Prospective Effectiveness and Safety Study of Cladribine in Participants Who Change First-line DMD Treatments for Multiple Sclerosis (CLAD CROSS)

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany256 enrolled

Overview

The main aim was to study in the real world setting the effectiveness of Cladribine tablets in terms of Annualized Relapse Rate (ARR) and disability progression, in participants who switched from a first line Disease Modifying Drug (DMD) (Interferons, Glatiramer Acetate, Teriflunomide, (Dymethyl fumarate) \[DMF\]) to treatment with Cladribine tablets in routine clinical practice.

Study Type

OBSERVATIONAL

Enrollment

256

Conditions

Multiple Sclerosis

Interventions

CladribineDRUG

No intervention will be administered as a part of this study. Participants who had switched from first-line DMD treatments to treatment with cladribine tablets in routine clinical practice will be assessed for 2 years in this study.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Participants with confirmed diagnosis of RRMS diagnosed by the treating physician according to applicable clinical practice guidelines -(currently McDonald 2017 criteria), with high disease activity * Participants should have been treated with the same first-line DMD (Interferons, Glatiramer Acetate, Teriflunomide, DMF) and at a stable dose for at least one year prior to switch to Cladribine tablets and should have been prescribed Cladribine tablets, according to the decision of the treating physician, prior to enrollment in the study. Any washout period and/or washout methods required before switching (such as elimination of Teriflunomide) must have been conducted, according to the decision of the treating physician * Required history data should be available: Multiple Sclerosis (MS) data for the 12-months pre-baseline period (annualized relapse rate); MS Medication History (prior DMDs) * Fulfilment of the criteria for treatment with Cladribine tablets per standard of care in accordance with the local Summary of Product Characteristics (SmPC) Exclusion Criteria: * Contraindications to use of cladribine tablets according to the SmPC * Participants with history of alcohol or drug abuse that could potentially interfere with their participation in the study * Participants that have received Cladribine in the past * Concurrent participation in an investigational study in which participant assessment and/or treatment may be dictated by a protocol

Outcomes

Primary Outcomes

Change in Annualized Relapse Rate (ARR) Between the Pre-Baseline 12-Month Period (Baseline) and Over the 12 Months Period Before the End of Study Follow-Up (2 Years)

ARR defined as the number of relapses per year. A relapse was defined as the appearance of new symptoms or the exacerbation of pre-existing symptoms that were attributed to Multiple Sclerosis (MS) and occurred over a minimum of 24 hours and separated from a previous attack by at least 30 days, in the absence of fever or infection. Baseline ARR was defined as the total number of relapses reported in the last 12 months prior to Cladribine treatment. ARR 12-months prior to End Of Study was calculated as the sum of the number of MS relapses reported at Visit 3 and Visit 4 divided by the number of days between Visit 4 date and Visit 2 date and multiplied by 365.25. For a change from baseline, 95 percent (%) Confidence Interval (CI) for the difference were presented together with summary statistics. These CIs were included as a descriptive measure of effect.

Time frame: 12-months pre-baseline (Baseline) and 12 Months Prior to End of Study follow up (2 years)

Secondary Outcomes

Change in ARR Between the Pre-Baseline 12-Month Period (Baseline) and Over the 12 Months Period After the Start of Cladribine (1 Year)

ARR defined as the number of relapses per year. A relapse was defined as the appearance of new symptoms or the exacerbation of pre-existing symptoms that were attributed to MS and occurred over a minimum of 24 hours and separated from a previous attack by at least 30 days, in the absence of fever or infection. ARR 12-months after start of Cladribine was calculated as the sum of the number of MS relapses reported at Visit 1 and Visit 2 divided by the number of days between Visit 2 date and Cladribine start date and multiplied by 365.25.For a change from baseline, 95% CIs for the difference were presented together with summary statistics. These CIs were included as a descriptive measure of effect.

Time frame: 12-month pre-baseline period (baseline) and over the 12 months period after start of Cladribine treatment (1 year)

Percentage of Participants With 6-Month Disability Progression Measured With Expanded Disability Status Scale (EDSS)

EDSS assessed disability in 8 functional systems. It was a scale based on a standardized EDSS neurological examination, which comprised optic, brain stem, pyramidal, cerebellar, sensory, and cerebral functions, as well as walking ability. An overall score ranged from 0 (normal) to 10 (death due to MS) was calculated. Progression on EDSS was defined as at least a 1-point increase in the score or an increase of at least 1.5 points if the baseline EDSS score was 0.

Time frame: At EOS (24 months follow-up)

Percentage of Participants With Overall 6-Month Disability Progression Measured With EDSS, Timed 25 Foot Walk (T25FW) or 9 Hole Peg Test (9HPT)

Disability progression was assessed if at least one assessment (EDSS, T25FW or 9HPT) was available. As per definition, disability progression was derived as "Yes" if at least one of the below cases occured: 1. Visit 4 EDSS is greater than (\>=) equal to (≥) 1 point \>= Visit 3 EDSS if Visit 3 EDSS is \> 0; 2. Visit 4 EDSS is 1.5 or \> when Visit 3 EDSS is 0; 3. 20% increase in the T25FW score (average of the two trials) from Visit 3 to Visit 4; 4. 20% increase in the 9HPT score (The two trials for each hand are averaged, converted to the reciprocals of the mean times for each hand and then the two reciprocals are averaged) from Visit 3 to Visit 4. If none of those cases occurred, disability progression will be set to "No". The percentage of participants with 6-month disability progression at the EOS was presented including associated 95% Clopper Pearson exact intervals.

Time frame: At EOS (24 months follow-up)

Percentage of Participants With 6-Month Disability Improvement Measured With EDSS

EDSS assessed disability in 8 functional systems. It was a scale based on standardized neurological examination which comprised of optic, brain stem, pyramidal, cerebellar, sensory \& cerebral functions, as well as walking ability. An overall score ranged from 0 (normal) to 10 (death due to MS) was calculated. Improvement on EDSS was defined as a decrease in EDSS by at least 1 point (1.5 points if baseline EDSS was 1.5).

Time frame: At EOS (24 months follow-up)

Percentage of Participants With Overall 6-Month Disability Improvement Measured With EDSS, Timed 25 Foot Walk (T25FW) or 9 Hole Peg Test(9HPT)

Disability improvement was assessed if at least one assessment (EDSS, T25FW or 9HPT) was available. As per definition, disability improvement was derived as "Yes" if at least one of the below cases occur:1. Visit 4 EDSS is ≥1 point smaller than Visit 3 EDSS if Visit 3 EDSS is greater than 1.5;2. Visit 4 EDSS is 0 when Visit 3 EDSS is 1.5;3. 20% decrease in the T25FW score (average of the two trials) from Visit 3 to Visit 4;4. 20% decrease in the 9HPT score (The two trials for each hand are averaged, converted to the reciprocals of the mean times for each hand and then the two reciprocals are averaged) from Visit 3 to Visit 4. If none of those cases occurred, disability improvement was set to "No". The percentage of participants with 6-month disability improvement at the end of study was presented including associated 95% Clopper Pearson exact intervals.

Time frame: At EOS (24 months follow-up)

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal relationship with this treatment. Therefore, an AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, regardless if it is considered related to the medicinal product. Serious AE: AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs are defined as AEs that were reported or worsened on or after start of study drug dosing through the Safety Follow-up Visit. TEAEs included both serious TEAEs and non-serious TEAEs.

Time frame: From start of study up to 2 years

Quality of Life as Assessed by Multiple Sclerosis Impact Scale (MSIS-29) Score: Physical and Psychological Impact

MSIS-29 was a 29-item self-report measure with 20 items related to physical scale and 9 items with psychological scale. All items have 5 options:1-not at all to 5-extremely. Each of2 scales are scored by summing responses across items, converting to 0-100 scale where 100 indicates great impact of disease on daily function (worse health). Physical impact score computed by summing items 1-20 inclusive (observed score). This score was then transformed to a score on a scale of 0-100 using the formula:\[100 multiplied by(observed score minus(-)20)\] divided by(100-20). The psychological impact score was computed by summing items number21-29 inclusive(observed score). This score was then transformed to score on scale of 0-100 using the formula:\[100 multiplied by(observed score minus 9)\]divided by(45-9). Total score range ranges from 0-100, lower total score shows less psychological/physical-related impact while a higher total score indicated greater psychological/physical-related impact.

Time frame: Baseline, Months 12 and 24

Quality of Life as Assessed by EuroQol Quality of Life Questionnaire 5 Dimensions 3 Levels (EQ-5D-3L)

Quality of Life was measured using the EQ-5D-3L questionnaire. The EQ-5D-3L asks participants to rate the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. EQ-5D-5L VAS was used to record a participants rating for his/her current health-related quality of life state and captured on a vertical VAS (0-100), where 0 =worst imaginable health state and 100 = best imaginable health state.

Time frame: Baseline, Months 12 and 24

Treatment Satisfaction as Assessed by Treatment Satisfaction Questionnaire for Medication Version 1.4 (TSQM v1.4) Scale

TSQM version 1.4 was a global satisfaction scale used to assess the overall level of participant's satisfaction or dissatisfaction with their medications. It comprises of 14 items assessing the following 4 domains: effectiveness (questions: 1-3), side effects (questions: 4-8), convenience (questions: 9-11), global satisfaction (questions:12-14). Global Satisfaction- Question 12 scored as 1 (not at all confident) to 5 (extremely confident); question 13 scored as 1 (not at all certain) to 5 (extremely certain); and question 14 scored as 1 (extremely dissatisfied) to 7 (extremely satisfied). The scores of the domain were added together and an algorithm was used to create a score of 0 to 100. Higher scores indicated greater satisfaction.

Time frame: Months 6, 12, 18 and 24

Number of Participants With Treatment Adherence

According to the World Health Organization (WHO), treatment adherence is defined as both compliance (taking the medication in the correct dose and according to the schedule prescribed) and persistency (maintenance of the drug regimen over the long-term). Adherence to treatment, calculated as 100 × Taken tablets/Prescribed tablets

Time frame: Up to Month 24

Prospective Effectiveness and Safety Study of Cladribine in Participants Who Change First-line DMD Treatments for Multiple Sclerosis (CLAD CROSS)

Overview

Conditions

Interventions

Eligibility

Locations (61)

Outcomes

Primary Outcomes

Secondary Outcomes