Medical Management of Gaucher Disease: Ask the Experts


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Dr John Barranger, Dr Roscoe Brady, Dr Gregory Grabowski, Dr Pram Mistry, Dr Gregory Pastores and Dr Raphael Schiffmann made up the Panel of Experts at the US Gaucher Conference in Arlington, Virginia, USA on 1 October 1999. Susan Lewis chaired the session.


Q When should someone begin enzyme replacement treatment? And under what circumstances would you not put a person on enzyme replacement therapy?

Dr Barranger said that individuals with neither signs nor symptoms of the disease are quite rare.

A sign means where something wrong is clinically observed eg a fracture on an Xray or a low platelet count from a blood test; a symptom means when you hurt or have something that bothers you.

Asymptomatic may mean someone who has signs of the disorder but does not feel bad.

When should we treat? We should use objective markers to gain some understanding of the progression of the disease. When it appears that there may be irreversible problems, then I would press for patients to be treated.

What of those who opt not to be treated? Patients can choose not to be treated and we must respect that.'

Dr Grabowski said once children are diagnosed, treatment should be given quickly. Children who come to a doctor's attention are in general significantly symptomatic.

About 20% of adult patients I see choose not to go on enzyme replacement therapy'.

Dr Mistry said that Gauchers disease is progressive and older patients should not be denied treatment because of their age. He gave examples of three patients earlier in the day where all three started to suffer bone fractures and other complications of Gauchers disease between the ages of mid 50s to mid 70s.

If they had started enzyme replacement therapy before then, the outcome could have been altered.'

Q What parameters do you rely on to decide on treatment in Type 1 Gauchers disease?

Dr Mistry said that the enzyme chitotriosidase allows a specific measure. Visceral disease (eg enlarged spleen and liver), haematological disease (eg low blood counts and other chemical markers), and X rays and MRI for bone marrow infiltration are all factors which go into the decision to treat patients with Gauchers disease.

Q What is the minimum dosage which a patient with Gauchers disease should receive?

Dr Grabowski said that he did not think there is any set dose. The minimum dose is that dose which maintains a positive response in the individual. 'I have found that less than 20 u/kg/bw (units per kilogram of bodyweight) every two weeks is not generally responsive.' Dr Barranger agreed.

Q Why is every two weeks better than every week?

Dr Mistry said that once a week can show a better response for patients who are not responding to once every two weeks.

Q What is the proper rate for an infusion?

Dr Pastores said that one hour is a reasonable minimum although during a trial for Cerezyme the dose was given from 7½ minutes to 1½ hours.

Dr Mistry recommended from 1 to 2 hours and Dr Brady agreed that if the dose was 60 u/kg/bw in one infusion, it should run for 2 hours; if 30 u/kg/bw for one hour. If anyone was getting 120 u/kg/bw, then the time should be extended to 4 hours.

Q Has anyone had to stop enzyme replacement therapy because of any side effects?

Dr Grabowski said that only four people out of more than 2,000 treated have had to stop treatment because of severe side effects.

Q: Can anyone comment on the drug OGT918?

Dr Barranger said that the concept of the drug is to block the formation of the lipid (glucocerebroside), which is the material stored in sufferers of Gauchers disease. In concept and theory, this is not wrong. In practice, is it safe and effective? There is currently a trial of 28 patients. Until the results are announced, it is impossible to comment.

Dr Mistry said that this may be a very exciting development especially for children with Type 3 disease and perhaps Type 2 disease, probably in combination with Cerezyme.

Dr Grabowski said this idea has been around for 30 years. His concern was that the trial will be incomplete as there may be no data on how the drug affects the central nervous system of Type 1 patients in the trial.

Dr Chris Moyses, Development Director of Oxford GlycoSciences, the pharmaceutical company which produces the drug, was in the audience and said that his company had started evaluating OGT918 from the initial clinical study and plans to make an announcement in the early part of the year 2000.

Q: In Types 2 and 3 patients, would a more frequent dose be better?

Dr Schiffmann said that in Type 2, infusions of enzyme replacement therapy do not work.

In the case of Type 3 patients, infusions work although there is no evidence that more frequent adminis-tration in such cases have more effect.

But it is important that the dose is individualised to each patient.

Dr Barranger said that the classification between Types 1, 2 and 3 Gauchers disease were without reliable markers except that Types 2 and 3 are distinct from Type 1 as Type 1 patients have no neurological symptoms.

However between Types 2 and 3, there are many surprises. Now there are children who turn out to be Type 3 who formerly were classified as Type 2 Gauchers disease.

Dr Mistry said that an erroneous diagnosis of Type 2 in a baby who is really Type 3 may lead to wrongly withholding treatment .

Q Does Cerezyme improve pulmonary hypertension (lung disease)?

Dr Mistry said he had looked at patients on treatment and those not on treatment. 32% of those not on treatment have indications of pulmonary hypertension whilst 18% of treated patients have hypertension. There is no evidence that enzyme treatment makes matters worse although sub-optimal treatment might cause the lung disease to worsen.

Q Most Gauchers patients have low HDL and low total cholesterol. Will this change due to enzyme replacement therapy?

Dr Grabowski said that there are changes in the blood serum lipid patterns. If there is a decrease in disease burden, the patient's metabolism changes. However he could not tell whether Gauchers disease has been a protection for heart disease.

Dr Barranger said that treated patients' cholesterol is rising but his impression is that patients with Gauchers disease have no higher incidence of heart disease or stroke.


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Source: Gaucher's News February 2000. © Copyright Gauchers Association 2000