Minocycline added to subcutaneous interferon β-1a in multiple sclerosis: Randomized RECYCLINE study

European Journal of Neurology

Volumn 23, Issue 5, 2016, Pages 861-870

  Sorensen P S ^a   Sellebjerg, F ^a   Lycke, J ^b   Farkkila M ^c   Creange A ^d   Lund, C G ^e   Schluep, M ^f   Frederiksen, J L ^a   Stenager, E ^g   Pfleger, C ^h   Garde, E ^a   Kinnunen, E ⁱ   Marhardt, K ^j  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b SAHLGRENSKA UNIVERSITY HOSPITAL   (Sweden)

^c HELSINKI UNIVERSITY CENTRAL HOSPITAL   (Finland)

^d HENRI MONDOR HOSPITAL   (France)

^e OSLO UNIVERSITY HOSPITAL   (Norway)

^f LAUSANNE UNIVERSITY HOSPITAL   (Switzerland)

^g LILLEBAELT HOSPITAL   (Denmark)

^h AALBORG UNIVERSITY HOSPITAL   (Denmark)

ⁱ HYVINKÄÄ HOSPITAL   (Finland)

^j Merck GmbH   (Austria)

more..

Author keywords

Combination therapy; Interferon ; Minocycline; Multiple sclerosis; Randomized controlled trial

Indexed keywords

BETA1A INTERFERON; MINOCYCLINE; NEUTRALIZING ANTIBODY; PLACEBO; ANTIINFECTIVE AGENT;

ADULT; ANTIBODY BLOOD LEVEL; ARTHRALGIA; ARTICLE; BRAIN SIZE; CONTROLLED STUDY; DEPRESSION; DIARRHEA; DISEASE ACTIVITY; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; FLU LIKE SYNDROME; HEADACHE; HUMAN; HYPERTRANSAMINASEMIA; MAJOR CLINICAL STUDY; MULTICENTER STUDY; MULTIPLE SCLEROSIS; NAUSEA; NEUROIMAGING; NUCLEAR MAGNETIC RESONANCE IMAGING; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RASH; RECURRENCE RISK; RELAPSE; RHINOPHARYNGITIS; SIDE EFFECT; ADOLESCENT; BRAIN; COMBINATION DRUG THERAPY; DIAGNOSTIC IMAGING; DRUG EFFECTS; FEMALE; MALE; MIDDLE AGED; ORGAN SIZE; PATHOLOGY; PROCEDURES; TREATMENT OUTCOME; YOUNG ADULT;

ADOLESCENT; ADULT; ANTI-BACTERIAL AGENTS; BRAIN; DOUBLE-BLIND METHOD; DRUG THERAPY, COMBINATION; FEMALE; HUMANS; INTERFERON BETA-1A; MAGNETIC RESONANCE IMAGING; MALE; MIDDLE AGED; MINOCYCLINE; MULTIPLE SCLEROSIS; ORGAN SIZE; TREATMENT OUTCOME; YOUNG ADULT;

EID: 84962799515     PISSN: 13515101     EISSN: 14681331     Source Type: Journal    
DOI: 10.1111/ene.12953     Document Type: Article

References (40)

1. Duquette P, Girard M, Despault L, et al. Interferon beta-1b is effective in relapsing-remitting multiple-sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology 1993; 43: 655-661.
2. Jacobs LD, Cookfair DL, Rudick RA, et al. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Ann Neurol 1996; 39: 285-294.
3. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group. Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. Lancet 1998; 352: 1498-1504.
4. Martinelli V, Capra R, Cocco E, et al. High incidence of acute leukaemia in multiple sclerosis patients treated with mitoxantrone: a retrospective multicentre Italian study. Mult Scler 2009; 15(Suppl. 9): S251.
5. Hartung HP, Gonsette R, Konig N, et al. Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial. Lancet 2002; 360: 2018-2025.
6. Hartung HP. New cases of progressive multifocal leukoencephalopathy after treatment with natalizumab. Lancet Neurol 2009; 8: 28-31.
7. Polman CH, O'Connor PW, Havrdova E, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006; 354: 899-910.
8. Yousry TA, Major EO, Ryschkewitsch C, et al. Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy. N Engl J Med 2006; 354: 924-933.
9. Yong VW, Wells J, Giuliani F, Casha S, Power C, Metz LM. The promise of minocycline in neurology. Lancet Neurol 2004; 3: 744-751.
10. Brundula V, Rewcastle NB, Metz LM, Bernard CC, Yong VW. Targeting leukocyte MMPs and transmigration: minocycline as a potential therapy for multiple sclerosis. Brain 2002; 125: 1297-1308.
11. Paemen L, Martens E, Norga K, et al. The gelatinase inhibitory activity of tetracyclines and chemically modified tetracycline analogues as measured by a novel microtiter assay for inhibitors. Biochem Pharmacol 1996; 52: 105-111.
12. Giuliani F, Hader W, Yong VW. Minocycline attenuates T cell and microglia activity to impair cytokine production in T cell-microglia interaction. J Leukoc Biol 2005; 78: 135-143.
13. Converse AK, Larsen EC, Engle JW, Barnhart TE, Nickles RJ, Duncan ID. 11C-(R)-PK11195 PET imaging of microglial activation and response to minocycline in zymosan-treated rats. J Nucl Med 2011; 52: 257-262.
14. Maier K, Merkler D, Gerber J, et al. Multiple neuroprotective mechanisms of minocycline in autoimmune CNS inflammation. Neurobiol Dis 2007; 25: 514-525.
15. Orsucci D, Calsolaro V, Mancuso M, Siciliano G. Neuroprotective effects of tetracyclines: molecular targets, animal models and human disease. CNS Neurol Disord Drug Targets 2009; 8: 222-231.
16. Popovic N, Schubart A, Goetz BD, Zhang SC, Linington C, Duncan ID. Inhibition of autoimmune encephalom-yelitis by a tetracycline. Ann Neurol 2002; 51: 215-223.
17. Nikodemova M, Lee J, Fabry Z, Duncan ID. Minocycline attenuates experimental autoimmune encephalomyelitis in rats by reducing T cell infiltration into the spinal cord. J Neuroimmunol 2010; 219: 33-37.
18. Giuliani F, Fu SA, Metz LM, Yong VW. Effective combination of minocycline and interferon-beta in a model of multiple sclerosis. J Neuroimmunol 2005; 165: 83-91.
19. Chen X, Pi R, Liu M, et al. Combination of methylprednisolone and minocycline synergistically improves experimental autoimmune encephalomyelitis in C57 BL/6 mice. J Neuroimmunol 2010; 226: 104-109.
20. Chen X, Hu X, Zou Y, et al. Combined treatment with minocycline and prednisone attenuates experimental autoimmune encephalomyelitis in C57 BL/6 mice. J Neuroimmunol 2009; 210: 22-29.
21. Giuliani F, Metz LM, Wilson T, Fan Y, Bar-Or A, Yong VW. Additive effect of the combination of glatiramer acetate and minocycline in a model of MS. J Neuroimmunol 2005; 158: 213-221.
22. Luccarini I, Ballerini C, Biagioli T, et al. Combined treatment with atorvastatin and minocycline suppresses severity of EAE. Exp Neurol 2008; 211: 214-226.
23. Metz LM, Li D, Traboulsee A, et al. Minocycline reduces the relative risk of multiple sclerosis in people experiencing their first clinical demyelinating event by 44.6%: results of a phase III doubleblind placebo controlled Canadian multicentre clinical trial. Mult Scler 2015; 23 (Suppl. 11): Abstract 227.
24. Metz LM, Zhang Y, Yeung M, et al. Minocycline reduces gadolinium-enhancing magnetic resonance imaging lesions in multiple sclerosis. Ann Neurol 2004; 55: 756.
25. Zhang Y, Metz LM, Yong VW, et al. Pilot study of minocycline in relapsing-remitting multiple sclerosis. Can J Neurol Sci 2008; 35: 185-191.
26. Metz LM, Li D, Traboulsee A, et al. Glatiramer acetate in combination with minocycline in patients with relapsing-remitting multiple sclerosis: results of a Canadian, multicenter, double-blind, placebo-controlled trial. Mult Scler 2009; 15: 1183-1194.
27. Polman CH, Reingold SC, Edan G, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the 'McDonald Criteria'. Ann Neurol 2005; 58: 840-846.
28. Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983; 13: 227-231.
29. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983; 33: 1444-1452.
30. Pocock SJ, Simon R. Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. Biometrics 1975; 31: 103-115.
31. Sorensen PS, Mellgren SI, Svenningsson A, et al. Nordic trial of oral methylprednisolone as add-on therapy to interferon beta-1a for treatment of relapsing-remitting multiple sclerosis (NORMIMS study): a randomised, placebo-controlled trial. Lancet Neurol 2009; 8: 519-529.
32. Veldhuis WB, Floris S, van der Meide PH, et al. Interferon-beta prevents cytokine-induced neutrophil infiltration and attenuates blood-brain barrier disruption. J Cereb Blood Flow Metab 2003; 23: 1060-1069.
33. Bernal F, Elias B, Hartung HP, Kieseier BC. Regulation of matrix metalloproteinases and their inhibitors by interferon-beta: a longitudinal study in multiple sclerosis patients. Mult Scler 2009; 15: 721-727.
34. Blanchette F, Neuhaus O. Glatiramer acetate: evidence for a dual mechanism of action. J Neurol 2008; 255(Suppl. 1): 26-36.
35. Minagar A, Alexander JS, Schwendimann RN, et al. Combination therapy with interferon beta-1a and doxycycline in multiple sclerosis: an open-label trial. Arch Neurol 2008; 65: 199-204.
36. Sorensen PS, Lycke J, Eralinna JP, et al. Simvastatin as add-on therapy to interferon beta-1a for relapsing-remitting multiple sclerosis (SIMCOMBIN study): a placebo-controlled randomised phase 4 trial. Lancet Neurol 2011; 10: 691-701.
37. Birnbaum G, Cree B, Altafullah I, Zinser M, Reder AT. Combining beta interferon and atorvastatin may increase disease activity in multiple sclerosis. Neurology 2008; 71: 1390-1395.
38. Bhardwaj S, Coleman CI, Sobieraj DM. Efficacy of statins in combination with interferon therapy in multiple sclerosis: a meta-analysis. Am J Health Syst Pharm 2012; 69: 1494-1499.
39. Lublin FD, Cofield SS, Cutter GR, et al. Randomized study combining interferon and glatiramer acetate in multiple sclerosis. Ann Neurol 2013; 73: 327-340.
40. Ravnborg M, Sorensen PS, Andersson M, et al. Methylprednisolone in combination with interferon beta-1a for relapsing-remitting multiple sclerosis (MECOMBIN study): a multicentre, double-blind, randomised, placebo-controlled, parallel-group trial. Lancet Neurol 2010; 9: 672-680.