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Campath 1-H treatment in patients with aggressive relapsing remitting multiple sclerosis

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Abstract

Campath 1-H (Alemtuzumab) is a humanised monoclonal antibody which targets the CD52 antigen, a low molecular weight glycoprotein present on the surface of most lymphocyte lineages, causing complement mediated lysis and rapid and prolonged T lymphocyte depletion. Following encouraging initial data from other centres we report our open label experience of using Campath 1-H as a treatment in aggressive relapsing multiple sclerosis in a consecutive series of 39 highly selected patients treated across three regional centres and followed for a mean of 1.89 years.

The mean annualised relapse rate fell from 2.48 pre treatment to 0.19 post treatment with 29% of documented relapses observed in the 12 weeks following initial infusion. Mean change in EDSS was –0.36 overall and –0.15 in those patients completing ≥1 year of follow- up. Eighty-three per cent of patients had stable or improved disability following treatment. Infusion related side effects were common including rash, headache and pyrexia but were usually mild and self limiting. Transient worsening of pre-existing neurological deficits during infusion was observed in 3 patients. 12 patients developed biochemical evidence of autoimmune dysfunction, 2 patients developed thyroid disease and 1 patient autoimmune skin disease.

We conclude that relapse rates fall following Campath 1-H. Whilst side effects were common these were normally self limiting or easily managed, suggesting Campath 1-H may be of use in the treatment of very active relapsing remitting multiple sclerosis.

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References

  1. Bennetto L, Totham A, Healy P, Massey E, Scolding N (2004) Plasma exchange in episodes of severe inflammatory demyelination of the central nervous system. A report of six cases. J Neurol 251:1515–1521

    Article  PubMed  Google Scholar 

  2. Bornstein MB, Miller A, Slagle S, Weitzman M, Drexler E, Keilson M, Spada V, Weiss W, Appel S, Rolak L, et al. (1991) A placebo-controlled, double-blind, randomized, two-center, pilot trial of Cop 1 in chronic progressive multiple sclerosis. Neurology 41:533–539

    PubMed  CAS  Google Scholar 

  3. Brett S, Baxter G, Cooper H, Johnston JM, Tite J, Rapson N (1996) Repopulation of blood lymphocyte sub-populations in rheumatoid arthritis patients treated with the depleting humanized monoclonal antibody, CAMPATH-1H. Immunology 88:13–19

    Article  PubMed  CAS  Google Scholar 

  4. Bronnum-Hansen H, Koch-Henriksen N, Hyllested K (1994) Survival of patients with multiple sclerosis in Denmark: a nationwide, long-term epidemiologic survey. Neurology 44:1901–1907

    PubMed  CAS  Google Scholar 

  5. Coles A, Deans J, Compston A (2004) Campath-1H treatment of multiple sclerosis: lessons from the bedside for the bench. Clin Neurol Neurosurg 106:270–274

    Article  PubMed  Google Scholar 

  6. Coles AJ, Cox A, Le Page E, Jones J, Trip SA, Deans J, Seaman S, Miller DH, Hale G, Waldmann H, Compston DA (2006) The window of therapeutic opportunity in multiple sclerosis. Evidence from monoclonal antibody therapy. J Neurol 253:98–108

    Article  PubMed  Google Scholar 

  7. Coles AJ, Wing M, Smith S, Coraddu F, Greer S, Taylor C, Weetman A, Hale G, Chatterjee VK, Waldmann H, Compston A (1999) Pulsed monoclonal antibody treatment and autoimmune thyroid disease in multiple sclerosis. Lancet 354:1691–1695

    Article  PubMed  CAS  Google Scholar 

  8. Coles AJ, Wing MG, Molyneux P, Paolillo A, Davie CM, Hale G, Miller D, Waldmann H, Compston A (1999) Monoclonal antibody treatment exposes three mechanisms underlying the clinical course of multiple sclerosis. Ann Neurol 46:296–304

    Article  PubMed  CAS  Google Scholar 

  9. Comi G, Filippi M, Barkhof F, Durelli L, Edan G, Fernandez O, Hartung H, Seeldrayers P, Sorensen PS, Rovaris M, Martinelli V, Hommes OR (2001) Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet 357:1576–1582

    Article  PubMed  CAS  Google Scholar 

  10. Compston A, Coles A (2002) Multiple sclerosis. Lancet 359:1221–1231

    Article  PubMed  Google Scholar 

  11. Compston A, Margolin DH, Haas JF, Magner J, Gonzales G, Valente WA, Coles AJ (2006) Two year interim analysis of thyroid abnormalities in a trail of Alemtuzumab Vs high dose interferon beta-1a for treatment of relapsing-remitting multiple sclerosis (abstract). European Neurological Society Meeting 2006

  12. Confavreux C, Aimard G, Devic M (1980) Course and prognosis of multiple sclerosis assessed by the computerized data processing of 349 patients. Brain 103:281–300

    Article  PubMed  CAS  Google Scholar 

  13. Confavreux C, Vukusic S, Moreau T, Adeleine P (2000) Relapses and progression of disability in multiple sclerosis. N Engl J Med 343:1430–1438

    Article  PubMed  CAS  Google Scholar 

  14. Eriksson M, Andersen O, Runmarker B (2003) Long-term follow up of patients with clinically isolated syndromes, relapsing- remitting and secondary progressive multiple sclerosis. Mult Scler 9:260–274

    Article  PubMed  Google Scholar 

  15. Fassas A, Passweg JR, Anagnostopoulos A, Kazis A, Kozak T, Havrdova E, Carreras E, Graus F, Kashyap A, Openshaw H, Schipperus M, Deconinck E, Mancardi G, Marmont A, Hansz J, Rabusin M, Zuazu Nagore FJ, Besalduch J, Dentamaro T, Fouillard L, Hertenstein B, La Nasa G, Musso M, Papineschi F, Rowe JM, Saccardi R, Steck A, Kappos L, Gratwohl A, Tyndall A, Samijn J (2002) Hematopoietic stem cell transplantation for multiple sclerosis. A retrospective multicenter study. J Neurol 249:1088–1097

    Article  PubMed  CAS  Google Scholar 

  16. Fox E, Mayer L (2006) Alemtuzumab treatment in relapsing remitting multiple sclerosis patients who have failed licenced beta-interferon treatment: one year data. (Abstract). European Neurological Society Meeting 2006

  17. Galetta SL (2001) The controlled high risk Avonex multiple sclerosis trial (CHAMPS Study). J Neuroophthalmol 21:292–295

    PubMed  CAS  Google Scholar 

  18. Genzyme (2006) Genzyme reports interim results from trial of Campath for Multiple Sclerosis. Retrieved 14 September 2006 from <http://www. genzyme. co. uk/corp/news/all news/ GENZ%20PR-091605. asp>

  19. Haider I, Cahill M (2004) Fatal thrombocytopaenia temporally related to the administration of alemtuzumab (Mab- Campath) for refractory CLL despite early discontinuation of therapy. Hematology 9:409–411

    Article  PubMed  CAS  Google Scholar 

  20. Hale G, Xia MQ, Tighe HP, Dyer MJ, Waldmann H (1990) The CAMPATH-1 antigen (CDw52). Tissue Antigens 35:118–127

    PubMed  CAS  Google Scholar 

  21. Jacobs LD, Cookfair DL, Rudick RA, Herndon RM, Richert JR, Salazar AM, Fischer JS, Goodkin DE, Granger CV, Simon JH, Alam JJ, Bartoszak DM, Bourdette DN, Braiman J, Brownscheidle CM, Coats ME, Cohan SL, Dougherty DS, Kinkel RP, Mass MK, Munschauer FE, 3rd, Priore RL, Pullicino PM, Scherokman BJ, Whitham RH, et al. (1996) Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Ann Neurol 39:285–294

    Article  PubMed  CAS  Google Scholar 

  22. Johnson KP, Brooks BR, Cohen JA, Ford CC, Goldstein J, Lisak RP, Myers LW, Panitch HS, Rose JW, Schiffer RB (1995) Copolymer 1 reduces relapse rate and improves disability in relapsing- remitting multiple sclerosis: results of a phase III multicenter, doubleblind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group. Neurology 45:1268–1276

    PubMed  CAS  Google Scholar 

  23. Lenihan DJ, Alencar AJ, Yang D, Kurzrock R, Keating MJ, Duvic M (2004) Cardiac toxicity of alemtuzumab in patients with mycosis fungoides/Sezary syndrome. Blood 104:655–658

    Article  PubMed  CAS  Google Scholar 

  24. Lundin J, Osterborg A, Brittinger G, Crowther D, Dombret H, Engert A, Epenetos A, Gisselbrecht C, Huhn D, Jaeger U, Thomas J, Marcus R, Nissen N, Poynton C, Rankin E, Stahel R, Uppenkamp M, Willemze R, Mellstedt H (1998) CAMPATH-1H monoclonal antibody in therapy for previously treated low-grade non-Hodgkin’s lymphomas: a phase II multicenter study. European Study Group of CAMPATH-1H Treatment in Low- Grade Non-Hodgkin’s Lymphoma. J Clin Oncol 16:3257–3263

    PubMed  CAS  Google Scholar 

  25. Matteson EL, Yocum DE, St Clair EW, Achkar AA, Thakor MS, Jacobs MR, Hays AE, Heitman CK, Johnston JM (1995) Treatment of active refractory rheumatoid arthritis with humanized monoclonal antibody CAMPATH-1H administered by daily subcutaneous injection. Arthritis Rheum 38:1187–1193

    Article  PubMed  CAS  Google Scholar 

  26. Mc Alpine D, Compston N (1952) Some aspects of the natural history of disseminated sclerosis. Q J Med 21:135–167

    CAS  Google Scholar 

  27. McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, McFarland HF, Paty DW, Polman CH, Reingold SC, Sandberg-Wollheim M, Sibley W, Thompson A, van den Noort S, Weinshenker BY, Wolinsky JS (2001) Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 50:121–127

    Article  PubMed  CAS  Google Scholar 

  28. Millefiorini E, Gasperini C, Pozzilli C, D’Andrea F, Bastianello S, Trojano M, Morino S, Morra VB, Bozzao A, Calo A, Bernini ML, Gambi D, Prencipe M (1997) Randomized placebo-controlled trial of mitoxantrone in relapsing- remitting multiple sclerosis: 24-month clinical and MRI outcome. J Neurol 244:153–159

    Article  PubMed  CAS  Google Scholar 

  29. Moreau T, Coles A, Wing M, Isaacs J, Hale G, Waldmann H, Compston A (1996) Transient increase in symptoms associated with cytokine release in patients with multiple sclerosis. Brain 119(Pt 1):225–237

    Article  PubMed  Google Scholar 

  30. Moreau T, Thorpe J, Miller D, Moseley I, Hale G, Waldmann H, Clayton D, Wing M, Scolding N, Compston A (1994) Preliminary evidence from magnetic resonance imaging for reduction in disease activity after lymphocyte depletion in multiple sclerosis. Lancet 344:298–301

    Article  PubMed  CAS  Google Scholar 

  31. Ostberg A, Pittas F, Taylor B (2005) Use of low-dose mitozantrone to treat aggressive multiple sclerosis: a singlecentre open-label study using patient self-assessment and clinical measures of multiple sclerosis status. Intern Med J 35:382–387

    Article  PubMed  CAS  Google Scholar 

  32. Osterborg A, Dyer MJ, Bunjes D, Pangalis GA, Bastion Y, Catovsky D, Mellstedt H (1997) Phase II multicenter study of human CD52 antibody in previously treated chronic lymphocytic leukemia. European Study Group of CAMPATH-1H Treatment in Chronic Lymphocytic Leukemia. J Clin Oncol 15:1567–1574

    PubMed  CAS  Google Scholar 

  33. Ostor AG (1993) Natural history of cervical intraepithelial neoplasia: a critical review. Int J Gynecol Pathol 12:186–192

    Article  PubMed  CAS  Google Scholar 

  34. Otton SH, Turner DL, Frewin R, Davies SV, Johnson SA (1999) Autoimmune thrombocytopenia after treatment with Campath 1H in a patient with chronic lymphocytic leukaemia. Br J Haematol 106:261–262

    Article  PubMed  CAS  Google Scholar 

  35. Paolillo A, Coles AJ, Molyneux PD, Gawne-Cain M, MacManus D, Barker GJ, Compston DA, Miller DH (1999) Quantitative MRI in patients with secondary progressive MS treated with monoclonal antibody Campath 1H. Neurology 53:751–757

    PubMed  CAS  Google Scholar 

  36. Paul F, Dorr J, Wurfel J, Vogel HP, Zipp F (2007) Early mitoxantrone-induced cardiotoxicity in secondary progressive multiple sclerosis. J Neurol Neurosurg Psychiatry 78:198–200

    Article  PubMed  CAS  Google Scholar 

  37. Pawson R, Dyer MJ, Barge R, Matutes E, Thornton PD, Emmett E, Kluin- Nelemans JC, Fibbe WE, Willemze R, Catovsky D (1997) Treatment of T-cell prolymphocytic leukemia with human CD52 antibody. J Clin Oncol 15:2667–2672

    PubMed  CAS  Google Scholar 

  38. Phadke JG (1987) Survival pattern and cause of death in patients with multiple sclerosis: results from an epidemiological survey in north east Scotland. J Neurol Neurosurg Psychiatry 50:523–531

    Article  PubMed  CAS  Google Scholar 

  39. Polman CH, O’Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips JT, Lublin FD, Giovannoni G, Wajgt A, Toal M, Lynn F, Panzara MA, Sandrock AW (2006) A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 354:899–910

    Article  PubMed  CAS  Google Scholar 

  40. Poser S, Poser W, Schlaf G, Firnhaber W, Lauer K, Wolter M, Evers P (1986) Prognostic indicators in multiple sclerosis. Acta Neurol Scand 74:387–392

    Article  PubMed  CAS  Google Scholar 

  41. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group (1998) Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/ remitting multiple sclerosis. Lancet 352:1498–1504

    Article  Google Scholar 

  42. Ramtahal J, Jacob A, Das K, Boggild M (2006) Sequential maintenance treatment with glatiramer acetate after mitoxantrone is safe and can limit exposure to immunosuppression in very active, relapsing remitting multiple sclerosis. J Neurol 253:1160–1164

    Article  PubMed  CAS  Google Scholar 

  43. Riechmann L, Clark M, Waldmann H, Winter G (1988) Reshaping human antibodies for therapy. Nature 332:323–327

    Article  PubMed  CAS  Google Scholar 

  44. Riise T, Gronning M, Aarli JA, Nyland H, Larsen JP, Edland A (1988) Prognostic factors for life expectancy in multiple sclerosis analysed by Cox-models. J Clin Epidemiol 41:1031–1036

    Article  PubMed  CAS  Google Scholar 

  45. Tang SC, Hewitt K, Reis MD, Berinstein NL (1996) Immunosuppressive toxicity of CAMPATH1H monoclonal antibody in the treatment of patients with recurrent low grade lymphoma. Leuk Lymphoma 24:93–101

    Article  PubMed  CAS  Google Scholar 

  46. The IFNB Multiple Sclerosis Study Group (1993) Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I Clinical results of a multicenter, randomized, doubleblind, placebo-controlled trial. Neurology 43:655–661

    Google Scholar 

  47. Tremlett H, Paty D, Devonshire V (2006) Disability progression in multiple sclerosis is slower than previously reported. Neurology 66:172–177

    Article  PubMed  Google Scholar 

  48. Trojano M, Avolio C, Manzari C, Calo A, De Robertis F, Serio G, Livrea P (1995) Multivariate analysis of predictive factors of multiple sclerosis course with a validated method to assess clinical events. J Neurol Neurosurg Psychiatry 58:300–306

    PubMed  CAS  Google Scholar 

  49. Visscher BR, Liu KS, Clark VA, Detels R, Malmgren RM, Dudley JP (1984) Onset symptoms as predictors of mortality and disability in multiple sclerosis. Acta Neurol Scand 70:321–328

    Article  PubMed  CAS  Google Scholar 

  50. Weinblatt ME, Maddison PJ, Bulpitt KJ, Hazleman BL, Urowitz MB, Sturrock RD, Coblyn JS, Maier AL, Spreen WR, Manna VK, et al. (1995) CAMPATH-1H, a humanized monoclonal antibody, in refractory rheumatoid arthritis. An intravenous dose-escalation study. Arthritis Rheum 38:1589–1594

    Article  PubMed  CAS  Google Scholar 

  51. Weinshenker BG, Bass B, Rice GP, Noseworthy J, Carriere W, Baskerville J, Ebers GC (1989) The natural history of multiple sclerosis: a geographically based study. 2. Predictive value of the early clinical course. Brain 112(Pt 6):1419–1428

    Article  PubMed  Google Scholar 

  52. Weinshenker BG, Rice GP, Noseworthy JH, Carriere W, Baskerville J, Ebers GC (1991) The natural history of multiple sclerosis: a geographically based study. 3. Multivariate analysis of predictive factors and models of outcome. Brain 114(Pt 2):1045–1056

    Article  PubMed  Google Scholar 

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Hirst, C.L., Pace, A., Pickersgill, T.P. et al. Campath 1-H treatment in patients with aggressive relapsing remitting multiple sclerosis. J Neurol 255, 231–238 (2008). https://doi.org/10.1007/s00415-008-0696-y

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