Relapse occurring during rituximab (RTX)-based maintenance remains a clinical challenge in patients with ANCA-associated vasculitis (AAV). Alternative or adjunctive immunosuppressive strategies, including mycophenolate mofetil (MMF), have been used, but evidence on their effectiveness specifically when introduced after relapse during RTX maintenance is limited. This single-center retrospective cohort study aimed to describe clinical outcomes following first relapse during RTX maintenance, comparing patients who had MMF added to their initial post-relapse regimen with those who did not.
This was a retrospective analysis of 17 patients with AAV who experienced their first relapse while on RTX-based maintenance after remission induction. Baseline for the analysis was defined as the time of the first relapse. The study categorized patients into two groups based on the initial strategy used after relapse: an MMF-added group (n = 9) and an MMF-not-added group (n = 8). All outcomes reported are descriptive.
Post-relapse management consisted of escalation of glucocorticoids and/or re-administration of RTX. In addition, some patients received MMF as part of the initial post-relapse plan. In the MMF-added group, MMF was initiated promptly after relapse, at a median of 0.4 months (interquartile range [IQR], 0.3–0.4 months; range, 0.3–0.5 months). Exact RTX scheduling, concomitant therapies, and physician-directed glucocorticoid tapering protocols differed between patients and between groups.
The median age of the cohort was 76 years (IQR, 73–81 years). The cohort was predominantly MPO-ANCA positive: 16 of 17 patients (94.1%) were MPO-ANCA-positive. The study does not report additional demographic breakdowns, organ involvement at relapse, or prior induction regimens in the abstract.
Patients were followed for a median of 28 months (IQR, 21–33 months). After intensification of treatment at relapse, all patients in both groups achieved remission.
During the follow-up period, second-relapse events differed between groups. In the MMF-added group, no second relapses were observed. In contrast, the MMF-not-added group experienced three second relapses. These observations are reported descriptively; no causal inference or statistical adjustment is presented in the abstract.
Another notable outcome was glucocorticoid use. All nine patients in the MMF-added group discontinued glucocorticoids during follow-up. Conversely, all eight patients in the MMF-not-added group continued glucocorticoids while being managed without MMF.
Severe infections requiring hospitalization were observed only in the MMF-not-added group: three patients experienced such infections. No patients in the MMF-added group had severe infections requiring hospital admission. The abstract does not provide details on types of infections, timing relative to therapies, or infection-related outcomes beyond hospitalization.
The authors emphasize important limitations that affect interpretation. Treatment allocation to MMF was non-randomized and clinician-directed. Post-relapse treatment strategies were heterogeneous: they differed with respect to RTX scheduling, use of concomitant therapies, and the approach to glucocorticoid tapering. Because of these differences and the study's retrospective, descriptive design, the independent effect of MMF on relapse prevention, glucocorticoid discontinuation, or infection risk cannot be determined from these data.
Additional limitations not detailed in the abstract include the small sample size (n = 17), single-center setting, and limited reporting of baseline disease characteristics and comorbidities in the abstract. These factors limit generalizability and the ability to control for confounding.
In this small retrospective cohort of mostly MPO-ANCA–positive elderly patients who relapsed during RTX maintenance, adding MMF to initial post-relapse therapy was associated, in descriptive analysis, with no second relapses, successful glucocorticoid discontinuation in all treated patients, and no severe infections requiring hospitalization. By contrast, patients managed without MMF experienced three second relapses, continued glucocorticoids, and had three severe infections requiring hospitalization.
Because of non-randomized treatment allocation and heterogeneity of concurrent management strategies, these findings should be considered hypothesis generating. The authors state that prospective, controlled studies are needed to determine whether MMF provides independent benefit after relapse during RTX-based maintenance and to better define safety signals in this clinical context.
This report is a single-center retrospective study published in PLoS One. The abstract includes the authors’ affiliations and notes that the authors declared no competing interests. The study's PubMed identifier (PMID) is 42743142 and DOI is 10.1371/journal.pone.0357836. The abstract indicates open access distribution under a Creative Commons Attribution License.