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Otolaryngology–Head and Neck Surgery, Vol 139, No 3, September 2008

Table 3 Change from baseline within each group after three months

Visit I vs visit III

Esomeprazole

Placebo

Difference

RSI

Total

14.27 1.58‡ 1.37 0.33‡ 1.80 0.26‡ 1.43 0.33† 1.40 0.31‡ 1.17 0.37† 0.87 0.27† 1.60 0.37† 2.27 0.28‡ 1.97 0.31‡ 4.60 0.63‡ 0.00 0.10 0.53 0.20* 0.77 0.20† 0.67 0.13‡ 0.83 0.16‡ 0.97 0.15‡ 0.07 0.07 0.67 0.20†

7.79 1.74‡ 1.18 0.36† 1.18 0.31† 0.96 0.27† 0.57 0.28 0.21 0.33 0.57 0.26* 1.07 0.34† 1.43 0.33† 0.64 0.42 2.32 0.76† 0.21 0.21 0.36 0.21 0.07 0.19 0.46 0.16† 0.36 0.13* 0.32 0.12* 0.00 0.15 0.58 0.25*

6.48 2.34* 0.19 0.48 0.62 0.41 0.47 0.43 0.83 0.42 0.95 0.50 0.30 0.38 0.53 0.51 0.84 0.43 1.32 0.52* 2.28 0.98* 0.21 0.24 0.18 0.28 0.70 0.27* 0.20 0.20 0.48 0.21* 0.65 0.19 0.07 0.16

Hoarseness Throat clear Throat mucus

Difficulty swallowing Coughing after meals Breathing difficulties Annoying cough Throat sensations

Heartburn

RFS

Total

Subglottic edema

Ventricular Erythema

Vocal fold edema

Diffuse laryngeal edema

Posterior commissure hypertrophy Granuloma/granulation tissue Thick endolaryngeal mucus

0.10 0.32 Data are given as mean differences standard error of the mean (SEM). The first two data columns show differences from baseline and the third demonstrates the difference between study groups. P values are from Wilcoxon signed rank test and Mann-Whitney U test as appropriate. * P 0.05; † P 0.01; ‡ P 0.001.

LPR. 7,8,13 After three months of treatment, however, the differences in symptom improvement between the two study groups became more obvious, reflected by a signifi- cantly stronger decrease in the total RSI after esomeprazole therapy. As a consequence, even in patients with suspected LPR reporting early symptom relief under PPI medication, the treatment should continue for at least three months. In contrast to Vaezi et al, 9 who had performed the largest double-blind and placebo-controlled trial evaluating a PPI effect on LPR symptoms and laryngeal signs, we could demonstrate that twice-daily esomeprazole was superior to placebo in improving both LPR symptoms and laryngeal findings. In the mentioned study, Vaezi et al included 145 patients receiving either 40 mg of esomeprazole (n 95) or placebo (n 50) twice daily for 16 weeks. From their findings, Vaezi et al concluded that compared with placebo the PPI therapy was of no therapeutic benefit on signs and symptoms associated with LPR. 9 However, they excluded patients with moderate to severe heartburn from their study. Thus, patients with a symptom typical for gastroesophageal reflux disease (GERD) but also relevant for LPR (6% to 43% of LPR patients suffer from heartburn 14,15 ) were not part of the large study population. This could have affected the study results. Another reason for this study result dif- fering from our findings might be the fact that Vaezi et al did not use the RFS for control of laryngeal changes due to its lack of external validation.

Four further studies in the past also revealed no statisti- cally significant benefit of a PPI therapy on characteristic LPR symptoms and signs compared to placebo. Havas et al performed a double-blind, placebo-controlled, and random- ized study with 15 LPR patients evaluating the therapeutic efficacy of 30 mg lansoprazole twice daily for 12 weeks. 6 From their findings the authors concluded that lansoprazole was not more effective than placebo in the treatment of cervical symptoms of LPR and posterior pharyngolaryngi- tis. As the study population was small and no regular sta- tistical analysis of the results was performed, the signifi- cance of this conclusion remains unclear. In a randomized, double-blind, crossover study by Eherer et al, pantoprazole 40 mg twice daily for three months did not significantly affect symptom or laryngeal scores compared with placebo in 14 LPR patients. 16 Nevertheless, the authors hypothesized that pantoprazole compared to placebo may have resulted in faster improve- ment of LPR symptoms. Again, the limitation of this study is a small sample size, which makes it difficult to draw meaningful conclusions from this data. Another double- blind, randomized trial by Steward et al, comparing two- month rabeprazole (20 mg twice daily) to placebo-control PPI treatment, also failed to demonstrate significantly greater improvement in reflux symptoms, health status, or laryngeal appearance. 7 However, for laryngeal symptoms such as hoarseness, dry cough, and throat clearing a statis-

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