Relapsing-Remitting Multiple Sclerosis
Conditions
Keywords
Multiple Sclerosis, Mavenclad ®, Cladribine
Brief summary
The main purpose of this study was to investigate the effectiveness of cladribine tablets in a UK real-world setting.
Interventions
None listed
Sponsors
Merck Serono Limited, UK
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Physician diagnosis of HDA-RRMS as defined by clinical or radiological features * Treatment initiation with cladribine tablet monotherapy on or after 22 August 2017 and at least 3 years before enrolment * Completion of Year 1 treatment of cladribine tablets (Week 1 and Week 2 treatment, per recommended dose in Year 1: 1.75 milligrams per kilogram \[mg/kg\] body weight, cumulatively)
Exclusion criteria
* Received cladribine tablet treatment within an interventional clinical trial during the study period * Received treatment with any investigational therapy for RRMS in the 6 months prior to cladribine tablet treatment initiation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annualized Relapse Rate in the Year Prior to Treatment Initiation With Cladribine Tablets | 1 Year prior to date of Cladribine tablet initiation | The annualized relapse rate for a participant is defined here as the number of clinician's confirmed relapses that occurred in the year prior to the date of Cladribine tablet initiation. |
| Annualized Relapse Rate in the Year One After Treatment Initiation With Cladribine Tablets | Year 1 after treatment initiation with Cladribine tablets | The annualized relapse rate for a participant is defined here as the number of clinician's confirmed relapses that occurred in Year 1 after treatment initiation with Cladribine tablets. |
| Annualized Relapse Rate in the Year 2 After Treatment Initiation With Cladribine Tablets | Year 2 after treatment initiation with Cladribine tablets | The annualized relapse rate for a participant is defined here as the number of clinician's confirmed relapses that occurred in Years 2 after treatment initiation with Cladribine tablets. |
| Annualized Relapse Rate in the Year 3 After Treatment Initiation With Cladribine Tablets | Year 3 after treatment initiation with Cladribine tablets | The annualized relapse rate for a participant is defined here as the number of clinician's confirmed relapses that occurred in Year 3 after treatment initiation with Cladribine tablets. |
| Annualized Relapse Rate in the Year 4 After Treatment Initiation With Cladribine Tablets | Year 4 after treatment initiation with Cladribine tablets | The annualized relapse rate for a participant is defined here as the number of clinician's confirmed relapses that occurred in Years 4 after treatment initiation with Cladribine tablets. |
| Annualized Relapse Rate in the Year 5 After Treatment Initiation With Cladribine Tablets | Year 5 after treatment initiation with Cladribine tablets | The annualized relapse rate for a participant is defined here as the number of clinician's confirmed relapses that occurred in Year 5 after treatment initiation with Cladribine tablets. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relapse-Free Rate in Each Year After Initiation of Cladribine Tablet Treatment | Year 1, 2, 3, 4 and 5 after treatment initiation with Cladribine tablets until relapse or death | Relapse-free is defined as the time from the on-treatment period start date until first relapse or death as assessed by the investigator. Relapse-free rate, i.e., the survival rate using Kaplan Meier method, was summarized every year. |
| Number of Participants With Grade 3 Lymphopenia, Grade 4 Lymphopenia, Herpes Infections, Serious Infections, Opportunistic Infections and Malignancies | At 2 years after treatment initiation with Cladribine tablets | Number of Participants with Grade 3 Lymphopenia, Grade 4 Lymphopenia, Herpes Infections, Serious Infections, Opportunistic Infections and Malignancies were reported. |
| Time From Cladribine Tablet Initiation to First Relapse | up to maximum 5 years after treatment initiation with Cladribine tablets | A qualifying relapse is defined as new, worsening or recurrent neurological symptoms attributed to Multiple Sclerosis (MS) that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. Percentage of participants with qualified relapse-free status at week 24 were reported. |
| Number of Participants Who Discontinued Cladribine Tablets | From Cladribine treatment initiation up to end of Cladribine treatment (assessed up end of Treatment Year 2) | The number of participants who discontinued treatment with cladribine are reported here. |
| Number of Participants Who Received Subsequent Disease-modifying Therapies (DMTs) After Cladribine Tablets Discontinuation/Treatment Completion | From Cladribine treatment initiation up to end of Cladribine treatment (assessed up end of Treatment Year 2) | The number of participants who received Subsequent Disease-modifying Therapies (DMTs) after Cladribine Tablets Discontinuation/Treatment Completion were reported here. |
| Number of Participants With Disability Progression Assessed by Expanded Disease Severity Scale (EDSS) at Treatment Initiation and Start of Treatment Year 2 | At Treatment Initiation and Start of Treatment Year 2 | he EDSS is an ordinal clinical rating scale in half-point increments. It assesses the following eight functional systems, areas of the central nervous system that control bodily functions: Pyramidal (ability to walk), Cerebellar (coordination), Brain stem (speech and swallowing), Sensory (touch and pain), Bowel and bladder functions, Visual, Mental, Other (includes any other neurological findings due to Multiple Sclerosis \[MS\]). EDSS overall score ranging from 0 (normal) to 10 (death due to MS). |
| Number of Participants With Disability Progression Confirmed Over 6 Months, Assessed by Expanded Disease Severity Scale (EDSS) at 2 Years After Cladribine Tablet Treatment Initiation | At 2 years after treatment initiation with Cladribine tablets | he EDSS is an ordinal clinical rating scale in half-point increments. It assesses the following eight functional systems, areas of the central nervous system that control bodily functions: Pyramidal (ability to walk), Cerebellar (coordination), Brain stem (speech and swallowing), Sensory (touch and pain), Bowel and bladder functions, Visual, Mental, Other (includes any other neurological findings due to Multiple Sclerosis \[MS\]). EDSS overall score ranging from 0 (normal) to 10 (death due to MS). |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cladribine Participants diagnosed with Highly-active Disease Relapsing-remitting Multiple Sclerosis (HDA-RRMS), who completed at least Year 1 of treatment with cladribine tablets in routine clinical practice were enrolled into this study and assessed up to maximum 5 years after cladribine tablets initiation. | 116 |
| Total | 116 |
Baseline characteristics
| Characteristic | Cladribine |
|---|---|
| Age, Continuous | 44 Years STANDARD_DEVIATION 9.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 116 Participants |
| Sex: Female, Male Female | 82 Participants |
| Sex: Female, Male Male | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 116 |
| other Total, other adverse events | 51 / 116 |
| serious Total, serious adverse events | 1 / 116 |
Outcome results
Primary
Annualized Relapse Rate in the Year 2 After Treatment Initiation With Cladribine Tablets
The annualized relapse rate for a participant is defined here as the number of clinician's confirmed relapses that occurred in Years 2 after treatment initiation with Cladribine tablets.
Time frame: Year 2 after treatment initiation with Cladribine tablets
Population: Full Analysis Set included all participants who were treated with at least one course of treatment with cladribine tablets.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cladribine | Annualized Relapse Rate in the Year 2 After Treatment Initiation With Cladribine Tablets | 0.052 Relapse per year |
Primary
Annualized Relapse Rate in the Year 3 After Treatment Initiation With Cladribine Tablets
The annualized relapse rate for a participant is defined here as the number of clinician's confirmed relapses that occurred in Year 3 after treatment initiation with Cladribine tablets.
Time frame: Year 3 after treatment initiation with Cladribine tablets
Population: Full Analysis Set included all participants who were treated with at least one course of treatment with cladribine tablets.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cladribine | Annualized Relapse Rate in the Year 3 After Treatment Initiation With Cladribine Tablets | 0.086 Relapse per year |
Primary
Annualized Relapse Rate in the Year 4 After Treatment Initiation With Cladribine Tablets
The annualized relapse rate for a participant is defined here as the number of clinician's confirmed relapses that occurred in Years 4 after treatment initiation with Cladribine tablets.
Time frame: Year 4 after treatment initiation with Cladribine tablets
Population: Full Analysis Set included all participants who were treated with at least one course of treatment with cladribine tablets.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cladribine | Annualized Relapse Rate in the Year 4 After Treatment Initiation With Cladribine Tablets | 0.060 Relapse per year |
Primary
Annualized Relapse Rate in the Year 5 After Treatment Initiation With Cladribine Tablets
The annualized relapse rate for a participant is defined here as the number of clinician's confirmed relapses that occurred in Year 5 after treatment initiation with Cladribine tablets.
Time frame: Year 5 after treatment initiation with Cladribine tablets
Population: Full Analysis Set included all participants who were treated with at least one course of treatment with cladribine tablets.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cladribine | Annualized Relapse Rate in the Year 5 After Treatment Initiation With Cladribine Tablets | 0.063 Relapse per year |
Primary
Annualized Relapse Rate in the Year One After Treatment Initiation With Cladribine Tablets
The annualized relapse rate for a participant is defined here as the number of clinician's confirmed relapses that occurred in Year 1 after treatment initiation with Cladribine tablets.
Time frame: Year 1 after treatment initiation with Cladribine tablets
Population: Full Analysis Set included all participants who were treated with at least one course of treatment with cladribine tablets.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cladribine | Annualized Relapse Rate in the Year One After Treatment Initiation With Cladribine Tablets | 0.101 Relapse per year |
Primary
Annualized Relapse Rate in the Year Prior to Treatment Initiation With Cladribine Tablets
The annualized relapse rate for a participant is defined here as the number of clinician's confirmed relapses that occurred in the year prior to the date of Cladribine tablet initiation.
Time frame: 1 Year prior to date of Cladribine tablet initiation
Population: Full Analysis Set included all participants who were treated with at least one course of treatment with cladribine tablets.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cladribine | Annualized Relapse Rate in the Year Prior to Treatment Initiation With Cladribine Tablets | 0.595 Relapse per year |
Secondary
Number of Participants Who Discontinued Cladribine Tablets
The number of participants who discontinued treatment with cladribine are reported here.
Time frame: From Cladribine treatment initiation up to end of Cladribine treatment (assessed up end of Treatment Year 2)
Population: Full Analysis Set included all participants who were treated with at least one course of treatment with cladribine tablets.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cladribine | Number of Participants Who Discontinued Cladribine Tablets | 4 Participants |
Secondary
Number of Participants Who Received Subsequent Disease-modifying Therapies (DMTs) After Cladribine Tablets Discontinuation/Treatment Completion
The number of participants who received Subsequent Disease-modifying Therapies (DMTs) after Cladribine Tablets Discontinuation/Treatment Completion were reported here.
Time frame: From Cladribine treatment initiation up to end of Cladribine treatment (assessed up end of Treatment Year 2)
Population: Full Analysis Set included all participants who were treated with at least one course of treatment with cladribine tablets.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cladribine | Number of Participants Who Received Subsequent Disease-modifying Therapies (DMTs) After Cladribine Tablets Discontinuation/Treatment Completion | 19 Participants |
Secondary
Number of Participants With Disability Progression Assessed by Expanded Disease Severity Scale (EDSS) at Treatment Initiation and Start of Treatment Year 2
he EDSS is an ordinal clinical rating scale in half-point increments. It assesses the following eight functional systems, areas of the central nervous system that control bodily functions: Pyramidal (ability to walk), Cerebellar (coordination), Brain stem (speech and swallowing), Sensory (touch and pain), Bowel and bladder functions, Visual, Mental, Other (includes any other neurological findings due to Multiple Sclerosis \[MS\]). EDSS overall score ranging from 0 (normal) to 10 (death due to MS).
Time frame: At Treatment Initiation and Start of Treatment Year 2
Population: Full Analysis Set included all participants who were treated with at least one course of treatment with cladribine tablets.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cladribine | Number of Participants With Disability Progression Assessed by Expanded Disease Severity Scale (EDSS) at Treatment Initiation and Start of Treatment Year 2 | 0 Participants |
Secondary
Number of Participants With Disability Progression Confirmed Over 6 Months, Assessed by Expanded Disease Severity Scale (EDSS) at 2 Years After Cladribine Tablet Treatment Initiation
he EDSS is an ordinal clinical rating scale in half-point increments. It assesses the following eight functional systems, areas of the central nervous system that control bodily functions: Pyramidal (ability to walk), Cerebellar (coordination), Brain stem (speech and swallowing), Sensory (touch and pain), Bowel and bladder functions, Visual, Mental, Other (includes any other neurological findings due to Multiple Sclerosis \[MS\]). EDSS overall score ranging from 0 (normal) to 10 (death due to MS).
Time frame: At 2 years after treatment initiation with Cladribine tablets
Population: Full Analysis Set included all participants who were treated with at least one course of treatment with cladribine tablets.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cladribine | Number of Participants With Disability Progression Confirmed Over 6 Months, Assessed by Expanded Disease Severity Scale (EDSS) at 2 Years After Cladribine Tablet Treatment Initiation | 0 Participants |
Secondary
Number of Participants With Grade 3 Lymphopenia, Grade 4 Lymphopenia, Herpes Infections, Serious Infections, Opportunistic Infections and Malignancies
Number of Participants with Grade 3 Lymphopenia, Grade 4 Lymphopenia, Herpes Infections, Serious Infections, Opportunistic Infections and Malignancies were reported.
Time frame: At 2 years after treatment initiation with Cladribine tablets
Population: Full Analysis Set included all participants who were treated with at least one course of treatment with cladribine tablets.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cladribine | Number of Participants With Grade 3 Lymphopenia, Grade 4 Lymphopenia, Herpes Infections, Serious Infections, Opportunistic Infections and Malignancies | Grade 3 Lymphopenia | 47 Participants |
| Cladribine | Number of Participants With Grade 3 Lymphopenia, Grade 4 Lymphopenia, Herpes Infections, Serious Infections, Opportunistic Infections and Malignancies | Grade 4 Lymphopenia | 0 Participants |
| Cladribine | Number of Participants With Grade 3 Lymphopenia, Grade 4 Lymphopenia, Herpes Infections, Serious Infections, Opportunistic Infections and Malignancies | Herpes infections | 6 Participants |
| Cladribine | Number of Participants With Grade 3 Lymphopenia, Grade 4 Lymphopenia, Herpes Infections, Serious Infections, Opportunistic Infections and Malignancies | Serious/opportunistic infections | 8 Participants |
| Cladribine | Number of Participants With Grade 3 Lymphopenia, Grade 4 Lymphopenia, Herpes Infections, Serious Infections, Opportunistic Infections and Malignancies | Malignancies | 1 Participants |
Secondary
Relapse-Free Rate in Each Year After Initiation of Cladribine Tablet Treatment
Relapse-free is defined as the time from the on-treatment period start date until first relapse or death as assessed by the investigator. Relapse-free rate, i.e., the survival rate using Kaplan Meier method, was summarized every year.
Time frame: Year 1, 2, 3, 4 and 5 after treatment initiation with Cladribine tablets until relapse or death
Population: Full Analysis Set included all participants who were treated with at least one course of treatment with cladribine tablets. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure and number analyzed signifies those participants who were evaluable at specified time points for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cladribine | Relapse-Free Rate in Each Year After Initiation of Cladribine Tablet Treatment | Year 1 | 0.92 estimated probability |
| Cladribine | Relapse-Free Rate in Each Year After Initiation of Cladribine Tablet Treatment | Year 2 | 0.85 estimated probability |
| Cladribine | Relapse-Free Rate in Each Year After Initiation of Cladribine Tablet Treatment | Year 3 | 0.81 estimated probability |
| Cladribine | Relapse-Free Rate in Each Year After Initiation of Cladribine Tablet Treatment | Year 4 | 0.78 estimated probability |
| Cladribine | Relapse-Free Rate in Each Year After Initiation of Cladribine Tablet Treatment | Year 5 | 0.75 estimated probability |
Secondary
Time From Cladribine Tablet Initiation to First Relapse
A qualifying relapse is defined as new, worsening or recurrent neurological symptoms attributed to Multiple Sclerosis (MS) that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. Percentage of participants with qualified relapse-free status at week 24 were reported.
Time frame: up to maximum 5 years after treatment initiation with Cladribine tablets
Population: Full Analysis Set included all participants who were treated with at least one course of treatment with cladribine tablets.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cladribine | Time From Cladribine Tablet Initiation to First Relapse | NA years |