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Research in the Arthritis Research Theme

Genetics of response to allopurinol

Allopurinol is the most commonly used urate lowering therapy. It is rapidly metabolised to oxypurinol, which is responsible for inhibition of xanthine oxidase (XO), the critical enzyme in urate production. Currently a large number of patients do not reach the target serum urate despite allopurinol. Potential reasons for this poor response include non-compliance with therapy, under-dosing of allopurinol, and/or partial resistance to allopurinol. We are particularly interested in partial resistance. There are three potential mechanisms for partial allopurinol resistance: i) decreased conversion of allopurinol to oxypurinol, ii) increased renal excretion of oxypurinol and iii) abnormality in XO structure and or function such that oxypurinol is rendered less effective. We have received HRC project funding to identify and characterise genetic variants which may contribute to allopurinol partial resistance.

Funded by

This funding is part of a larger HRC programme grant entitled ‘Urate and gout: genetic control, environmental and drug interactions’

Sites recruiting

Auckland and Christchurch

For further information

Associate Professor Tony Merriman
Email tony.merriman@otago.ac.nz
Tel +64 3 479 5798

Professor Lisa Stamp

Smoking and Rheumatoid arthritis

Rheumatoid arthritis is a common chronic disease resulting in joint damage requiring joint replacement surgery, disability and increased mortality due to cardiovascular disease.

Smoking has recently been shown to be a powerful environmental risk factor for onset of RA. Smoking also results in worse disease outcomes and reduces the efficacy of medications used to treat RA.

These effects, together with the increase in cardiovascular deaths make smoking cessation the most important modifiable lifestyle factor in RA. Such lifestyle changes are particularly difficult for patients living with the stress of a painful chronic disease.

This project will explore the knowledge and beliefs of patients with RA in relation to smoking as it affects their condition. Specific arthritis related factors that contribute to difficulties with smoking cessation will be explored.

A RA-specific smoking cessation programme will then be developed based on the findings and piloted in patients with RA with the help of Arthritis New Zealand.

Funded by

The Health Research Council in partnership with Arthritis New Zealand

Sites recruiting

Recruitment completed

For further information

Professor Lisa Stamp
Pip Aimer strph347@student.otago.ac.nz

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The Gut – Joint axis in Spondyloarthritis

There is well established relationship between gut inflammation and SpA. Endoscopic and histological studies have shown that 5-10% of AS patients have IBD[], and up to 65% of SpA patients, exhibit a subclinical gut inflammation which closely resembles Crohn’s disease (CD). These findings have led to the hypothesis that both IBD and SpA share an aetiology within the gut and are different expressions of the same disease process.

This international collaboration between New Zealand, Australia and Canada will investigate the correlation between bowel symptoms in patients with SpA and histological and immunological pathology at involved sites.

Patients with SpA will undergo capsule endoscopy and colonoscopy with biopsy. Patients with peripheral joint involvement will undergo sampling of synovial fluid for analysis of the immune response within the joint. This will include state of the art analysis of tiny fragments of genetic material -microRNAs- which may be associated with the inflammatory response in gut and joint.

New microbial techniques, such as pyrosequencing, allow the investigation patterns of oral bacterial colonisation in dental plaque of SpA patients., which has been implicated as an antigenic stimulus in a number of chronic inflammatory disorders.

Funded by

The Health Research Council

Sites recruiting

Dunedin, Brisbane- Australia

For further information

Dr Simon Stebbings

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Environment and onset of Wegener’s Granulomatosis

Wegener’s Granulomatosis (WG) affects the small/medium sized blood vessels.

In Canterbury the prevalence of WG is one of the highest in the world. Despite this, we are reliant on information from the Northern Hemisphere to guide us on outcomes, treatments and risk factors for the disease.

Whether there are differences in disease severity, prognostic markers and treatment response between the Northern and Southern Hemispheres is unknown.

We wish to undertake an epidemiological study of WG patients in Canterbury to characterise the risk factors for WG and compare them to those in the Northern Hemisphere.

Funded by

The University of Otago Division of Health Sciences Opportunities Fund
The Canterbury Rheumatology Immunology Trust

Sites recruiting

Recruitment completed

For further information

Professor Lisa Stamp

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The MOA Programme: Management of Osteoarthritis

logo - Management of OsteoarthritisThis programme of research investigates the Management of Osteoarthritis (MOA) at the interface between primary care and secondary care, with an emphasis on the contribution of non-pharmacological, non-surgical interventions; primarily exercise physiotherapy and manual physiotherapy.

The MOA programme of research incorporates a range of research methodologies, centred around clinical epidemiology and health technology assessment, to examine the health and economic implications of medical interventions, and inform clinical and policy decisions.

Projects:
1: The MOA Feasibility Study
2: The MOA Trial
3: Predicting a positive response to physiotherapy treatments for patients in the MOA Trial
4: Peoples’ attitudes and expectations regarding osteoarthritis (OA)
5: MOA 2: the BEMO trial – Boosters, Exercise and Manual therapy in Osteoarthritis
6: The Melbourne hip OA trial
7: Equity of access to joint replacement surgery in New Zealand
8: The Joint Clinic – initiation and programme evaluation of a new clinical service at Dunedin Hospital.
9: Optimising cost-effectiveness in the management of osteoarthritis

Visit the MOA home page for more information 

Funded by

Health Research Council, Lottery Health Grants Board, University of Otago Research Grant, Physiotherapy New Zealand, Arthritis New Zealand.

Sites recruiting

Recruitment completed.

For further information

Associate Professor J. Haxby Abbott

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Genetics of rheumatic diseases

Gout is the most common form of inflammatory arthritis that afflicts men in NZ.

The central cause of gout is excess uric acid (hyperuricaemia) caused by reduced renal excretion of uric acid.

This can lead to widespread deposition of urate crystals and very painful inflammatory attacks of gouty arthritis. Gout is often severe and disabling.

The impact of gout on health is further underscored by the association of hyperuricaemia and gout with aspects of the metabolic syndrome, in particular cardiovascular (CV) risk factors.

There is a significant role for inherited genetic factors in gout. We are using a genetic approach to extend our work on the understanding of the causes of gout. This is done by testing the genes for population-specific variants that play a role in gout.

Critical for this aim is recruitment of a much larger number of patients with gout.

Funded by

The Health Research Council of New Zealand

Sites recruiting

Auckland, Wellington, Hamilton, Christchurch.

For further information

Tony Merriman
tony.merriman@otago.ac.nz
Tel +64 3 479 5798

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Spondyloarthritis Genetics and the Environment – SAGE Study

Spondyloarthritis (SpA) is a chronic inflammatory arthritis of the spine which affects young adults and results in a life-time burden of disease that significantly decreases quality of life, employment options, and life expectancy.

Ankylosing spondylitis (AS) is considered the archetype, but SpA also includes SpA associated with inflammatory bowel disease (IBD).

Overseas data suggests that the incidence of SpA is similar to the incidence of rheumatoid arthritis and the reduction in quality of life experienced by AS patients is greater than the reductions reported by patients with cancer, asthma, heart disease, or diabetes.

SAGE aims to follow a cohort of patients over 300 with SpA for 5 years to ascertain the incidence and prevalence of SpA in New Zealand, the prevalence in Maori and Pacifica. SAGE will assess the effects of SpA on quality of life and employment, smoking habits and fatigue and bowel symptoms.

Genetic data will be analysed to investigate the prevalence of newly identified risk genes in SpA, particularly those that overlap with IBD.

Funded by

Heath Research Council

Sites recruiting

Wellington, Christchurch, Dunedin, Waikato

For further information

Dr Simon Stebbings

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Safety and efficacy of high dose allopurinol in the management of gout: a randomised interventional study

Gout is common in New Zealand, particularly in Māori and Pacific people. It is an extremely painful form of arthritis caused by uric acid crystals within joints. Repeated gout attacks cause joint damage.

To prevent gout attacks, blood urate levels must be lowered to <0.36mmol/L. The most commonly used medication is allopurinol, which inhibits the production of urate.

Current recommendations for allopurinol dose are based on kidney function. There is ample evidence that many patients fail to achieve adequate reduction in urate levels with the recommended dose.

We have preliminary evidence that increasing the dose above recommended dose is safe and effective. We wish to undertake a clinical trial to confirm our preliminary findings, especially with respect to the safety of this approach.

This study has the potential to provide a significant change in clinical practice and improve control of gout, thereby preventing joint damage and disability.

Funded by

The Health Research Council of New Zealand

Sites recruiting

Recruitment completed

For further information

Jill Drake, Research Nurse
Email Jill.drake@cdhb.govt.nz
Tel +64 3 378 6088

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Folate supplementation in RA patients receiving methotrexate – are we impairing the efficacy of MTX?

Methotrexate (MTX) remains the most commonly used drug for the treatment of rheumatoid arthritis (RA).

The exact mechanism of action of MTX remains unclear but it acts as a folate antagonist. Thus, it is recommended that all patients receiving MTX also receive at least 5mg/week of folic acid in an effort to reduce occurrence of MTX associated adverse effects.

Previous research has suggested that supplemental folic acid has no detrimental effects on control of RA.

However, we have shown that patients with higher red blood cell (RBC) concentrations of folic acid have more active RA compared to those with lower RBC folate concentrations.

We now wish to determine whether reducing the amount of extra folic acid patients receive will help improve disease control in those patients receiving MTX.

Funded by

Arthritis New Zealand

Sites recruiting

Recruitment completed

For further information

Jill Drake, Research Nurse 
Email Jill.drake@cdhb.govt.nz
Tel +64 3 378 6088

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Effect of vitamin C on serum urate in patients with gout

Gout occurs when blood urate increases and uric acid crystals deposit in joints. Repeated gouty attacks lead to joint damage and disability.

Prevention of gout requires sustained blood urate <0.36mmol/L. Allopurinol, which inhibits the production of urate, is the most commonly used medication. In some patients the dose is limited by side effects or renal impairment.

Recent evidence suggests that supplemental vitamin C will reduce blood urate levels in healthy controls.

We aim to determine whether it is feasible to use supplemental vitamin C in the management of gout.

We propose to randomise patients to standard treatment with allopurinol or supplemental vitamin C 500mg daily.

Outcomes will include the magnitude and timing of reduction in serum urate concentration and patient acceptability which are required to determine final study design.

Treatment options for patients poorly tolerant of allopurinol are limited and addition of a therapeutic alternative will provide significant benefit to patients.

Funded by

The Health Research Council of New Zealand

Sites recruiting

Recruitment completed

For further information

Jill Drake, Research Nurse
Tel +64 3 378 6088
Jill.drake@cdhb.govt.nz

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Outcome measures in rheumatic diseases

In order to follow the progress of patients with chronic diseases, where hard end-point are often impossible to identify, robust outcome measures are required. International expert committees such as OMERACT, OARSI and ASAS have assessed outcome measures in RA, OA and AS respectively. The development and validation of outcomes measures in gout and SpA is part of the research theme at Otago and has included international collaborations with the organisations above. Research into outcome measures in scleroderma and RA and AS is a focus of the Dunedin based rheumatologists and psychologists. In particular fatigue, bowel symptoms and quality of life measures have been adapted and validated for use in New Zealand.

Funded by

University of Otago

Sites recruiting

Dunedin.

For further information

Dr Gareth Treharne, (Department of Psychology)
Dr Simon Stebbings

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Exercise and self-efficacy interventions for patients with Rheumatoid Arthritis

Qualitative studies suggest that patients with RA often feel disempowered by the medical model of consultation.

Patients who feel they have little control over their illness often have a worse outcome compared with those who have high levels of ‘self-efficacy’

Exercise interventions are useful in many chronic diseases where muscular deconditioning can worsen disability and promote fatigue.

In conjunction with department of psychology and school of physiotherapy we are currently investigating the potential for a walking exercise intervention and a yoga based intervention to improve levels of activity, fitness and self efficacy.

Two students are currently undertaking PhDs to investigate these interventions.

Funded by

University of Otago

Sites recruiting

Dunedin

For further information

Prof David Baxter (School of Physiotherapy)
Dr Gareth Treharne (Department of Psychology)

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Pharmacokinetics of allopurinol and methotrexate

Funded by

The Health Research Council of New Zealand

For further information

Professor Lisa Stamp

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Identification of subtypes of Rheumatoid Arthritis through joint and serologic characterisation

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterized by painful, swelling of joints, joint damage and consequent disability.

A role for the cytokine IL-17A in RA has been a focus of our recent studies.

We have previously found that in joints where the cytokine IL-17A and CD21L genes are both expressed, the inflammation is dominated by large aggregates of lymphocytes and antibody production. Consequently a subtype of rheumatoid inflammation can be distinguished.

Separately, we have found that in patient’s sera, where TNF and high levels of IL-23 are both detectable, there are also high serum levels of IL-17.

The focus of this work is to determine if these joint and serum characteristics identify the same subgroup of patients. In addition we wish to determine we wish to determine whether these cytokines predict response t ocertain types of treatment. An ability to subtype RA and link to personalised treatment are the key outcomes sought from this work.

Funded by

Health Research Counxil of Dunedin

Sites recruiting

Christchurch and Dunedin

For further information

Dr Paul Hessian

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ACR-EULAR Gout Classification Criteria Project

Gout is the most common cause of inflammatory arthritis in men, is becoming more common over time and disproportionately affects Maori and Pacific people. Joint aspiration and synovial fluid examination is the standard diagnostic test but is not always practical in primary care or other settings. Accurate classification criteria are therefore needed to facilitate clinical and epidemiological research into gout.

This case-control study is one of a number of projects that will lead to updated classification criteria for gout. Participants with joint symptoms that may be due to gout are asked to undergo joint aspiration and synovial fluid examination by certificated observers and the presence or absence of a range of symptoms, signs, laboratory and imaging features are determined by clinical evaluation.

This is a world-wide collaborative effort that involves around 20 other rheumatology centres in Europe, Asia and North America, and is being coordinated from Wellington.

Funded by

The American College of Rheumatology and the European League against Rheumatism are funding the overall project. Arthritis New Zealand is funding the data collection within New Zealand.

Sites recruiting

Recruitment completed.

For further information

Associate Professor William Taylor
Mely Brown mel.brown@otago.ac.nz

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