B cell–depleting therapy with rituximab or ofatumumab in immunoglobulin A nephropathy or vasculitis with nephritis

Abstract

BackgroundApproximately 30% of adult patients with immunoglobulin A (IgA) nephropathy (IgAN) or IgA vasculitis with nephritis (IgAVN) develop end-stage renal disease during long-term follow-up. In particular, patients with nephritic–nephrotic syndrome have an increased risk of rapid progression. Conventional immunosuppressive therapy with corticosteroids (CSs) may be insufficient for disease control and is associated with a number of side effects. Rituximab (RTX) has been shown to be well tolerated and effective in a range of glomerular diseases, but there is little information on its therapeutic potential in IgAN. The humanized anti-CD20 monoclonal antibody ofatumumab (OFAB) may be an alternative drug for patients intolerant or unresponsive to RTX, but so far there is no report on its use in IgAVN or IgAN.MethodsWe describe clinical outcomes after 17–22 months in four adult patients with biopsy-confirmed IgAVN or IgAN treated with RTX or OFAB as well as CS soon after diagnosis. All presented with nephritic–nephrotic syndrome and one had crescentic IgAN. Rebiopsy was performed in two cases.ResultsRTX and OFAB were well tolerated. Albuminuria was <250 mg/day in three patients at last evaluation and two regained normal renal function. In all cases, renal function improved after therapy. In one patient with severe IgA vasculitis, rebiopsy showed disappearance of subendothelial but not mesangial immune complexes. In the case with crescentic IgAN, rebiopsy after 9 months showed no active necrotic lesions.ConclusionsB cell–depleting therapy may be an alternative treatment for patients with IgAN or IgAVN and nephritic–nephrotic syndrome. A possible CS-sparing effect should be further evaluated in randomized controlled clinical trials.

Is it the time to offer rituximab as a cost-benefit treatment for immunoglobulin A nephropathy? A short-review to current concepts

“…Accordingly in the study by Lundberg et al (20), electron microscopic examination of the repeated renal biopsy 50 months after the rituximab therapy revealed the disappearance of subendothelial. Reduced immunofluorescence staining for IgA after treatment with rituximab was established by Chancharoenthana et al (16).…”

“…The varying outcome in crescentic IgAN has been reported by Lv et al (21). This contradiction between these studies may be explained by the fact that initial plasma exchange may have further improved renal function in the investigation by Lundberg et al (20). The rationale behind these results, which has had favorable findings in some earlier reports on moderate to severe IgAN, is to rapidly delete circulating IgAcontaining immune complexes (22).…”

“…IgAN frequently leads to progressive chronic kidney disease (CKD), thus it requires much attention to prevent or slow the course of disease. While there are some benefits to adding immunosuppressive agents to standard therapy in IgAN, several studies have questioned safety and efficacy of these agents (3)(4)(5). B cell depletion potentially offers a new therapy (5).…”

“…While there are some benefits to adding immunosuppressive agents to standard therapy in IgAN, several studies have questioned safety and efficacy of these agents (3)(4)(5). B cell depletion potentially offers a new therapy (5). Rituximab (RTX) is a monoclonal antibody that specifically recognizes a large extracellular loop in CD20 molecule of B cells (6,7) and leads to significant depletion of these cells (8,9).…”

“…Lundberg et al (20) provided only two repeated courses in patients with proteinuria <3.5 g/d and four courses of this drug in the heavily nephrotic peoples. Based on the findings of pharmacokinetic studies performed in nephropathy has been shown that proteinuria may have an effect on the half-life of rituximab (27).…”