Background

Brain volumetry is an accepted monitoring tool for the diffuse, not relapse-related inflammatory activity in MS. As thalamus volume turned out to be most affected by the atrophic process in MS, a special focus is put on this region.

Objectives

We present first data from our ongoing study, addressing the effect of Cladribine Tablets on global and regional brain atrophy.

Methods

45 consecutive patients with highly active MS from our observational study are presented (mean age 39 y, mean EDSS 2.1, 31 female, 14 male). Clinical and brain MRI evaluations were carried out at baseline prior to Cladribine treatment and repeated after 6 and 12 months following Cladribine treatment initialization. All images were acquired with the same 3T Philips Achieva scanner using the same 3D MPRAGE protocol. Global and regional brain volumes were derived using a previously described atlas based volumetry approach implemented in SPM12 in cooperation with jung diagnostics. Quantified parameters include brain parenchymal volume (BPV), grey matter volume (GMV), white matter volume (WMV), Corpus callosum volume (CCV) and thalamus volume (THV). All atrophy parameters of the single subjects were tested against the normative database. All volumes were tranformated to age-corrected z-volumes. Z<-1.96 means significant atrophy. 0.0 equals the mean of the normative database.

Results

As expected, at baseline the regional brain volumetry revealed the highest pretreatment mean loss in THV, e.g. the highest sensitivity for the atrophic process in thalamus (z= -1.64), followed by CCV (z=-1.22), WMV (z=-1.67) and GMV (z=-0.54). 6 and 12 months after Cladribine initialization the z-differences from baseline to first visit and second visit to third visit were for BPV +0.21, -0.11; GMV +0.18, +0.01; WMV +0.07, -0.18; THV +0.21, +0.06; CCV +0.13, +0.02. GMV, THV and CCV are fully protected by Cladribine tablets for the entire first treatment year. For WMV and BPV respectively there is a slight trend to volume reduction. The z-difference in the second half of the first treatment year equals an estimated annual volume loss of age-corrected 0.2% which is still an excellent effect.

Conclusions

From the first data of this ongoing study can be concluded that the first treatment period with Cladribine tablets fully protects GMV including the highly sensitive thalamus. With the exception of CCV with good protection, the effect of Cladribine on WMV seems to decrease in the second half of the first treatment year.

Background

CLADQoL is a non-interventional study (NIS) in patients with RMS treated with cladribine tablets, focusing on quality of life. This is the first publication on the change in quality of life (examined by MSQoL-54) of patients treated with cladribine tablets in real world conditions at baseline and after 12 months. The recruitment period has ended in April 2020. Patient follow-up will continue and is planned for four years.

Objectives

Describing the patient population including pre-treatment and relapse rate and evaluating changes in patients’ quality of life (MSQoL-54 physical health and mental health composite scores) under therapy with cladribine tablets 12 months after treatment initiation.

Methods

Quality of life (QoL) was evaluated from the patient subset where MSQoL-54 was available both at baseline and month 12. Cut-Off date for analysis was January 31^st 2020.

Results

87 of 254 recruited patients were evaluated so far (mean age 37 years; 78.2% female; 93.1% RRMS). Most frequent last previous therapy for treated patients was fingolimod, dimethyl fumarate, glatiramer acetate and daclizumab.

For the subsets with valid MSQoL-54 at baseline and month 12 the physical health composite score showed a decrease -0.942 ±14.08 whereas the mental health composite score revealed an increase 0.711 ±17.33 (Change 12 months vs. baseline). None of the differences reached significance.

The number of relapses decreased from 1.0 ±1.09 (Mean ±SD) at baseline to 0.2 ±0.58 (Mean ±SD) at month 12.

Regarding safety, evaluation was performed for the overall study population (N=254). 82 patients experienced at least one AE and 15 patients at least one SAE.

Conclusions

Within the first year of treatment with cladribine tablets in patients with RRMS or SPMS with superimposed relapses there were minimal changes in QoL scores.

We observed a decrease in relapses and the safety results were in line with known safety profile of cladribine tablets.

The NIS is ongoing and patient subset is being followed up.

Background

Brain volumetry is an accepted monitoring tool for the diffuse, not relapse-related inflammatory activity in MS. As thalamus volume turned out to be most affected by the atrophic process in MS, a special focus is put on this region.

Objectives

We present first data from our ongoing study, addressing the effect of Cladribine Tablets on global and regional brain atrophy.

Methods

45 consecutive patients with highly active MS from our observational study are presented (mean age 39 y, mean EDSS 2.1, 31 female, 14 male). Clinical and brain MRI evaluations were carried out at baseline prior to Cladribine treatment and repeated after 6 and 12 months following Cladribine treatment initialization. All images were acquired with the same 3T Philips Achieva scanner using the same 3D MPRAGE protocol. Global and regional brain volumes were derived using a previously described atlas based volumetry approach implemented in SPM12 in cooperation with jung diagnostics. Quantified parameters include brain parenchymal volume (BPV), grey matter volume (GMV), white matter volume (WMV), Corpus callosum volume (CCV) and thalamus volume (THV). All atrophy parameters of the single subjects were tested against the normative database. All volumes were tranformated to age-corrected z-volumes. Z<-1.96 means significant atrophy. 0.0 equals the mean of the normative database.

Results

As expected, at baseline the regional brain volumetry revealed the highest pretreatment mean loss in THV, e.g. the highest sensitivity for the atrophic process in thalamus (z= -1.64), followed by CCV (z=-1.22), WMV (z=-1.67) and GMV (z=-0.54). 6 and 12 months after Cladribine initialization the z-differences from baseline to first visit and second visit to third visit were for BPV +0.21, -0.11; GMV +0.18, +0.01; WMV +0.07, -0.18; THV +0.21, +0.06; CCV +0.13, +0.02. GMV, THV and CCV are fully protected by Cladribine tablets for the entire first treatment year. For WMV and BPV respectively there is a slight trend to volume reduction. The z-difference in the second half of the first treatment year equals an estimated annual volume loss of age-corrected 0.2% which is still an excellent effect.

Conclusions

From the first data of this ongoing study can be concluded that the first treatment period with Cladribine tablets fully protects GMV including the highly sensitive thalamus. With the exception of CCV with good protection, the effect of Cladribine on WMV seems to decrease in the second half of the first treatment year.