American Journal of Kidney Diseases

Repository Corticotropin Versus Glucocorticoid for Nephrotic Syndrome: When Will We See the Evidence?

Published:February 11, 2019DOI:
      Despite little evidence supporting its superiority to glucocorticoid therapy, use and expenditures for repository corticotropin (rACTH) injection (H.P. Acthar Gel; Mallinckrodt) have increased dramatically in the last 5 years, particularly among a small number of nephrologists, rheumatologists, and neurologists. Recently, the manufacturer justified the extremely high and rapidly increasing cost of rACTH by citing the ongoing need to generate clinical data to support its use. We test this assertion by investigating the quality and provenance of the evidence likely to emerge in the foreseeable future. We identified all completed, in-progress, and proposed studies of rACTH registered at 75 studies representing 2,953 participants met inclusion criteria. Studies addressed primarily nephrologic (n = 23), rheumatologic (n = 28), and neurologic (n =22) indications. Of the 23 studies proposed for renal indications (enrollment, 33 ± 49 [mean ± SD]), 11 were not randomized, 8 compared only different rACTH treatment regimens, and 4 compared rACTH to placebo. No studies of rACTH proposed for renal indications included an rACTH-free arm receiving active treatment (ie, another form of immunosuppression). We conclude that evidence emerging in the foreseeable future is unlikely to broadly support rACTH use over lower-cost glucocorticoid-based alternatives for renal indications.

      Index Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to American Journal of Kidney Diseases
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Philbin M.
        • Niewoehner J.
        • Wan G.J.
        Clinical and economic evaluation of repository corticotropin injection: a narrative literature review of treatment efficacy and healthcare resource utilization for seven key indications.
        Adv Ther. 2017; 34: 1775-1790
        • Mallinckrodt Pharmaceuticals
        H.P. Acthar Gel package insert.
        Date accessed: December 29, 2018
        • Gilbert S.J.
        Does the kidney biopsy portend the future of nephrology?.
        Clin J Am Soc Nephrol. 2018; 13: 681-682
        • Bomback A.S.
        • Canetta P.A.
        • Beck Jr., L.H.
        • Ayalon R.
        • Radhakrishnan J.
        • Appel G.B.
        Treatment of resistant glomerular diseases with adrenocorticotropic hormone gel: a prospective trial.
        Am J Nephrol. 2012; 36: 58-67
        • Bomback A.S.
        • Tumlin J.A.
        • Baranski J.
        • et al.
        Treatment of nephrotic syndrome with adrenocorticotropic hormone (ACTH) gel.
        Drug Design Dev Ther. 2011; 5: 147-153
        • Madan A.
        • Mijovic-Das S.
        • Stankovic A.
        • Teehan G.
        • Milward A.S.
        • Khastgir A.
        Acthar gel in the treatment of nephrotic syndrome: a multicenter retrospective case series.
        BMC Nephrol. 2016; 17: 37
        • Hladunewich M.A.
        • Cattran D.
        • Beck L.H.
        • et al.
        A pilot study to determine the dose and effectiveness of adrenocorticotrophic hormone (H.P. Acthar(R) Gel) in nephrotic syndrome due to idiopathic membranous nephropathy.
        Nephrol Dial Transplant. 2014; 29: 1570-1577
        • Hogan J.
        • Bomback A.S.
        • Mehta K.
        • et al.
        Treatment of idiopathic FSGS with adrenocorticotropic hormone gel.
        Clin J Am Soc Nephrol. 2013; 8: 2072-2081
        • Wang C-s
        • Travers C.
        • McCracken C.
        • et al.
        Adrenocorticotropic hormone for childhood nephrotic syndrome: the ATLANTIS randomized trial.
        Clin J Am Soc Nephrol. 2018; 13: 1859-1865
        • Pollack A.
        Questcor finds profits, at $28,000 a vial.
        New York Times. December 29, 2012; (
        • Ornstein C.
        The obscure drug with a growing Medicare tab.
        ProPublica. August 4, 2014; (
        • Ornstein C.
        Top Acthar prescribers in Medicare have ties to its maker.
        ProPublica. August 4, 2014; (
        • Morgenson G.
        A costly drug, missing a dose of disclosure.
        New York Times. January 27, 2017; (
        • Alpert B.
        Questcor Acquired By Mallinckrodt for $5.6 Billion.
        Barron's. April 8, 2014; (
        • Liss D.
        • Brennan T.A.
        • Manaker S.
        Finding common ground: professionalism and Acthar prescribing practices.
        Chest. 2016; 149: 611-612
        • Hartung D.M.
        • Johnston K.
        • Van Leuven S.
        • Deodhar A.
        • Cohen D.M.
        • Bourdette D.N.
        Trends and characteristics of US Medicare spending on repository corticotropin.
        JAMA Intern Med. 2017; 177: 1680-1682
        • Irwin R.S.
        • Manaker S.
        • Metersky M.L.
        • et al.
        Higher priced older pharmaceuticals: how should we respond?.
        Chest. 2018; 153: 23-33
        • Hartung D.M.
        • Johnston K.
        • Cohen D.
        • Nguyen T.
        • Deodhar A.
        • Bourdette D.N.
        Industry payments to physician specialists who prescribe repository corticotropin.
        JAMA Network Open. 2018; 1: e180482
        • CMS
        Open Payments Data Explorer.
        (Accessed January 18, 2019)
      1. CMS. Medicare Part D Prescriber Data CY 2016.
        • Otulana T.
        Uses of H.P. Acthar Gel in the clinical setting.
        JAMA Intern Med. 2018; 178: 583
        • Rose A.S.
        • Kuzma J.W.
        • Kurtzke J.F.
        • Namerow N.S.
        • Sibley W.A.
        • Tourtellotte W.W.
        Cooperative study in the evaluation of therapy in multiple sclerosis. ACTH vs. placebo--final report.
        Neurology. 1970; 20: 1-59
        • Hrachovy R.A.
        • Frost Jr., J.D.
        • Kellaway P.
        • Zion T.E.
        Double-blind study of ACTH vs prednisone therapy in infantile spasms.
        J Pediatr. 1983; 103: 641-645
        • Baram T.Z.
        • Mitchell W.G.
        • Tournay A.
        • Snead O.C.
        • Hanson R.A.
        • Horton E.J.
        High-dose corticotropin (ACTH) versus prednisone for infantile spasms: a prospective, randomized, blinded study.
        Pediatrics. 1996; 97: 375-379
        • Ponticelli C.
        • Passerini P.
        • Salvadori M.
        • et al.
        A randomized pilot trial comparing methylprednisolone plus a cytotoxic agent versus synthetic adrenocorticotropic hormone in idiopathic membranous nephropathy.
        Am J Kidney Dis. 2006; 47: 233-240
        • Lal R.
        • Bell S.
        • Challenger R.
        • et al.
        Pharmacodynamics and tolerability of repository corticotropin injection in healthy human subjects: a comparison with intravenous methylprednisolone.
        J Clin Pharmacol. 2016; 56: 195-202
        • Carter M.E.
        • James V.H.
        Comparison of effects of corticotrophin and corticosteroids on pituitary-adrenal function.
        Ann Rheum Dis. 1971; 30: 91-97
        • Banfi G.
        • Moriggi M.
        • Sabadini E.
        • Fellin G.
        • D'Amico G.
        • Ponticelli C.
        The impact of prolonged immunosuppression on the outcome of idiopathic focal-segmental glomerulosclerosis with nephrotic syndrome in adults. A collaborative retrospective study.
        Clin Nephrol. 1991; 36: 53-59
        • Ponticelli C.
        • Villa M.
        • Banfi G.
        • et al.
        Can prolonged treatment improve the prognosis in adults with focal segmental glomerulosclerosis?.
        Am J Kidney Dis. 1999; 34: 618-625
        • Gong R.
        The renaissance of corticotropin therapy in proteinuric nephropathies.
        Nat Rev Nephrol. 2011; 8: 122-128
        • Berkovich R.
        • Agius M.A.
        Mechanisms of action of ACTH in the management of relapsing forms of multiple sclerosis.
        Ther Adv Neurol Disord. 2014; 7: 83-96
        • Mallinckrodt Pharmaceuticals
        Potential MOA.
        Date accessed: December 30, 2018
        • MedKnowledge F.D.B.
        First Databank, Inc.
        • Mallinckrodt Pharmaceuticals
        Date accessed: December 30, 2018