulinaemia. METHODS: We retrospectively reviewed the clinical charts of a consecutive series of 153 patients positive for cryoglobulinaemia in the University Hospital of Lyon (France). RI was defined either histologically or biologically if cryoglobulinaemia was the only possible cause of nephropathy. RESULTS: Among the 153 positive patients (mean age 55 years, 37% male), cryoglobulinaemia was associated with RI in 45 (29%) patients. Sixty-five percent of patients had Type II cryoglobulinaemia, 28% had Type III and 7% had Type I. Autoimmune diseases were the most common aetiology (48%), followed by infectious diseases (18%) and lymphoproliferative disorders (13%). Membranoproliferative glomerulonephritis was the main histological pattern (93% of the 14 histological analyses). A multivariable logistic regression showed that Type II cryoglobulinaemia, a high serum cryoglobulin concentration, the presence of an IgG kappa monoclonal component and diabetes were independently associated with the risk for developing RI. CONCLUSION: We identified several factors predictive of RI in patients with cryoglobulinaemia, which were different from the diagnostic criteria for cryoglobulinaemic vasculitis. This could suggest a specific pathophysiology for RI. We suggest performing an extensive renal monitoring and ensure nephroprotection when a diagnosis of cryoglobulinaemia is made in patients with these predictive factors.

Outcome of patients with sarcoidosis refractory to TNF antagonists: a case series.

Background: Tumor necrosis factor (TNF) antagonists have been reported as an efficient third-line therapy for sarcoidosis but there is no data regarding patients who do not respond to this treatment. Objective: To report the characteristics, the outcome and the response to therapy of patients with sarcoidosis resistant to TNF antagonists. Methods: Patients from the French STAT (Sarcoidosis Treatment with Anti-TNF) registry who were classified as non-responders and who were followed-up for >1 year were included. The response to further therapies was classified as complete response, or partial response, and the others were classified as non-responders. Results: Among the 132 patients from the registry, 14 were considered as non-responders to anti-TNF. Nine patients (66% of women; mean age 48 years) were analyzed. The mean number of organs involved was 4.2. Seven patients were previously treated with more than 2 immunosuppressive treatments. The mean duration of the anti-TNF treatment was 9 months (range, 3-24). After a mean follow-up duration of 58 months (median, 35; range, 19-128) a complete response was observed in 2/9 cases, a partial response in 5/9 cases, and 2/9 cases were considered as non-responders. In all but one patient, the immunosuppressant that allowed the clinical response had previously been used. Furthermore, the dosage was not necessarily increased to gain efficacy. Non-responders were treated by corticosteroids only because of their comorbidities or noncompliance. Conclusion: In patients who do not respond to TNF antagonists, previously used immunosuppressants may be useful. Excluding a differential diagnosis, assessing compliance and testing for anti-drug antibodies should be systematic. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 371-375).