Enteric Budesonide in Transplant and Native IgA Nephropathy: Real-World Clinical Practice

Lopez-Martinez, Marina; Bermejo, Sheila; Moreso, Francesc; García-Carro, Clara; Vergara, Ander; Ramos, Natália; Perelló, Manel; Gabaldon, Alejandra; Azancot, María A; Peruga, Mónica Bolufer; Toapanta, Néstor; Bestard, Oriol; Agraz, Irene; Soler, María José

doi:10.3389/ti.2022.10693

Cited by 8 publications

(5 citation statements)

References 10 publications

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“…A recent Spanish ‘real-world’ study reported on 14 IgAN patients, five of which had IgAN recurrence in their kidney transplant, who also experienced proteinuria improvement and stabilization of eGFR loss with TRF-budesonide [32]. Again, no new safety signal was noted.…”

Section: Immunosuppressive and Anti-inflammatory Therapymentioning

confidence: 99%

Novel agents for treating IgA nephropathy

Kunter

Seikrit

Floege

2023

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of reviewIn the past, the treatment of IgA nephropathy (IgAN), which is the most common glomerulonephritis worldwide, mostly relied on blockade of the renin–angiotensin system as a central component of so-called supportive therapy as well as on high-dose systemic corticosteroid therapy.Recent findingsThe supportive treatment arm has been expanded by the addition of sodium-glucose cotransporter-2 inhibitors, hydroxychloroquine, and, most recently, endothelin A receptor blockers. Treatment with high-dose systemic corticosteroids has become more controversial, with some studies observing no benefit and others documenting the protection of kidney function. However, all recent studies on systemic corticosteroids consistently found significant toxicity. An important novel approach to IgAN, therefore, is therapy with a targeted release formulation of budesonide with preferential release in the distal small intestine, given the mounting evidence for a gut–kidney axis in the pathophysiology of IgAN. In addition, emerging new therapeutic options include a variety of complement inhibitors as well as agents targeting B-cell proliferation and differentiation.SummaryIn recent years, IgAN has become the focus of a considerable number of clinical studies that will significantly advance the development of new therapy strategies.

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Section: Immunosuppressive and Anti-inflammatory Therapymentioning

confidence: 99%

Novel agents for treating IgA nephropathy

Kunter

Seikrit

Floege

2023

Current Opinion in Nephrology &Amp; Hypertension

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“…62 In the absence of a direct comparison with other enteric-coated budesonide preparations developed for the treatment of inflammatory bowel disease, the added value of TRF-budesonide compared with the much cheaper traditional budesonide formulations is speculative. 63,64 B-Cell and Plasma Cell-Targeted treatment In a RCT of 34 patients with IgA nephropathy, rituximab failed to affect proteinuria, kidney function, serum levels of Gd-IgA1, or antibodies against Gd-IgA1, despite adequate depletion of CD20(1) B cells. 65 These results imply that the cells pivotal for Gd-IgA1 and anti-Gd-IgA1 antibody formation may be CD20 (2) and thus unaffected by rituximab.…”

Section: Therapies That Target the Formation Of Gd-iga1 And Anti-gd-i...mentioning

confidence: 99%

Section: Therapies That Target the Formation Of Gd-iga1 And Anti–gd-i...mentioning

confidence: 99%

Treatment of IgA Nephropathy: A Rapidly Evolving Field

El Karoui,

Fervenza,

De Vriese

2023

JASN

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The pivotal event in the pathophysiology of IgA nephropathy is the binding of circulating IgA-containing immune complexes to mesangial cells, with secondary glomerular and tubulointerstitial inflammation and fibrosis. The paramount difficulty in the management of IgA nephropathy is the heterogeneity in its clinical presentation and prognosis, requiring an individualized treatment approach. Goal-directed supportive care remains the bedrock of therapy for all patients, regardless of risk of progression. SGLT2 inhibitors and sparsentan should be integral to contemporary supportive care, particularly in patients with chronic kidney damage. Pending the development of reliable biomarkers, it remains a challenge to identify patients prone to progression due to active disease and most likely to derive a net benefit from immunosuppression. The use of clinical parameters, including the degree of proteinuria, the presence of persistent microscopic hematuria and the rate of eGFR loss, combined with the MEST-C score, is currently the best approach. Systemic glucocorticoids are indicated in high-risk patients, but the beneficial effects wane after withdrawal and come at the price of substantial treatment-associated toxicity. Therapies with direct impact on disease pathogenesis are increasingly becoming available. While targeted release budesonide has garnered the most attention, anti-B cell strategies and selective complement inhibition will most likely prove their added value. We propose a comprehensive approach that tackles the different targets in the pathophysiology of IgA nephropathy according to their relevance in the individual patient.

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“…Other enteric formulations of budesonide have been used in IgAN, obtaining significant proteinuria reduction [ 46 , 47 ]. However, none were tested in randomised clinical trials, and doses were not comparable to that tested with TRF budesonide.…”

Section: Targeted Therapymentioning

confidence: 99%

Systemic and targeted steroids for the treatment of IgA nephropathy

Locatelli,

Del Vecchio,

Ponticelli

2023

Clinical Kidney Journal

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Immunoglobulin A nephropathy (IgAN) is a common glomerulonephritis partially correlated with mucosal immune system dysfunction. Progressive renal failure occurs in many patients, with about 30–50% of the patients with IgAN developing end-stage kidney disease (ESKD). Many treatments have been used for decades, despite uncertainty about their effectiveness and the ideal dose. Randomised controlled trials reported that systemic glucocorticoids can be an effective treatment for patients with persistent and significant proteinuria despite renin-angiotensin system inhibitors use possibly causing systemic side effects. The primary focus of IgAN management should be based on optimised supportive care, including renin-angiotensin system (RAS) blockade and now SGLT2 inhibitors. The novel targeted-release formulation (TRF) of budesonide has been tested to reduce the adverse events of systemic steroids by delivering the drug to the distal ileum. The local efficacy of TRF-budesonide may represent a novel and promising approach to treating IgAN. Two clinical trials showed that TRF-budesonide could significantly reduce proteinuria and haematuria and possibly preserve renal function while significantly reducing the side effects. However, the limited number of treated patients and the relatively short follow-up suggest caution before considering budesonide superior to the current six-months steroid pulses scheme. Long-term data on the efficacy and safety of TRF budesonide are awaited, together with the design of trials with a head-to-head comparison with systemic steroids before considering TRF-budesonide as the standard of care treatment for IgAN nephropathy.

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Enteric Budesonide in Transplant and Native IgA Nephropathy: Real-World Clinical Practice

Cited by 8 publications

References 10 publications

Novel agents for treating IgA nephropathy

Novel agents for treating IgA nephropathy

Treatment of IgA Nephropathy: A Rapidly Evolving Field

Systemic and targeted steroids for the treatment of IgA nephropathy

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