Since immunosuppressive therapy improved the outcome of AAV by reducing early death due to active disease, infections during follow-up have drawn increasing attention and remained a major issue in the management of AAV. Rituximab is a relatively new and effective treatment regimen for AAV. But severe infections were not rare in this subgroup of patients, and there seemed to be more infections than patients with other renal diseases [16–19] or rheumatic and musculoskeletal diseases (RMDs) [26] received rituximab administration. In RMDs patients, the event rate was 9.8 per 100 person-years [26], while in Kronbichler’s study, severe infections occurred in 25.52% patients and the event rate was 26.06 per 100 person-years in AAV patients receiving rituximab therapy [20]. In general, patients with AAV may have an increased risk of developing severe infections following rituximab therapy. Kidney involvement is quite common in AAV but renal dysfunction was unremarkable in Kronbichler’s study cohort [20]. The majority of patients had renal insufficiency in our cohort, so the current study could further extend the previous results of this topic.
Although the dose of rituximab in our study was remarkably lower as compared with MAINRITSAN study (followed for 28 months, fixed rituximab dose 3000 mg) [13] and Kronbichler’s study [20], severe infections were still very common, occurring in nearly 40% of the patients. Rituximab is an anti-CD20 monoclonal antibody resulting in B cell depletion. Recently, Salviani reported at the 19th International Vasculitis and ANCA Workshop that diagnosis of MPA and renal dysfunction significantly correlated to persistent B cell depletion after rituximab therapy [27]. There might be two reasons for the relatively high proportion of severe infection in our study. First, in China, there is a striking preponderance of MPA, constituting about 80% of patients with AAV [28]. Second, the majority of patients in the current study had renal insufficiency.
We found that pulmonary infections were the leading infectious complications (90%), which was consistent with previous studies [20, 29], and most infections occurred during the first 12 months of follow-up (80%), even within the first few months. Therefore, clinical manifestations and assessment of respiratory infection deserves more attention, especially during initial follow-up. Since most of the infections occurred during the first year after rituximab administration, we investigated the risk factors within this period. It was found that severe infection was independently associated with age and serum creatinine level. Older patients with renal insufficiency may benefit from a less intense rituximab treatment regimen, since they might be particularly vulnerable to severe infections, while they are more likely to have a very long-lasting B cell depletion.
To the best of our knowledge, this is first cohort study for infection complications after rituximab treatment in Chinese AAV patients, and the finding of association between renal function and severe infections further extended previous studies. However, there were several limitations of this study. First, since it was a retrospective study, data of continuous monitoring of B cells were incomplete, also the immunoglobulin levels at baseline and during follow-up. Second, only a few of the infectious cases had a positive microbial result.