2018 Section 5 - Rhinology and Allergic Disorders

Original Investigation Research

Subcutaneous Treatment for Chronic Sinusitis With Nasal Polyposis

Figure 4. End Points in Patients With Comorbid Asthma

Forced expiratory volume in the first second of expiration (FEV 1 ) by treatment group B

Endoscopic nasal polyp score (NPS) by treatment group A

P <.001

0.5 0 1.0

5.0 4.0 3.0 2.0 6.0 1.0 0

Placebo plus MFNS

P =.07

Dupilumab plus MFNS

–0.5 –1.0 –1.5 –2.0 –2.5 –3.0 –3.5 Least Squares Mean Change (95% CI) in NPS

–0.1 –0.2 –0.3 Least Squares Mean Change (95% CI) in FEV 1 , L

Dupilumab plus MFNS

Placebo plus MFNS

0

4

8

12

16

0

4

8

12

16

Week

Week

No. of patients Placebo plus MFNS Dupilumab plus MFNS

No. of patients Placebo plus MFNS Dupilumab plus MFNS

19 16

19 16

18 14

17 15

15 15

17 16

17 16

17 15

16 15

14 15

FEV 1

percent predicted by treatment group

5-Question Asthma Control Questionnaire (ACQ5) score by treatment group D

C

P =.04

10 12 14 16

0.5

Dupilumab plus MFNS

P <.001

Placebo plus MFNS

0

4 6 8 2

–0.5

0 –2 –4 –6 –8 Least Squares Mean Change (95% CI) in FEV 1 Percent Predicted

–1.0

Dupilumab plus MFNS

–1.5

–2.0 Least Squares Mean Change (95% CI) in ACQ5 Score

Placebo plus MFNS

0

4

8

12

16

0

4

8

12

16

Week

Week

No. of patients Placebo plus MFNS Dupilumab plus MFNS

No. of patients Placebo plus MFNS Dupilumab plus MFNS

17 16

17 16

17 15

16 15

14 15

16 16

16 16

16 15

13 15

12 15

The P value comparisons are for week 16. Compared with placebo plus mometasone furoate nasal spray (MFNS), dupilumab plus MFNS was associated with improvements in endoscopic NPS (maximum score = 8), FEV 1 , FEV 1

percent predicted, and ACQ5 score compared with placebo plus MFNS. Error bars indicate 95% CIs.

(a standard therapy for nasal polyposis) led to a mean change of −0.5 vs placebo. A study 21 using the same nasal polyp score as the current study showed a peak difference vs placebo of approximately −2.2 for systemic corticoste- roids alone, without intranasal corticosteroids, in patients with nasal polyposis. Because intranasal corticosteroids are the only approved treatment for nasal polyps, there is currently no suitable comparator drug available for long-term treatment. Further studies will be needed to investigate the potential use of dupilumab as adjunct therapy or in direct comparison with other medications or surgery. 24 In addition, 25% of partici- pants (7/30) in the placebo group discontinued therapy. How- ever, a sensitivity analysis using multiple imputation found similar results, suggesting that this dropout rate is unlikely to have biased the study findings.

As a proof-of-concept trial, this study had some limita- tions. The number of participants (60 patients) was small, al- though this sample size was based on calculations identify- ing it as adequate to test the central hypothesis. The study durationwas 16weeks, limiting our ability to comment on the effect of dupilumab during long-term treatment. In addition, the absence of an established MCID for nasal polyp score presents a challenge for interpreting the clinical effect of dupilumab on the primary end point of the study. The least squares mean change from baseline at week 16 was −0.30 (SE, 0.34) in the placebo group and −1.85 (SE, 0.30) in the dupilumab group (least squares mean difference, −1.55 [95% CI, −2.43 to −0.67]; P < .001). A previous study using a nasal polyp score with a nar- rower range (0-6 as opposed to 0-8 for the score in the cur- rent study) showed that intranasal corticosteroid treatment

(Reprinted) JAMA February 2, 2016 Volume 315, Number 5

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