Deferasirox film-coated tablets may improve adherence, reduce complications of iron overload

SAN DIEGO — A film-coated tablet formulation of deferasirox demonstrated higher patient satisfaction than the dispersible tablet formulation among patients with transfusion-dependent thalassemia and myelodysplastic syndromes, according to findings presented at the ASH Annual Meeting and Exposition.

“The once-daily dispersible tablet formulation of the iron chelator deferasirox has been available since 2005, offering an alternative to parenteral deferoxamine,” the researchers wrote. “Yet barriers remain to patient adherence, including the need to take the drug in a fasting state, palatability and gastrointestinal tolerability. A deferasirox film-coated tablet was developed that can be taken orally, once-daily with or after a light meal, and is potentially less burdensome to patients than the dispersible tablet formulation.”

Ali T. Taher, MD, PhD, of the American University of Beirut Medical Center in Lebanon, and colleagues examined the use of the film-coated tablet formulation of deferasirox compared with the dispersible tablet formulation among patients 10 years of age and older who had and had not been treated with iron chelation therapy. The researchers enrolled patients with serum ferritin level greater than 1000 ng/mL who had either transfusion-dependent thalassemia requiring iron chelation therapy at 30 mg/kg/day or greater of the deferasirox dispersible tablet or myelodysplastic syndrome requiring the same therapy at 20 mg/kg/day or greater.

Patients who had not been treated previously with iron chelation therapy received once-daily therapy with a 20 mg/kg dose of the dispersible tablet or a 14 mg/kg dose of the film-coated tablet. Patients who were previously treated received either the dispersible tablet or the film-coated tablet at a dose equivalent to their pre-washout dose.

Doses were adjusted using serum ferritin and investigator’s judgment after week 4 for patients who were treatment-naive and after month 3 among pre-treated patients (dispersible tablet, ± 5–10 mg/kg/day, maximum 40 mg/kg/day; film-coated tablet, ± 3.5–7 mg/kg/day, maximum 28 mg/kg/day). Dose adjustments due to safety concerns were allowed at any point during the study.

Patients completed the modified Satisfaction with Iron Chelation Therapy (SICT) instrument, which utilized domain scores on 5-point response scales to evaluate adherence, satisfaction/preference, and concern, as well as palatability, including taste, aftertaste, ability to consume medicine, and perception of medicine. The modified SICT instrument was completed at weeks 2, 3 and 13, and at the end of the treatment period. Patients also kept a daily gastrointestinal symptom diary, which included five items — belly pain, nausea, vomiting, constipation and diarrhea — and was rated on an 11-point scale.

Of the 173 patients included in the study, 87 received the film-coated tablets and 86 received the dispersible tablet. Rates of completion were comparable between formulations for the questionnaires (approximately 80% at the beginning of the study and approximately 70% by week 24) and the daily GI diary (approximately 70% at the beginning of the study and approximately 35% by Week 24).

Film-coated tablets superior

Patients receiving the film-coated tablets consistently demonstrated better adherence and reported greater satisfaction/preference and fewer concerns. Patients reported that it was easier to remember to take the film-coated tablets and that they were less likely to think about stopping the medication; they also followed the instructions from their physician more closely, found the medication easier to take and were less bothered by the amount of time it took to prepare the medication and the wait time before eating. The greater satisfaction/preference was reported in general and in administration of the film-coated tablets; the decreased number of concerns related to less worry about not consuming enough medication, fewer restrictions in terms of daily activities and less worry about side effects.

The researchers also examined which medication for iron overload was preferred most by patients. The choices included film-coated tablets, dispersible tablets or powder to sprinkle on food; patients could also select ‘I don’t know.’

At the end of the treatment period, 53 out of 60 (88.3%) evaluable patients who received the film-coated tablets reported a preference for that formulation and 41 out of 63 (65.1%) of evaluable patients who received the dispersible tablets indicated that they would select the film-coated tablets. Patients with film-coated tablets reported greater satisfaction in palatability scores; these patients reported no taste or aftertaste and were able to swallow the entire quantity of medication with the proper amount of liquid. The variance in scores between patients treated with the dispersible tablets and those treated with the film-coated tablets was greater than 1 point — a minimally important difference — for all domains and palatability at the majority of visits, which demonstrated a clinically meaningful difference between the formulations, according to the study results.

GI summary scores were low for both formulations, indicating that patients had “very little trouble/concern associated with GI symptoms.” Patients treated with the dispersible tablets reported more trouble/concern.

“These results show a clear preference in favor of deferasirox film-coated tablets in all domains for the modified SICT,” the researchers wrote. “Patients were satisfied with their medicine during the study period and more patients were satisfied with deferasirox film-coated tablets compared with dispersible tablets at all visits. Deferasirox film-coated tablets offer patients an improved formulation that does not require administration in a fasting state and has better palatability and very little concern associated with GI tolerability. Enhanced patient satisfaction with the new deferasirox film-coated tablet formulation may improve adherence, thereby reducing iron overload-related complications.” – by Julia Ernst, MS

Reference:

Taher AT, et al. Abstract 850. Presented at: ASH Annual Meeting and Exposition; Dec. 3-6, 2016; San Diego.

Disclosure: Taher reports receiving research funding from Celgene and honoraria and research funding from Novartis. Please see the full study for a list of all other researchers’ relevant financial disclosures.