Effect of ofatumumab versus placebo in relapsing multiple sclerosis patients from Japan and Russia: Phase 2 APOLITOS study

2021 ◽  
pp. 135245852110559
Author(s):  
Jun-ichi Kira ◽  
Jin Nakahara ◽  
Denis V Sazonov ◽  
Takayoshi Kurosawa ◽  
Isao Tsumiyama ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Opportunistic Infections ◽  
Open Label ◽  
Double Blind ◽  
Rate Versus ◽  
Open Label Extension ◽  
Clinical Benefits ◽  
Anti Cd20 ◽  
Multiple Sclerosis Patients ◽  
Relapsing Multiple Sclerosis

Background: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, has been developed as a treatment for relapsing multiple sclerosis (RMS) which can be self-administered at home. Objective: To investigate the efficacy and safety of ofatumumab in RMS patients from Japan and Russia. Methods: APOLITOS included a 24-week, double-blind, placebo-controlled core-part followed by an open-label extension-part. Patients were randomized (2:1) to subcutaneous ofatumumab 20 mg or placebo. Primary outcome was the number of gadolinium-enhancing (Gd+) T1 lesions per scan over 24 weeks. Results: Sixty-four patients were randomized (ofatumumab, n = 43; placebo, n = 21). Primary endpoint was met; ofatumumab reduced Gd + T1 lesions versus placebo by 93.6% ( p < 0.001) and the results were consistent across regions (Japan/Russia). Ofatumumab reduced annualized T2 lesion and relapse rate versus placebo by week 24. Both groups showed benefit from ofatumumab in the extension-part. Incidence of adverse events was lower with ofatumumab versus placebo (69.8% vs 81.0%); injection-related reactions were most common. No deaths, opportunistic infections, or malignancies were reported. Conclusion: Ofatumumab demonstrated superior efficacy versus placebo, with sustained effect through 48 weeks in RMS patients from Japan/Russia. Switching to ofatumumab after 24 weeks led to rapid radiological and clinical benefits. Safety findings were consistent with pivotal trials.

scholarly journals Long-term efficacy and safety of three times weekly dosing regimen of glatiramer acetate in relapsing multiple sclerosis patients: Seven-year results of the Glatiramer Acetate Low-frequency Administration (GALA) open-label extension study

2021 ◽  
Vol 7 (4) ◽  
pp. 205521732110615
Author(s):  
Peter Rieckmann ◽  
Robert Zivadinov ◽  
Alexey Boyko ◽  
Krzysztof Selmaj ◽  
Jessica K. Alexander ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Glatiramer Acetate ◽  
Low Frequency ◽  
Exposure Period ◽  
Similar Efficacy ◽  
Open Label ◽  
Open Label Extension ◽  
Multiple Sclerosis Patients ◽  
Relapsing Multiple Sclerosis

Objective Describe the long-term outcomes of early-start (ES) and delayed-start (DS) glatiramer acetate 40 mg/mL treatment three times weekly (GA40) for up to seven years in the Glatiramer Acetate Low-frequency Administration (GALA) study in patients with relapsing multiple sclerosis (RMS). Methods Patients were evaluated every three to six months. The primary efficacy endpoint was annualized relapse rate (ARR); additional endpoints were exploratory or post hoc. For efficacy, data from the entire exposure period were used for the ES and DS cohorts. For safety, exposure only under GA40 was considered. Results Of the patients who continued into the open-label extension (OLE), 580/834 (70%) ES and 261/419 (62%) DS completed the OLE. For the entire placebo-controlled and OLE study period, ARR was 0.26 for ES and 0.31 for DS patients (risk ratio = 0.83; 95% confidence interval [CI]: 0.70–0.99). ES prolonged median time to first relapse versus DS (4.9 versus 4.3 years; hazard ratio = 0.82; 95% CI: 0.6–0.96). OLE-only results showed DS patients experienced similar efficacy for relapse and disability outcomes as ES patients. Adverse events were consistent with the well-established GA safety profile. Conclusions GA40 treatment conferred clinical benefit up to seven years, resulting in sustained efficacy and was generally well tolerated in RMS patients.

scholarly journals Patients transitioning from non-pegylated to pegylated interferon beta-1a have a low risk of new flu-like symptoms: ALLOW phase 3b trial results

2019 ◽  
Vol 5 (1) ◽  
pp. 205521731882214 ◽  
Author(s):  
Robert T Naismith ◽  
Barry Hendin ◽  
Sibyl Wray ◽  
DeRen Huang ◽  
Fiorenza Gaudenzi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Interferon Beta ◽  
Pegylated Interferon ◽  
Symptom Duration ◽  
Open Label ◽  
Open Label Study ◽  
Management Guidance ◽  
Cumulative Duration ◽  
Multiple Sclerosis Patients ◽  
Relapsing Multiple Sclerosis

Background Flu-like symptoms are common adverse events associated with interferon beta relapsing multiple sclerosis therapies. Objectives To evaluate the incidence and severity of flu-like symptoms after transitioning from non-pegylated interferons to peginterferon beta-1a and assess flu-like symptom mitigation using naproxen. Methods ALLOW was a phase 3b open-label study in relapsing multiple sclerosis patients. Patients had received non-pegylated interferon for 4 or more months immediately before beginning a 4-week screening period. At baseline, patients switched to peginterferon beta-1a and were randomly assigned (1:1) to continue their current flu-like symptoms management regimen or start twice-daily naproxen 500 mg for 8 weeks. Patients then switched to their preferred regimen and were followed for 48 weeks in total. Results Of 201 patients, 89.6% did not experience new/worsening flu-like symptoms during their first 8 weeks on peginterferon beta-1a. Flu-like symptom severity remained low in current-regimen and naproxen patients, with no significant between-group differences. Median flu-like symptom duration per injection was 3.2 hours longer with peginterferon beta-1a versus prior interferon, but the 4-week cumulative duration was reduced 49–78%. No new safety signals were identified. Conclusion Most patients who switched from non-pegylated interferon to peginterferon beta-1a did not experience new/worsening flu-like symptoms. Flu-like symptom duration per injection increased, but the cumulative duration significantly decreased. These data may inform flu-like symptom management guidance.

Sustained clinical benefits of glatiramer acetate in relapsing multiple sclerosis patients observed for 6 years

2000 ◽  
Vol 6 (4) ◽  
pp. 255-266 ◽  
Author(s):  
K P Johnson ◽  
B R Brooks ◽  
C C Ford ◽  
A Goodman ◽  
J Guarnaccia ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Glatiramer Acetate ◽  
Relapse Rate ◽  
Open Label ◽  
Double Blind ◽  
Open Label Study ◽  
Label Study ◽  
Open Label Phase ◽  
Multiple Sclerosis Patients ◽  
To Receive

In a randomized, placebo-controlled, double-blind study, glatiramer acetate (Copaxone®) reduced the relapse rate and slowed accumulation of disability for patients with relapsing-remitting multiple sclerosis. Of the original 251 patients randomized to receive glatiramer acetate or placebo, 208 chose to continue in an open-label study with all patients receiving active drug. The majority of the original double-blind cohort continues to receive glatiramer acetate by daily subcutaneous injection and are evaluated at 6-month intervals and during suspected relapse. The data reported here are from approximately 6 years of organized evaluation, including the double-blind phase of up to 35 months and the open-label phase of over 36 months. Daily subcutaneous injections of 20 mg glatiramer acetate were well tolerated. The mean annual relapse rate of the patients who received glatiramer acetate since randomization and continued into the open-label study was 0.42 (95% confidence interval (CI), CI=0.34-0.51). The rate per year has continued to drop and for the sixth year is 0.23. Of the group who have received glatiramer acetate without interruption for 5 or more years, 69.3% were neurologically unchanged or have improved from baseline by at least one step on the Expanded Disability Status Scale (EDSS). Patients who left the open-label phase were surveyed by questionnaire. The majority responded, providing information about their current status and reasons for dropping out. This study demonstrates the sustained efficacy of glatiramer acetate in reducing the relapse rate and in slowing the accumulation of disability in patients with relapsing forms of multiple sclerosis.

scholarly journals Long-term follow-up of a phase 2 study of oral teriflunomide in relapsing multiple sclerosis: safety and efficacy results up to 8.5 years

2012 ◽  
Vol 18 (9) ◽  
pp. 1278-1289 ◽  
Author(s):  
Christian Confavreux ◽  
David K Li ◽  
Mark S Freedman ◽  
Philippe Truffinet ◽  
Hadj Benzerdjeb ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Opportunistic Infections ◽  
Oral Disease ◽  
Controlled Study ◽  
Phase 2 ◽  
Open Label ◽  
The Core ◽  
Open Label Extension ◽  
Sensory Disturbances ◽  
Long Term Follow Up

Background: Teriflunomide, an oral disease-modifying therapy in development for patients with relapsing forms of multiple sclerosis (RMS), was well tolerated and effective in reducing magnetic resonance imaging (MRI) lesions in 179 RMS patients in a phase 2 36-week, placebo-controlled study. Methods: A total of 147 patients who completed the core study entered an open-label extension. Teriflunomide patients continued their assigned dose, and placebo patients were re-allocated to teriflunomide, 7 mg/day or 14 mg/day. An interim analysis was performed at a cut-off on January 8 2010. Results: The mean and median duration of study treatment, including both the core and extension phase, from baseline to the interim cut-off, was 5.6 years (standard deviation: 2.7 years) and 7.1 years (range: 0.05–8.5 years), respectively. Of 147 patients, 62 (42.2%) discontinued (19% due to treatment-emergent adverse events (TEAEs)). The most common TEAEs were mild infections, fatigue, sensory disturbances and diarrhoea. No serious opportunistic infections occurred, with no discontinuations due to infection. Asymptomatic alanine aminotransferase increases (≤3× upper limit of normal (ULN)) were common (7 mg, 64.2%; 14 mg, 62.1%); increases >3×ULN were similar across groups (7 mg, 12.3%; 14 mg, 12.1%). Mild decreases in neutrophil counts occurred; none led to discontinuation. The incidence of malignancies was comparable to that of the general population, and cases were not reminiscent of those observed in immunocompromised patients. Annualised relapse rates remained low, minimal disability progression was observed, with a dose-dependent benefit with teriflunomide 14 mg for several MRI parameters. Conclusion: Teriflunomide had a favourable safety profile for up to 8.5 years.

An open-lebel trial of gabapentin treatment of paroxysmal symptoms in multiple sclerosis patients

Neurology ◽  
1998 ◽  
Vol 51 (2) ◽  
pp. 609-611 ◽  
Author(s):  
C. Solaro ◽  
G. L. Lunardi ◽  
E. Capello ◽  
M. Inglese ◽  
Messmer M. Uccelli ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Complete Resolution ◽  
Controlled Trial ◽  
Open Label ◽  
Double Blind ◽  
Sustained Improvement ◽  
Double Blind Placebo ◽  
Open Label Trial ◽  
Multiple Sclerosis Patients ◽  
Tonic Spasms

We conducted an open-label trial of gabapentin (GBP) as therapy for paroxysmal symptoms (PS) in 21 MS patients, including trigeminal neuralgia (6 patients), painful tonic spasms (11), dysesthetic or paresthetic symptoms (3) and ocular ataxia (1). Complete resolution of symptoms or partial improvement was obtained, respectively, in 14 and 4 of 18 patients who ended the study. Sustained improvement with minor side effects was obtained at dosages ranging from 600 to 1200 mg/d. Our findings suggest that GBP may be effective for PS in MS and warrant a further study in a double-blind placebo-controlled trial.

Voxel-wise magnetization transfer imaging study of effects of natalizumab and IFNβ-1a in multiple sclerosis

2011 ◽  
Vol 18 (8) ◽  
pp. 1125-1134 ◽  
Author(s):  
R Zivadinov ◽  
MG Dwyer ◽  
S Hussein ◽  
E Carl ◽  
C Kennedy ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Magnetization Transfer ◽  
Imaging Study ◽  
Progressive Multiple Sclerosis ◽  
Magnetization Transfer Ratio ◽  
Healthy Controls ◽  
Open Label ◽  
Healthy Control ◽  
Multiple Sclerosis Patients ◽  
Relapsing Multiple Sclerosis

Objective: To determine the effects of intravenous natalizumab and intramuscular interferon beta-1a (IFNβ-1a) on the volume of white-matter (WM) lesions and normal appearing brain tissue (NABT) undergoing voxel-wise (VW) increases in magnetization transfer ratio (MTR) suggestive of remyelination in patients with relapsing multiple sclerosis. Methods: This prospective, open-label, single-blinded study enrolled patients with relapsing–remitting multiple sclerosis (RRMS) and relapsing secondary progressive multiple sclerosis (RSPMS) as well as a group of age/sex-matched healthy controls ( n=22). Patients with multiple sclerosis were assigned to receive natalizumab monotherapy ( n=77; RRMS/RSPMS) or intramuscular IFNβ-1a ( n=26) as either monotherapy (RRMS) or combined with pulsed i.v. methylprednisolone, as needed (RSPMS). The primary endpoint was the two-year change in volume of NABT VWMTR, by quantifying the number of voxels that increased (suggesting remyelination) or decreased (suggesting demyelination) in their MTR value. Results: The volume of tissue undergoing increases in VWMTR was significantly larger in natalizumab compared with IFNβ-1a-treated patients (year 1: p=0.001 in NABT and p<0.006 in WM lesions; year 2: p=0.008 in NABT) and compared with healthy control subjects (year 1: p=0.05 and year 2: p=0.007 in NABT). The larger volume within NABT undergoing decreases in VWMTR was detected in multiple sclerosis patients compared with healthy controls ( p<0.001), and in the IFNβ-1a group compared with the natalizumab group (year 1: p=0.05; year 2: p=0.002). One patient on natalizumab died from progressive multifocal leukoencephalopathy eight months after completing the study. Conclusion: Natalizumab may promote remyelination and stabilize demyelination in lesions and NABT in relapsing multiple sclerosis, compared with intramuscular IFNβ-1a.

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