International meeting of Rheumatologists Bristol Nov 2009 re Clinical trials
An Account of an International Meeting of Rheumatologists to Discuss the Setting-Up of Clinical Trials to Test New Versions of Glucocorticoids by Mary Osborne Hart, a Member of the Patient Group
( Glucocorticoids are steroids produced naturally in the body by the adrenal glands. One of their roles is to inhibit the inflammation process. They are also artificially made and prescribed under various names, including Prednisone and Prednisolone, for various conditions including rheumatic diseases.)
The aim of the day was to agree on a formula for setting up clinical trials to study new variations of Prednisone/Prednisolone type drugs which would have fewer, less severe adverse effects than the current drugs.
As any patient with PMR will know, the benefits of glucocorticoids are considerable but there are inevitably side-effects associated with their use. The higher the dose and the longer the course of treatment, the more severe the adverse effects.
There is currently no hard evidence of high quality to help in deciding dosage, and no consensus of opinion between rheumatologists as to the best method to use. At the moment patients are treated with either a high initial dose followed by a rapid reduction in dosage (which generally leads to more relapses but a lower cumulative dose) or a moderate initial dose followed by a slow reduction in dosage (which generally leads to fewer relapses but a higher cumulative dose).
A relapse was considered to be a return of symptoms severe enough to require an increase of medication. Up to 5mgs of Prednisone/Prednisolone was considered to be a low dose and one at which the benefits of the drug definitely outweighed the risks. A moderate dose was considered to be between 7.5mgs and 30mgs and one at which the benefits and risks were approximately equal. Anything above 30mgs was considered a high dose, and at this level the adverse effects might begin to outweigh the benefits.
The aim of current pharmacological research is to produce a new product that will work as effectively as those used at present, while having a lower glucocorticoid(GC) content. This could be achieved by, for example, using selective GC antagonists that will “trick” the body into thinking it has received more steroids than in fact it has, or combining the GCs with another drug that will amplify their effect, or encapsulating the GCs in liposomes to reduce systemic exposure.
As Polymyalgia Rheumatica is a disease that responds well to high/moderate doses of GCs followed by a lengthy period of gradual dose reduction, it was felt that these patients were an ideal group on which to base the necessary clinical trials for these new drugs.
The various issues around the setting-up of a clinical trial were highlighted by a Clinical Research expert and a Chief Medical Officer from a pharmaceutical company, and eventually a consensus of opinion was reached on the likely way forward.
It was also felt desirable to research and compare the two treatment methods (i.e. high dosage, rapid reduction and moderate dosage, slow reduction) so consequently the research would preferably be done in two groups to discover whether one method was better than the other.
Other Information I Found to be of Interest
1) Only a very small proportion of people with PMR also have/develop GCA, although around half of GCA patients also have PMR.
2) It was the general opinion that PMR should be treated in secondary care because it is a very complicated disease that is more difficult to diagnose than rheumatoid arthritis. In some areas of the country there are rapid access clinics for suspected PMR patients, the aim being to diagnose and begin treatment within 3 weeks.
3) Inflammation levels in the body fluctuate during a 24 hour period, the highest point occurring in the middle of the night. Ideally medication should be taken around 2am but this is totally impractical.
I found this a very interesting and informative day. I was particularly impressed by the openness of the discussions and the willingness of those present to listen to and to take on board the questions/contributions made by the patient group. Oh – and the food was very good too!
