Background

There are different disease-modifying therapies (DMTs) for treating patients with Relapsing-Remitting Multiple Sclerosis (RRMS). Oral Cladribine was commercialized in 2018.

Objectives

To analyze the first year of treatment with Cladribine in RRMS patients: tolerability, security and initial approach to its effectiveness.

Methods

Retrospective, longitudinal and unicenter study in RRMS patients treated with Cladribine. We analyzed its security measuring overall lymphocyte count by Friedman Test and time to appearance of lymphopenia by Kaplan-Meier. We studied its effectiveness by comparing the following variables with the Wilcoxon Test: relapses, Expanded Disability Status Scale (EDSS) score and gadolinium enhancing lesions before and one year after starting Cladribine (statistically significant p<0’05).

Results

53 patients were studied. 88,7% were women with a mean age of 44,8 years old (DS10,25). 56,6% of the patients had a RRMS evolution of less than 10 years, 32,1% between 10 and 20 years, and 9,4% between 20 and 30 years. 64,1% had been previously treated with one or two DMTs. Patients were exposed to Cladribine for 8 months as a median (percentiles P15=2 months, P85=15 months): 36,4% patients for 6 months, 34,1% between 6-12 months and 29,5% for more than 12 months. The overall lymphocyte count reduction regarding the basal level after starting the drug was statistically significant (p<0’05). The lymphocyte count reduction rate was 52,89% during the first year of treatment and 58,99% during the second one. Tolerability was good in 93,02% of the patients. We observed significant reduction of the relapses rate after one year of treatment.

Conclusions

Cladribine seems to be a secure treatment. The most common adverse effect was lymphopenia (81,8%) but it was severe only in 9,09% of the patients and not associated with severe infections. Its tolerability was very good. Effectiveness results are positive, but, to date, they are preliminary.

Background

The new coronavirus SARS-CoV-2 infection has spread worlwide becoming a pandemic never before seen. Multiple Sclerosis (MS) patients in a state of immunosuppression (IS) may be exposed to a greater risk of COVID-19 complications, although there is increasing evidence postulating a possible protective role of selective IS.

Objectives

To describe the real-world experience in MS patients with SARS-CoV-2 infection at a MS Unit of a hospital in Madrid, Spain. We describe clinical evolution and MS treatment actions

Methods

Observational, prospective and usual clinical practice study in MS patients affected by SARS-CoV-2 infection with clinical diagnosis (at least three of the following: fever, anosmia, cough, diarrhea, myalgia) and/or microbiological diagnosis (PCR in nasopharyngeal swabs and/or serology).

Results

41 SARS-CoV-2 infection cases were registered. 21 were women with a mean age of 39,4 years old (DS10,3). 38 were relapsing-remitting MS patients and 3 had a progressive MS. The mean MS time course was nine years (DS1,4). 39 patients were treated with disease-modifying therapies (DMTs): 46,3% with oral agents, 39% with monoclonal antibodies and 10% with injectable agents. 27 patients were previously treated with other DMTs. The median Expanded Disability Status Scale (EDSS) was 2,5 (DS0,7). 11 patients had clinical activity the previous year. 18 cases were confirmed by PCR and/or serology and 23 were clinically diagnosed. 17% of the patients were admitted to hospital (6 were diagnosed with pneumonia) and none required admission to the intensive care unit. There were no deaths.Three patients had other comorbidities. Admitted patients were older and had higher EDSS score without statistical significance. MS got worse in 7 patients. DMTs were stopped or delayed in 10 patients due to the SARS-CoV-2 infection.

Conclusions

All the MS patients studied had a good outcome of the SARS-CoV-2 infection. Only 17% of them required admission to hospital and 14,6% of the cases were asymptomatic. 95% of the patients were treated with DMTs. From our experience, the SARS-CoV-2 infection does not seem to entail a more aggressive form of the disease in this group of patients. Selective IS may favor the good evolution. Larger clinical registers are needed to establish solid conclusions.

Background

Cladribine in a desoxiadenosine analogue approved for Multiple Sclerosis (MS) treatment. It produces rapid B and T cells depletion, associating lymphopenia in some cases the first months after treatment. Neutropenia is extremely rare.

Objectives

We present one patient with MS that develops severe neutropenia after the second dose of the first cycle of cladribine.

Methods

We reviewed patient's clinical history, complementary tests and outcome, as well as available bibliography about this topic.

Results

53 year-old female with past medical history of psoriasis. She suffered from an optic neuritis in 2008. Brain MRI done then showed typical MS lesions. Because of clinical and radiological stability, she did not receive any disease modifying therapy until 2018. Then, she was started on dimethyl fumarate that was discontinued a few months later due to lymphopenia and joints pain. Once the lymphocyte count was normal, she was started on cladribine in December 2019. One week after the second dose of the first cycle, she presented with asthenia. Gabapentine had also been added due to neuropathic pain. Blood test revealed severe leucopenia (0.51 x 10⁹/l), grade IV lymphopenia (0.19 x 10⁹/l) and grade IV neutropenia (0.20 x 10⁹/l). Rest of the bool count and smear were normal. Bone marrow aspirate showed slight hypocellularity with good representation of the three series, suggestive of post-chemotherapy aplasia recovery, indicative of cladribine induced neutropenia. Granulocyte colony stimulating factor was administered during 2 days, with progressive recovery until normal neutrophil count was achieved within 10 days. Grade II lymphopenia persists (0.74 x 10⁹/l) after 3 months. The patient has remained afebrile and without any incidence. Evaluation of the second cycle of cladribine according to clinical, radiological and blood test evolution is still pending.

Conclusions

Neutropenia is a very rare adverse effect of cladribine in MS treatment, but it may be life-threatening. Thus, clinical and blood test monitoring is essential. In the case presented, we postulated that gabapentine may have an additive effect in cladribine hematologic toxicity.

Background

Tocilizumab is a monoclonal antibody against IL-6 that has been used to treat Neuromyelitis Optica spectrum disorders (NMOSD), generally intravenous. The evidence about its subcutaneous formulation to treat these diseases is scarce, but its efficacy seems to be similar. During SARS-CoV-2 pandemic, decreasing hospital attendance became a priority. According to this, subcutaneous formulations may represent a good therapeutic option in this context.

Objectives

We present 3 cases of NMSOD who initiated subcutaneous tocilizumab during SARS-CoV-2 pandemic, with very good tolerability in all the cases.

Methods

Retrospective and observational study. We reviewed clinical charts, patients’ outcomes and available bibliography.

Results

Patient 1: 74 year-old male, diagnosed with Neuromyelitis Optica (NMO) in 2010. He was started on rituximab in 2012. In 2018, he suffered from two optic neuritis (despite the absence of CD19+ and CD27+ cells in peripheral blood). Because of that, in 2019, rituximab was switched to intravenous tocilizumab, with good response and tolerability. In April 2020, due to SARS-CoV-2 pandemic, it was switched to subcutaneous tocilizumab in order to avoid hospital attendance, with very good tolerability.

Patient 2: 40 year-old female, diagnosed with NMOSD vs CRION (chronic relapsing inflammatory optic neuropathy). Positive anti-NMO antibodies and negative anti-MOG antibodies were found. She was started on rituximab in 2015. In December 2019, she suffered from an optic neuritis despite having no CD19+ cells in peripheral blood. Hence, rituximab was switched to intravenous tocilizumab without any incidence. In March 2020, she was started on subcutaneous tocilizumab once a week because of the pandemic, with very good tolerability.

Patient 3: 28 year-old female, diagnosed with seropositive NMO in 2012, treated with rituximab since 2014, free of relapses since them. In May 2020, we decided to switch to tocilizumab (subcutaneous to decrease hospital visits due to SARS-CoV-2 pandemic) because of hypogammaglobulinemia and repeated respiratory tract infections.

Conclusions

Tocilizumab may be an option to treat NMOSD patients. Subcutaneous form decreases hospital visits and, according to our experience, is very well tolerated. Therefore, we postulate it can be a good alternative in the current situation.

Background

Background: Cognitive complaints have been previously related to depressive symptoms in multiple sclerosis (MS), whereas self-reported executive performance has been postulated as generally reliable. Nevertheless, little is known about dysexecutive complaints (DC) and its relationship with depression and anxiety.

Objectives

Objective: (i) Study self-reported dysexecutive symptoms in attention, motivation, executive control, social behavior and emotional regulation in MS compared to control group (HC). (ii) Analyse the relation between cognitive complaints and emotional symptoms.

Methods

Methods: We collect 30 MS patients from the clinic (63% women; mean age, 43.93 y.o.; 10 years of evolution of the disease; EDSS mean 2.4; 16.6 years of schooling) and 30 healthy controls (HC) (58% women; mean age, 39.6. y.o.; 15.03 years of schooling). Participants are requested to complete the Inventory of Prefrontal Symptoms (IPS), the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI). Statistical analysis was performed.

Results

Results: Significant differences were found in the IPS sub-scales: attention (p<0.00), Motivation (p<0.00) and social behavior (p<0.00) between MS and HC; no differences were found in executive control and emotional regulation. Significant differences were also found in BDI and Trait Anxiety (TA) between both groups, but not in state anxiety (SA). Significant correlations (p<0.05) were found between emotional symptoms and IPS Subscales. A linear regression was performed finding that BDI and trait anxiety explained 87.3% of variance for IPS total score; in addition, TA explained 38.7% of the variance of motivation, 38.5% of executive control, 26.5% of social behavior and 42.3% of emotional regulation for MS group, while SA explained 26% of the attention complaints.

Conclusions

Conclusion: MS report more subjective complaints of attention, motivation and social behavior than HC and more TA and depression symptoms. Whereas SA significantly predicts a high percentage of attention symptoms, TA predicts social inadequacy, emotional regulation problems, lack of motivation for action and difficulties in executive control. These results consider the extent to which DC are related to emotional problems, objective cognitive deficits or personality factors and whether anxious personality in MS is as an emotional consequence of the disease or whether this pattern is related to structural changes that affect the tools to deal with stressful situations.

Background

Pediatric Multiple Sclerosis (MS) is defined as MS with an onset before age 18. It is an infrequent disease that entails between 3% and 5% of all MS diagnoses. It can accrue significant disability at a younger age than adult MS, therefore it is a more aggressive disease. Disease-modifying therapies (DMTs) in children and adolescents are used based on clinical experience. Fingolimod is the first DMT approved in data sheet as a treatment for pediatric MS after the clinical trial PARADIGMS.

Objectives

We present our experience with 7 patients with pediatric MS. We describe tolerability, security and effectiveness in our patirents.

Methods

Observational, retrospective and usual clinical practice study in pediatric MS patients treated with Fingolimod.

We analyzed security and effectiveness: relapses, Expanded Disability Status Scale (EDSS) score and gadolinium enhancing lesions before and after starting Fingolimod

Results

We present 7 patients with pediatric MS (5 girls and 2 boys). The mean age of onset of the disease was 15,1 years old (DS1,5). The mean annualized relapse rate in the year before Fingolimod was 1,6 (DS0). The mean number of enhancing lesions in basal Magnetic Resonance Imaging (MRI) was 3,7 (DS6,4) and the mean number of lesions in T2 sequences was 20 (DS2,8). Six patients had spinal cord lesions. The median age at onset of Fingolimod was 16 years old. Three patients were naive and the rest of them had been previously treated with injectable agents. Patients were exposed to Fingolimod for 22,3 months as an average (DS25). They did not present new relapses nor radiological activity on MRI after starting Fingolimod. No adverse effects were reported during the treatment.

Conclusions

The mean age of our patients is similar to the pivotal clinical trial, mostly postpubertal and with a highly active disease. Fingolimod seems to be a very effective and secure treatment in our patients with pediatric MS, with a very good tolerability and adhesion.