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

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.

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.