OFFLABEL USE OF RITUXIMAB IN NEUROLOGY EXPERIENCE IN
OFF-LABEL USE OF RITUXIMAB IN NEUROLOGY, EXPERIENCE IN RIGA EAST UNIVERSITY HOSPITAL, DEPARTMENT OF GENERAL NEUROLOGY Author: Eva Šankova 1, 2 Scientific research supervisors: Ph. D Daina Pastare 1, 2 Assoc. prof. Guntis Karelis 1, 2 1 Rīga Stradiņš University, Latvia 2 Riga East University Hospital, Department of Neurology and Neurosurgery, Latvia Introduction Rituximab is a chimeric monoclonal antibody that selectively depletes CD 20+ B-cells. There is no standardized protocol for rituximab usage in neurological diseases. Its use is mainly limited to retrospective case studies and case series. They have shown favorable outcomes following treatment in neurological patients with autoimmune disorders. Aim of the project To analyze the indications, treatment regimen, side effects, efficacy and outcome of rituximab usage in neurological diseases at the Riga East University Hospital, Department of General Neurology. Materials and methods In this retrospective study outcome data were collected from the medical records of five patients treated with rituximab from January to December 2018. Results Five patients were included (2 women and 3 men), aged 36 -58 years. CASE 1 - 58 years old man Diagnosis: Chronic inflammatory demyelinating polyneuropathy. Symptoms: Progressive weakness in legs and arms from 2015. Balance problems, peripheral tetraparesis, paresthesia in legs. Received in therapy plasma exchange (5 procedures), methylprednisolone 1000 mg per day for 5 days, treatment with intravenous immunoglobulin (IVIG) 35 g per day for 3 days. Methotrexate 10 mg once a week from 2016 till now. Prednisolone from 2016 till October 2018. Received three doses of rituximab – 2 doses given 2 weeks apart and third after 8 months because of the progression of symptoms on the previous treatment received. Muscle strength (0 -5) Arms Legs Proximal Distal 2016 January 2018 October 2018 5 3 4 0 5 5 3 3 4 4 3 1 -2 Had no worsening, the disease did not progress. As described in the table above, muscle strength of the distal muscle groups increased in the arms and legs. After first dose patient had fever and cough (most likely cold) but he received also second dose without any side effects. CASE 2 - 46 years old man Diagnosis: Chronic inflammatory demyelinating polyneuropathy. Symptoms: Ataxia, tetraparesis, dysphonia, peripheral sensory disturbance - stocking-glove type hypoesthesia. Symptoms are progressing from 2015. Received in therapy plasma exchange (5 procedures), methylprednisolone 500 mg one dose, after which side effects occured. 6 month course of azathioprine, intravenous immunoglobulin and 3 doses of subcutaneous immunoglobulin. Because of the symptom progression received three doses of rituximab – 2 doses of rituximab 500 mg given 2 weeks apart and third (rituximab 1000 mg) after 6 months. Muscle strength (0 -5) Arms Legs 2017 April 2018 October 2018 Proximal Distal 5 5 4 4 4 3 4 4 After 2 doses of rituximab patient is feeling better, reduced sensory ataxia, the patient started to move independently. Muscle strength described in the table above, muscle strength increased in the distal muscle groups of the legs. Rituximab was well tolerated, no side effects were observed. Paper ID 23435 CASE 3 - 50 years old man Diagnosis: Rapidly progressive demyelinating multifocal brain pathology. Symptoms: progressive gait disturbance, cerebellar ataxia from 2014, paresthesia on the left side of the face from 2013. From 2017 progressing weakness in the legs and arms, dysarthria. From 2018 - urinary incontinence. MRI showed lesions of unclear origin on brain and spinal cord. Had extensive investigation – brain biopsy with non specific findings. In positron emission tomography - metabolic activity in the left hemisphere of the brain and in the middle cerebellar leg. Infections, autoimmune diseases, vasculitis, etc. pathology excluded. Received in therapy plasma exchange (5 procedures), 5 day course of methylprednisolone 1000 mg, 2 courses of 3 days with cyclophosphamide 800 -600 mg i/v. After that received two doses of rituximab 1000 mg because of the symptom progression. Rituximab was well tolerated, no side effects were observed. The symptoms have not diminished, but do not progress after therapy with rituximab. CASE 4 - 48 years old woman Diagnosis: Neuromyelitis optica spectrum disorder. Symptoms: Repeated optic neuritis episodes with vision loss from 2012 - eye pain that worsens with movement of the eye, blurring of vision, loss of color vision periodically. From 2012 to 2017, optic neuritis episodes repeated an average once a year. At the beginning it was considered that patient has relapsingremitting multiple sclerosis. Received in therapy interferon beta-1 a (Rebif) from 2015 to August 2017. The patient has repeatedly negative aquaporin 4 antibodies. Received in therapy plasma exchange (5 procedures), prednisolone 40 mg per day from August 2017 to March 2018, azathioprine 100 mg per day from August 2017 to March 2018. Started to use mycophenolate mofetil 1000 mg twice a day from January 2018. Because of the repeated episodes of optic neuritis on above mentioned therapy, patient received four doses of rituximab – 2 doses of rituximab 1000 mg given 2 weeks apart and third after 6 months. The patient herself notes that she feels better, but still has a generalized weakness. The patient has not had an episodes of relapse of the optic neuritis, neurologically without progression. CASE 5 - 36 years old woman Diagnosis: autoimmune encephalitis - Anti-NMDA receptor encephalitis. Symptoms: headache, behavioral disorders, hallucinations, blurred vision, diplopia. Detected specific NMDA receptor antibodies in cerebrospinal fluid. Started therapy with 5 day course of methylprednisolone 1000 mg but without a positive effect. Due to inefficiency of first line therapy, received rituximab as a second line therapy. Received two doses of rituximab 500 mg given one week apart. On the background of received therapy, patient still had hallucinations, bizarre behavior. Motor and non-motors seizures with impaired awareness and pulmonary embolism joined. Received second course of rituximab – two doses of 1000 mg given two weeks apart. After medication patient is orientated in time, place and person, hallucinations, behavioral disorders are reduced. Conclusions Rituximab was prescribed to patients with 4 different diagnoses chronic inflammatory demyelinating polyneuropathy, neuromyelitis optica spectrum disorder, autoimmune encephalitis and rapidly progressive demyelinating multifocal brain pathology. Rituximab for neurological indications may be used as two 1000 mg infusion doses given 2 weeks apart and continuing 1000 mg every 6 -8 months. The patients tolerated the medication well, without side effects. Stabilization of the disease was observed in all patients. Experience is, however, too limited and follow up is needed.
- Slides: 1