Background Cystic fibrosis transmembrane conductance regulator (CFTR) modulators were initially commissioned for use by NHS England in 2019 and since then the age of eligibility has reduced to include younger patients.¹ The introduction of these therapies has been readily welcomed by patients, families and Cystic Fibrosis (CF) healthcare teams.¹ Pharmacists have been instrumental in the initiation of these life-altering treatments for patients across the country. More recently, the focus for pharmacists has changed to understanding and altering treatments in response to adverse effects patients may be experiencing. Whilst manufacturers provide information about managing derangement of liver function tests, there is little information available nationally about how to manage adverse effects such as behavioural changes and sleep disturbances. We would like to share our experiences from within the paediatric CF multidisciplinary (MDT) team.

At present, we have 131 patients actively on CFTR modulator treatment – 5 on ivacaftor, 19 on Orkambi and 107 on Kaftrio.

Our team has seen behavioural changes in 1 patient on Orkambi, 1 patient who was on Symkevi (but stopped taking this) and 5 patients on Kaftrio who experienced behavioural changes and/or sleep disturbances.

Our MDT decisions around managing these side effects were as a result of discussion with other centres across the country, communication with the Medicines Information department at the manufacturer Vertex and always in conjunction with our patients and their families. With any patients with significant changes in behaviour (to include but not limited to aggressive or highly emotional verbal and physical outbursts at home and/or school) we’ve utilised different approaches that have been individual to the child or young person in question. We adopted a number of strategies to manage issues around sleep disturbances and encouraged patients and their families to keep diaries whilst implementing any recommendations. Overall, any issues affecting sleep have resolved.

Lessons learned The CF Trust highlights the importance of access to a CF pharmacist for all patients, particularly as we enter an era of unknowns, with new treatments available and complications that may be a result of an ageing CF population.^{2 3} As a team, we have appreciated the importance of communication with other centres in this post CFTR-implementation era, particularly as we learn more about these CFTR modulator treatments. Any adverse effects experienced whilst on CFTR modulators have been reported to the MHRA via the Yellow Card Scheme.⁴

We’ve learnt as a team that whilst physical and mental health changes may coincide with initiating CFTR modulator treatment in patients, it is always important to explore all possible causes for these as these treatments may not always be the root cause!

References

1. NHS England. Clinical Commissioning Urgent Policy Statement Cystic Fibrosis Modulator Therapies Access Agreement for licensed mutations [200810P]. https://www.england.nhs.uk/wp-content/uploads/2020/08/Policy-statement-CFTR-Modulator-Therapies-Licensed-mutations.pdf

2. Bentley S, Bowman E, Makhecha S. Clinical impact of CFTR modulator therapy roll-out. Pharmaceutical Journal 2022:309;7966.

3. Cystic Fibrosis Trust. Pharmacy standards in cystic fibrosis care in the UK. 3rd Edition. September 2022. https://www.cysticfibrosis.org.uk/sites/default/files/2022-11/CF%20Trust%20Pharmacy%20Standards%20of%20Care_FINAL_Oct_2022.pdf

4. Medicines and Healthcare products Regulatory Agency. Yellow Card scheme. https://yellowcard.mhra.gov.uk/