Understanding the prevalence and impact of comorbidities on people with multiple sclerosis

Multiple Sclerosis (MS) is a chronic disease of the central nervous system that affects more than 25,600 Australians and 2.8 million people worldwide. Recent evidence shows that comorbidities, medical conditions that co-occur with an index disease, are common and could detrimentally affect the clinical course of people with MS. The overarching aim of this thesis is to conduct studies on comorbidities and MS that deliver novel information which could strengthen the current recommendations or contribute new recommendations for preventing and/or managing comorbidities in the MS population. This thesis used data from three surveys of the Australian MS Longitudinal Study (AMSLS). The AMSLS is a large, ongoing research-based project since 2002 that has maintained a national cohort of approximately 3,000 adult Australian volunteers with MS. The first study (Chapter 3) focused on identifying the changes in the prevalence of comorbidities between MS symptom onset and at follow-up at a mean of 20.5 years post-symptom onset. The prevalence of comorbidities, particularly of depression, anxiety, hypertension, osteoarthritis, high cholesterol, eye diseases, osteoporosis and cancer, increased substantially between symptom onset and the time of study. The age-and-sex standardised prevalence of anaemia, cancer, anxiety, depression, migraine, psoriasis and epilepsy was significantly higher in people with MS compared to the general Australian population at the time of study. No significant differences were seen by MS onset-types. This study provides supporting evidence that comorbidities are already common in early stages of MS and accumulate more in people with MS than would be expected with normal aging, regardless of MS onset-type. The second study (Chapter 4) focused on identifying the key comorbidities that could be targeted for early detection and treatment to achieve better health-related quality of life (HRQoL) outcomes in people with MS. The number of comorbidities was strongly associated with lower HRQoL in a dose-dependent fashion. Compared to those without comorbidities, those with two or three comorbidities had a HRQoL that was 0.08 lower, and those with four or more comorbidities, the HRQoL was 0.18 units lower. This study also highlighted that mental health disorders were by far the largest contributor to the overall and psychosocial super-dimension of the HRQoL. Musculoskeletal disorders, on the other hand, were the largest contributors to the physical super-dimension and were the second largest contributor to overall HRQoL. The third study (Chapter 5) provided key evidence on the associations between the total number of comorbidities and the severity of MS symptoms. This study also determined which comorbidities made the strongest contributions to the severity of the most common symptoms experienced by people with MS. Comorbidities were strongly associated with the severity of all MS symptoms, with the strongest associations being for symptoms of feelings of anxiety, feelings of depression and pain (ratios of means ‚Äöv¢‚Ä¢0.12 per comorbidity increase). Comorbidities together explained from 3.7% up to 22.0% of the variance of the severity of different symptoms. Further, mental health disorders (i.e. depression) and musculoskeletal disorders (i.e. osteoporosis) were the largest contributors to the severity of the most common symptoms in MS. We recognise that comorbidities are a complex phenomenon and simultaneously managing multiple comorbidities is challenging with potential for serious adverse events. Shifting from a single-disease paradigm‚ÄövÑvp to a multi-morbidity approach‚ÄövÑvp may offer more personalised approaches to comorbidity prevention and treatment. In this regard, we conducted the final study (Chapter 6) to determine the patterns of comorbidities that exist in MS and their association with the demographics and clinical characteristics of people with MS. We identified five statistically distinct and clinically meaningful comorbidity patterns in MS and classified them as: 1) minimally-diseased 2) metabolic 3) non-metabolic 4) mental health-allergy and 5) severely-diseased. Age, sex, obesity and disability level were associated with the probabilities of belonging to different comorbidity classes, while no associations were found with MS onset-types, disease modifying therapy status, education attainment and relative socioeconomic status. The overall clinical message of my PhD thesis is that early detection and optimal management of comorbidities in MS is important. Hence, people with MS and health professionals can both play a proactive role in the identification and management of comorbidities. To assist in the process, we recommend that people with MS engage themselves in self-monitoring of their conditions and be proactive in updating and reporting of any comorbidities or symptoms that they may experience to their healthcare providers to allow for timely advice and management. Moreover, we encourage them to adopt and commit to a positive health behaviours and lifestyle changes. For health professionals, my work showed support for early screening as well as routine screening for possible risk factors and comorbidities. Health professionals may wish to focus their efforts on the common comorbidities with the largest impact, such as mental health and musculoskeletal disorders. Lastly, with the demonstrated impact of comorbidities on HRQoL and the severity of common MS symptoms, optimal management of comorbidities is important. To optimise care for a person with MS with comorbidities, we encourage healthcare providers to create an individualised management plan that considers the purpose of care, the patient goals, the total treatment burden, and an assessment of benefits and harm of the treatments. Effective collaboration with other healthcare professionals, family members and carers are likely to further improve the care of people with MS with comorbidities.