Switching From Imiglucerase to Miglustat for Gaucher Disease
Switching From Imiglucerase to Miglustat for Gaucher Disease
This case series provides a real-world insight into the types of therapeutic response that can be encountered among adult patients with GD1 who have been switched from long-term ERT to miglustat. In clinical practice settings patients can be switched from ERT to SRT at their own request or based on physician recommendations for a number of reasons. In our presented cases, reasons for switching were unwillingness to continue intravenous therapy (Patient 1), unavailability of imiglucerase (Patient 2), and the occurrence of immune reactions to intravenous therapy (Patient 3).
Previous clinical trial data have shown that miglustat can maintain clinical stability in some, but not in all patients previously stabilized on ERT. All three of our patients showed improvements in key hematological and visceral disease parameters during initial 3 to 6 years of ERT. All three patients showed maintenance of platelets, hemoglobin and plasma chitotriosidase during a period of 4 to 8 years of subsequent miglustat therapy. Overall, these patients showed few GD1-related bone manifestations. Patient 2 developed osteopenia during 6 years of ERT, but showed no new bone manifestations or any significant progressive decrease in BMD during 2 years of subsequent miglustat therapy. Similarly, lumbar spine and femur BMD T-scores indicated osteoporosis in Patient 3 after 3 years of ERT, but bone status appeared stable during 3 years of miglustat therapy.
Two patients in this case series experienced diarrhea and/or flatulence during the initial months of miglustat therapy. However, gastrointestinal tolerability was generally good due to gradual dose escalation coupled with dietary modifications, as has been reported previously. Two patients showed initial decreases in body weight, with regains noted at later follow up. Mild-to-moderate reductions in body weight are a known side effect of miglustat therapy, and should be managed with regular monitoring and dietary changes.
As in two of the three patients presented here, mild, transient peripheral tremor has been observed during the initial months of miglustat therapy in previous clinical trials, but usually it did not impair day-to-day function and resolved during continued treatment. We chose to discontinue miglustat in Patient 1 as a safety precaution following his development of peripheral neuropathy, but it was difficult to ascertain the cause of peripheral neuropathy in this patient as he had diabetes. To date, his pains have stabilized since miglustat therapy was stopped, but it is too early to evaluate whether there was any relationship to miglustat. This case demonstrates the importance of appropriate neurological assessment, including EMG, prior to starting treatment with miglustat.
The recent approval of another small-molecular oral SRT, eliglustat, for treating GD opens up the possibility for greater flexibility in our treatment approach. It is expected that time will tell as to whether the issues encountered in this case series will be met in future years.
Discussion
This case series provides a real-world insight into the types of therapeutic response that can be encountered among adult patients with GD1 who have been switched from long-term ERT to miglustat. In clinical practice settings patients can be switched from ERT to SRT at their own request or based on physician recommendations for a number of reasons. In our presented cases, reasons for switching were unwillingness to continue intravenous therapy (Patient 1), unavailability of imiglucerase (Patient 2), and the occurrence of immune reactions to intravenous therapy (Patient 3).
Previous clinical trial data have shown that miglustat can maintain clinical stability in some, but not in all patients previously stabilized on ERT. All three of our patients showed improvements in key hematological and visceral disease parameters during initial 3 to 6 years of ERT. All three patients showed maintenance of platelets, hemoglobin and plasma chitotriosidase during a period of 4 to 8 years of subsequent miglustat therapy. Overall, these patients showed few GD1-related bone manifestations. Patient 2 developed osteopenia during 6 years of ERT, but showed no new bone manifestations or any significant progressive decrease in BMD during 2 years of subsequent miglustat therapy. Similarly, lumbar spine and femur BMD T-scores indicated osteoporosis in Patient 3 after 3 years of ERT, but bone status appeared stable during 3 years of miglustat therapy.
Two patients in this case series experienced diarrhea and/or flatulence during the initial months of miglustat therapy. However, gastrointestinal tolerability was generally good due to gradual dose escalation coupled with dietary modifications, as has been reported previously. Two patients showed initial decreases in body weight, with regains noted at later follow up. Mild-to-moderate reductions in body weight are a known side effect of miglustat therapy, and should be managed with regular monitoring and dietary changes.
As in two of the three patients presented here, mild, transient peripheral tremor has been observed during the initial months of miglustat therapy in previous clinical trials, but usually it did not impair day-to-day function and resolved during continued treatment. We chose to discontinue miglustat in Patient 1 as a safety precaution following his development of peripheral neuropathy, but it was difficult to ascertain the cause of peripheral neuropathy in this patient as he had diabetes. To date, his pains have stabilized since miglustat therapy was stopped, but it is too early to evaluate whether there was any relationship to miglustat. This case demonstrates the importance of appropriate neurological assessment, including EMG, prior to starting treatment with miglustat.
The recent approval of another small-molecular oral SRT, eliglustat, for treating GD opens up the possibility for greater flexibility in our treatment approach. It is expected that time will tell as to whether the issues encountered in this case series will be met in future years.
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