Treatment of moderately to severely active systemic lupus erythematosus with adrenocorticotropic hormone: a single-site, open-label trial

J J Fiechtner, T Montroy, J J Fiechtner, T Montroy

Abstract

Background: Alternative therapeutic options are needed for patients with systemic lupus erythematosus (SLE) not adequately controlled with or intolerant to traditional treatments. This study evaluated the efficacy of Acthar® Gel (ACTH(1-39)) for reducing active SLE severity among patients receiving underlying conventional maintenance therapies.

Methods: Ten females (mean age = 49 yrs, disease duration = 7 yrs, Systemic Lupus Erythematosus Disease Activity Index-2000 [SLEDAI-2 K] = 10) currently on maintenance self-administered ACTH(1-39) gel 1 mL (80 U/mL) for 7-15 days and were assessed weekly for 28 days. Outcome measures included Physician and Patient Global Assessments, SLEDAI-2 K, Lupus Quality of Life scale, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale, erythrocyte sedimentation rate, and C-reactive protein. Student's t-test compared data obtained at days 7, 14, and 28 with those from baseline.

Results: The primary endpoint of SLEDAI-2 K improvement was reached at all observation times (p < 0.05) and statistically significant improvements were observed for most other parameters. No treatment-related serious or unexpected adverse events were observed.

Conclusions: The trial results reveal that among SLE patients in need of therapeutic alternatives, ACTH(1-39) gel may provide significant disease activity reduction.

Keywords: Adrenocorticotropic hormone gel; SLEDAI-2 K; disease activity; systemic lupus erythematosus.

© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

References

    1. American College of Rheumatology. Guidelines for referral and management of systemic lupus erythematosus in adults. American College of Rheumatology Ad Hoc Committee on Systemic Lupus Erythematosus Guidelines. Arthritis Rheum 1999; 42: 1785–1796.
    1. Ruperto N, Hanrahan LM, Alarcon GS, et al. International consensus for a definition of disease flare in lupus. Lupus 2011; 20: 453–462.
    1. Panopalis P, Yazdany J, Gillis JZ, et al. Health care costs and costs associated with changes in work productivity among persons with systemic lupus erythematosus. Arthritis Rheum 2008; 59: 1788–1795.
    1. Turchetti G, Yazdany J, Palla I, Yelin E, Mosca M. Systemic lupus erythematosus and the economic perspective: a systematic literature review and points to consider. Clin Exp Rheumatol 2012; 30(4 suppl 73): S116–S122.
    1. Bertsias G, Ioannidis JP, Boletis J, et al. EULAR recommendations for the management of systemic lupus erythematosus. Report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics. Ann Rheum Dis 2008; 67: 195–205.
    1. Tsokos GC. Systemic lupus erythematosus. N Engl J Med 2011; 365: 2110–2121.
    1. Luijten RK, Fritsch-Stork RD, Bijlsma JW, Derksen RH. The use of glucocorticoids in systemic lupus erythematosus. After 60 years still more an art than science. Autoimmun Rev 2012; 12: 617–628.
    1. Bertsias G, Cervera R, Boumpas DT. Systemic lupus erythematosus: pathogenesis and clinical features. EULAR textbook on rheumatic diseases, Geneva, Switzerland: European League Against Rheumatism, 2012, pp. 476–505.
    1. Slominski A, Wortsman J, Luger T, Paus R, Solomon S. Corticotropin releasing hormone and proopiomelanocortin involvement in the cutaneous response to stress. Physiol Rev 2000; 80: 979–1020.
    1. Slominski AT, Zmijewski MA, Skobowiat C, Zbytek B, Slominski RM, Steketee JD. Sensing the environment: regulation of local and global homeostasis by the skin’s neuroendocrine system. Adv Anat Embryol Cell Biol 2012; 212: 1–115.
    1. Slominski A, Zbytek B, Nikolakis G, et al. Steroidogenesis in the skin: implications for local immune functions. J Steroid Biochem Mol Biol 2013; 137: 107–123.
    1. Slominski AT, Zmijewski MA, Zbytek B, Tobin DJ, Theoharides TC, Rivier J. Key role of CRF in the skin stress response system. Endocr Rev 2013; 34: 827–884.
    1. Questcor Pharmaceuticals, Inc. H.P. Acthar® Gel (repository corticotropin injection) [prescribing information]. Hayward, CA: Questcor Pharmaceuticals, Inc., September 2012.
    1. Baram TZ, Mitchell WG, Tournay A, Snead OC, Hanson RA, Horton EJ. High-dose corticotropin (ACTH) versus prednisone for infantile spasms: a prospective, randomized, blinded study. Pediatrics 1996; 97: 375–379.
    1. Bomback AS, Tumlin JA, Baranski J, et al. Treatment of nephrotic syndrome with adrenocorticotropic hormone (ACTH) gel. Drug Des Devel Ther 2011; 5: 147–153.
    1. Pranzatelli MR, Chun KY, Moxness M, Tate ED, Allison TJ. Cerebrospinal fluid ACTH and cortisol in opsoclonus-myoclonus: effect of therapy. Pediatr Neurol 2005; 33: 121–126.
    1. Simsarian JP, Saunders C, Smith DM. Five-day regimen of intramuscular or subcutaneous self-administered adrenocorticotropic hormone gel for acute exacerbations of multiple sclerosis: a prospective, randomized, open-label pilot trial. Drug Des Devel Ther 2011; 5: 381–389.
    1. Levine T. Treating refractory dermatomyositis or polymyositis with adrenocorticotropic hormone gel: a retrospective case series. Drug Des Devel Ther 2012; 6: 133–139.
    1. Catania A, Gatti S, Colombo G, Lipton JM. Targeting melanocortin receptors as a novel strategy to control inflammation. Pharmacol Rev 2004; 56: 1–29.
    1. Brzoska T, Luger TA, Maaser C, Abels C, Bohm M. α-Melanocyte-stimulating hormone and related tripeptides: biochemistry, anti-inflammatory and protective effects in vitro and in vivo, and future perspectives for the treatment of immune-mediated inflammatory diseases. Endocr Rev 2008; 29: 581–602.
    1. Manna SK, Aggarwal BB. Alpha-melanocyte-stimulating hormone inhibits the nuclear transcription factor NF-kappa B activation induced by various inflammatory agents. J Immunol 1998; 161: 2873–2880.
    1. Ichiyama T, Sakai T, Catania A, Barsh GS, Furukawa S, Lipton JM. Systemically administered α-melanocyte-stimulating peptides inhibit NF-κB activation in experimental brain inflammation. Brain Res 1999; 836: 31–37.
    1. Gladman DD, Ibanez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. J Rheumatol 2002; 29: 288–291.
    1. Yee CS, Farewell VT, Isenberg DA, et al. The use of Systemic Lupus Erythematosus Disease Activity Index-2000 to define active disease and minimal clinically meaningful change based on data from a large cohort of systemic lupus erythematosus patients. Rheumatology 2011; 50: 982–988.
    1. Abu-Shakra M, Mader R, Langevitz P, et al. Quality of life in systemic lupus erythematosus: a controlled study. J Rheumatol 1999; 26: 306–309.
    1. Lai JS, Beaumont JL, Ogale S, Brunetta P, Cella D. Validation of the functional assessment of chronic illness therapy-fatigue scale in patients with moderately to severely active systemic lupus erythematosus, participating in a clinical trial. J Rheumatol 2011; 38: 672–679.
    1. Kosinski M, Gajria K, Fernandes AW, Cella D. Qualitative validation of the FACIT-Fatigue scale in systemic lupus erythematosus. Lupus 2013; 22: 422–430.
    1. Isenberg DA, Rahman A, Allen E, et al. BILAG 2004. Development and initial validation of an updated version of the British Isles Lupus Assessment Group’s disease activity index for patients with systemic lupus erythematosus. Rheumatology 2005; 44: 902–906.
    1. Yee CS, Isenberg DA, Prabu A, et al. BILAG-2004 index captures systemic lupus erythematosus disease activity better than SLEDAI-2000. Ann Rheum Dis 2008; 67: 873–876.
    1. Schurmeyer TH, Tsokos GC, Avgerinos PC, et al. Pituitary-adrenal responsiveness to corticotropin-releasing hormone in patients receiving chronic, alternate day glucocorticoid therapy. J Clin Endocrinol Metab 1985; 61: 22–27.
    1. Agency for Healthcare Research and Quality. Antinuclear antibody, rheumatoid factor, and cyclic-citrullinated peptide tests for evaluating musculoskeletal complaints in children, Rockville, MD: Agency for Healthcare Research and Quality, March 2012.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere