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P44 Management of cell division cycle 42 (cdc42) mutation in a paediatric patient
  1. Kalindi Rajani1,
  2. Ka Yu Yung1,
  3. Iek Cheng2
  1. 1Great Ormond Street Hospital, London
  2. 2UCL GOS Institute of Child Health


Background Cell Division Control Protein 42 homolog(CDC42), encodes a small Rho family GTPase which regulates multiple signalling pathways that control cell migration, polarity, endocytosis, and cell progress. Mutations in CDC42 may predispose in the development of macrophage activation syndrome and haemophagocytic lymphohistiocytosis(HLH),1 which can be fatal if left untreated.

A 2-month-old patient was admitted to a paediatric hospital, presenting with persistent pancytopenia, fever and rash that was non-responsive to corticosteroid treatment with a history of multiple hospital admissions requiring oxygen. Due to patient’s age, limited treatment options are available for symptom management. The patient was initiated on anakinra, an interleukin 1 and 18 inhibitor2 alongside concomitant corticosteroid therapy due to hyperinflammation, with elevated ferritin and high CRP levels, concurrent rash and fever. A diagnosis was made of heterozygous CDC42 mutation, c.556C>T(p.Arg186Cys). Corticosteroid therapy was tapered slowly over several weeks once fevers had subsided and patient was stabilised. However, rebound fevers and persistent neutropenia at lower doses prevented patient from steroid cessation. Subsequently, baricitinib, an immune modulator targeting Janus Kinase 1 and 2 receptors3 was added in adjunct to anakinra and corticosteroids as a steroid-sparing agent with the aim to reduce corticosteroid dosing prior to corrective haematopoietic stem cell therapy(HSCT) and manage hyperinflammation.

Pharmacist involvement Due to the unlicensed and off-label use of anakinra and baricitinib, a literature search was undertaken to determine safe and effective doses for each. Pre-medication bloods included viral screens, full blood count and liver function tests. Local governance processes were adhered to with pharmacists’ support and both funding and medications were approved for use by the Trust’s Drug and Therapeutics Committee (DTC). Ethics approval was also sought for the addition of baricitinib therapy. Risk of side effects were discussed with immunology consultants before treatment initiation. Subcutaneous anakinra was commenced at 2 mg/kg/day and increased by 2 mg/kg to maximum 10 mg/kg/day. Baricitinib was commenced at 2 mg three times a day, tablets were crushed and administered enterally. Dose was escalated and rounded to 4 mg BD for ease of administration and to reduce pill burden. Families were counselled about medication administration, side effects and patient information leaflets were provided.

Outcome The combination of anakinra and baricitinib for 3 months enabled successful weaning of corticosteroids to facilitate a HSCT to be undertaken. However, due to multiple comorbidities, the patient did not survive post-HSCT. A local in-house policy is being developed to support the use of anakinra and baricitinib.

Lessons learned It is uncommon to utilise potent immunosuppressant’s like baricitinib in combination with a biologic in the paediatric population. There were limited studies investigating the safety of this concomitant immunosuppressive therapy; risks include, severe life- threatening infections and neoplasms. Risk versus benefit of treatment must be assessed and discussed with clinical teams prior to initiation, demonstrating the need for collaboration within a multi-disciplinary team. Pharmacists must understand genetic conditions of patients to support complex patient counselling for novel therapy and identify side effects with treatment. Strict monitoring must be implemented for increased risk of infection and side effects related to the medications.


  1. Gernez Y, de Jesus AA, Alsaleem H, et al. Severe autoinflammation in 4 patients with C terminal variants in cell division control protein 42 homolog (CDC42) successfully treated with IL-1β inhibition. J Allery Clin Immunol 2019;144:1122–1125.

  2. Summary of Product Characteristics (2022) Kineret 100 mg solution for injection in a pre-filled syringe. (Accessed 25 June 2023).

  3. Summary of Product Characteristics (2023) Olumiant 2 mg film coated tablets. (Accessed 25 June 2023).

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