Efficacy and safety of a three-times-weekly dosing regimen of glatiramer acetate in relapsing–remitting multiple sclerosis patients: 3-year results of the Glatiramer Acetate Low-Frequency Administration open-label extension study

Khan, Omar; Rieckmann, Peter; Boyko, A. N.; Selmaj, Krzysztof; Ashtamker, Natalia; Davis, Mat D.; Kolodny, Scott; Zivadinov, Robert

doi:10.1177/1352458516664033

Cited by 36 publications

(32 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Both formulations of GA appear equivalent from the safety standpoint [64,91,94]. In the GALA study AEs associated with administration of GA 40 mg/mL three times a week were found to be consistent with the known safety profile of GA 20 mg/mL once daily.…”

Section: Safetymentioning

confidence: 78%

“…The tolerability of GA 40 mg/mL three times weekly has been shown to be similar to that of the 20 mg/mL once-daily formulation [8,91]. Importantly, in the GLA-CIER study [94], three times weekly GA was found to be better tolerated than the once-daily formulation in terms of injection-related adverse events (IRAEs): the adjusted mean annualized rate of IRAEs was reduced by 50 % in patients receiving the new formulation (35.3 events per year vs. 70.4 events per year, respectively; p = 0.0006), while the rate of moderate/severe events was reduced by 60 % (0.9 events per year vs. 2.2 events per year, respectively; p = 0.0021).…”

Section: Tolerabilitymentioning

confidence: 87%

“…Significant reductions compared with placebo in relapse rate (34.0 %; p < 0.0001), cumulative number of gadolinium-enhancing T1 lesions (44.8 %; p < 0.0001) and new or enlarged T2 lesions (34.7 %; p < 0.0001) were reported; the numerical values of these parameters were very similar to those observed in the pivotal studies with the 20 mg/mL once daily dose. Three-year results of the open-label extension of the GALA study demonstrated sustained efficacy on ARR and MRI parameters of disease activity [91]. Patients switched from placebo to GA after the double blind phase reported significant gains in efficacy, but those treated with GA from study entry showed a significantly lower relapse rate (ARR 0.23 vs 0.30, respectively, p = 0.0052) and significantly fewer enhancing T1 lesions and new or enlarged T2 lesions (RR = 0.660, p = 0.0005 for T1; RR = 0.680, p < 0.0001 for T2) compared with patients with delayed treatment.…”

Section: Three Times Weekly Formulationmentioning

confidence: 91%

“…In the GALA study AEs associated with administration of GA 40 mg/mL three times a week were found to be consistent with the known safety profile of GA 20 mg/mL once daily. Moreover, no new AEs emerged during treatment with high-dose GA [8,91].…”

Section: Safetymentioning

confidence: 99%

See 3 more Smart Citations

The heritage of glatiramer acetate and its use in multiple sclerosis

Comı

Amato

Bertolotto

et al. 2016

Mult Scler Demyelinating Disord

View full text Add to dashboard Cite

Multiple sclerosis (MS) is a chronic and progressively debilitating disease of the central nervous system. Treatment of MS involves disease-modifying therapies (DMTs) to reduce the incidence of relapses and prevent disease progression. Glatiramer acetate (Copaxone®) was the first of the currently approved DMTs to be tested in human subjects, and it is still considered a standard choice for first-line treatment. The mechanism of action of glatiramer acetate appears to be relatively complex and has not been completely elucidated, but it is likely that it involves both immunomodulating and neuroprotective properties. The efficacy of glatiramer acetate 20 mg/mL once daily as first-line treatment in relapsingremitting MS is well established, with ample evidence of efficacy from both placebo-controlled and active-comparator controlled clinical trials as well as real-world studies. There is also a considerable body of evidence indicating that the efficacy of glatiramer acetate is maintained in the long term. Clinical trial and real-world data have also consistently shown glatiramer acetate to be safe and well tolerated. Notably, glatiramer acetate has a good safety profile in women planning a pregnancy, and is not associated with foetal toxicity. Until recently, glatiramer acetate was only approved as 20 mg/mL once daily, but a new formulation with less frequent administration, 40 mg/mL three times weekly, has been developed and is now approved in many countries, including Italy. This review examines the mechanism of action, clinical efficacy, safety and tolerability of glatiramer acetate to provide suggestions for optimizing the use of this drug in the current MS therapeutic scenario.

show abstract

Section: Safetymentioning

confidence: 78%

Section: Tolerabilitymentioning

confidence: 87%

Section: Three Times Weekly Formulationmentioning

confidence: 91%

Section: Safetymentioning

confidence: 99%

See 2 more Smart Citations

The heritage of glatiramer acetate and its use in multiple sclerosis

Comı

Amato

Bertolotto

et al. 2016

Mult Scler Demyelinating Disord

View full text Add to dashboard Cite

show abstract

“…More recently, in a three year study aimed at analysing efficacy and safety of 40 mg GA three-times-weekly in RRMS, patients that were early treated with GA showed significantly smaller changes in GM volume (p = 0.015) compared to patients that were treated with placebo for one year before starting active treatment [94].…”

Section: Effects Of Disease-modifying Drugs On Brain and Gm Atrophymentioning

confidence: 99%

Effects of disease modifying therapies on brain and grey matter atrophy in relapsing remitting multiple sclerosis

Favaretto

Lazzarotto

Margoni

et al. 2018

Mult Scler Demyelinating Disord

View full text Add to dashboard Cite

Background: Progressive brain atrophy is a major feature of multiple sclerosis (MS) pathology and is actually considered a major determinant of the progressive accumulation of physical and cognitive disability in MS patients. Although brain atrophy may have different pathological substrates, several lines of evidence suggest that in disease modifying drug (DMD)-treated MS patients, the higher is the anti-inflammatory effect of the DMD the lower is the progression of brain volume loss, grey matter atrophy and the accumulation of disability. Areas covered: Magnetic resonance imaging (MRI)-based measurements of inflammation (focal white matter and grey matter lesions) and neurodegeneration (decrease in brain volume, cortical and deep grey matter atrophy) are currently included among the primary or secondary end-points of Phase II and III randomized clinical trials (RCT). This review summarizes literature data on the effects of DMDs on either whole brain or grey matter atrophy emerged from RCT and from post-marketing studies.

show abstract

The current standing of autologous haematopoietic stem cell transplantation for the treatment of multiple sclerosis

et al. 2022

View full text Add to dashboard Cite

Autologous haematopoietic stem cell transplantation (aHSCT) is gaining traction as a valuable treatment option for patients affected by severe multiple sclerosis (MS), particularly the relapsing–remitting form. We describe the current literature in terms of clinical trials, observational and retrospective studies, as well as immune reconstitution following transplantation, with a focus on the conditioning regimens used for transplantation. The evidence base predominantly consists of non-randomised, uncontrolled clinical trials or data from retrospective or observational cohorts, i.e. very few randomised or controlled trials. Most often, intermediate-intensity conditioning regimens are used, with promising results from both myeloablative and lymphoablative strategies, as well as from regimens that are low and high intensity. Efficacy of transplantation, which is likely secondary to immune reconstitution and restored immune tolerance, is, therefore, not clearly dependent on the intensity of the conditioning regimen. However, the conditioning regimen may well influence the immune response to transplantation. Heterogeneity of conditioning regimens among studies hinders synthesis of the articles assessing post-aHSCT immune system changes. Factors associated with better outcomes were lower Kurtzke Expanded Disability Status Scale, relapsing–remitting MS, younger age, and shorter disease duration at baseline, which supports the guidance for patient selection proposed by the European Society for Blood and Marrow Transplantation. Interestingly, promising outcomes were described for patients with secondary progressive MS by some studies, which may be worth taking into account when considering treatment options for patients with active, progressive disease. Of note, a significant proportion of patients develop autoimmune disease following transplantation, with alemtuzumab-containing regimens associated with the highest incidence.

show abstract

Efficacy and safety of a three-times-weekly dosing regimen of glatiramer acetate in relapsing–remitting multiple sclerosis patients: 3-year results of the Glatiramer Acetate Low-Frequency Administration open-label extension study

Abstract: GA40 conferred treatment benefit over 3 years: sustained low ARR and lesion activity and favorable safety.

Cited by 36 publications

References 29 publications

The heritage of glatiramer acetate and its use in multiple sclerosis

The heritage of glatiramer acetate and its use in multiple sclerosis

Effects of disease modifying therapies on brain and grey matter atrophy in relapsing remitting multiple sclerosis

The current standing of autologous haematopoietic stem cell transplantation for the treatment of multiple sclerosis

Contact Info

Product

Resources

About