scholarly journals 090 The effect of cladribine tablets on delaying the time to conversion to clinically definite multiple sclerosis (MS) or McDonald MS is consistent across subgroups in the ORACLE-MS study

2019 ◽  
Vol 90 (e7) ◽  
pp. A29.1-A29
Author(s):  
James Bowen ◽  
Alan Gillett ◽  
Doris Damian ◽  
Yann Hyvert ◽  
Fernando Dangond ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Phase 3 ◽  
Double Blind ◽  
T2 Lesions ◽  
Definite Multiple Sclerosis ◽  
Clinically Definite Multiple Sclerosis ◽  
Baseline Characteristics ◽  
Post Hoc ◽  
Delayed Time ◽  
Patient Subgroups

IntroductionIn the Phase 3 ORACLE-MS trial in 616 subjects with a first demyelinating event at high risk of converting to multiple sclerosis (MS), treatment with cladribine tablets 10 mg (3.5 mg/kg or 5.25 mg/kg cumulative dose over 2 years [CT3.5 and CT5.25, respectively]) significantly delayed time to conversion to clinically definite multiple sclerosis (CDMS) according to Poser criteria (67% or 62% risk reduction [RR], respectively) and time to conversion to 2005 McDonald MS (50% or 57% RR, respectively), versus placebo. The objective was to analyze the effect of cladribine tablets vs placebo on converstion to CDMS and McDonald MS across ORACLE-MS patient subgroups based on baseline characteristics.MethodsIn this post-hoc analysis, time-to-conversion to CDMS or McDonald MS over the double-blind period was analyzed for patients treated with CT5.25 (N=204), CT3.5 (N=206) or placebo (N=206) across different subgroups. Subgroups were defined by baseline characteristics which have been investigated as potential predictors of CDMS conversion (age [<30 or ≥30 years], gender, first classification demyelinating event [monofocal or multifocal], presence of T1 Gd+ lesions and number of T2 lesions [<9 or ≥9]).ResultsTreatment with CT3.5 or CT5.25 was consistently efficacious across the subgroups examined on conversion to CDMS versus placebo for most comparisons (RR range: CT3.5, 39%–72%; CT5.25, 36%–79%). Similarly, treatment effect of both doses on conversion to 2005 McDonald MS was consistent across subgroups (CT3.5,40%–59%;CT5.25,42%–79%).ConclusionsThe effect of cladribine tablets on delaying the time-to-conversion to CDMS, or to McDonald MS, is consistent across subgroups.

scholarly journals The Efficacy of Interferon Beta in Delaying Conversion to Clinically Definite Multiple Sclerosis

2010 ◽  
Vol 12 (1) ◽  
pp. 42-50 ◽  
Author(s):  
Marcelo Kremenchutzky ◽  
R. Philip Kinkel
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Interferon Beta ◽  
White Matter Lesions ◽  
Clinically Isolated Syndrome ◽  
Resonance Imaging ◽  
Phase 3 ◽  
Definite Multiple Sclerosis ◽  
Clinically Definite Multiple Sclerosis ◽  
Post Hoc

More than half of patients with a clinically isolated syndrome (CIS) develop clinically definite multiple sclerosis (CDMS). Patients at high risk for CDMS often present with asymptomatic lesions characteristic of CDMS on magnetic resonance imaging scans, although an absence of asymptomatic lesions is not atypical. Phase 3 studies of interferon beta in patients with a CIS suggest that this treatment can delay conversion to CDMS and reduce the risk of new asymptomatic white matter lesions. We reviewed phase 3 studies (CHAMPS, BENEFIT, and ETOMS) and post hoc analyses assessing the efficacy of interferon beta in delaying CDMS in patients with a CIS. The evidence supports early initiation of treatment.

scholarly journals Rituximab vs placebo induction prior to glatiramer acetate monotherapy in multiple sclerosis

Neurology ◽  
2019 ◽  
Vol 92 (7) ◽  
pp. e723-e732 ◽  
Author(s):  
Justin M. Honce ◽  
Kavita V. Nair ◽  
Stefan Sillau ◽  
Brooke Valdez ◽  
Augusto Miravalle ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Glatiramer Acetate ◽  
Controlled Study ◽  
Short Term ◽  
Double Blind ◽  
T2 Lesions ◽  
Time To Treatment Failure ◽  
Sustained Change ◽  
Baseline Characteristics ◽  
Relapsing Multiple Sclerosis

ObjectiveTo examine whether rituximab induction followed by glatiramer acetate (GA) monotherapy is more effective than GA alone for the treatment of relapsing multiple sclerosis with active disease.MethodsThis was a single-center, double-blind, placebo-controlled study. Fifty-five participants were randomly assigned (1:1 ratio) to either rituximab (R-GA) or placebo (P-GA) induction, followed by GA therapy initiated in all participants. Participants were followed up to 3 years. The primary endpoint was the number of participants with no evidence of disease activity (NEDA): those without relapse, new MRI lesions, and sustained change in disability.ResultsTwenty-eight and 27 participants received rituximab and placebo induction, respectively, with one participant in each arm withdrawing before 6-month MRI. There were no significant differences in baseline characteristics. At end of study, 44.44% of R-GA participants demonstrated NEDA vs 19.23% of P-GA participants (p = 0.049). Treatment failed for a smaller proportion of R-GA participants (37.04% R-GA vs 69.23% P-GA, p = 0.019), and time to treatment failure was longer (23.32 months R-GA vs 11.29 months P-GA, p = 0.027). Fewer participants in the R-GA arm had new lesions (25.93% R-GA vs 61.54% P-GA, p = 0.009), and there were fewer new T2 lesions (0.48 R-GA vs 1.96 P-GA, p = 0.027). Probability of demonstrating NEDA in the R-GA arm returned to baseline within the study period. There were no differences in adverse events.ConclusionsInduction therapy with rituximab followed by GA may provide superior efficacy in the short term than GA alone in relapsing multiple sclerosis, but this benefit appears to wane within the study period. Larger studies are needed to assess sustainability of results.ClinicalTrials.gov identifierNCT01569451.

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

2017 ◽  
Vol 3 (4) ◽  
pp. 205521731773280 ◽  
Author(s):  
Mark S Freedman ◽  
Thomas P Leist ◽  
Giancarlo Comi ◽  
Bruce AC Cree ◽  
Patricia K Coyle ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinically Isolated Syndrome ◽  
Expanded Disability Status Scale ◽  
Post Hoc Analysis ◽  
Nominal Significance ◽  
Disability Status ◽  
Definite Multiple Sclerosis ◽  
Clinically Definite Multiple Sclerosis ◽  
Post Hoc ◽  
In Cis

Background Multiple sclerosis (MS) diagnostic criteria have changed since the ORACLE-MS study was conducted; 223 of 616 patients (36.2%) would have met the diagnosis of MS vs clinically isolated syndrome (CIS) using the newer criteria. Objective The objective of this paper is to assess the effect of cladribine tablets in patients with a first clinical demyelinating attack fulfilling newer criteria (McDonald 2010) for MS vs CIS. Methods A post hoc analysis for subgroups of patients retrospectively classified as fulfilling or not fulfilling newer criteria at the first clinical demyelinating attack was conducted. Results Cladribine tablets 3.5 mg/kg ( n = 68) reduced the risk of next attack or three-month confirmed Expanded Disability Status Scale (EDSS) worsening by 74% vs placebo ( n = 72); p = 0.0009 in patients meeting newer criteria for MS at baseline. Cladribine tablets 5.25 mg/kg ( n = 83) reduced the risk of next attack or three-month confirmed EDSS worsening by 37%, but nominal significance was not reached ( p = 0.14). In patients who were still CIS after applying newer criteria, cladribine tablets 3.5 mg/kg ( n = 138) reduced the risk of conversion to clinically definite multiple sclerosis (CDMS) by 63% vs placebo ( n = 134); p = 0.0003. Cladribine tablets 5.25 mg/kg ( n = 121) reduced the risk of conversion by 75% vs placebo ( n = 134); p < 0.0001. Conclusions Regardless of the criteria used to define CIS or MS, 3.5 mg/kg cladribine tablets are effective in patients with a first clinical demyelinating attack. ClinicalTrials.gov registration: The ORACLE-MS study (NCT00725985).

A double-blind, placebo-controlled trial of extracorporeal photopheresis in chronic progressive multiple sclerosis

1999 ◽  
Vol 5 (3) ◽  
pp. 198-203 ◽  
Author(s):  
A M Rostami ◽  
R A Sater ◽  
S J Bird ◽  
S Galetta ◽  
R E Farber ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Controlled Trial ◽  
Progressive Multiple Sclerosis ◽  
Plaque Burden ◽  
Extracorporeal Photopheresis ◽  
Double Blind ◽  
Definite Multiple Sclerosis ◽  
Chronic Progressive Multiple Sclerosis ◽  
Clinically Definite Multiple Sclerosis ◽  
Double Blinded

Extracorporeal photopheresis is a safe therapy for cutaneous T-cell lymphoma and may have efficacy in certain autoimmune disorders. We performed a randomized, double-blinded, placebo-controlled trial of monthly photopheresis therapy in 16 patients with clinically definite multiple sclerosis (MS). All patients had progressed during the preceding year with entry Expanded Disability Status Scale (EDSS) scores between 3.0 and 7.0. Patients received photopheresis or sham therapy for 1 year and were followed for an additional 6 to 12 months. Patients were clinically evaluated by three disability scales: (1) EDSS; (2) Ambulation index and (3) Scripp's quantitative neurologic assessment. No serious side effects occurred in either group. There were no differences between the photopheresis and sham therapy groups by the disability measures. Additionally, there were no differences in progression of MRI plaque burden or evoked potential latencies. In this limited study, photopheresis was found to be safe but did not significantly alter the course of chronic progressive MS.

scholarly journals Early MRI outcomes in participants with a first clinical demyelinating event at risk of multiple sclerosis in the ORACLE-MS study

2021 ◽  
Vol 7 (1) ◽  
pp. 205521732199085
Author(s):  
Mark S Freedman ◽  
Patricia K Coyle ◽  
Giancarlo Comi ◽  
Susan L Scarberry ◽  
Doris Damian ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Resonance Imaging ◽  
Phase 3 ◽  
Post Hoc Analysis ◽  
T2 Lesions ◽  
Mri Scans ◽  
The Mean ◽  
Magnetic Resonance Imaging Mri ◽  
Post Hoc

Background In the Phase 3, 96-week ORACLE-MS study, cladribine tablets 10 mg (3.5 or 5.25 mg/kg cumulative dosage over two years) significantly reduced lesions associated with multiple sclerosis versus placebo in participants following a first clinical demyelinating event (FCDE). Objective To determine the timing of effects of cladribine tablets on lesion activity assessed by magnetic resonance imaging (MRI). Methods This post hoc analysis assessed the effect of cladribine tablets versus placebo in ORACLE-MS on secondary MRI endpoints including T1 gadolinium-enhancing (Gd+), new or enlarging T2 lesions, and combined unique active lesions assessed on MRI scans performed at screening and every 3 months thereafter. Results Compared to placebo, cladribine tablets 3.5 mg/kg treatment appeared to lead to a trend of reductions in the mean number of T1 Gd+ lesions by Week 13 (first post-baseline scan: 0.37 vs. 1.00), new or enlarging T2 (0.20 vs. 1.01) and combined unique active (0.29 vs. 1.91) lesions by Week 24. Low lesion counts were maintained with cladribine tablets throughout 96 weeks. Similar results were observed with the 5.25 mg/kg dosage. Conclusion In participants with an FCDE, cladribine tablets appeared to reduce lesion numbers within 13 weeks (time of first evaluation).

scholarly journals 2289. Bacterial Causes of Acute Bacterial Skin and Skin Structure Infections (ABSSSI) in Patients with Intravenous Drug Use (IVDU): Phase 3 REVIVE Studies

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S784-S785
Author(s):  
David B Huang ◽  
Stephanie S Noviello ◽  
Barbara Balser ◽  
Amy E Scaramucci ◽  
Eve Desplats ◽  
...  
Keyword(s):  
Surgical Intervention ◽  
Signs And Symptoms ◽  
The United States ◽  
Lesion Size ◽  
Intravenous Drug Use ◽  
Wound Edge ◽  
Phase 3 ◽  
Double Blind ◽  
Baseline Characteristics ◽  
Post Hoc

Abstract Background Opioid addiction in the United States has reached epidemic proportions threatening public health. This analysis evaluates the baseline characteristics and bacterial causes of ABSSSI in patients who were IVDU from two parallel Phase 3 trials comparing the treatment of iclaprim with vancomycin. Methods A total of 621 patients who were IVDU from two parallel Phase 3, double-blind, randomized (1:1), active-controlled, multinational, multicenter trials (REVIVE-1 and REVIVE-2) were analyzed both separately and pooled. This post-hoc analysis summarizes the baseline bacterial causes of ABSSSI identified among IVDU. Per protocol, ABSSSI (major abscesses, cellulitis, or wound infections) were defined as having either the presence of purulent or seropurulent drainage before or after surgical intervention of the wound or at least 3 of the following signs and symptoms: discharge, erythema (extending at least 2 cm beyond the wound edge in any direction), swelling and/or induration, heat and/or localized warmth, and/or pain and/or tenderness to palpation. IVDU was defined based on subjected-reported medical history. At the baseline visit, ABSSSI were sampled for microbiological culture. Cultures were performed locally, and isolates were submitted to the central microbiology laboratory. Results Among IVDU with ABSSSI, average age was 44 years, 67.6% were male, average lesion size was 322 cm2, 10.8% had abnormal renal function (CrCl ≤ 90 mL/minute), and 3.9% had bacteremia. The bacterial causes of ABSSSI among IVDU are shown in the Table. Conclusion IVDU, a growing population, are vulnerable to ABSSSI. S. aureus, including MRSA, and S. anginosus group were the most commonly identified bacterial causes of ABSSSI in patients who are IVDU. Therefore, antibiotic selection should cover these bacteria among IVDU who present with an ABSSSI. Disclosures All authors: No reported disclosures.

Sign in / Sign up

Export Citation Format

Share Document