P62 Cyclophosphamide and maintenance mycophenolate mofetil for the treatment of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis in a paediatric patient

Abstract

BackgroundAnti-NMDAR encephalitis is one of the commonest known types of autoimmune encephalitis with an increasing recognition in the paediatric population.1 2 It is characterised by abnormal behavioural and cognitive symptoms, seizures and movement disorders where treatment failure or failure to treat can result in long term disabilities or mortality.1A 4-year-old patient with a background of autism was admitted to the paediatric intensive care unit (PICU) due to encephalitis with convulsive status epilepticus where he remained intubated for 22 days and was later diagnosed with anti-NMDAR encephalitis. The patient had persistent abnormal choreoathetoid movements and intermittent seizures despite multiple anti-epileptics, two courses of corticosteroids, two courses of intravenous immunoglobulin, two cycles (10 sessions per cycle) of plasmapheresis and a course of weekly rituximab. Due to the lack of response from these initial pharmacological interventions, the use of cyclophosphamide and mycophenolate mofetil was considered. Cyclophosphamide and mycophenolate mofetil inhibits the proliferations of B- and T-lymphocytes3 4 which acts as the basis of its immunosuppressive actions. However, available evidence on the dosing and monitoring information in the paediatric population for this unlicensed indication is limited.Pharmacy ContributionsAfter discussion with the multi-disciplinary team (MDT) with extensive input from the paediatric neurologist, a literature search was conducted to determine an appropriate dosing regimen. As this was an off-label use, the paediatric neurologist and the attending consultant took clinical responsibility. Intravenous cyclophosphamide was started at 750 mg/m2 once a month for three cycles and oral mycophenolate mofetil was started at 600 mg/m2 twice a day as maintenance therapy a week after. The specialist pharmacist explained the individualised treatment plan for the patient to the MDT and ensured measures (hydration and mesna) for the prevention of cyclophosphamide-induced haemorrhagic cystitis were appropriately prescribed on the electronic prescribing system with the appropriate timings of administration. Monitoring parameters to determine adverse effects were closely observed. A local guideline was developed during the treatment cycles to ensure all members of the MDT were following the correct procedures.OutcomeThe patient responded to cyclophosphamide and clinically improved after the completion of three cycles of monthly treatment. Maintenance mycophenolate mofetil was subsequently stopped a month after the last cycle of cyclophosphamide due to neutropenia. A review of the patient one year after first presentation shows the patient is almost back to their baseline.Lessons LearnedAlthough there are potentially serious side effects, cyclophosphamide and mycophenolate mofetil has been successful in the treatment of anti-NMDAR encephalitis. The recovery of this patient required extensive support from the entire MDT.ReferencesNHS England. Clinical Commissioning Policy: Rituximab for second line treatment for anti-NMDAR autoimmune encephalitis (all ages). March 2018.Salvucci A, Devine IM, Hammond D, et al. Pediatric anti-NMDA (N-methyl D-Aspartate) receptor encephalitis. Pediatric Neurology 2014;50:507–510.Summary of Product Characteristics. Cyclophosphamide 1000 mg Powder for Solution for Injection or Infusion. Last updated on eMC on 27-Jun-2017. Available at https://www.medicines.org.uk/emc/product/3525/smpc# [Accessed 04 July 2019]Summary of Product Characteristics. CellCept 1 g/5 mL powder for oral suspension. Last updated on eMC on 16-Mar-2018. Available at https://www.medicines.org.uk/emc/product/1569/smpc [Accessed 04 July 2019]