The efficacy of cladribine tablets in CIS patients retrospectively assigned the diagnosis of MS using modern criteria: Results from the ORACLE-MS study

Freedman, Mark S.; Leist, Thomas; Comı, Gıancarlo; Cree, Bruce A. C.; Coyle, Patricia K.; Hartung, Hans‐Peter; Vermersch, Patrick; Damian, Doris; Dangond, Fernando

doi:10.1177/2055217317732802

Cited by 33 publications

(41 citation statements)

References 22 publications

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“… 17 The blinding of participants and personnel was sufficient in two studies 13 , 16 except for four studies. 14 , 19 – 21 The blinding of the outcome assessment was sufficient in three studies except for three, one was unknown, and two were high risk. All of the study protocols reported a follow-up percentage loss between 5% and 20%.…”

Section: Resultsmentioning

confidence: 99%

A systematic review of the effect of omega-3 supplements on meibomian gland dysfunction

Al-Namaeh

2020

Ophthalmol Eye Dis

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Introduction: Meibomian gland dysfunction (MGD) is the leading cause of dry eye syndrome (DES). Many ocular disorders including DES and blepharitis can be linked to MGD. If we treat MGD, we can treat related diseases easily. Purpose: This systematic review is intended to determine the efficacy of omega-3 supplementation in MGD patients. Methods: This systematic review included an electronic search on PubMed and Clinicaltrials.gov to include all randomized clinical trials (RCTs) using omega-3 as a treatment for MGD. Results: Database search yielded to one RCT and six clinical trials through the MEDLINE of a total of 350 participants for the systematic review and meta-analysis study. The investigated treatment group (omega-3 group) had a positive effect on MGD protection in the invasive sodium fluorescein-tear break up time (NaFl-TBUT) score compared with the placebo group (odd ratio = 8.72, 95% confidence interval: 4.73, 16.09; p < 0.001). These data suggest that the odd ratios of the omega-3 group to control group increased the likelihood of the improved stated outcome tear break up time (TBUT) being achieved in the treatment group. No evidence of publication bias was detected in the funnel plot inspection or the Egger’s statistical test ( p = 0.2944). Conclusions: A moderate daily dose of omega-3 may be a beneficial therapeutic for MGD. Omega-3 has been beneficial in many diseases, such as heart attack prevention and agerelated macular degeneration, and this systematic review emphasizes its protection against MGD. In addition, this review emphasizes the precision of noninvasive TBUT (NITBUT) compared with invasive NaFl-TBUT which may suggest the importance of NITBUT in the clinic.

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Section: Resultsmentioning

confidence: 99%

A systematic review of the effect of omega-3 supplements on meibomian gland dysfunction

Al-Namaeh

2020

Ophthalmol Eye Dis

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“…Patients who received placebo during CLARITY were assigned to two courses of cladribine tablets with a cumulative dose of 3.5 mg/kg . ORACLE-MS was a 96-week Phase III, double-blind, randomized, placebo-controlled multicenter study which evaluated the safety and efficacy of 2 doses of treatment with cladribine tablets 3.5 and 5.25 mg/kg (cumulative dose) in patients with a first clinical demyelinating event, including patients who were subsequently found to have met the 2010 McDonald criteria (Leist et al, 2014;Freedman et al, 2017). The PREMIERE registry is a prospective, observational, long-term safety study of patients with MS that commenced in 2009 and is open to patients who had participated in one of the clinical studies of cladribine tablets (CLARITY, CLARITY Extension, ORACLE-MS or ONWARD).…”

Section: Monotherapy Oral Cohortmentioning

confidence: 99%

“…Cladribine tablets 10 mg (MAVENCLAD ® ; 3.5 mg/kg cumulative dose over 2 years, referred to as cladribine tablets 3.5 mg/kg) have shown efficacy across the spectrum of patients with relapsing multiple sclerosis (MS), including those at a higher risk of disease progression or with active disease while on a disease modifying drug (DMD) (Giovannoni et al, 2010;Giovannoni et al, 2011;Comi et al, 2013;Rammohan et al, 2012;Giovannoni et al, 2018;Giovannoni et al, 2017;Leist et al, 2014;Freedman et al, 2017;Montalban et al, 2016). Treatment with cladribine tablets leads to a transient reduction of lymphocyte counts and a minimal effect on innate immune function, followed by gradual reconstitution of the lymphocyte populations towards baseline levels (Giovannoni, 2017;Wiendl, 2017).…”

Section: Introductionmentioning

confidence: 99%

Safety of cladribine tablets in the treatment of patients with multiple sclerosis: An integrated analysis

Cook

Leist

Comi

et al. 2019

Multiple Sclerosis and Related Disorders

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107

133

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A B S T R A C TBackground: Treating patients with relapsing multiple sclerosis (MS) with cladribine tablets (two times 4 or 5 days of treatment each year for 2 years) results in long-lasting efficacy, with continued stability in many patients for 4 or more years. Safety and tolerability outcomes from individual clinical studies with cladribine tablets have been reported previously. Objective: Report safety data from an integrated analysis of clinical trials and follow-up in patients with MS to further characterize the safety profile of cladribine tablets. Methods: Data for patients treated with cladribine tablets 10 mg (MAVENCLAD ® ; 3.5 mg/kg cumulative dose over 2 years, referred to as cladribine tablets 3.5 mg/kg) as monotherapy (n = 923) or placebo (n = 641) in Phase III clinical trials (CLARITY, CLARITY Extension and ORACLE-MS) and followed up in the PREMIERE registry were aggregated (Monotherapy Oral cohort). To better characterize rare events, additional data from earlier studies which involved the use of parenteral cladribine in patients with MS, and the ONWARD study, in which patients were given cladribine tablets in addition to interferon (IFN)-β or placebo plus IFN-β were included in an All Exposed cohort (cladribine, n = 1926; placebo, n = 802). Adjusted adverse events incidences per 100 patient-years (Adj-AE per 100 PY) were calculated for the integrated analyses. Results: The incidence rate of treatment-emergent adverse events (TEAEs) in the Monotherapy Oral cohort was 103.29 vs. 94.26 Adj-AEs per 100 PY for placebo. TEAEs that occurred more frequently with cladribine tablets were mainly driven by the TEAEs of lymphopenia (Adj-AE per 100 PY 7.94 vs. 1.06 for placebo) and lymphocyte count decreased (Adj-AE per 100 PY 0.78 vs. 0.10 for placebo) as anticipated due to the mode of action of cladribine. An increase in TEAE incidence rate was also observed in the cladribine tablets 3.5 mg/kg group vs. placebo for herpes zoster (Adj-AE per 100 PY 0.83 vs. 0.20, respectively). There were no cases of systemic, serious disseminated herpes zoster attributed to treatment with cladribine tablets. In general there was no increase in the risk of infections including opportunistic infections with cladribine tablets versus placebo, except for herpes zoster. Periods of severe lymphopenia (< 0.5 × 10 9 cells/L) were associated with an increased frequency of infections, but the nature of these was not different to that observed in the overall patient group treated with cladribine tablets 3.5 mg/kg. Within the constraints of a limited sample size, malignancy rates in the overall clinical program for cladribine in MS did not show evidence of an increase compared to placebo-treated patients and there was no increase in the incidence of malignancies over time in cladribine-treated patients. Conclusion: The AE profile for cladribine tablets 3.5 mg/kg as a monotherapy has been well-characterized in a pooled population of patients from early to more advanced relapsing MS. There was no increased risk for infections in general e...

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“…With respect to CIS, injectable [19][20][21][22][23] and oral 24,25 DMTs have been shown to slow the development of RMS by reducing the chances of having relapses, MRI lesions, or disease progression, an effect that appears to be sustained during long-term follow-up. While new diagnostic criteria now categorize many CIS patients as having MS, treatment benefits have been demonstrated even in contemporary CIS cohorts (i.e., not fulfilling 2017 McDonald criteria at their first attack), 26 and some of these patients can be offered therapy. The impact of early treatment on longer-term disability outcomes is less certain.…”

Section: Treatment Initiation -Relapsing Msmentioning

confidence: 99%

Treatment Optimization in Multiple Sclerosis: Canadian MS Working Group Recommendations

Freedman

Devonshire

Duquette

et al. 2020

Can. J. Neurol. Sci.

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Abstract:The Canadian Multiple Sclerosis Working Group has updated its treatment optimization recommendations (TORs) on the optimal use of disease-modifying therapies for patients with all forms of multiple sclerosis (MS). Recommendations provide guidance on initiating effective treatment early in the course of disease, monitoring response to therapy, and modifying or switching therapies to optimize disease control. The current TORs also address the treatment of pediatric MS, progressive MS and the identification and treatment of aggressive forms of the disease. Newer therapies offer improved efficacy, but also have potential safety concerns that must be adequately balanced, notably when treatment sequencing is considered. There are added discussions regarding the management of pregnancy, the future potential of biomarkers and consideration as to when it may be prudent to stop therapy. These TORs are meant to be used and interpreted by all neurologists with a special interest in the management of MS.

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The efficacy of cladribine tablets in CIS patients retrospectively assigned the diagnosis of MS using modern criteria: Results from the ORACLE-MS study

Cited by 33 publications

References 22 publications

A systematic review of the effect of omega-3 supplements on meibomian gland dysfunction

A systematic review of the effect of omega-3 supplements on meibomian gland dysfunction

Safety of cladribine tablets in the treatment of patients with multiple sclerosis: An integrated analysis

Treatment Optimization in Multiple Sclerosis: Canadian MS Working Group Recommendations

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