scholarly journals CLICK-MS and MASTER-2 Phase IV trial design: cladribine tablets in suboptimally controlled relapsing multiple sclerosis

2021 ◽  
Author(s):  
Augusto A Miravalle ◽  
Joshua Katz ◽  
Derrick Robertson ◽  
Brooke Hayward ◽  
Danielle E Harlow ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Patient Reported Outcomes ◽  
Real World Data ◽  
Disease Modifying Drugs ◽  
Secondary Progressive ◽  
Patient Reported ◽  
Relapsing Remitting ◽  
Registration Number ◽  
Disease Modifying ◽  
Phase Iv

Cladribine tablets 10 mg (3.5 mg/kg cumulative dose over 2 years) are approved for the treatment of relapsing forms of multiple sclerosis (MS), including relapsing-remitting MS and active secondary progressive MS. However, real-world data on cladribine tablets are limited. CLICK-MS and MASTER-2 are single arm, observational, 30-month, Phase IV studies in the US evaluating the effectiveness and safety of cladribine tablets 3.5 mg/kg in patients with relapsing-remitting MS or active secondary progressive MS who had suboptimal response to prior injectable (CLICK-MS), or infusion/oral (MASTER-2) disease-modifying therapy. The primary end point is 24-month annualized relapse rate. Key secondary end points include patient-reported outcomes on quality of life measures, treatment adherence and adverse events. Studies began in 2019 and are expected to be completed in 2023. Trial registration number • CLICK-MS: NCT03933215 (ClinicalTrials.gov) Full title; CLadribine tablets: observational evaluation of effectIveness and patient-reported outcomes in suboptimally Controlled patients previously taKing injectable disease-modifying drugs for relapsing forms of Multiple Sclerosis • MASTER-2: NCT03933202 (ClinicalTrials.gov) Full title; Cladribine tablets: observational evaluation of effectiveness and patient-reported outcomes in suboptiMAlly controlled patientS previously Taking oral or infusion disEase-modifying dRugs for relapsing forms of multiple sclerosis

Discontinuation of disease-modifying therapy in patients with multiple sclerosis over age 60

2018 ◽  
Vol 25 (5) ◽  
pp. 699-708 ◽  
Author(s):  
Le H Hua ◽  
Tracey H Fan ◽  
Devon Conway ◽  
Nicolas Thompson ◽  
Tyler G Kinzy
Keyword(s):  
Multiple Sclerosis ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Clinical Relapse ◽  
Real World Data ◽  
Disease Modifying Therapy ◽  
Patient Reported ◽  
Relapsing Remitting ◽  
Patient Health ◽  
Disease Modifying

Background: The risk–benefit ratio of continuing immunomodulating disease-modifying therapy (DMT) in older multiple sclerosis (MS) patients is unknown. Objective: To evaluate clinical and patient-reported outcomes after stopping DMT in older MS patients. Methods: Retrospective, observational study identifying patients from our MS clinics who were aged over 60 and on DMT > 2 years. Cause-specific Cox proportional hazards regression modeled time to discontinuation and time to reinitiation of therapy. Pre- and post-discontinuation comparisons of Performance Scales (PS), Timed 25-Foot Walk, and Patient Health Questionnaire-9 (PHQ9) were analyzed using linear mixed models. Results: A total of 600 patients were included, with 178 (29.7%) discontinuing. Discontinuers were 2.2 years older, had 3.2 years longer disease duration, and 1.6 years lesser treatment exposure. Providers initiated discontinuation more than patients (68.0%). Only one clinical relapse occurred in discontinuers. A proportion (10.7%) reinitiated DMT. Provider-initiated discontinuers restarted less often (hazard ratio (HR): 0.34; 95% confidence interval (CI): 0.12–0.9). In discontinuers, relapsing-remitting patients had lower PS on average than primary progressive. Provider-initiated discontinuation was associated with lower PS than patient- initiated discontinuation. PHQ9 scores appeared higher in those stopping intravenous (IV) therapies than interferons. Lower PS and PHQ9 indicate better outcomes. Conclusion: Most patients over age 60, who discontinued DMT, remained off DMT. This study provides real-world data that may guide clinicians considering discontinuing DMT.

scholarly journals Long-term effectiveness in patients previously treated with cladribine tablets: a real-world analysis of the Italian multiple sclerosis registry (CLARINET-MS)

2020 ◽  
Vol 13 ◽  
pp. 175628642092268 ◽  
Author(s):  
Francesco Patti ◽  
Andrea Visconti ◽  
Antonio Capacchione ◽  
Sanjeev Roy ◽  
Maria Trojano ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Real World ◽  
Event Analysis ◽  
Treatment Change ◽  
Real World Data ◽  
Indirect Measure ◽  
Disease Modifying Drugs ◽  
Disease Modifying ◽  
Using Data

Background: The CLARINET-MS study assessed the long-term effectiveness of cladribine tablets by following patients with multiple sclerosis (MS) in Italy, using data from the Italian MS Registry. Methods: Real-world data (RWD) from Italian MS patients who participated in cladribine tablets randomised clinical trials (RCTs; CLARITY, CLARITY Extension, ONWARD or ORACLE-MS) across 17 MS centres were obtained from the Italian MS Registry. RWD were collected during a set observation period, spanning from the last dose of cladribine tablets during the RCT (defined as baseline) to the last visit date in the registry, treatment switch to other disease-modifying drugs, date of last Expanded Disability Status Scale recording or date of the last relapse (whichever occurred last). Time-to-event analysis was completed using the Kaplan–Meier (KM) method. Median duration and associated 95% confidence intervals (CI) were estimated from the model. Results: Time span under observation in the Italian MS Registry was 1–137 (median 80.3) months. In the total Italian patient population ( n = 80), the KM estimates for the probability of being relapse-free at 12, 36 and 60 months after the last dose of cladribine tablets were 84.8%, 66.2% and 57.2%, respectively. The corresponding probability of being progression-free at 60 months after the last dose was 63.7%. The KM estimate for the probability of not initiating another disease-modifying treatment at 60 months after the last dose of cladribine tablets was 28.1%, and the median time-to-treatment change was 32.1 (95% CI 15.5–39.5) months. Conclusion: CLARINET-MS provides an indirect measure of the long-term effectiveness of cladribine tablets. Over half of MS patients analysed did not relapse or experience disability progression during 60 months of follow-up from the last dose, suggesting that cladribine tablets remain effective in years 3 and 4 after short courses at the beginning of years 1 and 2.

scholarly journals HIV infection and multiple sclerosis: a case with unexpected “no evidence of disease activity” status

2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199957
Author(s):  
Fernando Labella ◽  
Fernando Acebrón ◽  
María del Carmen Blanco-Valero ◽  
Alba Rodrígez-Martín ◽  
Ángela Monterde Ortega ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Hiv Infection ◽  
Disease Activity ◽  
Demyelinating Disease ◽  
Clinical Course ◽  
Disease Modifying Drugs ◽  
Immunodeficiency Virus ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Disease Modifying

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system whose etiology remains unclear. It has been suggested that MS can be triggered by certain viruses; however, human immunodeficiency virus (HIV) infection is associated with reduced incidence of MS. We present the case of a young patient diagnosed with active relapsing-remitting MS whose clinical course substantially improved following HIV infection and treatment. The patient achieved no evidence of disease activity status without any disease-modifying drugs. Both HIV-induced immunosuppression and antiretroviral therapy may have attenuated the clinical course in this patient.

scholarly journals Patient-Reported Disease-Modifying Therapy Adherence in the Clinic: A Reliable Metric?

2018 ◽  
Vol 4 (2) ◽  
pp. 205521731877789 ◽  
Author(s):  
Devon S Conway ◽  
Maria Cecilia Vieira ◽  
Nicolas R Thompson ◽  
Kaila N Parker ◽  
Xiangyi Meng ◽  
...  
Keyword(s):  
Regression Models ◽  
Patient Reported Outcomes ◽  
Patient Reporting ◽  
Lesion Formation ◽  
Logistic Regression Models ◽  
Disease Modifying Therapy ◽  
Patient Reported ◽  
Relapsing Remitting ◽  
Disease Modifying ◽  
The Relationship

Background Adherence to multiple sclerosis (MS) disease-modifying therapy (DMT) is commonly assessed through patient reporting, but patient-reported adherence is rarely studied. Objective To determine rates of DMT adherence reported from patient to clinician, reasons for nonadherence, and relationships between adherence and outcomes. Methods We identified relapsing–remitting MS patients on DMT for ≥3 months. DMT adherence was defined as taking ≥80% of doses. Linear and logistic regression models were created used to determine the association of baseline adherence with several patient reported outcomes and the timed 25-foot walk at 6 months, 1 year, 2 years, and 3 years after the index visit. Results The analysis included 1148 patients, of whom 501 had data at 6 months, 544 at 1 year, 331 at 2 years, and 247 at 3 years. Baseline adherence was 94.9% and overall adherence was 93.1%. Forgetting was the most common reason for missed doses. In the adjusted models, adherence was not associated with the outcomes. Conclusions Higher than expected adherence and a lack of association between adherence and outcomes suggests patient reported adherence may not be reliable. Further research is needed to clarify the relationship between patient-reported adherence and relapses or new lesion formation.

scholarly journals When to Initiate Disease-Modifying Drugs for Relapsing Remitting Multiple Sclerosis in Adults?

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Mona Alkhawajah ◽  
Joel Oger
Keyword(s):  
Multiple Sclerosis ◽  
Decision Making ◽  
Glatiramer Acetate ◽  
Major Question ◽  
Disease Modifying Drugs ◽  
Relapsing Remitting ◽  
Disease Modifying ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

For patients with Relapsing Remitting Multiple Scierosis Beta Interfaerons and Glatiramer Acetate were the first to be licensed for treatment. This review deals with one major question: when to initiate therapy? Through exploring the unique characteristics of the disease and treatement we suggest an approach that should be helpful in the process of decision-making.

scholarly journals Onset of secondary progressive multiple sclerosis is not influenced by current relapsing multiple sclerosis therapies

2018 ◽  
Vol 4 (2) ◽  
pp. 205521731878334 ◽  
Author(s):  
Francisco Coret ◽  
Francisco C Pérez-Miralles ◽  
Francisco Gascón ◽  
Carmen Alcalá ◽  
Arantxa Navarré ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Secondary Progressive ◽  
Disease Modifying Therapies ◽  
Relapsing Remitting ◽  
Disease Modifying ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Background Disease-modifying therapies are thought to reduce the conversion rate to secondary progressive multiple sclerosis. Objective To explore the rate, chronology, and contributing factors of conversion to the progressive phase in treated relapsing–remitting multiple sclerosis patients. Methods Our study included 204 patients treated for relapsing–remitting multiple sclerosis between 1995 and 2002, prospectively followed to date. Kaplan–Meier analysis was applied to estimate the time until secondary progressive multiple sclerosis conversion, and multivariate survival analysis with a Cox regression model was used to analyse prognostic factors. Results Relapsing–remitting multiple sclerosis patients were continuously treated for 13 years (SD 4.5); 36.3% converted to secondary progressive multiple sclerosis at a mean age of 42.6 years (SD 10.6), a mean time of 8.2 years (SD 5.2) and an estimated mean time of 17.2 years (range 17.1–18.1). A multifocal relapse, age older than 34 years at disease onset and treatment failure independently predicted conversion to secondary progressive multiple sclerosis but did not influence the time to reach an Expanded Disability Status Scale of 6.0. Conclusions The favourable influence of disease-modifying therapies on long-term disability in relapsing–remitting multiple sclerosis is well established. However, the time to progression onset and the subsequent clinical course in treated patients seem similar to those previously reported in natural history studies. More studies are needed to clarify the effect of disease-modifying therapies once the progressive phase has been reached.

Multiple sclerosis

2019 ◽  
pp. 417-436
Author(s):  
Manoj Sivan ◽  
Margaret Phillips ◽  
Ian Baguley ◽  
Melissa Nott
Keyword(s):  
Multiple Sclerosis ◽  
Young Adult ◽  
Adult Life ◽  
Rehabilitation Medicine ◽  
Younger Adults ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Disease Modifying ◽  
Criteria For Diagnosis ◽  
The Impact

Multiple sclerosis (MS) is the commonest of the demyelinating CNS conditions and is the most frequent condition causing neurological disability in younger adults. It causes a combination of physical and cognitive disabilities, which, when combined with starting in young adult life and with an uncertain rate of progression, make it both challenging and responsive to rehabilitation. It is important to understand the criteria for diagnosis both to be able to discuss prognosis with patients and because symptoms may become apparent later which affect the diagnosis. It is more likely that rehabilitation medicine clinicians will see those with primary or secondary progressive MS than relapsing–remitting MS because the impact of disability tends to be greater and the current benefits from disease-modifying therapies less in progressive MS.

Sign in / Sign up

Export Citation Format

Share Document