ABSTRACT
Fostamatinib, a recently approved syk inhibitor used in adult primary immune thrombocytopenia (ITP), has been shown to be safe and effective in this disorder. However, clinical trial results may not be similarly reproduced in clinical practice. Here 138 ITP patients (both primary and secondary) from 42 Spanish centers who had been treated with fostamatinib were evaluated prospectively and retrospectively. The median age of our cohort (55.8% women) was 66 years (interquartile range, IQR, 56-80 years). The median time since ITP diagnosis at fostamatinib initiation was 51 months (IQR, 10-166 months). The median number of therapies prior to fostamatinib initiation was 4 (IQR, 2-5), including eltrombopag (76.1%), romiplostim (57.2%) and intravenous immunoglobulins (IVIG) (44.2%). Fifty-eight patients (42.0%) had signs/symptoms of bleeding in the month prior to treatment initiation. 79.0% of patients responded to fostamatinib with 53.6% complete responses (platelet count > 100 x 109 /L). Eighty-three patients (60.1%) received fostamatinib monotherapy achieving a high response rate (85.4%). The proportion of time in response during the 27-month period examined was 83.3%. The median time to platelet response was 11 days (IQR, 7-21 days). Sixty-seven patients (48.5%) experienced adverse events, mainly grade 1-2, the commonest of which were diarrhea (n = 28) and hypertension (n = 21). One patient had deep venous thrombosis and one patient developed acute myocardial infarction. Fostamatinib was shown to be effective with good safety profile in patients with primary and secondary ITP across a wide age spectrum in this real-world study.
ABSTRACT
We report data from a prospective, observational study (ZAGAL) evaluating miglustat 100mg three times daily orally. in treatment-naïve patients and patients with type 1 Gaucher Disease (GD1) switched from previous enzyme replacement therapy (ERT). Clinical evolution, changes in organ size, blood counts, disease biomarkers, bone marrow infiltration (S-MRI), bone mineral density by broadband ultrasound densitometry (BMD), safety and tolerability annual reports were analysed. Between May 2004 and April 2016, 63 patients received miglustat therapy; 20 (32%) untreated and 43 (68%) switched. At the time of this report 39 patients (14 [36%] treatment-naïve; 25 [64%] switch) remain on miglustat. With over 12-year follow-up, hematologic counts, liver and spleen volumes remained stable. In total, 80% of patients achieved current GD1 therapeutic goals. Plasma chitotriosidase activity and CCL-18/PARC concentration showed a trend towards a slight increase. Reductions on S-MRI (p=0.042) with an increase in BMD (p<0.01) were registered. Gastrointestinal disturbances were reported in 25/63 (40%), causing miglustat suspension in 11/63 (17.5%) cases. Thirty-eight patients (60%) experienced a fine hand tremor and two a reversible peripheral neuropathy. Overall, miglustat was effective as a long-term therapy in mild to moderate naïve and ERT stabilized patients. No unexpected safety signals were identified during 12-years follow-up.
