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Treatment of Acute Relapses in Multiple Sclerosis

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Neurotherapeutics

Summary

Multiple sclerosis (MS) is a chronic progressive inflammatory demyelinating disease affecting the central nervous system. The most common clinical type of MS tends to follow a relapsing course, affecting the vast majority of patients living with this disease. Relapses are a hallmark of MS, and are often associated with significant functional impairment and decreased quality of life. Although usually followed by a period of remission, residual symptoms after MS relapses may persist and lead to sustained disability. Adequate management of MS relapses is important, as it may help to shorten and lessen the disability associated with their course. Historically, treatment of MS relapse was the first approach (and for a period of time, the only approach) to MS treatment in general. Systemic corticosteroids and adrenocorticotropic hormone (ACTH) have broad regulatory approval and remain the most established and validated treatment options for MS relapse. Therapeutic mechanisms of ACTH were previously associated (perhaps mistakenly) with only corticotropic actions; however, recently the direct anti-inflammatory effects and immunomodulatory activity of ACTH gel acting through melanocortin pathways have been shown. Second-line treatments of steroid-unresponsive MS relapses and a possible algorithm for MS relapse management are also reviewed in this article.

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References

  1. Lublin FD, Baier M, Cutter G. Effect of relapses on development of residual deficit in multiple sclerosis. Neurology 2003;61:1528–1532.

    Article  PubMed  Google Scholar 

  2. Frohman EM, Shah A, Eggenberger E, et al. Corticosteroids for multiple sclerosis: I. Application for treating exacerbations. Neurotherapeutics 2007;4:618–626.

    Article  PubMed  CAS  Google Scholar 

  3. Repovic P, Lublin FD. Treatment of multiple sclerosis exacerbations. Neurol Clin 2011;29:389–400.

    Article  PubMed  Google Scholar 

  4. Hoch E. Ergebnisse verschiedener Behandlungsversuche der multiplen Sklerose an der neurologischen Abteilung der Medizinische und Nervenklinik der Universitat Wiirzburg wahrend der Jahre 1935/ 1936. Wiirzburg: Inaugural-Dissertation. Leipzig: Schneider and Mischkewitz, Naunhof, 1937.

  5. Pette H. Die akut entziindlichen Erkrankungen des Nervensystems. Leipzig: Thieme 1942:516–517.

  6. Schaltenbrand G. Die multiple Sklerose des Menschen. Leipzig: Thieme 1943:238–246.

  7. Miller H, Newell DJ, Ridley A. Multiple sclerosis. Treatment of acute exacerbations with corticotrophin (ACTH). Lancet 1961;11:1120–1122.

    Article  Google Scholar 

  8. Fog T. Nord. Med 1951;46:1742.

    PubMed  CAS  Google Scholar 

  9. Jӧnsson B, von Reis G, Sahlgren E. Acta Psychiat 1951;74:60.

    Google Scholar 

  10. Alexander L, Cass LJ. The present status of ACTH therapy in multiple sclerosis. Ann Intern Med 1963:58:454–471.

    PubMed  CAS  Google Scholar 

  11. Millar JHD, Belf MD, Vas CJ, et al. Long-term treatment of multiple sclerosis with corticotrophin. The Lancet 1967;7513:429–431.

    Article  Google Scholar 

  12. Rinne UK, Sonninen V, Tuovinen T. Corticotrophin treatment in multiple sclerosis. Acta Neurologica Scandinavica 1967;31:185–186.

    Google Scholar 

  13. Rose AS, Kuzma JW, Kurtzke JF, Sibley WA, Tourtellotte WW. Cooperative study in the evaluation of therapy in multiple sclerosis: ACTH vs placebo in acute exacerbation. Trans Am Neurol Assoc 1969;94:126–133.

    PubMed  CAS  Google Scholar 

  14. Rose AS, Kuzma JW, Kurtzke JF, Namerow NS, Sibley WA, Tourtellotte WW. Cooperative study in the evaluation of therapy in multiple sclerosis: ACTH vs. placebo — final report. Neurology 1970;20:1–59.

    PubMed  CAS  Google Scholar 

  15. Questcor Pharmaceuticals, Inc. H.P. Acthar® Gel (repository corticotrophin injection) [prescribing information]. Hayward, CA: Questcor Pharmaceuticals, Inc.; June 2011.

  16. Hoogstraten MC, Cats A, Minderhoud JM. Bed rest and ACTH in the treatment of exacerbations in multiple sclerosis patients. Acta Neurol Scand 1987;76:346–350.

    Article  PubMed  CAS  Google Scholar 

  17. Hoogstraten MC, Minderhoud JM. Long-term effect of ACTH treatment of relapse in multiple sclerosis. Acta Neurol Scand 1990;82:74–77.

    Article  PubMed  CAS  Google Scholar 

  18. Miller DM, Weinstock-Guttman B, Bethoux F, et al. A meta-analysis of methylprednisolone in recovery from multiple sclerosis exacerbations. Mult Scler 2000;6:267–273.

    PubMed  CAS  Google Scholar 

  19. Abbruzzese G, Gandolfo C, Loeb C. "Bolus" methylprednisolone versus ACTH in the treatment of multiple sclerosis. Ital J Neurol Sci 1983;2:169–172.

    Article  Google Scholar 

  20. Barnes M, Bateman D, Cleland P, et al. Intravenous methylprednisolone for multiple sclerosis in relapse. J Neurol Neurosurg Psychiatry 1985;48:157–159.

    Article  PubMed  CAS  Google Scholar 

  21. Milanese C, La Mantia L, Salmaggi A, et al. Double-blind randomized trial of ACTH versus dexamethasone versus methylprednisolone in multiple sclerosis bouts. Clinical, cerebrospinal fluid and neurophysiological results. Eur Neurol 1989;29:10–14.

    Article  PubMed  CAS  Google Scholar 

  22. Thompson AJ, Kennard C, Swash M, et al. Relative efficacy of intravenous methylprednisolone and ACTH in the treatment of acute relapse in MS. Neurology 1989;39:969–971.

    Article  PubMed  CAS  Google Scholar 

  23. Durelli L, Cocito D, Riccio A, et al. High-dose intravenous methylprednisolone in the treatment of multiple sclerosis: clinical-immunologic correlations. Neurology 1986;36:238–243.

    Article  PubMed  CAS  Google Scholar 

  24. Milligan NM, Newcombe R, Compston DA. A double-blind controlled trial of high dose methylprednisolone in patients with multiple sclerosis: 1. clinical effects. J Neurol Neurosurg Psychiatry 1987;50:511–516.

    Article  PubMed  CAS  Google Scholar 

  25. Beck RW, Cleary PA, Anderson MM, et al. A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. N Engl J Med 1992;9:581–588.

    Article  Google Scholar 

  26. Sellebjerg F, Frederiksen JL, Nielsen PM, Olesen J. Double-blind, randomized, placebo-controlled study of oral, high-dose methylprednisolone in attacks of MS. Neurology 1998;51:529–534.

    Article  PubMed  CAS  Google Scholar 

  27. Barnes D, Hughes RAC, Morris RW, et al. Randomised trial of oral and intravenous methylprednisolone in acute relapses of multiple sclerosis. Lancet 1997;349:902–906.

    Article  PubMed  CAS  Google Scholar 

  28. Martinelli V, Rocca MA, Annovazzi P, et al. A short-term randomized MRI study of high-dose oral vs intravenous methylprednisolone in MS. Neurology 2009;73:1842–1848.

    Article  PubMed  CAS  Google Scholar 

  29. Cass LJ, Alexander L, Enders M. Complications of corticotropin therapy in multiple sclerosis. JAMA 1966;197:173–178.

    Article  PubMed  CAS  Google Scholar 

  30. Lukert BP, Raisz LG. Glucocorticoid-induced osteoporosis: pathogenesis and management. Ann Intern Med 1990;112:352–364.

    PubMed  CAS  Google Scholar 

  31. Schwid SR, Goodman AD, Puzas JE, et al. Sporadic corticosteroid pulses and osteoporosis in multiple sclerosis. Arch Neurol 1996;8:753–757.

    Article  Google Scholar 

  32. Zorzon M, Zivadinov R, Locatelli L, et al. Long-term effects of intravenous high dose methylprednisolone pulses on bone mineral density in patients with multiple sclerosis. Eur J Neurol 2005;7:550–556.

    Article  Google Scholar 

  33. Weiner ES, Abeles M. Aseptic necrosis and glucocorticois in systemic lupus erythematosus: a reevaluation. J Rheumatol 1989;16:604–608.

    PubMed  CAS  Google Scholar 

  34. Fardet L, Kassar A, Cabane J, et al. Corticosteroid-induced adverse events in adults: frequency, screening and prevention. Drug Saf 2007;30:861–881.

    Article  PubMed  CAS  Google Scholar 

  35. Gurwitz JH, Bohn RL, Glynn RJ, et al. Glucocorticoids and the risk for initiation of hypoglycemic therapy. Arch Intern Med 1994;154:97–101.

    Article  PubMed  CAS  Google Scholar 

  36. Feldman-Billard S, Lissak B, Kassaei R, et al. Short-term tolerance of pulse methylprednisolone therapy in patients with diabeles mellitus. Ophthalmology 2005;112:511–515.

    Article  PubMed  Google Scholar 

  37. Bomback AS, Tumlin JA, Baranski J, et al. Treatment of nephrotic syndrome with adrenocorticotropic horone (ACTH) gel. Drug Des Devel Ther 2011;5:147–153.

    Article  PubMed  CAS  Google Scholar 

  38. 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.

    Article  PubMed  Google Scholar 

  39. Stafstrom CE, Arnason BG, Baram TZ, et al. Treatment of infantile spasms: emerging insights from clinical and basic science perspectives. J Child Neurol 2011;11:1411–1421.

    Article  Google Scholar 

  40. Catania A, Gatti S, Colombo G, Lipton JM. Targeting melanocortin receptors as a novel strategy to control inflammation. Pharmacol Rev 2004;56:1–29.

    Article  PubMed  CAS  Google Scholar 

  41. Catania A. Neuroprotective actions of melanocortins: a therapeutic opportunity. Trends Neurosci 2008;31:353–360.

    Article  PubMed  CAS  Google Scholar 

  42. Arnason B, Berkovich R, Catania A., et al. Therapeutic mechanisms of action of adrenocorticotropic hormone (ACTH) and other melanocortin peptides for the clinical management of patients with MS. 2012;(in press).

  43. Poser CM. Corticotropin is superior to corticosteroids in the treatment of MS. Arch Neurol 1989;46:946.

    Article  PubMed  CAS  Google Scholar 

  44. Berkovich R, Fernandez M, Subhani D. Adrenocorticotropic hormone treatment of multiple sclerosis exacerbations. Presented at the Consortium of Multiple Sclerosis Centers; June 2, 2012; San Diego.

  45. Zaidi M, Sun L, Robinson LJ, et al. ACTH protects against glucocorticoid-induced osteonecrosis of bone. Proc Natl Acad Sci USA 2010;107:8782–8787.

    Article  PubMed  CAS  Google Scholar 

  46. Weinstein RS. Clinical practice. Glucocorticoid-induced bone disease. N Engl J Med 2011;365:62–70.

    Article  PubMed  CAS  Google Scholar 

  47. Berkovich R, Subhani D, Steinman L. Autoimmune Comorbid Conditions in Multiple Sclerosis. US Neurol 2011;7:132–138.

    Google Scholar 

  48. Weiner HL, Dau PC, Khatri BO, et al. Double-blind study of true vs. sham plasma exchange in patients treated with immunosupression for acute attacks of multiple sclerosis. Neurology 1989;38:1143–1149.

    Article  Google Scholar 

  49. Weinshenker BG, O’Brien PC, Petterson TM, et al. A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease. Ann Neurol 1999;46:878–886.

    Article  PubMed  CAS  Google Scholar 

  50. Keegan M, Pineda AA, McClelland RL, et al. Plasma exchange for severe attacks of CNS demyelination: predictors of response. Neurology 2002;58:143–146.

    Article  PubMed  CAS  Google Scholar 

  51. Keegan M, Konig F, Mcclelland R, et al. Relation between humoral pathological changes in multiple sclerosis and response to therapeutic plasma exchange. Lancet 2005;366:579–582.

    Article  PubMed  Google Scholar 

  52. Barile-Fabris L, Ariza-Andraca R, Olguín-Ortega L, et al. Controlled clinical trial of IV cyclophosphamide versus IV methylprednisolone in severe neurological manifestations in systemic lupus erythematosus. Ann Rheum Dis 2005;64:620–625.

    Article  PubMed  CAS  Google Scholar 

  53. Greenberg BM, Thomas KP, Krishnan C, et al. Idiopathic transverse myelitis: corticosteroids, plasma exchange, or cyclophosphamide. Neurology 2007;68:1614–1617.

    Article  PubMed  CAS  Google Scholar 

  54. Noseworthy JH, O’Brien PC, Petterson TM, et al. A randomized trial of intravenous immunoglobulin in inflammatory demyelinating optic neuritis. Neurology 2001;56:1514–1522.

    Article  PubMed  CAS  Google Scholar 

  55. Tselis A, Perumal J, Caon C, et al. Treatment of corticosteroid refractory optic neuritis in multiple sclerosis patients with intravenous immunoglobulin. Eur J Neurol 2008;15:1163–1167.

    Article  PubMed  CAS  Google Scholar 

  56. Visser LH, Beekman R, Tijssen CC, et al. A randomized, double-blind, placebocontrolled pilot study of i.v. immune globulins in combination with i.v. methylprednisolone in the treatment of relapses in patients with MS. Mult Scler 2004;10:89–91.

    Article  PubMed  CAS  Google Scholar 

  57. Sorensen PS, Haas J, Sellebjerg F, et al. IV immunoglobulins as add-on treatment to methylprednisolone for acute relapses in MS. Neurology 2004;63:2028–2033.

    Article  PubMed  CAS  Google Scholar 

  58. Roed HG, Langkilde A, Sellebjerg F, et al. A double-blind, randomized trial of IV immunoglobulin treatment in acute optic neuritis. Neurology 2005;64:804–810.

    Article  PubMed  CAS  Google Scholar 

  59. O’Connor PW, Goodman A, Willmer-Hulme AJ, et al. Randomized multicenter trial of natalizumab in acute MS relapses: clinical and MRI effects. Neurology 2004;62:2038–2043.

    Article  PubMed  Google Scholar 

  60. Cortese V, Chaudhry YT, So F, et al. Evidence-based guideline update: plasmapheresis in neurologis disorders: report of the therapeutics and technology assessment subcommittee of the Americal Academy of Neurology. Neurology 2011;76:294–300.

    Google Scholar 

  61. Perumal JS, Caon C, Hreha S, et al. Oral prednisone taper following intravenous steroids fails to improve disability or recovery from relapses in multiple sclerosis. Eur J Neurol 2008;7:677–680.

    Article  Google Scholar 

  62. Brod SA, Morales MM. Bio-equivalence of intramuscular and subcutaneous H.P. Acthar Gel. Biomed Pharmacother 2009;63:251–253.

    Article  PubMed  CAS  Google Scholar 

  63. 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.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Regina Berkovich.

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Berkovich, R. Treatment of Acute Relapses in Multiple Sclerosis. Neurotherapeutics 10, 97–105 (2013). https://doi.org/10.1007/s13311-012-0160-7

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