HSC Section 6 Nov2016 Green Book

Table 2. Data presented for percent (number) of patients with histological and endoscopic findings in pretreatment and posttreatment

Fluticasone

Esomeprazole

Pre

Post

% Improve a

Pre

Post

% Improve a

Histological findings

Basal cell hyperplasia

100% (21)

81% (17)

19% (4/21)

100% (21)

52% (11)

43% (9/21)

Intercellular edema

100% (21)

76% (16)

24% (5/21)

86% (18)

57%(12)

35% (7/18)

Eosinophilic microabscess

86% (18)

52% (11)

44% (8/18)

71% (15)

38% (8)

67% (10/15)

Eosinophilic degranulation

95% (20)

52% (11)

50% (10/20)

76% (16)

43% (9)

50% (8/16)

95% (20)

76% (16)

25% (5/20)

90% (19)

48%(10)

47% (9/19)

Eosinophilic distribution b

Endoscopic findings

Stenosis on index endoscopy

24% (5)

14% (3)

80% (4/5)

24% (5)

10% (2)

80% (4/5)

Concentric rings

76% (16)

76% (16)

13% (2/16)

76% (16)

52% (11)

44% (7/16)

Longitudinal furrows

81% (17)

76% (16)

18% (3/17)

81% (17)

52% (11)

41% (7/17)

White plaques

19% (4)

29% (6)

50% (2/4)

24% (5)

0% (0)

100% (5/5)

% improve, % improvement; pre, pretreatment; post, posttreatment. Percent improvement is among a subgroup of patients who had a pretreatment finding. There was no statistically significant difference in improvement between treatment arms. a Percent improvement is among patient who had a pretreatment finding. b Involving entire thickness of epithelium.

P =0.001

P =0.162

therapy. Interestingly, no significant clinical improvement was noted when compared with placebo. The relatively poor response seen in many randomized stud- ies may at least partially be due to a lack of uniformity in medi- cation dosage, duration of therapy, the definition of response, and delivery method. Additionally, variability in the definition of EoE exists in the literature (15) and in many studies EoE is often synonymous with esophageal eosinophilia. Alexander et al. (14) used a higher dose of swallowed fluticasone (880mcg twice daily), which may reflect the higher response rate seen in their study compared with other randomized controlled studies using topical fluticasone for EoE. Five patients developed esopha- geal candidiasis, compared with one patient in our study, suggest- ing this may be dose dependent. Another reason our response rate may have been different when compared with other randomized studies may be due to the definition of response. Variability exists in the literature with some studies using a change in histological grade (12) and even a decrease in percent eosinophils in compari- son with baseline (14,16). The majority of the studies have used absolute changes in eosinophil count as an end point to include 1 eos/hpf (11), 5 eos/hpf (13,17), and <7 eos/hpf (18). We chose to use <7 eos/hpf as a target end point. However, we also examined our data using <5 eos/hpf and obtained identical results (19% fluticasone and 33% for esomeprazole). Another explanation for the low response to FP may be related to the mechanism of drug delivery. FP is an aerosolized medication administered through a metered dose inhaler, which is intended for the airways, and it is unclear how much drug is actually deliv- ered to the esophagus. One would assume that response may be superior in the proximal esophagus than the distal esophagus with this type of delivery. However, when we compared the histological response between the proximal and distal esophagus, there was no

80

80

60

60

40

40

20

20

0

0

Before

After

Before After Esomeprazole ( n =21)

Fluticasone ( n =21)

Figure 2. Change in Mayo dysphagia questionnaire (MDQ) score following treatment. There was significant clinical improvement in ESO but not in the FP treatment arm. Dashed lines indicate gastroesophageal reflux disease (GERD)-positive patients.

Response to topical steroids for EoE has varied in the literature with small case series and retrospective studies reporting response rates in up to 80% (1,10). In contrast, data from prospective con- trolled studies have demonstrated lower response rates. Konikoff et al. (11) reported a 50% efficacy (10/20) in a pediatric population with histological response defined as ≤ 1 eos/hpf. Again, complete histological response was seen in 50% (18/36) of patients after 4 weeks of therapy with FP (12). In another study comparing the efficacy of topical steroids to PPI therapy in adults with EoE, only 15% achieved complete histological response with FP, defined as 5 eos/hpf (13). A recent study by Alexander et al. (14) reported a 62% histological response to fluticasone, defined as a more than 90% decrease in mean levels of eosinophils following 6 weeks of

The American Journal of GASTROENTEROLOGY

123