Rituximab for Idiopathic and IgG4-Related Retroperitoneal Fibrosis

Background/Purpose: Untreated retroperitoneal fibrosis (RPF) can lead to chronic back and flank pain and/or renal failure. The mainstay of treatment for non-malignant (IgG4-related disease [RD] or idiopathic) RPF is glucocorticoid (GC) therapy which often has insufficient efficacy or is complicated by toxicity.  We performed a retrospective review of patients with RPF treated with rituximab (RTX).

Methods: We reviewed the database of the Massachusetts General Hospital’s Center for IgG4-RD and identified all patients with RPF treated with RTX who had follow-up (2010-2016). RPF was diagnosed by CT or MRI following commonly accepted radiographic criteria (Lancet 2011;378:338). Demographics, date of diagnosis, symptoms, co-morbidities, laboratory values, use of stents or percutaneous nephrostomy (PCN) tubes, biopsy results, and symptomatic response to treatment were collected from the database. A board-certified radiologist (AS) reviewed baseline and follow-up imaging. Response to treatment was defined as symptom improvement and/or radiographic improvement defined as reduction in lesion size in at least two radiographic planes (Lancet 2011;378:338).

Results: Twenty-six RPF patients received RTX (Table 1). The median age was 55 years (IQR 43, 58) and a majority was male (85%) and former or current smokers (85%). Pathology was available in 20 (77%) patients. In 17/20 (85%) patients, diagnostic features of IgG4-RD were present; in the remaining 3/20 (15%), malignancy and infection were ruled out.  Of the six patients not biopsied, 2 (33%) met clinical diagnostic criteria for IgG4-RD and four had typical radiographic idiopathic RPF with no clinical suspicion of infection or malignancy.  Ten of 26 (39%) patients had previously failed GC therapy. RTX was used as monotherapy in 20 (77%) patients and in combination with GC in 6 patients (23%); ten (39%) patients required ureteral stents or PCN tubes. Of the 21 patients with baseline symptoms (e.g., pain), all (100%) had improvement.  Twenty-two (88%) of the 25 patients with follow-up imaging had radiographic improvement; in the remaining 3 patients, the RPF remained stable. Of the 10 patients with a stent or PCN, 4 (40%) had it successfully removed.  Four of the six patients whose stents or PCN were not removed had disease duration for greater than 1 year prior to RTX.  

Conclusion: In this retrospective study of patients with idiopathic or IgG4-related RPF, peripheral B cell depletion with RTX was highly effective, used as monotherapy in the majority of patients. A striking proportion (85%) of patients were current or former smokers. Future research could explore whether patients with disease for greater than 1 year prior to RTX respond less well.