PNH治療の変遷を振り返る

We performed our first trial of eculizumab in PNH in Leeds just over 10 years ago. Before that time, the disease was really quite a dismal disease for patients to be diagnosed with, about half the patients died as a direct result of the PNH and most of the patients had really quite profound symptoms due to the disease. Patients developed complications such as thrombosis, kidney failure, other problems, as a direct result of that PNH and those complications were very difficult to treat. So soon as a patient started to develop complications, we knew that they were likely to go in a downwards spiral until they eventually died of their disease.

From the first trial that we performed in PNH with eculizumab, which is from May 2002, the effects for patients were dramatic. The symptoms were almost completely resolved of hemolysis, abdominal pain, severe lethargy, difficulty swallowing, almost disappeared almost immediately. And most patients in our experience now have become transfusion independent and lead almost normal life with the disease. We now have patients on treatment for over 10 years and those patients have remained well over that period of time, and for the majority, have not required further transfusions.

Before we had eculizumab for PNH, patients died of the disease, about half the patients died as a direct cause. What we have shown in the last 10 years is that for the most part, the symptoms of PNH, the underlying problems, have stopped with eculizumab. And the survival of our patients now is very similar to that of the normal population within our country. So we seemed to have stopped all of the complications due to hemolysis, due to thrombosis, due to renal failure. And therefore the survival of patients is now almost normalized.

Before we had effective treatment for PNH, patients with the disease were very disabled by the disease. Many patients couldn’t, for example, get out of bed during the day because of the severe lethargy that is seen with the disease, and couldn’t function normally, for example, looking after their family or working normally. Since starting treatment, almost all patients go back to a normal life, whether participating in family life, working fully and are very productive for themselves and for society. So we found a dramatic change for patients on treatment. In fact, what we also found is because we have a national service for PNH in the UK, is that we have patient groups now where patients start to communicate with each other and lobby for each other, and that’s been a very productive part of our treatment.

At the moment we are trying to optimize the therapy with eculizumab to try to get the right dose for every patient to get the best out of the drug, and that is certainly helping with patients. Also identifying which patients will benefit. Initially we were just treating patients who were transfusion dependent or had thrombosis, for example, with the disease, but it’s obvious that some patients have quite profound symptoms from PNH and would benefit from eculizumab. So that’s our current pressure. Over the next few years, there are a number of drugs in development, which may be more convenient than eculizumab. One of the issues with eculizumab is it has to be given every two weeks as an intravenous infusion, which is somewhat inconvenient for patients, although in the UK it is given in patients’ homes. So some of the novel therapies that are in development may well be easier to give, perhaps for the patient self-administering therapy. I think over the next 10 years or more, we are beginning to understand more about the pathophysiology of PNH, and the ultimate aim I think would be to have a therapy that is effective in curing the disease rather than just controlling the disease. And that would be our ultimate aim.