To Örebro University

Introduction: Cladribine is a deoxyadenosine analogue prodrug that selectively induces immune reconstitution by targeting B- and T-lymphocytes. Cladribine tablets (CladT) are administered in two courses, 12 months apart, for patients with relapsing multiple sclerosis (RMS). CladT are included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology”(IMSE).

Objectives: To assess the safety and effectiveness of CladT with focus on patients treated at least 12 months.

Methods: Data  of  Extended  Disability  Status  Scale  (EDSS),  Multiple   Sclerosis  Severity   Scale   (MSSS),   Symbol   Digit   Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29),  European  Quality  of  Life  -  5  Dimensions Test  (EQ-5D),  Visual Analog Scale (VAS), relapses and Adverse Events (AEs) is obtained    from    the    nationwide    Swedish    Neuro    Registry    (NeuroReg).   Effectiveness    measures    were    assessed    using    Wilcoxon  Signed  Rank Test  and  relapse  rates  were  tested  using  paired samples T-test.

Results: 208 patients were included in the IMSE 10 study since the  Swedish market  launch  in  April  2018  with  an  overall  drug  survival  rate  of  94.2%. 12 patients  discontinued  treatment,  of  which 1 later restarted. The most common reason for discontinuation was lack of effect (83%). 21 AEs were reported of which 7 were serious. The most common AE reported were infection and infestation (8 reports).139  patients  were  treated  for  at  least  12  months.  29  %  of  the patients was treated with CladT as their first MS drug. 19 % were treated with natalizumab and 10 % with dimethyl fumarate prior to  CladT.  The  number  of relapses  decreased  significantly  from  249  per  1,000  patient  years  before treatment  start  to  73  during  treatment.  12  patients  in  this  cohort  have experienced  a  relapse  during treatment. Significant  improvements  in  mean values  at  12  months  of  treatment compared to baseline were noted for MSSS (p=0.005) and MSIS29  Psychological(p=0.033).  MSIS-29  Physical  showed  a tendency  for  improvement  while  all  other  tests  remained  stable  after one year of treatment.Lymphocyte levels decreased from a mean of 1.9 x 109/L at treat-ment  start  (n=80)  to  1.1  x  109/L  after  12  months  of  treatment (n=71).

Conclusions: CladT  treatment  demonstrates  clinical  stability  in  patients treated 12  months.  However,  continued  follow-up  is  needed  to  assess  the effectiveness  and  safety  of  CladT  over  a  longer  time  to  assess  if  these results  sustain  after  the  final  treatment course has been administered.