Risks associated with oral deferiprone in the treatment of infratentorial superficial siderosis

Abstract

Objective Deferiprone is an iron chelator that has recently been used to treat patients with infratentorial superficial siderosis (iSS). It is considered to have a generally favourable safety profile but concerns have been raised due to the risk of agranulocytosis. We aimed to evaluate the safety and tolerability of oral deferiprone as a treatment for patients with iSS. Methods We present a case series of 10 consecutive patients presenting with classical iSS treated with deferiprone. Results Ten patients were followed up for a mean period of 2.3 years (range 0.5-5.5 years). Four patients (40%) were withdrawn from treatment because of treatment-related side effects. The reasons for treatment discontinuation were neutropenic sepsis (n = 3) and fatigue (n = 1). In 2 out of the 3 cases of neutropenic sepsis, patients initially developed neutropenia without sepsis. The mean time to neutropenic sepsis following deferiprone was 1.2 years (range 0.3-2.5) with mean neutrophil count of 0.4 (range 0.3-0.5). Six patients (60%) reported no change in neurological function while on treatment, and four patients (40%) reported that their condition deteriorated. Conclusions Deferiprone was poorly tolerated, with 40% of patients withdrawing from treatment, most commonly due to neutropenic sepsis, after an average of 2 years on treatment. This study increases the number of reported cases of agranulocytosis in patients with iSS treated with deferiprone. Clinicians treating iSS patients with deferiprone should be aware that this drug has a potentially life-threatening side effect of neutropenic sepsis, and should ensure that appropriate haematological monitoring is in place.

Treatment Response of Deferiprone in Infratentorial Superficial Siderosis: a Systematic Review

“…The data on the duration of illness prior to commencing treatment was not routinely reported. Of those studies which reported it, the duration of disease prior to therapy was between 6 months [ 24 ] and 276 months [ 12 ]. The average documented disease duration for positive outcomes was 77.3 months and for mixed outcomes was 115.6 months, raising the possibility of earlier intervention providing better outcomes for patients.…”

“…This treatment regime has been used in multiple other cases including a pilot safety trial for the drug [ 14 – 16 , 18 , 20 ]. However, other treatment doses have been reported in literature including 30 mg/kg/day over 5 days [ 21 ], 15 mg/kg/day [ 19 , 22 ], 10–30 mg/kg/day [ 24 ], 1000 mg twice a day for 5 days [ 12 ], 1500 mg twice a day [ 23 ] and 1000 mg three times a day [ 17 ]. These doses are lower than the therapeutic 75 mg/kg/day licensed use for thalassaemia.…”

Case Report: Auditory Neuropathy and Central Auditory Processing Deficits in a Neuro-Otological Case-Study of Infratentorial Superficial Siderosis

“…The importance of comprehensive audiovestibular assessments to identify the site of lesion in patients with neurodegenerative conditions is highlighted. Due to progressive, and possibly irreversible, nature and significant morbidity, it is necessary to determine the features that differentiate iSS-related and age-related hearing loss for timely diagnosis and to provide needs- and deficit-specific management strategies, with further efforts to halt disease progression by means of prompt surgical repair ( 61 , 62 ), or by using iron chelating agents ( 1 , 63 , 64 ) and ultimately, may inform research on novel therapeutic agents. Dedicated and longitudinal studies that correlate the audiovestibular assessments, patients' symptoms and the degree of functional impairment with the respective imaging would help establish MRI usefulness in functional assessment of patients with iSS.…”

Neurological update: neuroimaging in dementia

“…In Alzheimer’s disease, iron is found in the plaques and tangles that characterise the disease, though there is still some work required to establish what exactly is being identified, for example whether ferrous or ferric iron is picked up by QSM. Although iron chelation therapy is now being trialled in some of these condition, the drugs can cause life-threatening complications of agranulocytosis and neutropenia which tempers ones enthusiasm for them [ 83 ], but nevertheless this imaging modality may yet shed light on the role of iron in the aetiology of neurodegeneration, and prove to be a useful non-invasive biomarker.…”