An Open-Label Pilot Study of Adrenocorticotrophic Hormone in the Treatment of IgA Nephropathy at High Risk of Progression

Abstract

Introduction: IgA nephropathy (IgAN) is the most common glomerulonephritis with high risk of progression to end-stage renal disease in patients with proteinuria >1 g/24 hours. There are no known effective treatments in patients with IgAN. Methods: We conducted a prospective open-label pilot study in patients with IgAN using adrenocorticotrophic hormone (ACTH) (Acthar Gel, Mallinckrodt Pharmaceuticals, Bedminster, NJ) at a dosage of 80 units subcutaneously twice weekly for a total of 6 months and followed patients for a total of 12 months. Patients had to have urinary protein >1 g/24 hours despite adequate renin-angiotensin-aldosterone system (RAAS) blockade and estimated glomerular filtration rate (eGFR) >30 ml/min at enrollment. Results: A total of 19 patients were recruited and followed for 1 year. At baseline, the mean age was 34.9 AE 10.5 years with 11 men and 8 women, and 14 Caucasian and 5 Asian individuals. At 12 months, there was a statistically significant decline in 24-hour urinary protein from 2.6 to 1.3 g (P ¼ 0.007) and significant increase in serum albumin (3.79 to 3.93, P ¼ 0.02). There was no significant change in eGFR (65.5 to 61.1 ml/ min, P ¼ 0.1). There were 0 complete remissions and 8 partial remissions (42%). There were a total of 6 infections: 2 were viral and 4 required antibiotic therapy (2 sinusitis, 1 pneumonia, 1 otitis media). The most common adverse events included acne, hot flashes, soreness, and anxiety. Conclusion: In summary, patients with IgAN with >1 g/24-hour urinary protein and eGFR >30 ml/min had a significant reduction in 24-hour urinary protein with stable eGFR at 12-month follow-up after being treated with 6 months of ACTH.

Pharmacokinetics and Pharmacodynamics of Repository Corticotropin Injection Compared With Synthetic ACTH1‐24 Depot and Methylprednisolone in Healthy Subjects

“…Nevertheless, both studies found RCI to have a substantially lower prednisone‐equivalent dose than clinically relevant doses of synthetic ACTH 1‐24 depot. Despite having a low estimated daily prednisone‐equivalent dose, RCI has previously demonstrated clinical efficacy in patients with inflammatory conditions that have shown a poor clinical response to corticosteroids 8–18 . This further supports a therapeutic effect of RCI that is independent of cortisol production and suggests that RCI may be an efficacious alternative for patients who have become resistant to the effects of corticosteroids or are unable to tolerate their side effects.…”

“…Repository corticotropin injection (RCI; Acthar Gel) has demonstrated therapeutic benefit for persistent inflammatory disorders and other conditions that have exhibited an inadequate response to corticosteroids and standard‐of‐care treatments 8–18 . RCI is approved by the US Food and Drug Administration for the treatment of infantile spasms and various allergic, autoimmune, inflammatory, and rheumatic diseases.…”

Emerging Modes of Treatment of IgA Nephropathy

“…Administration of a 6-month course of ACTH gel in patients with IgAN at high risk of progression (proteinuria > 1 g per 24 h despite documented ACEI/ARB therapy and adequate blood pressure control for >3 months, 24-h creatinine clearance >30 mL/min/1.73 m 2 ) was prospectively investigated in an open-label pilot study (NCT 02282930). A significant decline in 24-h urinary protein (2.6 to 1.3 g; p = 0.007) with no significant changes in eGFR (65.5 to 61.1 mL/min, p = 0.1) was detected at 12-month follow-up in patients with IgAN treated with 6 months of ACTH [58].…”

A case of relapsing immunoglobulin A nephropathy secondary to immunotherapy

“…[13][14][15][16] A recent pilot study using adrenocorticotropic hormone (ACTH) treatment in a patient with a high risk of IgA progression showed a significant reduction of proteinuria with stable estimated glomerular filtration rate (eGFR) at 12 months post-therapy with no significant adverse events. 17 The mechanism for anti-proteinuric effect of ACTH therapy is not fully understood, but in addition to corticosteroid release the effect may be related to the activation of the melanocortin-1 receptor, which has a podocyte protective effect. 18…”