Interferons in multiple sclerosis: Ten years' experience
Section snippets
Efficacy of interferons: a review
Interferons (IFNs) are made by recombinant DNA technology in tissue culture and are highly purified. IFNβ-1b is not glycosylated and is issued from recombinant bacterial cell product, with a serine substituting for cysteine at position 17. IFNβ-1a is glycosylated and produced by recombinant mammalian cells. Its amino acid sequence is identical to that of natural IFNβ.
IFNβ-1b was approved after the publication in 1993 of a first multicentre United States double-blind versus placebo controlled
Interferon-beta treatment is associated with side effects
Interferon-beta is usually well tolerated. Side effects partially depend on the route of administration and on the dosage used. In most studies, the percentage of patients discontinuing treatment because of side effects was low [1], [5], [7].
The most important and valuable side effects for all preparations are flu-like reactions (fever, myalgia, arthralgia, general discomfort) lasting for 24 to 48 h after injections, and decreasing over time. Treatment of these symptoms is based on preventive
Should all patients be treated with IFNs?
In the 1990s, based on class I evidence from controlled clinical trials, it was recommended to treat with IFNs ambulatory patients (EDSS 5.5 or lower), aged 18 to 50 years with a definite MS, a RR course, and active disease defined by at least two acute exacerbations during the previous two years [11]. After the publication of the results of intramuscularly injected IFN, the definition of active disease was extended to two attacks during the three previous years.
In the late 1990s, it was also
What about patients with no MRI risk? With a possible benign predictable course?
Two important unresolved questions concern patients with CDMS without clinical activity, and those with a first demyelinating event with poor or no MRI lesions. In other words, what is the predictable value of MRI for the individual patient in clinical practice? This question is important as more and more MRIs are prescribed for another reason and may exhibit lesions responding to spatial and even temporal dissemination as defined by MacDonald et al. in 2001 [18] and Polman et al. in 2005 [19].
Other unresolved issues
Beta-IFNs may stimulate the formation of neutralizing antibodies (NABs). Their frequency (up to 35%) is different from one IFN to another, and may depend on dosage and route of administration. It is as yet unclear if their appearance has a clinical individual interest. In some patients, high NAB titres associated with a reappearance of clinical activity after 2 to 3 years of treatment may indicate decreased IFN efficacy.
A second question concerns the selection of responders before initiating the
Concluding remarks
Introducing IFNs in the treatment of MS is the result of methodologically robust data indicating an efficacy in preventing exacerbations and limiting lesion accumulation on MRI. There may be a tendency to limit progressive worsening and possibly to improve quality of life. However, this remains more uncertain. IFN activity may depend on the course of the disease which influences trial organization: short duration, weak sensitivity for EDSS of 4 and higher, a longer steady phase for EDSS between
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Cited by (17)
The interferon-dependent orchestration of innate and adaptive immunity after transplantation
2012, BloodCitation Excerpt :Type I IFN promotes the maturation of DCs34 and enhances cross-presentation to CD8 T cells by CD8α+ DC and subsequent rejection of tumor.35 The mechanism by which IFN-β administration induces beneficial outcomes in multiple sclerosis patients has been investigated in experimental autoimmune encephalitis.36 These studies demonstrate that type I IFN signaling down-regulates the Th17-mediated inflammatory response by inhibiting osteopontin expression in DCs, resulting in derepression of the potent inhibitory cytokine IL-27.37,38
The prospects of minocycline in multiple sclerosis
2011, Journal of NeuroimmunologyCitation Excerpt :Many studies about minocycline combined with other drugs in EAE and MS have been reported (Tables 3 and 4). Three IFN-β preparations, IFNβ-1b subcutaneous (Betaseron®), IFNβ-1a intramuscular (Avonex®) and IFNβ-1a subcutaneous (Rebif®), have been approved as first-line immunomodulatory treatments of MS. It has been confirmed that the number of relapse rate and severity of exacerbations in MS patients were significantly decreased by IFN-β (reviewed by Tourbah and Lyon-Caen, 2007). But the interferons were thought to enter minimally into the central nervous system and were shown to be proteolytically cleaved by matrix metalloproteinases (MMPs), which were upregulated in MS. (reviewed by Antel and Miron, 2008; Yong et al., 2001).
New lessons about old molecules: How type I interferons shape Th1/Th17-mediated autoimmunity in the CNS
2010, Trends in Molecular MedicineCitation Excerpt :Together, these recent investigations provide useful insights into disease-limiting mechanisms that might open possibilities for cell-type specific IFN-β-based therapies that minimize the severe adverse effects. Therapeutic intervention with IFN-β is a major treatment option for MS that has proven to be beneficial as demonstrated by decreased inflammatory lesions in the CNS, visualized by magnetic resonance imaging (MRI), prolonged remissions and lower relapse rates [6,52]. However, in up to a third of the cases, the efficacy of IFN-β therapy ceases after a year, in part because many patients develop autoantibodies against IFN-β [53] (Box 2).
The activity and expression of NTPDase is altered in lymphocytes of multiple sclerosis patients
2010, Clinica Chimica ActaMemory and naïve B-cell subsets in patients with multiple sclerosis
2009, Neuroscience LettersInterferon-alpha controls IL-17 expression in vitro and in vivo
2008, Immunobiology