Acthar gel in the treatment of nephrotic syndrome: a multicenter retrospective case series

Abstract

BackgroundCurrent first-line anti-proteinuric treatments for nephrotic syndrome (NS) do not produce an effective response in all patients and are not tolerated by some patients. Additional effective and tolerable treatment options in NS are strongly needed. This retrospective case series is the largest to date to examine Acthar gel (adrenocorticotropic hormone, ACTH) in patients with varied-etiology NS.MethodsThis multicenter retrospective case series included adult patients with NS (N = 44) treated with Acthar gel at 6 clinical practices. NS etiologies included idiopathic focal segmental glomerulosclerosis (FSGS, 15), idiopathic membranous nephropathy (iMN, 11), IgA nephropathy (IgAN, 5), diabetic nephropathy (DN, 4), systemic lupus erythematosus class V membranous lupus nephritis (MLN, 2), minimal change disease (MCD, 2), membranoproliferative glomerulonephritis (MPGN, 1), fibrillary glomerulonephritis (FGN, 1), and unbiopsied NS (3). Proteinuria response was assessed as percent reduction from baseline and percent of patients meeting complete remission (final proteinuria <500 mg/d), partial remission (≥50 % reduction in proteinuria from baseline and final proteinuria 500–3500 mg/d), clinical response (≥30 % reduction in proteinuria from baseline that did not meet criteria for complete or partial remission), and no response (failed to meet remission or clinical response criteria) following Acthar gel therapy. Safety and tolerability were examined using adverse event (AE) frequency reported by patients or treating nephrologists and frequency of early discontinuation of treatment due to AEs.Results68.2 % (30/44) of patients had received prior NS treatment with immunosuppressive or cytotoxic therapies. Thirty-seven patients completed Acthar gel treatment. Seven patients (15.9 %) had early termination due to AEs, including weight gain (2), hypertension (2), edema (1), fatigue (1), seizures (1) and for reasons not stated (2). Proteinuria reduction ≥30 % was shown in 81.1 % (30/37) of patients and 62.2 % (23/37) showed ≥50 % proteinuria reduction. Proteinuria responses were greatest in MCD (n = 2/2 complete remission), MLN (n = 2/2 partial remission), MPGN (n = 1/1 partial remission), FSGS (n = 12/15 [80.0 %] partial remission or clinical response), and iMN (n = 8/11 [72.7 %] complete remission, partial remission, or clinical response).ConclusionsActhar gel may meet an important treatment need in patients with treatment-resistant NS in response to first-line therapies, patients unable to tolerate first-line therapies, and in patients with advanced disease.

Adrenocorticotropic Hormone for Childhood Nephrotic Syndrome

“…The negative trial findings contrast with recent case series that have suggested that ACTH is effective in reducing proteinuria in adults with nephrotic syndrome (18,(23)(24)(25)(26). Our trial differs from adult experiences in several important ways.…”

“…However, by the 1960s, ACTH was replaced by oral prednisone for its ease of administration and the belief that ACTH acts via stimulation of corticosteroid production (8,13,14). More recently, several case series of patients with steroid-and multidrug-resistant nephrotic syndrome reported ACTH to be efficacious in inducing and sustaining disease remission and improving GFR, which suggests that ACTH has effects beyond steroidogenesis (13,(15)(16)(17)(18). In addition, one randomized trial demonstrated similar efficacy when comparing ACTH with methylprednisolone and a cytotoxic agent in membranous nephropathy, renewing interest in ACTH for nephrotic syndrome treatment (19).…”

Focal Segmental Glomerulosclerosis

“…Achtar gel is unusual in that it was approved in the 1950s by the US Food and Drug Administration for nephrotic syndrome under criteria that were less stringent than required today. Small case series suggest limited efficacy of Acthar in some individuals with FSGS (117,118) as has been reviewed (119); a randomized, controlled trial is in progress. Galactose, proposed as therapy for recurrent FSGS, has been shown to lack efficacy in steroid-resistant primary FSGS in children (120).…”

Therapeutic Response of Natural Adrenocorotropin in Treatment of Proteinuria due to ANCA Negative Pauci-Immune Crescentic Glomerulonephritis

“…Currently Acthar has re-emerged and is the most promising treatment option for proteinuria in patients with nephrotic syndrome, patients for treatment-resistant to first-line therapies, patients unable to tolerate first-line therapies and patients with advanced disease [7][8][9]. Acthar is a repository corticotrophin which binds to the Melanocortin 1 receptors (MC1Rs) and potentially providing a different way to impact various cells including podocytes [10,11], thus help regulate protein filtration by reducing podocyte foot process effacement and podocyte loss [7].…”

“…Acthar is a repository corticotrophin which binds to the Melanocortin 1 receptors (MC1Rs) and potentially providing a different way to impact various cells including podocytes [10,11], thus help regulate protein filtration by reducing podocyte foot process effacement and podocyte loss [7]. The patients treated with Acthar got full or partial remission for long term effect [8]. Here, we report the case of a patient suffering from proteinuria due to a mixed nephritic-nephrotic syndrome.…”