Methods of treating eosinophilic esophagitis and reducing candidiasis
Disclosed herein are methods for treating eosinophilic oesophagitis with corticosteroids. The methods for treating eosinophilic oesophagitis disclosed herein result in reduced corticosteroid side effects, e.g. candidiasis. Dosages, formulations, and methods for administration of corticosteroids are provided.
1 . A method of treating eosinophilic esophagitis (EoE) in a patient in need thereof comprising administering to the patient an orally disintegrating tablet (ODT) comprising about 1.5 mg to about 3 mg of fluticasone propionate, wherein the ODT is orally administered once daily for at least 12 weeks, wherein at Week 12:
a. the patient's risk of candidiasis is less than about 10%, and
b. the patient shows an improvement in at least one of the following outcomes compared to a patient that is administered the fluticasone propionate twice daily:
i. at least one symptom score measured using a patient reported outcome symptom evaluation (PROSE) instrument after an episode of dysphagia;
ii. EoE Endoscopic Reference (EREFS) score;
iii. EoE Activity Index (EEsAI) avoidance, modification, and slow swallowing (AMS) score;
iv. Global EoE score;
v. Patient global impression of severity (PGIS); and
vi. Patient global impression of change (PGIC).
2 . The method of claim 1 , wherein fluticasone propionate is administered at bedtime or at nighttime.
3 . The method of claim 1 , wherein the patient's risk of candidiasis about 5% or less.
4 . The method of claim 1 , wherein the candidiasis is oral candidiasis or esophageal candidiasis.
5 . The method of claim 1 , wherein the candidiasis is oral candidiasis.
6 . The method of claim 5 , wherein the patient's risk of oral candidiasis is less than about 4%, less than about 3%, less than about 2%, or less than about 1%.
7 . The method of claim 1 , wherein the candidiasis is esophageal candidiasis.
8 . The method of claim 7 , wherein the patient's risk of esophageal candidiasis is about 4.8%.
9 . The method of claim 1 , wherein the symptom score comprises:
(i) on a scale ranging from 0 to 10, a difficulty getting food down;
(ii) on a scale ranging from 0 to 10, a worst discomfort with food;
(iii) on a scale ranging from 0 to 10, a worst pain with food;
(iv) a mean score of any combination of (i), (ii), and (iii);
(v) a number of dysphagia episodes;
(vi) a daily rate of dysphagia episodes; or
(vii) a number of dysphagia-free days.
10 . The method of claim 9 , wherein the symptom score is:
(a) a daily mean of (i), (ii), and (iii) over a 14 day period;
(b) a mean score of (i), (ii), and (iii) for the worst episode per day of dysphagia over a 14 day period;
(c) a score for the worst symptom of dysphagia over a 14 day period;
(d) a number of dysphagia episodes;
(e) a daily rate of dysphagia episodes; or
(f) a number of dysphagia-free days.
11 . The method of claim 1 , wherein at least one symptom score is improved by 0.5 to 4 points.
12 . The method of claim 1 , wherein the symptom score, the mean score, the worst episode score, or the worst symptom score is determined using data from 2 weeks of entries immediately prior to Week 12 and Week 26.
13 . The method of claim 1 , wherein the EREFS score is improved by about 0.3 to 1.5 points.
14 . The method of claim 1 , wherein the Global EoE score is improved by about 1 to 4 points.
15 . The method of claim 1 , wherein the PGIS score shifts to improvement by about 1 to 5 severity categories.
16 . The method of claim 1 , wherein the EEsAI score is improved by about 2 to 15 points.
17 . The method of claim 1 , wherein the patient further shows improvement in Eosinophilic Esophagitis Quality of Life Questionnaire (EoO-QoL-A).
18 . The method of claim 17 , wherein the EoO-QoL-A score is improved by about 1 to 3 points.
19 . The method of claim 1 , wherein the eosinophil count in the patient's esophagus is reduced compared to the patient's baseline eosinophil level.
20 . The method of claim 19 , wherein the eosinophil count is reduced to no more than 6 eosinophils per high power field (hpf).
21 . The method of claim 20 , wherein the eosinophil count is measured in the distal portion of the esophagus, the proximal portion of the esophagus, or both.
22 . The method of claim 21 , wherein eosinophil count in the distal portion of the esophagus is no more than 6 eosinophils per hpf.
23 . The method of claim 21 , wherein eosinophil count in the proximal portion of the esophagus is no more than 6 eosinophils per hpf.
24 . The method of claim 1 , wherein the number of dysphagia episodes is decreased compared to a patient that is administered the fluticasone propionate twice daily.
25 . The method of claim 1 , the number of dysphagia-free days is increased compared to a patient that is administered the fluticasone propionate twice daily.
26 . The method of claim 1 , wherein (a) and (b) are measured at week 12.
27 . The method of claim 1 , wherein (a) and (b) are measured again at week 26 and/or week 52.
28 . The method of claim 1 , wherein the patient shows an improvement in at least one of the following outcomes compared to a patient that is administered the fluticasone propionate twice daily:
i. at least one symptom score measured using a patient reported outcome symptom evaluation (PROSE) instrument after an episode of dysphagia;
ii. EoE Endoscopic Reference (EREFS) score; or
iii. Global EoE score.
29 . The method of claim 1 , wherein the symptom score is the number of dysphagia episodes over 14 days.
30 . The method of claim 1 , wherein the symptom score is one or more of:
i. number of dysphagia free days over a 14 day period;
ii. the average daily episode severity score over a 14 day period;
iii. symptom burden over a 14 day period.
31 . The method of claim 1 , wherein the patient shows an improvement in the visual dysphagia question (VDQ) composite score compared to a patient that is administered the fluticasone propionate twice daily.
32 . The method of claim 1 , wherein the patient shows an improvement in the EEsAI total score compared to a patient that is administered the fluticasone propionate twice daily.