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

BACKGROUND: Current 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. METHODS: This 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. RESULTS: 68.2 % (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). CONCLUSIONS: Acthar 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.

Repository corticotropin injection in a patient presenting with focal segmental glomerulosclerosis, rheumatoid arthritis, and optic neuritis: a case report.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) causes scarring or sclerosis of glomeruli that act as tiny filters in the kidneys, damage to which results in diminished ability to properly filter blood, resulting in the urinary loss of plasma proteins and subsequent proteinuria. CASE PRESENTATION: A 60-year-old, white female with a history of intermittent proteinuria was referred by her primary care physician for renal dysfunction. Biopsy confirmed FSGS and she was treated with an angiotensin-converting enzyme inhibitor. She also had rheumatoid arthritis (RA) but no active synovitis and was maintained on prednisone 5 mg/d. She also complained of worsening vision in her right eye and was diagnosed with optic neuritis (ON). She remained stable for about 8 months when examination indicated FSGS relapse, and she reported painful RA flares. She was treated with Acthar(®) Gel (40 mg biweekly) for 6 months, after which proteinuria and urine protein-to-creatinine ratio decreased to about half. Her ON improved, and she reported that she had fewer RA flares and pain improved by 50%. This case of confirmed FSGS showed an improved response to treatment with Acthar Gel for FSGS with concomitant RA and ON. CONCLUSION: This referral case is relevant to primary care practitioners who treat disorders that may be responsive to corticosteroid therapy. The antiproteinuric effects and ancillary improvement in RA and ON symptoms during treatment with Acthar Gel are not entirely explained by its steroidogenic actions. ACTH is a bioactive peptide that, together with α-melanocyte-stimulating hormone, exhibits biologic efficacy by modulating proinflammatory cytokines and subsequent leukocyte extravasation and may have autocrine/paracrine effects in joints. While Acthar Gel was primarily administered in this case to treat proteinuria, it also showed ancillary benefits in patients with concomitant inflammatory disease states.