Background/Purpose: Rituximab (RTX) is an efficacious alternative to cyclophosphamide for treatment of granulomatosis with polyangiitis (GPA). However, relapses have been observed, long-term efficacy is not known and strategies to reduce risk of relapses after RTX-induced remission are just beginning to be explored. This study was performed to evaluate long-term efficacy and risks of RTX when used alone or in conjunction with another immunosuppressive agent other than steroids.

Methods: Single center retrospective review: patients (pts) with GPA who fulfilled 1990 ACR criteria and were treated with at least 1 course of RTX. Subset analysis included the effect of receiving a 2^nd immunosuppressive agent, other than steroids. Remission defined as BVAS/WG=0. 

Results: Total of 110 pts, 56 F, 54 M, received 211 courses of RTX. In 77% of cases, 2 infusions of 1gm were given 2 weeks apart. Mean age at 1^st RTX (RTX1) was 50 yrs. Indications for RTX1 were: new onset (5), relapsing (85), persistent disease (15) and remission maintenance (5). At the time of RTX1, median BVAS/WG was 4 (range 1-11). Median follow up after RTX1 was 23 months (mo) (range 1-137). Apart from 3 pts with worsening or persistent lung involvement, complete remission was achieved in 99/102 pts with active disease and available information. 45 pts (42%) received only 1 course of RTX and remained in remission during follow up (median 10mo); 66% of these pts were on 2^nd agent after RTX1. Among 21 pts followed >2 years after RTX1, 38% sustained long-lasting remissions, for up to 6 yrs. Fifty pts experienced 79 relapses after RTX1. Median time to 1^st relapse was 13mo (range 2.5-66). Median dose of prednisone at time of relapse vs without relapse was 5 mg (range 0-30) vs 3.5 mg (range 0-25), respectively. The incidence of relapse over time after RTX1 was lower in patients who received a 2^nd agent (figure; p=0.006). Among pts who received a 2^nd agent (52), 42% relapsed vs. 65% of those who did not receive a 2^nd agent (43). The 2^nd agents used were: AZA (29), MTX (15) and MMF (8). Median follow up in the 2 groups was 13 and 11mo and median time to relapse was 16mo vs 11mo, respectively. Of pts who relapsed while on a 2^nd agent, 27% had at least 1 major organ involved per BVAS/WG vs 39% of pts who were not on a 2^nd agent. Serious adverse events did not differ between groups. Serious infections occurred after RTX1 in 7.6% (2^nd agent subset) and 6.9% (no 2^nd agent subset), respectively. At the time of relapse, 42.2% of pts were peripheral blood B cell depleted (data for 45 relapses in 31 pts).

Conclusion: RTX is a very effective remission-inducing agent for GPA. 97% of treated pts achieved remission. Within a subset treated once and followed for > 2 yrs, remissions endured for 2-6 yrs in 38%. While 46% of pts had ≥1 relapses, use of a 2^nd immunosuppressive agent diminished likelihood of relapse. A 2^nd agent did not result in a greater number of serious adverse events.