Open-label Randomized Controlled Trial of Controlled-release Formulation Budesonide in Indian Proteinuric IgA Nephropathy Patients

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Introduction IgA nephropathy (IgAN) in India is reported to have an onset at a younger age with faster progression to kidney failure requiring replacement therapy, where safe immunosuppression may improve the outcome. The gut-renal connection and multihit pathogenesis of IgAN targeted by an oral targeted-release formulation of budesonide available in the Western world showed that the molecule is safe and effective. In this study, we aimed to assess the safety and efficacy of oral controlled-release budesonide preparation in Indian patients with IgAN. Methods We report a single-center open-label randomized controlled trial conducted in a tertiary care hospital in Eastern India, where adult patients with biopsy-proven IgAN with proteinuria > 1 g and estimated glomerular filtration rate (eGFR) > 45 mL/min/1.73 m 2 were included after they had completed a run-in phase of 6 months with a maximized dose of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker. 53 patients were randomized to the control (26, only therapy angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, standard-of-care [SOC]) and intervention arms (27, 18 mg budesonide daily on top of SOC). The primary outcome was efficacy evaluation in terms of change in proteinuria and eGFR in the intervention arm; secondary outcomes mainly included treatment-emergent adverse events. Results All baseline parameters, including blood pressure, glycemic status, 24-hour urine protein levels, and eGFR, were comparable in both arms. At the end of 9 months, the mean 24-hour proteinuria was lower ( P -value < 0.001) and the mean eGFR was significantly better ( P -value < 0.001) in the intervention arm receiving budesonide plus SOC than in the control arm receiving only SOC. The total incidence of treatment-emergent adverse events was similar across both groups. Conclusions Controlled-release budesonide may be considered an effective and safe disease-specific therapy in Indian patients with IgAN. Plain-Language Summary The need for safe, effective and cost-friendly immunosuppression for IgA nephropathy in India had inspired this randomized controlled study in a subset of IgAN patients with eGFR >45 ml/min and proteinuria> 1 gm/day, where the intervention arm received 18 mg of controlled released budesonide on top of SOC that includes maximised ACEI /ARB and the other arm received SOC only. Controlled released budesonide was safe and well tolerated and satisfied the need for significant proteinuria reduction and eGFR improvement, the two important surrogate markers of long term outcome in IgA nephropathy. It may be considered as safe cost-friendly alternative of TRF budesonide formulation, proved effective in similar clinical scenario of Western world.

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