Latest Research Studies
into PMR and GCA

There are still a number of things we do not know about PMR and GCA. Doctors and other researchers are carrying out studies to fill in the gaps of our knowledge.

There are strict rules governing research. Enrolment into research projects is a voluntary process, and you would be fully informed about any project so you can make an informed choice whether you want to take part or not. You would never have research performed on you without your full knowledge and consent.

Lately, rheumatologists, other professionals and even the pharmaceutical companies have been getting more interested in both conditions. Here is a round-up of some of the research studies that are taking place around the country

Diagnosis

Temporal Artery Biopsy vs. Ultrasound (TABUL)
Purpose: To improve accurate diagnosis in GCA

The Temporal Artery Biopsy -vUltrasound in diagnosis of Giant Cell Arteritis (TABUL) study is being led by Prof. Raashid Luqmani at the Nuffield Orthopaedic Centre in Oxford. This NIHR (National Institute of Health Research) portfolio adopted study has been designed to investigate the specificity and sensitivity of temporal artery biopsy compared to ultrasound for the diagnosis of Giant Cell Arteritis (GCA). The study is funded by the NIHR Health Technology Assessment (HTA, Reference Number HTA Project 08/64/01).

GCA causes inflammation and narrowing of blood vessels, and can cause blindness in one third of patients. It is highly important that a prompt, accurate diagnosis of GCA is made and a steroids treatment is given for two or more years. Temporal Artery Biopsy (TAB) is the current ‘gold-standard’ but imperfect test for diagnosis of GCA.

The patient will have a biopsy of a temporal artery (a minor procedure performed under local anaesthetic to remove a sample of one of the scalp arteries), however, around 4 out of 10 patients will have a normal falsely negative result which will provide an imprecise diagnosis.

As part of the TABUL study, an ultrasound scan of the arteries in the side of the head and under the arms will be performed before he patient go for their TAB. Ultrasound seems to be useful in the identification of GCA and does not involve surgery; the test can be performed as an outpatient. The TABUL study will compare the temporal artery ultrasound to temporal artery biopsy, and aims to discover whether ultrasound is as reliable as biopsy, whether it is as acceptable to patients, and whether it is cost effective.

Ultrasound Scans			The researchers aim to have 430 patients involved in the study. There are around 25-30 hospitals that have signed up to this study with patients enrolled in hospitals located in Oxford, Southend and Stoke Mandeville to date. So far the study has reached approximately 40% of the target enrollment. Patients can only be recruited into this study when they are first suspected of having GCA, and they must not have had steroids recently for any reason apart from PMR. They will receive an initial clinical assessment, blood tests, ultrasound and biopsy within 7 days of starting high dose steroid treatment. The study includes three visits (baseline, after 2 weeks and at 6 months) and otherwise patients are seen in the normal clinic as required. Further information on: http://www.ndorms.ox.ac.uk/clinicaltrials.php?trial=tabul
Longitudinal scan	Transverse scan
		A and B Normal Temporal Artery
		C and D ‘Halo’ sign in GCA

Treatment

Novartis study – PMR
Purpose: To assess the efficacy of two new drugs for PMR

This study will test two new drugs: canakinumab and AIN457. They may block chemicals in the body which are thought to be involved in PMR. The study aims that using these drugs at the beginning of disease will lead to fewer flare ups and lower overall doses of steroid needing to be used in the long term. Patients will be recruited at their first diagnosis of PMR, and this must be before they receive any steroid treatment. They will be chosen randomly to receive a single dose of one of these two test drugs for a period of two weeks, and will also receive steroids. Patients will be followed up for 6 months in the study.


Lodotra (delayed release prednisolone) in GCA
Purpose: To tackle inflammation at most appropriate time

Morning stiffness is one of the most frequent symptoms in inflammatory diseases. This is because it has been found that the chemicals involved in inflammation are at their highest level at about 4 am. This can be avoided with prednisolone administered two hours earlier but this is inconvenient for most people. Lodotra, a modified-release form of prednisolone, is a new version where the drug is contained in a slow release tablet which breaks down to release the prednisolone at about 2-3 am in the morning. Therefore, the prednisolone
should ‘hit’ the inflammation at the most appropriate time of day. Lodotra has shown to be effective in rheumatoid arthritis, and also because the prednisolone is available at the key time, lower doses are needed.

Southend Hospital is planning to set up a small-scale 6-month pilot study to see whether this concept works in GCA as well. It aims to recruit 30 patients from 2 or 3 hospitals. If it is successful, a wider scale study would be planned.


Leflunomide in GCA
Purpose: Use of the drug for treating uncontrolled PMR or GCA

Sometimes PMR and GCA do not respond to steroids alone. Leflunomide is an alternative drug commonly used as an anti-rheumatic drug in rheumatoid arthritis. It is showing promise in patients with PMR and GCA who are having trouble reducing the dose of steroids because of relapses.

A number of leading UK rheumatologists have put an application into Arthritis Research UK for funding towards a large study of leflunomide in GCA. This is currently going through Arthritis Research UK’s review and approval process.


Blood Test

Currently, several studies looking at blood samples are been carried out as blood tests have been used for the diagnosis of PMR and GCA. Although no blood test is 100% reliable for diagnosis of either conditions. Researchers are looking at substances in the blood that may be implicated in the development of inflammation in PMR and GCA, and also possible underlying genes.

For instance, there is a chemical in the blood called Annexin which is seen in high levels in people with inflammatory conditions, but seems to be found in ever higher levels in PMR and GCA. Experts think this is a reliable finding and then Annexin could be a useful target for the development of new drugs. This can also be useful for the diagnosis and monitoring of these conditions.


Biobank

Several studies in GCA and PMR are also asking patients whether they would be happy to supply samples to be kept in a biobank. This is to build up an anonymous ‘library’ of blood samples and temporal artery samples.

The concept of a Biobank will help researchers to access to samples more rapidly. Therefore, whenever in the future other studies are set up looking at chemicals in the blood, these samples could be available to use.

 

This is a selection of a number of research projects published in our Newsletter N 4.