Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): a double-blind, randomised, placebo-controlled phase 2b trial

Fellström, Bengt; Barratt, Jonathan; Cook, H. Terence; Coppo, Rosanna; Feehally, John; Fijter, Johan W. de; Floege, Jürgen; Hetzel, Gerd R.; Jardine, Alan G.; Locatelli, Francesco; Maes, Bart; Mercer, Alex; Ortiz, Fernanda; Praga, Manuel; Sørensen, Søren Schwartz; Tesař, Vladimı́r; Vecchio, Lucia Del

doi:10.1016/s0140-6736(17)30550-0

Cited by 315 publications

(245 citation statements)

References 32 publications

Supporting

Mentioning

225

Contrasting

Unclassified

Order By: Relevance

“…We retrieved the full text for the remaineding 80 articles, and 12 clinical trials [10-12, 20-28] eligible for the inclusion criteria (Fig. 1).…”

Section: Resultsmentioning

confidence: 99%

“…However, this study that had the short follow-up for evaluating the renal function deterioration included patients who were on only > 0.75 g/day of proteinuria (thus showing slow progress). Moreover, recent data from the Therapeutic Evaluation of Steroids in IgA Nephropathy Study (TESTING) [11] and Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN) [12] have provided further evidence on the benefits and side effects of corticosteroid treatment in patients with IgAN. These studies remain the latest and the largest in the world for the steroids therapy of IgAN.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Corticosteroid for IgA Nephropathy: Are They Really Therapeutic?

et al. 2018

View full text Add to dashboard Cite

Background: IgA nephropathy (IgAN) is a common chronic glomerular disease that, in most patients, slowly progresses to end-stage kidney disease. The therapy with corticosteroid in IgAN is still a worldwide problem that is confusing the clinicians. Methods: MEDLINE, EMBASE, the Cochrane Library, and article reference lists were searched for randomized controlled trials (RCTs) that compared corticosteroids with placebo and any other non-immunosuppressive agents in treating IgAN. Twelve RCTs involving 1,057 patients were included. Results: Overall, we found that steroids had statistically significant effects in preventing the decline in renal function (relative risk 0.42, 95% CI 0.25–0.71, p < 0.001) and reducing proteinuria (SMD: –0.58 g/day, 95% CI –0.80 to –0.36 g/day) in patients with IgAN. The association between glucocorticoid and risk of kidney outcome was not modified by steroids’ type (prednisone or methylprednisone), dose (≤30 or > 30 mg/day), duration (≤8 or > 8 months), or serum creatinine (< 1.10 or ≥1.10 mg/dL). But steroids increased the risk of side effects such as gastrointestinal and endocrinium symptoms. Conclusion: This study provides the clear beneficial effects of the steroids therapy on the kidney function and proteinuria, although it should be used with caution.

show abstract

“…We retrieved the full text for the remaineding 80 articles, and 12 clinical trials [10-12, 20-28] eligible for the inclusion criteria (Fig. 1).…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Corticosteroid for IgA Nephropathy: Are They Really Therapeutic?

et al. 2018

View full text Add to dashboard Cite

show abstract

“…An enteric formulation of budesonide has been developed that targets release of the drug in the distal ileum wherein it affects local lymphoid tissue, with theoretically high first-pass metabolism in the liver resulting in low systemic exposure. The NEFIGAN trial compared this novel targeted release formulation of budesonide (TRF budesonide) with placebo [31]. The RCT was double blinded and placebo controlled and included a 6-month run-in, 9-month treatment, and 3-month follow-up period.…”

Section: Indications For Corticosteroid Therapy For Igan In Europe Dementioning

confidence: 99%

“…The enteric formulation of budesonide seems to provide similar favorable results without serious side effects of steroids [31]. …”

Section: Conclusion From Recent European Studies On Corticosteroid Trmentioning

confidence: 99%

IgA Nephropathy: A European Perspective in the Corticosteroid Treatment

Coppo

2018

Kidney Dis

Self Cite

View full text Add to dashboard Cite

Background: IgA nephropathy (IgAN) is detected in Europe in 22% of glomerular diseases diagnosed by biopsy. The frequency of IgAN as cause of ESRD in Europe has increased in the last decades, accounting for 35% of young and adult transplanted patients. These data justify the interest for risk factors and a possible therapeutic approach. Summary: Insight into a European perspective of IgAN was allowed by the multicenter study VALIGA, on 1,147 patients, almost all Caucasians, with follow-up of 4.7 years. The predictive value of mesangial hypercellularity (M), segmental sclerosis (S), tubular atrophy interstitial fibrosis (T) as independent biomarkers of progression was validated. Endocapillary hypercellularity was predictive of increased follow-up proteinuria. Two groups of patients selected by a propensity score to perfectly match for histologic features (MEST) and clinical data treated with renin-angiotensin system blockers (RASBs) and corticosteroids, or RASBs alone were compared and a beneficial effect of corticosteroids in addition to RASB was found in patients with proteinuria > 1 g/day, with an initial eGFR < 50 mL/min/1.73 m². On the contrary, the STOP-IgAN RCT found that immunosuppressive therapy in addition to optimal supportive care did not provide substantial kidney-related benefits in European patients with IgAN, because there was no difference in the rate of decrease in eGFR, although corticosteroid/immunosuppressive therapy induced complete remission of proteinuria more frequently than supportive care alone. The NEFIGAN trial evaluated a targeted release formulation of budesonide (TRF budesonide) delivering the drug in the distal ileum. TRF budesonide, additionally to optimized RAS blockade, reduced proteinuria and maintained eGFR in IgAN patients, suggesting a reduced risk of future progression to ESRD. Key Messages: In Europe, there is a reasoned search of a balanced approach to corticosteroid therapy for patients with IgAN, with particular attention to selecting the patients at risk of progression while limiting the unwanted systemic adverse events.

show abstract

“…The way forward may be to deliver more specific therapy by (1) targeting the relevant lymphoid tissue, or (2) inhibiting selective immune mechanisms. Recently, targeted release of budesonide was tested in the Targeted-Release Budesonide Versus Placebo in Patients with IgA Nephropathy (NEFIGAN), a phase 2b trial (9). The aim was to suppress gastrointestinal mucosal production of IgA1, without exposing patients to systemic side effects of corticosteroids.…”

mentioning

confidence: 99%