Isotretinoin Associated Rhabdomyolysis: Monitoring Creatine Kinase and Educating Patients

Monitoring specific values at baseline and throughout treatment is standard of care for isotretinoin therapy; however, creatine kinase (CK) blood monitoring is often excluded. Herein, we describe the importance of CK monitoring during isotretinoin therapy to assess the risk of rhabdomyolysis and potential renal damage, regardless of muscle-related symptom presentation. We present 2 patients with hyperCKemia: a 16-year-old male on isotretinoin whose CK levels were elevated (7,325 U/L) when rhabdomyolysis symptoms were present, and an asymptomatic 18-year-old male with elevated CK levels (35,000 U/L) before starting isotretinoin. Based on our experience, we strongly recommend obtaining CK levels to monitor for and potentially prevent rhabdomyolysis and its associated complications.

Annual physical health checks within a forensic inpatient service

AimsPatients prescribed antipsychotics are at risk of ill effects to their physical health. Our aims were to assess whether inpatients within a forensic service, on antipsychotic medications, were receiving annual physical health monitoring in accordance with current NICE and SIGN Guidelines. Based on these Guidelines the following objectives were identified: 1: Physical examination, BMI and blood pressure recorded within the past year2: FBC recorded within the past year3: U&Es recorded within past year4: LFTs recorded within the past year5: HbA1C / random glucose / fasting glucose recorded within the past year6: Random lipids / fasting lipids recorded within the past yearMethodInclusion Criteria: Patients admitted for longer than a year currently prescribed an antipsychotic.Data were collected cross-sectionally on 24/7/20 for all inpatients meeting the inclusion criteria. Medical notes and the blood results system were reviewed for results of any annual physical examinations and blood monitoring over the past year.Anonymized data were analysed using Excel.Result13 out of 17 inpatients fulfilled the inclusion criteria. Of these 13 inpatients, 9 (69.2%) were prescribed clozapine, 1 (7.7%) zuclopenthixol, 1 (7.7%) paliperidone and 1 (7.7%) amisulpride.All patients had BMI and blood pressures recorded within the preceding month. Only 1 patient (7.7%) had an annual physical health examination within the past year.Findings for bloods taken within the past year were as follows:12 patients (92.3%) had an FBC recorded9 patients (69.2%) had U + Es recorded9 patients (69.2%) had LFTs recorded11 patients (84.6%) had HBA1c recorded7 patients (53.8%) had lipids recordedConclusionThere is scope for improvement with both annual physical examinations and blood monitoring.All patients had regular BMIs and blood pressure recorded which is largely attributable to nursing staff protocols. Low compliance with full annual physical examination could be explained by there being no local system in place for annual physical health checks and also frequent changes in junior doctor ward cover.Blood monitoring showed variable compliance with established standards. FBC monitoring had the best compliance, likely because the vast majority of our patients are prescribed clozapine, which necessitates minimal monthly FBC monitoring.This audit was presented to the Forensic Team and thereafter it was agreed for a local system to be put in place for annual physical health checks in the summer each year. This will improve oportunities to optimise our patients health. We plan to re-audit at this time.

AB0215 COMPARISON BETWEEN RITUXIMAB ORIGINATOR THERAPY AND ITS BIOSIMILAR IN THE INCIDENCE OF LATE-ONSET NEUTROPENIA IN ADULT PATIENTS WITH RHEUMATOID ARTHRITIS AND OTHER AUTOIMMUNE DISEASES

Background:Late-onset neutropenia (LON) occurs when the absolute neutrophil count drops below 1.5 × 10(9)/L four weeks after Rituximab infusion.1 It is a condition recognised more in haematological malignancy patients treated with Rituximab with a reported prevalence of 8% or higher.2 LON was reported in 6.5% of rheumatological patients1, while a French registry found a prevalence of 1.3% in rheumatoid arthritis patients.3Almost all patients receiving Rituximab originator therapy at our Rheumatology department were switched to its biosimilar starting from November 2017. Our haematology team observed LON cases in their patients after this period.Objectives:We wanted to establish whether there is increased LON occurrence with the biosimilar than the originator therapy, requiring specific monitoring.Methods:This is a cross-sectional retrospective review of 12 months period before and after switching to the biosimilar of all patients who received Rituximab for the first time. We reviewed the patients’ blood monitoring for up to 12 months after receiving Rituximab. We used a proforma to collect the age, sex, diagnosis, date of the first infusion, use of other DMARDs, LON occurrence within 12 months after the infusion and neutropenia within the 12 months before it in addition to the frequency of the blood monitoring after the infusion.Results:For the originator, between 1/1/2016 and 31/12/2016, 142 patients received Rituximab, 47 (33.09%) of them were given the treatment for the first time. Their median age was 62 years, 28 (59.5%) were females. The most common diagnosis was rheumatoid arthritis 38 (80.8%), and 35 (74.4%) patients were on other disease-modifying agents (DMARDs). Two patients (4.2%) developed LON. In both patients, this occurred during admission for septic arthritis whilst on antibiotics, and both had Grade 2: ≥1,000– < 1,500/mm3 neutropenia.For the Biosimilar cohort, between 1/4/2019 and 31/3/2020, 161 patients received Rituximab, 36 (22.3%) of them were given the treatment for the first time. Their median age was 59 years, 27 (75%) of them were females. The most common diagnosis was rheumatoid arthritis 25 (69.4%), and 26 (72.2%) were on other DMARDs. One patient (2.77%) developed grade 2 LON one month after Rituximab. Another patient with known autoimmune neutropenia was excluded. In all the Three patients with LON in both groups, neutrophil count recovered in less than a month, and they had normal IgG before the infusion.The frequency of blood monitoring after Rituximab infusion was done 1-3 monthly in 32 (68%) patients and 23 (63.8%) patients in the originator and biosimilar groups, respectively.Four (8.5%) patients and three (8.3%) patients in the originator and biosimilar groups respectively had a frequency of blood monitoring done less than six-monthly.Conclusion:In our patients’ cohort, LON incidence following switching to the Rituximab biosimilar was not higher than the originator therapy.References:[1]Monaco, W. E., Jones, J. D. & Rigby, W. F. C. Rituximab associated late-onset neutropenia-a rheumatology case series and review of the literature. Clin Rheumatol35, 2457–2462 (2016).[2]Dunleavy, K., Tay, K. & Wilson, W. H. Rituximab-Associated Neutropenia. Seminars in Hematology47, 180–186 (2010).[3]Salmon, J. H. et al. Late-onset neutropenia after treatment with Rituximab for rheumatoid arthritis and other autoimmune diseases: data from the AutoImmunity and Rituximab registry. RMD Open1, e000034 (2015).Acknowledgements:The authors would like to thank pharmacist Christine Hay for her help in providing the Rituximab databases.Disclosure of Interests:Mostafa Meshaal Ahmad: None declared, Euan McRorie Speakers bureau: I have spoken at meetings sponsored by Roche several years ago, Consultant of: I have sat on advisory boards for Roche several years ago., Grant/research support from: I was the local investigator for the ORBIT study, published in the Lancet in 2016.

P019 Audit of prostanoid use in severe Raynaud’s and adherence to treatment of digital ulcers in patients with SSc NHSE pathway: commissioning policy cost analysis and alternative therapeutic pathway proposed

Background/Aims Severe Raynaud’s phenomenon (RP) can lead to digital ulcers (DU), ischaemia, infection and gangrene. In 2015, NHS England published a commissioning policy enabling the use of bosentan for digital ulceration in SSc in patients refractory to intravenous 6-8 weekly prostanoid in combination with sildenafil following standard therapy (including calcium channel blockers (CCB), ACE inhibitors, losartan and fluoxetine). Bosentan is licensed to prevent new DUs in SSc. Specialist MDT ratification and Blueteq registration is required. RCTs showed bosentan reduced the formation of new DU by 30-50% in at risk individuals. It is a well-tolerated drug. It is now off-patent so its cost has reduced from £22,000 to £650 per year. Aim To audit current departmental practice in patients receiving prostanoid (epoprostenol) for severe RP from any cause and check adherence to the patient pathway for treatment escalation prior to prostanoid therapy. To determine approximate costs of alternative therapeutic approaches. Methods We retrospectively audited patients attending our day unit for epoprostenol infusions over a 12-month period between 2018 and 2019. Using our centre’s admissions database and electronic patient records, we identified which oral medications patients were currently co-prescribed or had previously trialled. Using pharmacy data and tariff costings, we calculated the cost of epoprostenol infusions and oral medications with blood monitoring. Results Between 2018 and 2019, 73 patients attended for epoprostenol infusions: 31 SSc, 25 RP, 17 other diagnoses (mixed/undifferentiated CTD, SLE, vasculitis). The mean number of epoprostenol infusions per patient per year was 5.92 days (range 1-25). The percentage of patients who had first been trialled on the following medications include: CCB 77.4%, ACEi/ARB 41.1%, fluoxetine 9.59%, sildenafil 87.1% and tadalafil 25.8%. In the SSc group 22.6% had also trialled bosentan. Only 2 SSc patients (6.45%) had trialled all of the drugs on the pathway prior to prostanoid reflecting the relative lack of efficacy of some first line therapies. The departmental tariff per prostanoid infusion is £450, resulting in an estimated average annual cost of £2700 per patient. The annual cost of supplying bosentan 125mg twice daily plus blood monitoring for the first year is approximately £1350. Conclusion Epoprostenol is used in our unit for patients with severe RP from a range of conditions. Sildenafil and CCB have been trialled in the majority of our patients prior to escalation. Only a minority of patients have received bosentan according to current guidelines and licensing. Given the reduction in cost, combined with the importance of avoiding hospital admissions with COVID-19, we would suggest that bosentan could be used earlier in the treatment pathway for a broader range of indications. NHSE is revising the SSc commissioning policy. Disclosure A. Young: None. B. Griffiths: None. J. Vila: None.