Latest Research Studies into PMR and GCA

After many years in the shadows, polymyalgia rheumatica and giant cell arteritis are at last coming into the spotlight of research interest among rheumatologists and other scientists.  It is part of the mission of PMRGCAuk to encourage more research because there is still more gap than there is research-based knowledge about these conditions.  There is so much we still need to learn about what causes these illnesses, what is happening in the body and what treatments are appropriate.  That is before we even start thinking about prevention or cure.

Things are improving.  For example, in 2013 GCA was included in a list of research priorities for sight research by Fight for Sight, the charity supporting research into eye diseases and sight loss.  Future decisions about funding research will be on the basis of these priorities, so it is hugely important.

For the first time in 2009, an international group of experts formed evidence-based recommendations for looking after individuals with GCA.  In 2010, recommendations were formed in Britain.  Both sets of recommendations have been updated in 2020.  2017 saw the publication of the first international trial of a drug – tocilizumab – that has gone on to become licensed for the treatment of GCA. In 2019, this drug was approved for use in the NHS for people with relapsing disease.

From time to time there are opportunities for patients to become involved in research studies and occasionally we publish these.  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.

Working groups of rheumatologists, general practitioners and other experts (with patient representatives involved) are currently working on new or revised sets of guidelines for clinicians for the diagnosis and management of both PMR and GCA.  We will include updates on these.

An exploratory cross-sectional study of subclinical vascular damage in patients with polymyalgia rheumatica. Featured paper January 2021

Authors: Rossana Scrivo , Valeria Silvestri, Francesco Ciciarello, Paola Sessa, Iolanda Rutigliano, Cristina Sestili, Giuseppe La Torre, Cristiana Barbati, Alessio Altobelli, Cristiano Alessandri, Fulvia Ceccarelli, Manuela Di Franco, Roberta Priori, Valeria Riccieri, Antonio Sili Scavalli, Francesca Romana Spinelli, Luciano Agati, Francesco Fedele, Bruno Gossetti, Fabrizio Conti, Guido Valesini

Journal: Scientific Reports
Date of publication: July 2020
Digital Object Identifier: https://doi.org/10.1038/s41598-020-68215-8

Description of the research:
The question: Do people with PMR have damage to their blood vessels?

How did they approach the problem?
They measured parameters acquired by imaging techniques (thickness of the carotid artery in the neck -IMT, stiffness of the arteries – CAVI, size of the aorta in the tummy – APAD) and blood tests for chemicals (leptin, adiponectin and resistin) secreted by body fat in people with PMR and compared them to people without PMR (but who had other major risk of cardiovascular disease – people with hypertension, diabetes, high cholesterol, obesity and cigarette smokers).

What did they find?
They recruited 48 individuals with PMR and 56 with controls with major cardiovascular risk factors. The only meaningful difference between the two groups was the exposure to prednisolone. The individuals with PMR had been treated with an average 7 mg of prednisolone for over 28 months. All three measurements acquired by imaging techniques were meaningfully worse in individuals with PMR and two of the three chemical levels (leptin and adiponectin) were also higher in individuals with PMR.

Limitations of the study
• They diagnosed PMR using a criteria formulated in 2012. Since then, there have been some publications that a number of people with PMR may also have had GCA to begin with. So it is possible that some of their PMR group may have had GCA. Nevertheless, the findings are significant.
• The difference in prednisolone exposure may mean that the findings are a result of prednisolone exposure rather than because of PMR. But since one goes with the other, the findings are still meaningful.

Take-away messages
• Individuals with PMR also have damage to their arteries (perhaps because some of them may also have GCA that is unrecognised).
• This sets the ball rolling for future studies to look at the need for greater vigilance for events like heart attacks and strokes in individuals suffering with PMR.

Prevalence of Giant Cell Arteritis Relapse in Patients Treated with Glucocorticoids: A Meta‐Analysis. Featured Paper December 2020

Authors: Sabine Mainbourg, Alexandra Addario, Maxime Samson, Xavier Puéchal, Mathilde François, Stéphane Durupt, François Gueyffier, Michel Cucherat, Isabelle Durieu, Quitterie Reynaud, Jean‐Christophe Lega

Journal: Arthritis Care & Research
Date of publication: June 2020
Digital Object Identifier: https://doi.org/10.1002/acr.23901

Description of the research:
The question: What is the relapse rate in patients with GCA treated with steroids alone?

How did they approach the problem?
They searched a medical literature database (Medline) to identify all relevant research up to December 2017. All identified literature was studied and included in their analysis if it had information about patients with GCA who were treated just with steroids. After checking the quality of the studies, the researchers pooled the data from the various small studies to make one large study.

What did they find?
The researchers found 300 studies, of which 34 studies (which included 2505 participants) had looked at this problem. The relapse rate was 47.2%. The relapse rate was higher (65.8%) in studies that attempted steroid withdrawal before 12 months, when compared to those studies that planned to use the steroids for longer (relapse rate 34.5%).

Limitations of the study
• The way that GCA was diagnosed and relapse was confirmed differed in the various studies, which may have affected the result.
• The nature of the relapses (minor shoulder pains versus full blown GCA) was not differentiated.

Take-away messages
• About half of all sufferers with GCA are likely to have a relapse at some point
• Rapid taper of steroids increases the likelihood of relapse

Research into PMR

There are several ‘themes’ of research around polymyalgia rheumatica (PMR) being published at the moment.  There is lots of interest defining what PMR actually is and it was suggested at the 2013 British Society for Rheumatology (BSR) conference that it might be a group of conditions that all present in the same way.  There is also lots of interest in the diagnosis of both PMR and GCA and some very early evidence is emerging around potential new treatments and management strategies.

Diagnosis
Ultrasound Scanning is emerging as a popular new tool to help the medical profession with diagnosis.  In PMR, there is interest in looking at the shoulders to find signs of inflammation.  Other areas of interest in the diagnosis of PMR at the moment are the use of a blood test for levels of plasma fibrinogen, which could be an alternative to commonly used ESR or CRP tests (McCarthy et al. 2013).

Treatment and outcomes
There are also a few studies looking at other types of imaging in PMR.  These studies are not necessarily trying to find new ways to diagnose the condition but are doing scans of people with PMR to try to better understand it.  Some studies presented at the BSR conference in April 2020 suggest that, like GCA, PMR is potentially a form of vasculitis.  This finding may fit with a recent systematic review of the published literature, which suggests a higher risk of vascular events such as heart attacks and strokes in people with PMR (Hancock et al. 2013).  This begs the question of whether people with PMR (and GCA) should be screened for vascular problems.  This has been discussed in a recent article by Dr Sarah Mackie, a rheumatologist in Leeds (and PMRGCAuk’s patron) who explains how screening is only helpful if it changes the treatment patients received (Mackie et al 2012).  In terms of GCA, another study has show that the risk of developing GCA is lower in people taking statins, but these drubs did not change the course or severity of the condition in those people who did develop it (Schmidt et al. 2013).

Another recently published study from a group of Italian researchers has looked at a range of other outcomes in PMR, mainly related to steroid treatments (Mazzantini et al. 2012). They showed that dose and duration of treatment was associated with osteoporosis and fractures. A UK study, which was presented at the BSR in 2012, also linked PMR to fatigue (Green et al. 2012).

At Keele University in Staffordshire, Professor Christian Mallen is leading a programme of work into PMR in primary care, where most patients are treated for the whole of the course of their disease. At the moment, Keele is running a questionnaire to study in people diagnosed with PMR very recently, with GPs referring patients into the study on the day that they are diagnosed (Muller et al 2012).This group of researchers is also conducting a study of people who have been diagnosed with PMR in the last 4 years to see how they are what treatments they have had and how their PMR has affected them.  They will soon begin in-depth interviews with GPs about how they diagnose and treat the condition too. In another primary care study, Dr Helen Twohig at the University of Sheffield is designing a new questionnaire to assess how PMR affects patients from their point of view.

Dr Sarah Mackie at the University of Leeds is carrying out several interlinked research studies into PMR, GCA and the various side-effects of steroids. She is very keen to engage with patients, relatives, carers and the public at every stage of the research process, from initial identification of research priorities to final dissemination of research findings. For information on her current research please visit her webpage. Please note she cannot provide individual medical advice to patients, unless they are already under her direct care as a doctor.

PMR OMERACT group

Finally, the PMR OMERACT (Outcome Measures in Rheumatology) group are in the process of developing outcome measures to be used for future clinical trials in PMR. The group’s initial findings will be presented at the OMERACT conference in May this year.

NEW GCA GUIDELINES 2020

New Guidelines for GCA were published in January 2020.  You can find them HERE or at the bottom of this page in the resources section.

From time to time the charity becomes aware of ongoing research into both the conditions and related material. We will add it here once we are confident with the source. Wherever possible we provide a link to the originating website.

Guidelines published by the British Society for Rheumatology (BSR) and British Health Professionals (BHPR) in Rheumatology for Polymyalgia Rheumatica (correct as at spring 2014) and Giant Cell Arteritis (correct as at January 2020) please click these links PMR or GCA.

You may have seen reference to the ‘Quick and Kirwin’ paper on various forums and websites. Please follow THIS LINK to access a copy. Of particular interest please see the PMR and GCA treatment regimes which can be found on page 344 and 346.

Versus Arthritis periodically publish papers for health professionals and students under the general heading ‘Hands On’. In spring 2014 (when it was known as Arthritis UK) the topic was Polymyalgia Rheumatica and is a very worthwhile read that can be found by following THIS LINK. If you wish, a PDF can be downloaded from there. Other useful subjects in this series that may be of interest if you have Other conditions.

A clinical review of Polymyalgia Rheumatica co-authored by Dr Sarah L Mackie (clinical lecturer) and Professor Christian D Mallen can be found by following THIS LINK.

If you are interested in the Design of the Tocilizumab (TCZ) in Giant Cell Arteritis (GCA) Trial (GiACTA) you can find it by following THIS LINK

If you would like to help The Marijke Foundation in their attempts to generate more international public awareness and media attention for the issue of Early Recognition/Diagnosis of the diseases GCA and PMR (and MGCA) please see the following.

Patients who already have a diagnosis Giant Cell Arteritis and/or Polymyalgia Rheumatica and are being treated or already cured, are invited to fill out the Feedback Symptomatrix’.

Their data are important for the epidemiological research of the Marijke Foundation. This research is the source for continuous fine tuning and improvements of the Diagnostic Symptomatrix.

The charity has had a close working relationship with the foundation for many years but please be aware that they are an independent organisation so any communication you have with them will not be shared with PMRGCAuk.

If you are having difficulty retrieving a printed version of any of these documents to take to your GP or other medical practitioner, please contact us on info@pmrgca.org.uk giving us your email address and location and we will send on to you.