Background

Multiple sclerosis is a chronic disease of the central nervous system, most often with relapsing-remitting (RRMS) course.

Cladribine tablets was tested against placebo in randomized controlled trials (RCT) in RRMS.

As there is lack of head-to-head trials directly comparing CT to other highly active DMTs, an indirect comparison via network meta-analysis (NMA) was performed with placebo as a common comparator.

Objectives

To compare probabilities of sustained disability improvement (SDI) on the EDSS, in patients with relapsing-remitting multiple sclerosis (RRMS), treated with cladribine tablets (CT) or fingolimod (FIN), natalizumab (NAT), alemtuzumab (ALE) and ocrelizumab (OCR).

Methods

In compliance with the Polish HTA guidelines, a systematic review was conducted in Pubmed, Embase and Cochrane to identify clinical trials (RCT or non-RCT) evaluating 6-month SDI. An indirect comparison via network meta-analysis (NMA) was performed. Bayesian inference with Markov chains Monte Carlo methods were applied, using the WinBUGS© software.

Results

Finally, 6 trials presenting SDI results and applicable for NMA were included: 5 non-RCTs, with control groups selected by propensity score matching (Kalincik 2018, Kalincik 2015, Kalincik 2017, Barnocini 2016, Guger 2018) and 1 RCT (CARE MS II), allowing for comparison of CT vs FIN, NAT, ALE. Due to the lack of proper data, comparison with OCR was not possible. Additionally, there were only 37 patients treated with CT with SDI data available (Kalincik 2018). NMA results revealed that Hazard Ratios (95% CrI) for achieving 6-month SDI with CT was statistically significantly higher in comparison with all other high efficacy disease modifying treatments studied in this analysis: CT vs FIN – 5,17 (1,81; 15,01), CT vs NAT – 3,06 (1,06; 8,62), CT vs ALE – 9,45 (2,79; 31,94).

Conclusions

Cladribine tablets treatment was associated with higher probability of sustained recovery from disability compared to fingolimod, natalizumab and alemtuzumab in RRMS patients with highly active disease. The conclusion is based on limited quality of identified clinical data.

Background

Alemtuzumab is a monoclonal antibody directed against antigen CD52 on cells of the immune system. It is used in the treatment of highly active multiple sclerosis. Immune reconstitution inflammatory syndrome (IRIS) develops due to reconstruction of cellular immunity and inflammation in the central nervous system, in most cases after progressive multifocal leukoencephalopathy (PML). Sometimes IRIS can also occur in the absence of PML.

Objectives

IRIS in a patient treated with alemtuzumab eight years earlier is described. A series of images of MR of the brain will be presented.

Methods

A 38-year-old male patient was admitted because of dysphasia, bulbar syndrome and severe agitation. In 2011 and 2012 he was treated with alemtuzumab because of highly active MS. After 7 years of remission, in 2019 he had a relapse, and in February 2020 he developed severe neurological exacerbation.

Results

MRI of the brain showed multiple big confluencing lesions hyperintensive in T2 weighted images, in the white matter, both supra- and infratentorially, associated with mass effect and contrast enhancement. The patient was treated with prolonged steroids therapy and plasma exchange. JCV-DNA was negative in the CSF. On series of control MRI there was gradual regression of lesions. Neurological state of the patient improved.

Conclusions

IRIS can be a complication of alemtuzumab treatment and arise from the restoration of the previously suppressed immune response, in the absence of active infection i.e. PML.

Background

Susac syndrome is a retinocochleocerebral autoimmune microangiopathy manifesting as vision disorders (due to branch retinal artery occlusion), encephalopathy and sensory neural hearing loss. In the MRI of the brain in the white matter focal disseminated lesions are present, especially along the corpus callosum.

Objectives

To present a case of Susac syndrome and to underline importance of differential diagnosis in demyelinating process in case of characteristic triad of symptoms.

Methods

A 28-year-old female patient was admitted due to sudden visual impairment of the left eye. Additionally, she had had progressive hearing loss lasting about 2 years and was also treated due to psychiatric disorders.

Results

Additional examinations (MRI of the brain, audiogram, fluorescein angiography of retina) confirmed the diagnosis. Steroids were used in the treatment and azathioprine was introduced. About 7 months later retinal arterial occlusions occurred in the right eye.

Conclusions

In the differential diagnosis of demyelinating process Susac syndrome should be included. It is a multidisciplinary problem, often misdiagnosed as it mimics many other diseases.

Background

Multiple sclerosis (MS), a chronic disabling disease requiring long-term treatment and regular monitoring, is associated with negative effects on health-related quality of life (HRQoL). CLARIFY-MS (NCT03369665) aims to assess the impact of cladribine tablets (CT) 10 mg (3.5 mg/kg cumulative dose over 2 years; CT3.5) on HRQoL and treatment satisfaction in patients with highly-active relapsing MS (RMS).

Objectives

To present an interim analysis of CLARIFY-MS at 6 months after initiating treatment with CT, assessing treatment satisfaction through the Treatment Satisfaction Questionnaire for Medication (TSQM) v1.4 and safety through the collection of safety assessments in highly-active RMS patients.

Methods

CLARIFY-MS is an ongoing phase IV, open label, single arm, multicenter, 2-year study. Patients with RMS received CT3.5, with 2 weeks of active treatment per course (week 1 and 5 of each year). TSQM v1.4 was used to assess patient-reported treatment satisfaction (a score of 100 is the best possible rating). The TSQM measures 14 items across four domains: effectiveness (three items), side effects (five items), convenience (three items), and global satisfaction (three items).Treatment-emergent adverse events (TEAEs), serious adverse events (AEs), and lymphocyte counts were recorded.

Results

Treatment satisfaction: Of 554 patients screened, 482 received CT. The age and Expanded Disability Status Scale adjusted global treatment satisfaction score (95% confidence interval) at Month 6 was 70.0 (66.6–73.5). Treatment-experienced patients (prior treatment with disease-modifying drugs [DMDs]) reported similar treatment satisfaction scores to DMD-naïve patients (70.2 vs 68.7). At Month 6, >75% of patients rated the TSQM side effects score with 100. The mean side effects score was 91.9, mean convenience 86.6. Safety: 275 patients (57.1%) experienced ≥1 TEAE after drug initiation, most commonly headache and lymphopenia. Most post-baseline lymphopenias were of grade 1-2; 33 patients (6.8%) experienced grade 3 lymphopenia and no grade 4 lymphopenia was observed.

Conclusions

This interim analysis of CLARIFY-MS found that at 6 months, patients were generally satisfied with CT treatment. The convenience of CT treatment and side effect profile were especially important to patients. Safety results at 6 months post-treatment are consistent with the known safety profile, with no new emerging safety signal; most lymphopenias were grade 1-2.