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Irish Society of Rheumatology Annual Meeting 2018

Record-breaking attendance and leading international and national scientific updates

A record 225 delegates attended this year’s 2018 Irish Society for Rheumatology (ISR) Autumn Meeting in Naas on 19-21 September.

The meeting featured leading international speakers on a range of rheumatic-related topics, covering genetics and genomics, metabolic aspects of spondyloarthritis, early detection of psoriatic arthritis, mechanical stress and effects on MRI and the care of rheumatic patients pre and peripartum, as well as an expanded programme of Irish research presentations.

Speaking to the Medical Independent (MI), ISR President Dr Sinead Harney thanked her colleagues Dr John Ryan and Dr Grainne Murphy for helping her put together the varied and interesting programme.

“The Society is going from strength-to-strength. This was our biggest meeting to date, with 225 participants, and I think the venue and central location meant that all parts of Ireland were represented, including our colleagues from Belfast, Derry, west of Ireland, south of Ireland, and obviously Dublin.”

One particular highlight of the meeting was the lecture by Professor of Biochemistry at Trinity College Dublin (TCD) Prof Luke O’Neill on the role of the re-programmed Krebs cycle in the therapeutics of inflammatory disease, she said.

“I think Prof O’Neill is at the start of really good, exciting work. I think the whole understanding of glycolysis and the role it has to play [is very important] and we have seen therapeutic targets that might come out of the TCD group.

“I think the level of the scientific and oral presentations were probably better than any other year, and this has all evolved over the last 20 years to quite a high standard. Our Belgian colleague here [Prof Dirk Elewaut] was surprised at the numbers and standards of the science. I think there is a lot of good work being done, a huge amount from TCD and UCD, and also pockets of work being done in Cork, Galway, Sligo, Limerick and Belfast. I think the continued unrestricted funding from UCB for this Rheumatology Patient Improvement Fund (RPIF) also means that junior researchers who would not have been funded before to do clinical projects that affect patient care are getting funded, from all corners of Ireland.”

Another highlight of this year’s meeting was the awarding of the ISR Lifetime Achievement Award to leading Irish consultant rheumatologist and researcher Prof Oliver Fitzgerald at the gala dinner. “He has been known on the international circuit for years and is the new President of GRAPPA [Group for Research and Assessment in Psoriasis and Psoriatic Arthritis]. There has never been an Irish President of a European organisation so while he is retiring from clinical practice, he will be keeping up our profile abroad.”

Welcoming the new National Model of Care for Rheumatic and Musculoskeletal Disorders document, which was officially presented to the ISR at the meeting by National Clinical Programme for Rheumatology lead Prof David Kane, Dr Harney said its implementation would need significant manpower and resources for the specialty.

Dr Harney also commented on the importance of the meeting’s Private Practice and Clinical Advisory Group meetings: “The private practice rheumatologists are as important as the public practice and are very much part of the Society, and then the Clinical Advisory Group, with Prof Kane, is advocating the doubling of consultant numbers.”

So all in all, a lot of work to do to ensure rheumatology receives the attention it deserves to deal with ever-increasing demand.

“The downside for me is the persistent lack of infrastructure. It is particularly bad in the southern region; Cork, Kerry is a real black-spot with no political will to do anything down there, so that is the only real negative, but I think with time and energy, that will change. We have an awful lot of younger female and male trainees coming through so I think the specialty is in a really good place. And the addition of the Bernard Connor Student Medal means we are identifying younger doctors who want to come into our specialty,” she told MI.

Bernard Connor Medal 2018

The ISR established the Bernard Connor Medal to encourage medical student participation in rheumatology during their undergraduate education and to support student engagement with its activities.

This year’s Bernard Connor Medal winner, Mr Dylan McGagh, a third-year graduate-entry medical student at Magdalen College, University of Oxford, UK, who graduated from Trinity College Dublin in 2016 with a gold medal and first-class honours degree in Human Health and Disease, gave a very well-received presentation at the ISR 2018 Autumn Meeting on his research, titled: ‘Could patient-reported outcomes help to inform a holistic treat-to-target approach in rheumatology?’

Dylan McGagh ( Winner of Bernard Connor Medal ) & Dr Sinead Hearney ISR President

Mr Dylan McGagh, Bernard Connor Medal Winner

Mr McGagh explained how while undertaking a shadowing placement of a rheumatology clinic during medical school, he came to believe that the standard rheumatic disease measurement tools (BASDAI, the DAS-28 and the PsARC scoring tools) and their usage led to opportunities for discordance between treatment targets and disease activity. Essentially, they did not give a true picture of the patient’s individual experience or tie in with the concept of treat-to-target.

From one-to-one discussions with patients, he found that placing an emphasis on patient-reported outcomes (PROs) and individual treatment goals as a core foundation of the patient journey was the best approach. Such an approach is especially suited to the specialty of rheumatology because of the effects rheumatic conditions can have on daily life, such as the pain, stiffness and fatigue associated with conditions such as rheumatoid arthritis and psoriatic arthritis (PsA), and ankylosing spondylitis, Mr McGagh stated. “The consequences that these symptoms can have on a person’s confidence, independence and functioning provides a unique opportunity to measure these factors and provide an objective evaluation on subjective inputs, ultimately guiding holistic recovery, which is valued by those most important — the patient and their families and carers.”

Mr McGagh reiterated that in order to best treat these chronic and complex conditions, patients should be placed at the centre of their care, also saying there is scope to utilise more detailed PRO questionnaires.

Summarising his research findings, Mr McGagh said: “For true targets to be reached in a holistic treat-to-target approach placing the patient as the central participant, the patient’s perceptions need to be integrated with current objective measures of disease activity. As I had the privilege of exploring, people with rheumatic conditions have fears and desires for treatment regimens, which are integral to their sense of self. In order to truly treat these chronic and complex conditions, accounting for these individual factors, there is scope to utilise more detailed PRO questionnaires, either on digital platforms while patients await their consultation or via a regular diary between consultations.

“If the tools we employ work effectively and barriers to their functionality are removed, there is an opportunity to bridge the gap between the clinical and the patient worlds, only elevating the value we place on the clinical history and human interaction.”

Thus, rheumatology clinicians should outline individualised goals with their patients early on and “target sustained remission or low disease activity in every patient”, he concluded.

ISR President Dr Sinead Harney then presented Mr McGagh with the Bernard Connor 2018 Medal to a round of applause.

The meeting also heard from the ISR Young Investigator Award 2018 winner Dr Sarah Wade, who gave a presentation on her research project.

Dr Wade is an Arthritis Ireland postdoctoral researcher in the Molecular Rheumatology Research Lab at Trinity College Dublin. Her project proposed that microRNA, miR-125, modulates endothelial cell (EC) bioenergetics and orchestrates joint angiogenesis as characterised by ex vivo associations, in vitro assays and novel CRISPR/cas9 in-vivo zebrafish models.

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Dr Sarah Wade, Young Investigator Award winner

The findings to date are that decreased expression of miR-125 in PsA synovium and in vivo models is strongly associated with pro-angiogenic mechanisms. Elevated glycolysis following miR-125 inhibition enabled ECs to meet the increased energy demands for new vessel formation. Correcting these miRNA deficiencies and their resulting metabolic shift, either by conventional pharmacological or as novel drug targets, may provide therapeutic benefit, especially in early disease, she said.

New national rheumatology model of care presented to ISR

The new HSE National Model of Care for Rheumatic and Musculoskeletal Disorders document was officially presented to the Irish Society for Rheumatology (ISR) at its 2018 Autumn Meeting in Naas.

Prof David Kane, National Clinical Lead of the National Clinical Programme for Rheumatology, and Consultant Rheumatologist at Tallaght University Hospital, Dublin, made the presentation. He also officially presented the document to patient support organisation Arthritis Ireland at the meeting.

The model of care has had a long gestation period taking seven years to complete, with Prof Kane taking over the reins from former National Clinical Lead Prof Oliver Fitzgerald in 2015 to oversee the finalisation of the document, which received input from a large multidisciplinary stakeholder group.

The new model of care for rheumatology and musculoskeletal (MSK) disorders aims to ensure that every rheumatology and MSK patient is seen, assessed and treated by the right person in the right place and in the timeliest manner.

It notes that Ireland has one of the lowest ratios of rheumatologists-to-population in the EU, but when implemented, the model of care will bring service provision for arthritis and allied conditions in Ireland in line with evidence-based practice and international standards of care.

The document foreword acknowledges that currently, the delivery of care to these patients is largely limited by deficiencies in resources, including staffing and infrastructure in the specialty across both primary and secondary care, and by the absence of clear management guidelines and integrated care pathways.

These deficiencies have led to significant access issues, with lengthy waiting lists and delays in assessment, diagnosis and treatment for rheumatology and MSK patients. The document also points to the predicted dramatic increase in the prevalence of rheumatic and MSK disorders in the next decade due to an increasing and ageing population.

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Prof David Kane

The “ambitious and achievable” model of care envisages expansion of rheumatology services in a ‘hub-and-spoke’ model of tertiary centres operating within six rheumatology networks as per the HSE Hospital Group structure, integrated with primary care services through the HSE’s Community Healthcare Organisations (CHOs). “This will provide co-ordinated care and uniform standards of service delivery for patients across the networks and across primary, secondary and tertiary care, which is supported by the development of clear referral protocols, pathways and therapeutic standards,” the document states.

Key secondary care waiting list targets outlined by the model include the reduction of all rheumatology referrals to under six months within a year’s time, and to under three months within two years. It also wants to allow ‘fast-tracking’ of early inflammatory arthritis and systemic disease to reduce waiting times for such urgent referrals to under two weeks within a year’s time.

Staffing wise, the model wants to increase consultant rheumatology time by 40 per cent within a year, through taking all rheumatology consultants off general internal medicine call and by appointing new rheumatology consultants (double the current numbers). It also seeks to increase multidisciplinary team staffing — only one third of the recommended nurse specialists and occupational therapists are in place nationally — and to further develop the scope of team members to increase their care and management of rheumatology and MSK patients.

The model also proposes a number of value solutions, such as the development of national guidelines for the use of biologic medicines, including biosimilars; a review of usage of drugs within the GMS, in particular those where efficacy is unproven; the introduction of a fracture liaison programme, including a falls risk assessment; measures to reduce MSK-related disability costs to the State; and the reduction of  ‘did not attend’ rates in rheumatology outpatient departments to 12 per cent, as per national targets.

In a nutshell, the model recommends an integrated approach across primary and secondary care, which encourages the development of an appropriate role for all members of the multidisciplinary team within the model.

Current rheumatology manpower and service deficits are highlighted throughout the document and will have to be addressed for the model’s implementation. “While some of the costs involved could be met through identifying inefficiencies within the system, it is without doubt that investment, both in staffing and in infrastructure, will be required to facilitate the implementation of this model of care and in shaping future rheumatology services,” Prof Kane and Prof Fitzgerald wrote jointly in the foreword to the document.

Speaking to the Medical Independent (MI), Prof Kane said the National Programme for Rheumatology plans to have an official launch for the model of care shortly and they have asked Minister for Health Simon Health to officiate. “We now have consensus on what we would see as optimal quality metrics in rheumatology and also consensus on what we would need to achieve those and it is clear there is a well-recognised deficit in the numbers of consultant rheumatologists, specialist nurses, physiotherapists and other allied health professionals needed to deliver rheumatology care to the standards that Ireland needs.”

He said the next step is to get support to implement the model of care, with two strands already on the way to being successfully implemented. These include the roll-out of specialist physiotherapy access and advanced nurse practitioners in rheumatology, with 23 in training. “They will see patients at a high level, equivalent to a doctor, thereby expanding our capacity, so consultants can see newer and more acute patients and that will help with the waiting lists. Though ultimately we need more consultants, and we are aiming to get it up to one per 79,000 of population, which is the UK equivalent,” Prof Kane told MI.

An economic analysis of the costs of implementing versus not implementing the model will now go ahead, he confirmed, which should take about a year, though he stressed this should not delay the implementation of the document’s proposals.

In addition, the Programme is also now working on the development of clinical guidelines and treatment pathways for a number of rheumatic diseases, Prof Kane said.

Irish research to the forefront of ISR Autumn Meeting

rish research was a key focus of this year’s ISR Autumn meeting, with a significant number of oral basic science and clinical presentations from local researchers who had submitted their projects to the ISR for consideration for the research prizes.

One of those to present was Best Scientific Presentation prize-winner Dr Charlene Foley, National Centre for Paediatric Rheumatology, Dublin, who outlined her project on the comparison of B- and T-cell subsets, cytokine expression and synovial pathology in Down’s arthritis (DA) and juvenile idiopathic arthritis (JIA).

Dr Foley explained how a pathological feature of Down syndrome (DS) is dysregulation of the immune system, which almost certainly contributes to the observed high incidence of autoimmune diseases in this cohort: Previous work by her group suggests that the prevalence of DA is 18-to-21 fold greater than JIA.

Children with DA often follow an erosive, polyarticular course of disease, with small joint involvement observed in a significantly greater proportion of children than expected in a typical JIA cohort, Dr Foley noted. The DA clinical phenotype may be distinct from JIA, however little is known about the differences in synovial pathology or immunological regulation. No studies to date have examined these entities in DA, thus Dr Foley and colleagues examined B-cell subsets and T-cell cytokine profiles; and characterised and compared the synovial membrane immunohistochemistry in children with DA and JIA.

The study found that there are significant differences in B-cell populations, T-cell cytokine production and immunohistochemical features of synovial tissue in children with DA and JIA but more work is required to verify these results.

Dr Foley highlighted the need for awareness of the risk of DA in children with DS, as they are often diagnosed very late, by which time they have suffered irreversible joint damage.

“So in summary, DA does appear to be a distinct clinical phenotype with an increased risk compared to JIA. The majority of children present with a polyarticular rheumatoid factor-negative arthritis with predominance in the small joints of the hands and wrists… DA and JIA represent distinct conditions with different clinical features, immunology and synovial histology.”

The meeting also heard from the five inaugural (2017) winners of the new ISR research funding initiative, the Rheumatology Patient Initiative Fund (RPIF).

The initiative is intended for innovative researchers undertaking a body of research in rheumatology in Ireland that will directly impact on patient care and quality of life.

One of the RPIF 2017 winners was Prof Gerry Wilson, Consultant Rheumatologist in the Mater Misericordiae University Hospital and Professor of Rheumatology at UCD, who gave an update on the work of the Irish Arthritis Research Coalition (ARC). The ARC was established in 2016, and he highlighted how clinicians can help classify and stratify subtypes of diseases and identify patient cohorts to improve research quality and impact in Irish rheumatology. He briefly outlined the impressive research outputs already underway through ARC, including a number of projects in paediatric rheumatology, and a planned one on rheumatoid arthritis, with the primary aim of the ARC biobank to recruit patients with common rheumatic diseases, and obtain biosamples that will underpin clinical research. A secondary aim is to increase national involvement in clinical trials of novel therapeutic agents.

“The aim of ARC is really to undertake good clinical translational research, which we have seen in the great presentations here, highlighting the importance of having well-characterised clinical cohorts for undertaking patient-centred research,” Prof Wilson commented.

The growing role of genetics in healthcare highlighted

Human genes hold the key to unlocking new disease treatments and cures and we now have the technology to unlock that information in Ireland, the ISR 2018 Autumn Meeting heard.

Dr Jeff Gulcher, a neurologist and co-Founder of Genomics Medicine Ireland (GMI), gave a topical presentation on the role of genetics in healthcare.

GMI is a privately-funded Irish genomic studies company, with its own purpose-built genome sequencing laboratory in Dublin that is working in partnership with the medical community, patients, academic researchers and the global biotech and pharmaceutical sectors to obtain new insights to help with the development of new treatments and diagnostics across a spectrum of chronic health conditions for the people of Ireland and beyond.

It uses large gene-sequenced well-characterised cohorts for its work on drug target discovery and validation, and is currently recruiting 45,000 patients across seven diseases in a collaboration with AbbVie. Ireland’s population structure and relative homogeneity increases the power of gene discovery, he said.

Dr Gulcher highlighted some of the projects GMI is currently partnering on in Ireland, including one looking at the genomic basis of chronic respiratory conditions, such as asthma and asthma-COPD overlap (ACO), in collaboration with St Vincent’s University Hospital, Dublin, and University College Dublin (UCD).

Recently, the company announced its collaboration with the Department of Clinical Neurosciences at the University of Cambridge, UK, to expand GMI’s research examining the underlying genetic factors contributing to multiple sclerosis (MS).

The collaboration will leverage up to 15,000 DNA-extracted MS samples from a biobank the University has established. This large dataset, when combined with samples already being collated via GMI’s ongoing Irish cross-border MS research study, will result in one of the world’s largest MS-focused genomic studies ever conducted.

In the field of rheumatology, GMI is working in partnership with University Hospital Limerick on a landmark genomic study on ankylosing spondylitis and non-radiographic axial spondyloarthritis with the objective of identifying commonalities and linkages that can help diagnose the diseases early on, predict their severity, and suggest personalised treatments — or even a cure.

During his presentation, Dr Gulcher discussed the results of his own gene sequencing, and the particular risk factors and familial disease links his genome data uncovered. He explained how he had altered his lifestyle, losing weight, and became more active to offset his risk of diabetes as identified in his data, and was also aware of the importance of screening for particular cancers and diseases that he had a higher risk of developing.

He posited the health risk-prediction value of everyone having their genome sequenced, though privacy concerns and the potential for abuse of this data were raised by some audience members during the Q&A session.

Meanwhile, in the final presentation of the conference, Dr Lihi Eder, Assistant Professor of Medicine, University of Toronto, Canada, discussed cardio-metabolic diseases in psoriatic arthritis (PsA).

Quoting a number of studies, she said it is now known that PsA is associated with a much higher risk of cardiovascular (CV) events — over 40 per cent higher than the general population. She said this is likely due to a complex mix of traditional risk factors and systemic inflammation. Dr Eder said raising awareness of this particular risk in PsA patients is very important and they should be CV risk-stratified and screened where appropriate. She also noted that TNF inhibition (ie, suppressing inflammation) may be associated with a reduction of CV risk.

Management of rheumatic diseases during pregnancy update

The management of pregnant women with rheumatic diseases is evolving, with medication continuance now an increasing practise for some drug classes, the ISR 2018 Autumn Meeting heard.

Dr Ian Giles, Consultant Rheumatologist, University College Hospital London, UK, and lead author of the British Society for Rheumatology (BSR) 2016 guidelines on prescribing anti-rheumatic drugs in pregnancy and breastfeeding, addressed the meeting on changing practise in the area.

He noted the management of these patients is complicated by several factors, including an increased burden of pregnancy morbidity compared to the general population, which is partly due to increased disease activity. Some studies have shown an increased risk of adverse pregnancy outcomes in the presence of elevated levels of TNF-alfa.

Dr Giles also maintained that pregnancy does not induce remission in as many rheumatic patients as commonly believed, showing some recent data to support this.

He also commented that pain and discomfort during pregnancy is normal and it is important to remember this when trying to distinguish normal aches and stiffness from actual arthritis activity.

While traditionally, women have been advised to discontinue their medications prior to conception and during pregnancy, this is now changing as discontinuing biologics, for example, can have potentially worse outcomes for the pregnancy than continuing them.

Now, many patients continue biologic therapy for at least a portion of pregnancy, ie, first trimester at least, and international guidelines are changing to reflect this, with recent data showing supportive and reassuring results for some biologics, noted Dr Giles. He pointed out that certolizumab pegol (CZP), a novel anti-TNF agent that is used for patients with moderate-to-severe active rheumatoid arthritis (RA), recently had its EU approval extended to include women who are pregnant or breastfeeding following a number of positive studies showing a lack of adverse pregnancy outcomes.

However, there remains a general lack of data on medication usage during pregnancy, with most data looking at foetal as opposed to maternal health, while very few drugs are specifically licensed for usage during pregnancy. Thus, safety concerns around some drugs persist, while in others, not enough is known about the long-term safety profile. As a result, many potentially beneficial drugs are still being unnecessarily withdrawn in pregnancy due to a mistaken belief that the drugs themselves may be harmful, thus allowing an increase in disease activity, which is itself more harmful to the pregnancy.

Careful pre-conception planning with rheumatic patients is key and some medications, such as methotrexate, remain contraindicated, while dosage and compliance are also very important, said Dr Giles.

The BSR guidelines advise stopping methotrexate, leflunomide, mycophenolate mofetil and cyclophosphamide pre-conception, and during pregnancy, switching patients on warfarin to low molecular-weight heparin and starting aspirin in lupus patients. In the second and third trimesters, the guidelines say to consider stopping anti-TNF therapies, Dr Giles summarised.

Prompt post-partum care and appropriate re-initiation of rheumatic therapies are also key, as flare risk is high, but if mothers are breastfeeding, therapies must be compatible, he concluded.

Gut linked to both inflammatory bowel disease and axial spondyloarthritis with high cross-risk ratio

There is a clear link between gut inflammation, axial spondyloarthritis (SpA) and the development of inflammatory bowel disease (IBD), the ISR 2018 Autumn Meeting heard.

Prof Dirk Elewaut, Professor of Rheumatology and Immunology, Ghent University, Belgium, discussed the link between the gut in SpA versus the joint in IBD. Prof Elewaut posited that gut inflammation is a driver of joint inflammation in SpA. His research team has found that about 50 per cent of patients presenting to rheumatologists with a clinical presentation of SpA have microscopic gut inflammation, regardless of subtype, and unrelated to clinical gastrointestinal symptoms.

Subclinical gut inflammation is associated with long-term outcomes of joint symptoms, more extensive disease and, conversely, remission of gut inflammation is associated with disappearance of joint symptoms, he maintained.

Persistence of gut inflammation has been specifically linked to the evolution of Crohn’s disease and ankylosing spondylitis (AS) and is also associated with an accelerated need for biologic therapy, the professor stated.

He also quoted Icelandic genealogy data highlighting the common genetic background for IBD and AS, with a three-fold elevated cross-risk radio of developing IBD if a first-degree relative has AS, and vice versa.

The findings suggest that one or more undiscovered genetic variants may underlie the risk of both diseases.

Meanwhile, a separate meta-analysis suggested that up to 20 per cent of IBD patients can have axial spondyloarthritis, though he cautioned that it was based primarily on imaging and was uncertain if it would be replicated if it was analysed in a prospective manner by rheumatological experts. “So it is common, but I think a little bit less common than this study suggests.” Prof Elewaut added that detection can be hampered by the fact that when IBD patients are placed on steroids and immunosuppressants, they can mask/alleviate any relevant joint symptoms so clinicians need to investigate such symptoms during the diagnosis period.

Concluding, Prof Elewaut said further refinement and validation of biomarkers (including multiparameter sets) are needed for the optimal management of arthritic diseases.

Speaking to the Medical Independent, Prof Elewaut said it is important that clinicians are aware of the presence of gut inflammation and how it can determine severity of disease. “In patients with IBD and SpA manifestations, there are common pathways but also different pathways, so you can have a disconnect between what is happening in the gut and what is happening in the spine or peripheral joints, so that is something to be aware of when treating a patient with SpA or IBD.”