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01-08-2016 | Original Communication

Relapse frequency in transitioning from natalizumab to dimethyl fumarate: assessment of risk factors

Authors: Jonathan Zurawski, Ashley Flinn, Lindsay Sklover, Jacob A. Sloane

Published in: Journal of Neurology | Issue 8/2016

Abstract

Risk of relapse after natalizumab (NAT) cessation and switch to dimethyl fumarate (DMF) is unknown. The objective of this paper is to identify the risk and associated risk factors for relapse after switching from NAT to DMF in relapsing-remitting multiple sclerosis. Patients (n = 30) were treated with NAT for ≥12 months and then switched to DMF in a mean of 50 days. Patient age, annualized relapse rates (ARR), Expanded Disability Status Scale scores (EDSS), and lymphocyte counts were assessed. Overall, eight patients (27 %) had relapses after switching to DMF. Five patients (17 %) suffered severe relapses with multifocal clinical and radiological findings. New lesions by MRI (T2 hyperintense or enhancing) were observed in 35 % of patients. Relapses occurred at a mean of 3.5 months after NAT cessation. Patient age and elevated ARR prior to NAT use were significantly associated with risk of relapse after switch to DMF. Once on DMF for 4 months prior to relapse, lymphocyte count decreased more significantly in patients without relapses than those with relapses. Switching from NAT to DMF correlated with increased relapses. Young patient age, high ARR and stability of lymphocyte counts were risk factors for relapse after transition from NAT to DMF.

Bloomgren G, Richman S, Hotermans C et al (2012) Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med 366:1870–1880CrossRefPubMed

Plavina T, Subramanyam M, Bloomgren G et al (2014) Anti-JC virus antibody levels in serum or plasma further define risk of natalizumab-associated progressive multifocal leukoencephalopathy. Ann Neurol 76:802–812CrossRefPubMed

Miller DH, Khan OA, Sheremata WA et al (2003) A controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 348:15–23CrossRefPubMed

Fox RJ, Cree BA, De Seze J et al (2014) MS disease activity in RESTORE: a randomized 24-week natalizumab treatment interruption study. Neurology 82:1491–1498CrossRefPubMedPubMedCentral

Killestein J, Vennegoor A, Strijbis EM et al (2010) Natalizumab drug holiday in multiple sclerosis: poorly tolerated. Ann Neurol 68:392–395CrossRefPubMed

Kerbrat A, Le Page E, Leray E et al (2011) Natalizumab and drug holiday in clinical practice: an observational study in very active relapsing remitting multiple sclerosis patients. J Neurol Sci 308:98–102CrossRefPubMed

West TW, Cree BA (2010) Natalizumab dosage suspension: are we helping or hurting? Ann Neurol 68:395–399CrossRefPubMed

Vidal-Jordana A, Tintore M, Tur C et al (2015) Significant clinical worsening after natalizumab withdrawal: predictive factors. Mult Scler 21:780–785CrossRefPubMed

Salhofer-Polanyi S, Baumgartner A, Kraus J, Maida E, Schmied M, Leutmezer F (2014) What to expect after natalizumab cessation in a real-life setting. Acta Neurol Scand 130:97–102CrossRefPubMed

10.

Gueguen A, Roux P, Deschamps R et al (2014) Abnormal inflammatory activity returns after natalizumab cessation in multiple sclerosis. J Neurol Neurosurg Psychiatry 85:1038–1040CrossRefPubMed

11.

O’Connor PW, Goodman A, Kappos L et al (2011) Disease activity return during natalizumab treatment interruption in patients with multiple sclerosis. Neurology 76:1858–1865CrossRefPubMed

12.

Borriello G, Prosperini L, Marinelli F, Fubelli F, Pozzilli C (2011) Observations during an elective interruption of natalizumab treatment: a post-marketing study. Mult Scler 17:372–375CrossRefPubMed

13.

Melis M, Cocco E, Frau J et al (2014) Post-natalizumab clinical and radiological findings in a cohort of multiple sclerosis patients: 12-month follow-up. Neurol Sci 35:401–408CrossRefPubMed

14.

Sorensen PS, Koch-Henriksen N, Petersen T, Ravnborg M, Oturai A, Sellebjerg F (2014) Recurrence or rebound of clinical relapses after discontinuation of natalizumab therapy in highly active MS patients. J Neurol 261:1170–1177CrossRefPubMed

15.

Clerico M, Schiavetti I, De Mercanti SF et al (2014) Treatment of relapsing-remitting multiple sclerosis after 24 doses of natalizumab: evidence from an Italian spontaneous, prospective, and observational study (the TY-STOP Study). JAMA Neurol 71:954–960CrossRefPubMed

16.

Rigau V, Mania A, Befort P et al (2012) Lethal multiple sclerosis relapse after natalizumab withdrawal. Neurology 79:2214–2216CrossRefPubMed

17.

Benkert TF, Dietz L, Hartmann EM et al (2012) Natalizumab exerts direct signaling capacity and supports a pro-inflammatory phenotype in some patients with multiple sclerosis. PLoS One 7:e52208CrossRefPubMedPubMedCentral

18.

Hartung HP (2009) New cases of progressive multifocal leukoencephalopathy after treatment with natalizumab. Lancet Neurol 8:28–31CrossRefPubMed

19.

Hauser SL, Johnston SC (2009) Balancing risk and reward: the question of natalizumab. Ann Neurol 66:A7–A8

20.

de Seze J, Ongagna JC, Collongues N et al (2013) Reduction of the washout time between natalizumab and fingolimod. Mult Scler 19:1248CrossRefPubMed

21.

Rinaldi F, Seppi D, Calabrese M, Perini P, Gallo P (2012) Switching therapy from natalizumab to fingolimod in relapsing-remitting multiple sclerosis: clinical and magnetic resonance imaging findings. Mult Scler 18:1640–1643CrossRefPubMed

22.

Jokubaitis VG, Li V, Kalincik T et al (2014) Fingolimod after natalizumab and the risk of short-term relapse. Neurology 82:1204–1211CrossRefPubMedPubMedCentral

23.

Sempere AP, Martin-Medina P, Berenguer-Ruiz L et al (2013) Switching from natalizumab to fingolimod: an observational study. Acta Neurol Scand 128:e6–e10CrossRefPubMed

24.

Centonze D, Rossi S, Rinaldi F, Gallo P (2012) Severe relapses under fingolimod treatment prescribed after natalizumab. Neurology 79:2004–2005CrossRefPubMed

25.

Cohen M, Maillart E, Tourbah A et al (2014) Switching from natalizumab to fingolimod in multiple sclerosis: a French prospective study. JAMA Neurol 71:436–441CrossRefPubMed

26.

Laroni A, Brogi D, Milesi V, Abate L, Uccelli A, Mancardi G (2013) Early switch to fingolimod may decrease the risk of disease recurrence after natalizumab interruption. Mult Scler 19:1236–1237CrossRefPubMed

27.

Hoepner R, Havla J, Eienbroker C et al (2014) Predictors for multiple sclerosis relapses after switching from natalizumab to fingolimod. Mult Scler 20:1714–1720CrossRefPubMed

28.

Foley JF, Hoyt T, Christensen A, Blatter D (2014) A pilot study to assess disease state stability, efficacy, and tolerability in a natalizumab to dimethyl fumarate crossover design. ACTRIMS abstract P877

29.

Rosenkranz T, Novas M, Terborg C (2015) PML in a patient with lymphocytopenia treated with dimethyl fumarate. N Engl J Med 372:1476–1478CrossRefPubMed

30.

Hoepner R, Faissner S, Klasing A et al (2015) Progressive multifocal leukoencephalopathy during fumarate monotherapy of psoriasis. Neurol Neuroimmunol Neuroinflamm 2:e85CrossRefPubMedPubMedCentral

31.

Sweetser MT, Dawson KT, Bozic C (2013) Manufacturer’s response to case reports of PML. N Engl J Med 368:1659–1661CrossRefPubMed

32.

Ermis U, Weis J, Schulz JB (2013) PML in a patient treated with fumaric acid. N Engl J Med 368:1657–1658CrossRefPubMed

33.

van Oosten BW, Killestein J, Barkhof F, Polman CH, Wattjes MP (2013) PML in a patient treated with dimethyl fumarate from a compounding pharmacy. N Engl J Med 368:1658–1659CrossRefPubMed

34.

Nieuwkamp DJ, Murk JL, van Oosten BW et al (2015) PML in a patient without severe lymphocytopenia receiving dimethyl fumarate. N Engl J Med 372:1474–1476CrossRefPubMed

35.

Stoppe M, Thoma E, Liebert UG et al (2014) Cerebellar manifestation of PML under fumarate and after efalizumab treatment of psoriasis. J Neurol 261:1021–1024CrossRefPubMed

36.

Bartsch T, Rempe T, Wrede A et al (2015) Progressive neurologic dysfunction in a psoriasis patient treated with dimethyl fumarate. Ann Neurol 78:501–514CrossRefPubMed

37.

Longbrake EE, Cross AH (2015) Dimethyl fumarate associated lymphopenia in clinical practice. Mult Scler 21:796–797CrossRefPubMed

38.

Spencer CM, Crabtree-Hartman EC, Lehmann-Horn K, Cree BA, Zamvil SS (2015) Reduction of CD8(+) T lymphocytes in multiple sclerosis patients treated with dimethyl fumarate. Neurol Neuroimmunol Neuroinflamm 2:e76CrossRefPubMedPubMedCentral

39.

Berkovich R, Weiner LP (2015) Effects of dimethyl fumarate on lymphocyte subsets. Mult Scler Relat Disord 4:339–341CrossRefPubMed

40.

Khatri BO, Garland J, Berger J et al (2015) The effect of dimethyl fumarate (Tecfidera™) on lymphocyte counts: a potential contributor to progressive multifocal leukoencephalopathy risk. Mult Scler Relat Disord 4:377–379CrossRefPubMed

41.

Treumer F, Zhu K, Glaser R, Mrowietz U (2003) Dimethylfumarate is a potent inducer of apoptosis in human T cells. J Invest Dermatol 121:1383–1388CrossRefPubMed

42.

Linton PJ, Dorshkind K (2004) Age-related changes in lymphocyte development and function. Nat Immunol 5:133–139CrossRefPubMed

43.

Lo Re M, Capobianco M, Ragonese P et al (2015) Natalizumab discontinuation and treatment strategies in patients with multiple sclerosis (MS): a retrospective study from two Italian MS centers. Neurol Ther 4:147–157CrossRefPubMedPubMedCentral

44.

Iaffaldano P, Lucisano G, Pozzilli C et al (2015) Fingolimod versus interferon beta/glatiramer acetate after natalizumab suspension in multiple sclerosis. Brain 138:3275–3286CrossRefPubMed

45.

Kappos L, Radue EW, Comi G et al (2015) Switching from natalizumab to fingolimod: a randomized, placebo-controlled study in RRMS. Neurology 85(1):29–39CrossRefPubMedPubMedCentral

46.

Putzki N (2014) Characteristics of PML cases in multiple sclerosis patients switching to fingolimod from natalizumab. ECTRIMS abstract FC3.1

47.

Bartsch T, Rempe T, Wrede A et al (2015) Progressive neurologic dysfunction in a psoriasis patient treated with dimethyl fumarate. Ann Neurol. 78(4):501–514CrossRefPubMed

48.

Kappos L, Giovannoni G, Gold R et al (2015) Time course of clinical and neuroradiological effects of delayed-release dimethyl fumarate in multiple sclerosis. Eur J Neurol 22(4):664–671CrossRefPubMedPubMedCentral

49.

Longbrake EE, Naismith RT, Parks BJ et al (2015) Dimethyl fumarate-associated lymphopenia: risk factors and clinical significance. Mult Scler J Exp Transl Clin. 1:2055217315596994PubMedPubMedCentral

Title: Relapse frequency in transitioning from natalizumab to dimethyl fumarate: assessment of risk factors
Authors: Jonathan Zurawski
Ashley Flinn
Lindsay Sklover
Jacob A. Sloane
Publication date: 01-08-2016
Publisher: Springer Berlin Heidelberg
Published in: Journal of Neurology / Issue 8/2016
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-016-8162-8

2024 ASCO Annual Meeting

Springer Medicine

Relapse frequency in transitioning from natalizumab to dimethyl fumarate: assessment of risk factors

Abstract

2024 ASCO Annual Meeting

Springer Medicine

Abstract

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