Op0122 Incidence, Prevalence, Natural History, and Primary Care Treatment of Mixed Connective Tissue Disease in the United Kingdom, 2000-2022: A Population-Based Cohort Study

Background: Mixed connective tissue disease (MCTD) is a rare autoimmune disorder characterised by features of multiple connective tissue diseases including systemic sclerosis, systemic lupus erythematosus (SLE) and polymyositis (PM). Little is known about the epidemiology of MCTD in the United Kingdom, or the medications used in this patient population. Objectives: The objectives of the study were to calculate the incidence and prevalence of MCTD in the United Kingdom, and to describe the common symptoms, co-morbidities, and treatments recorded in routinely collected healthcare data in patients with this disease. Methods: We performed a cohort study using the Clinical Practice Research Datalink (CPRD GOLD), a large database containing primary care records from 17 million individuals in the United Kingdom. Individuals were identified for inclusion based on a diagnostic code of MCTD between 01/01/2000 and 01/07/2022, with no restriction on prior or subsequent observation time. Individuals exited our cohort at the earliest of: end of continuous observation or death. A sensitivity analysis was performed where individuals also exited the cohort upon receipt of a diagnostic code for a specific single rheumatic disease for the first time following MCTD diagnosis. Age and sex were summarised at the time of index diagnosis. Incidence and prevalence were calculated yearly. The occurrence of other medical conditions or symptoms, medication use, and laboratory measurements were explored at a number of pre-determined time periods before and after MCTD diagnosis. Results: Four hundred and twenty-one cases of MCTD were identified in the study period. The mean age at time of diagnosis was 48 years (IQR 36-59 years), and 87% were female (Figure 1A). The incidence of MCTD remained consistently below 1 per 100,000 person years during the study period, although a step-change increase was seen in incidence pre- and post-2007 (Figure 1B). The prevalence of MCTD appeared to rise steadily through the study period, peaking at 5.1 cases per 100,000 in 2021 in adults. This reduced to 4.5 cases per 100,000 in the sensitivity analysis. Relatively few patients had a recorded diagnostic code of another rheumatic disease prior to their MCTD diagnosis, although almost half had been recorded as having been seen by rheumatology services (46.3%) (Table 1). Following their MCTD diagnosis, relatively few patients went on to have recorded diagnostic code of a more specific rheumatic disease (Table 1). 2.9% of patients with MCTD were subsequently diagnosed with pulmonary arterial hypertension, all at least 1 year following index diagnosis (Table 1). The most common disease-modifying medications used in the first year following MCTD diagnosis were hydroxychloroquine (37.0%), and steroids including prednisolone (32.9%) and hydrocortisone (14.8%) (Table 1). Proton-pump inhibitors, such as omeprazole (25.5%) were also commonly prescribed, as were analgesics including paracetamol (32.7%), non-steroidal anti-inflammatory drugs (ibuprofen 10%, naproxen 11.7%), and opioids (codeine 22.4%, tramadol 7.4%, dihydrocodeine 6.2% and morphine 1.7%). Table 1. Frequency of selected measurements, medical conditions, and medications among subjects with mixed connective tissue disease, at pre-defined time points prior to and following diagnosis. Conclusion: MCTD is a rare disease and most commonly diagnosed in middle-aged female patients. Low numbers of patients had previous diagnoses of rheumatic diseases coded in their primary care health records, although significant proportions had previous contact with rheumatology services. Patients with MCTD commonly received hydroxychloroquine and steroids. The low prevalence of MCTD means potential treatments would potentially meet the European Medicine Agency's criteria for orphan designation. REFERENCES: NIL. Acknowledgements: Partial support from the Oxford National Institute for Health and Care Research (NIHR) Biomedical Research Centre (BRC), United Kingdom. Disclosure of Interests: Francesco Dernie: None declared, Albert Prats-Uribe: None declared, Wai Yi Man: None declared, Antonella Delmestri: None declared, Daniel Prieto-Alhambra DPA's research group has received consultancy fees from Astra Zeneca and UCB Biopharma., DPA's department has received grant/s from Amgen, Chiesi-Taylor, Lilly, Janssen, Novartis, and UCB Biopharma. Amgen, Astellas, Janssen, Synapse Management Partners and UCB Biopharma have funded or supported training programmes organised by DPA's department.