Chronic rhinosinusitis with nasal polyps (CRSwNP) is a prevalent condition that significantly impacts the quality of life for many individuals, particularly through the loss of smell. This booklet delves into the complexities of olfactory dysfunction associated with CRSwNP, exploring its causes, symptoms, and the profound effects it has on daily living. With insights from recent research, we aim to shed light on the often-overlooked burden of losing one's sense of smell.
How does the loss of smell affect CRSwNP patients? Read this booklet to discover more about the hidden challenges faced by patients with CRSwNP.

CHRONIC-RHINOSINUSITIS-WITH-NASAL-POLYPS-CRSWNP

RESPIRATORY

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Navigating the Complexities of Smell Loss in Patients with CRSwNP.

Uncovering the Hidden Burden: Understanding Loss of Smell in CRSwNP

<h2>Indication1</h2>
DUPIXENT is indicated as an add-on therapy with intranasal corticosteroids for the treatment of adults with severe CRSwNP for whom therapy with systemic corticosteroids and/or surgery do not provide adequate disease control.
CRS, chronic rhinosinusitis;&nbsp;CRSwNP, chronic rhinosinusitis with nasal polyps.

<h2 id="nptype2">NP &amp; Type 2 inflammation</h2>

<h3>Unmet need–Cycle of Recurrence</h3>
CRS with nasal polyps is not just an obstructive disease 
 CRS WITH NASAL POLYPS IS A CHRONIC TYPE 2 INFLAMMATORY DISEASE4-9
~9 out of 10 patients with CRS with nasal polyps have Type 2 inflammation, an underlying driver of complications including polyp formation4-9

BREAK THE CYCLE WITH A BIOLOGIC THAT TARGETS TYPE 2 INFLAMMATION4-9

SCS, systemic corticosteroids.

<h3 id="moa">MOA graphic</h3>
<h5>DUPIXENT CENTRALLY TARGETS UNDERLYING TYPE 2 INFLAMMATION IN CRS WITH NASAL POLYPS1-3</h5>

<h2 id="efficacy">Efficacy and Burden data</h2>
<h3 id="smell">Smell</h3>
<h5>PATIENTS REGAINED SMELL AS EARLY AS DAY 312,a</h5>
DUPIXENT improved smell loss (LoS) as early as Day 3, with a significantly greater proportion of patients with sense of smell (UPSIT score &gt;18) vs placebo at Week 24 and sustained through Week 52 in patients receiving INCS1,12-14

Change in UPSIT score through Week 52 in SINUS-52 (secondary endpoint)13

The figure is reproduced by Sanofi based on table S3C.13 a&nbsp;LSM difference between DUPIXENT (n=438) and placebo (n=286): -0.07 (95% CI: -0.12, -0.02). b&nbsp;79% (n=228/287) of patents in the pooled arm taking DUPIXENT 300 mg Q2W + INCS had anosmia at baseline, which was reduced to 30% (n=84/280) as per UPSIT score at Week 24. Anosmia, UPSIT score ≤18;&nbsp;INCS, intranasal corticosteroids;&nbsp;LoS, loss of smell score is a patient-collected assessment of the daily symptom severity of decreased or loss of smell;&nbsp;LSM, least squares mean;&nbsp;Q2W, once every 2 weeks;&nbsp;UPSIT, University of Pennsylvania Smell Identification Test.

2 OUT OF 3 PATIENTS WERE ABLE TO SMELL AGAIN AT WEEK 521,13,b

Smell loss burden

<h3>Nasal congestion</h3>
<h5>RAPID IMPROVEMENT IN NASAL CONGESTION AT DAY 2 SUSTAINED OVER 52 WEEKS1,12,13</h5>
DUPIXENT improved NC score vs placebo as early as Day 2, with significant results at Week 24 and sustained through Week 52 in patients receiving INCS1,12,13

Change in NC score through Week 52 in SINUS-52 (secondary endpoint)13

The figure is reproduced by Sanofi based on figure 2B13 -1.25 improvement at Week 24&nbsp;(co-primary endpoint) from a baseline score of 2.46 with DUPIXENT 300 mg Q2W + INCS (n=295, pooled DUPIXENT arms) vs&nbsp;-0.38 improvement&nbsp;from a baseline score of 2.38 with placebo + INCS (n=153) (LSM difference: -0.87 [95% CI: -1.03, -0.71])1 HRQoL, health-related quality of life;&nbsp;NC, nasal congestion/obstruction.

Nasal congestion burden

<h3 id="surgery">Surgery Reduction</h3>
<h5>LESS SURGERY FOR A MAJORITY OF PATIENTS1,13</h5>
DUPIXENT significantly reduced the need for sinus surgery vs placebo in over 52 weeks in patients receiving INCS1,13

83% reduction in the need for initial or repeat sinus surgery1,13 
 From a prespecified pooled analysis (dupilumab 300 mg Q2W [Arm A] and 300 mg Q2W–Q4W [Arm B] pooled; First 24 weeks only for Arm B).2 
 †100 mg MFNS in each nostril twice daily.2 
 ‡Saline nasal lavage, systemic antibiotics, short-course SCS, or sinonasal surgery were permitted as needed during the treatment and follow-up periods.13&nbsp;Pooled placebo n=286, Pooled dupilumab n=438.

Surgery burden

<h3>Steroid Reduction</h3>
<h5>DUPIXENT TARGETS TYPE 2 INFLAMMATION TO REDUCE THE NEED FOR SYSTEMIC STEROIDS1,13</h5>
DUPIXENT significantly reduced the need for systemic steroids vs placebo over 52 weeks in patients receiving INCS1,13

74% reduction in the need for systemic corticosteroid use1,13 
 From a prespecified pooled analysis (dupilumab 300 mg Q2W [Arm A] and 300 mg Q2W–Q4W [Arm B] pooled; first 24 weeks only for Arm B).2 
 †100 mg MFNS in each nostril twice daily.2 
 ‡Saline nasal lavage, systemic antibiotics, short-course SCS, or sinonasal surgery were permitted as needed during the treatment and follow-up periods.13 
 Pooled placebo n=286, Pooled dupilumab n=438.

DUPIXENT REDUCES OR ELIMINATES STEROID BURDEN REGARDLESS OF PRIOR SURGERY1

SCS burden

<h3>NP Score</h3>
<h5>THE ONLY BIOLOGIC TO REPORT A &gt;2-POINT NPS IMPROVEMENT IN PHASE 3 TRIALS1,25,26</h5>
DUPIXENT significantly reduced the size of nasal polyps vs placebo as measured by bilateral endoscopic NPS as early as Week 4, sustained through Week 521,25,26

37% improvement at Week 521,13

-1.71 improvement at Week 24&nbsp;(co-primary endpoint) from a baseline score of 6.18 with DUPIXENT 300 mg Q2W + INCS (n=295, pooled DUPIXENT arms) vs&nbsp;0.10 worsening&nbsp;from a baseline score of 5.96 with placebo + INCS (n=153) (LSM difference: -1.80 [95% CI: -2.10, -1.51])1
-2.24 improvement at week 52&nbsp;from a baseline score of 6.07 (secondary endpoint) with DUPIXENT 300 mg Q2W + INCS (n=150) vs&nbsp;3% worsening&nbsp;with placebo + INCS (n=153) (0.15 from a baseline score of 5.96) (LSM difference: -2.40 [95% CI: -2.77, -2.02])1

NPS burden

<h3>LMK-CT</h3>
<h5>TARGET UNDERLYING TYPE 2 INFLAMMATION TO SEE SUSTAINED DECREASES IN SINUS OPACIFICATION1</h5>
DUPIXENT significantly decreased LMK-CT scan score vs placebo at Week 24, with greater improvement seen at Week 521

Baseline vs Week 52

THE ONLY BIOLOGIC TO REPORT LMK-CT RESULTS IN THE APPROVED LABEL1,25,26

5.21 improvement at Week 24&nbsp;from a baseline score of 18.12 (secondary endpoint) with DUPIXENT 300 mg Q2W + INCS (n=295, pooled DUPIXENT arms) vs&nbsp;0.09 improvement&nbsp;(from a baseline score of 17.65) with placebo + INCS (n=153) (LSM difference: -5.13 [95% CI: -5.80, -4.46])1
6.83 improvement&nbsp;at Week 52 from a baseline score of 18.42 (secondary endpoint) with DUPIXENT 300 mg Q2W + INCS (n=150) vs&nbsp;0.11 worsening&nbsp;from a baseline score of 17.65 with placebo + INCS (n=153)(LSM difference: -6.94 [95% CI: -7.87, -6.01])1
Lund-Mackay computed tomography scan (LMK-CT) score 
 Reader assesses a CT scan of each sinus and assigns a score from 0 (normal) to 2 (complete opacification). For all sinus systems (except the ostiomeatal complex), the total score is the sum from both the right and left sinuses with a maximum of 24. Lower score indicates lower opacification.

<h3>Secondary Efficacy</h3>
<h3>Quality of Life</h3>
<h5>PATIENTS REPORTED IMPROVED SYMPTOMS AND HEALTH-RELATED QUALITY OF LIFE1,13</h5>
DUPIXENT significantly decreased SNOT-22 score vs placebo as early as Week 4, sustained through Weeks 24 and 521,13

Change in SNOT-22 score through Week 52 in SINUS-5213

The figure is reproduced by Sanofi based on table S913

DUPIXENT IMPROVED A COMPOSITE SCORE, INCLUDING PHYSICAL SYMPTOMS, SLEEP AND FATIGUE ISSUES, AND PSYCHOSOCIAL LIMITATIONS1,13

<table border="1" cellpadding="1" cellspacing="1" style="width:100%;border: 1px solid #fff;background: #d5eae5;">
 <tbody>
 <tr>
 <td colspan="3" style="text-align: center;border: 1px solid #fff;padding: 1rem;">
 <h4 style="padding-bottom: 0px; text-align: left;font-size: 1.3rem;color: #0d9b83;">The SNOT-22 questionnaire is a patient-reported assessment of 22 symptoms and consequences of CRS with nasal polyps, including29:</h4></td>
 </tr>
 <tr>
 <td colspan="3" style="border: 1px solid #fff;padding: 1rem;">
 <ul>
 <li>Nasal obstruction</li>
 <li>Nasal discharge</li>
 <li>Ear fullness/pain</li>
 <li>Sneezing</li>
 <li>Cough</li>
 <li>Loss of smell/taste</li>
 <li>Difficulty falling asleep</li>
 <li>Waking up at night</li>
 <li>Fatigue</li>
 <li>Reduced productivity and concentration</li>
 <li>Frustration, restlessness, and irritability</li>
 <li>Sadness and embarrassment</li>
 </ul></td>
 </tr>
 </tbody>
</table>

22-item Sino-Nasal Outcome Test (SNOT-22) 
 Patients assess 22 symptoms and consequences of CRS with nasal polyps. The maximum score is 110. 
 The meaningful clinically important difference is 8.9. Lower score indicates better health-related quality of life.

<h3>Coexisting Asthma</h3>
<h5>In patients who have CRS with nasal polyps and coexisting asthma, 
 DUPIXENT IMPROVED BREATHING AND QUALITY OF LIFE13</h5>
DUPIXENT significantly improved lung function and asthma control (ACQ-6) while simultaneously improving CRS with nasal polyps outcomes13

Change in lung function through Week 24 in SINUS-5213

<h4>Pre-bronchodilator FEV1</h4>
170 mL improvement at Week 24&nbsp;from baseline in pre-bronchodilator FEV1 with DUPIXENT 300 mg Q2W + INCS (n=176, pooled DUPIXENT arms) vs&nbsp;-50 mL worsening&nbsp;with placebo (LSM difference vs placebo: 210 mL [95% CI: 110, 320 mL])13
<h4>ACQ-6</h4>
-0.78 improvement at Week 24&nbsp;from a baseline ACQ-6 score of 1.55 with DUPIXENT 300 mg Q2W + INCS (n=176, pooled DUPIXENT arms) vs&nbsp;0.08 worsening&nbsp;from a baseline score of 1.63 with placebo (LSM difference -0.87 [95% CI: -1.07, -0.66])13
ACQ-6, Asthma Control Questionnaire, 6-item version;&nbsp;FEV1, forced expiratory volume in 1 second. 
 A patient-reported measure of asthma control (5 questions about symptoms, and 1 question about reliever medication use). The maximum score is 6. The meaningful clinically important difference is 0.5. Lower score indicates better asthma control.

SINUS-24 and SINUS-52 Study Designs

<h2 id="patientprofiles">Patient Profiles</h2>
<h5>IDENTIFY TYPE 2 INFLAMMATION IN PATIENT TYPES LIMITED BY CRS WITH NASAL POLYPS SYMPTOMS2,9</h5>
Look for signs of type 2 inflammation and increased disease severity to break the cycle with biologic therapy2,9,30

The surgery-naive patient can also suffer from coexisting type 2 inflammatory conditions.

Anosmia can often be the first symptom to recur postsurgery.

The symptoms often return 2 months after the steroid burst.

The different patient types are representative and are not actual DUPIXENT patients.

<table border="1" cellpadding="1" cellspacing="1" style="width:100%;border: 1px solid #fff;background: #d5eae5;">
 <tbody>
 <tr>
 <td colspan="3" style="text-align: center;border: 1px solid #fff;padding: 1rem;">
 <h4 style="padding-bottom: 0px; text-align: left;font-size: 1.3rem;color: #0d9b83;">Signs of type 2 inflammation include:2,9</h4></td>
 </tr>
 <tr>
 <td colspan="3" style="border: 1px solid #fff;padding: 1rem;">
 <ul>
 <li>Coexisting type 2 inflammatory conditions, such as: 
 <ul>
 <li>AERD</li>
 <li>Allergic rhinitis</li>
 <li>Asthma</li>
 <li>NSAID hypersensitivity</li>
 </ul></li>
 <li>Impairment to sense of smell</li>
 <li>Polyp or symptom recurrence</li>
 </ul></td>
 </tr>
 </tbody>
</table>

AERD, Aspirin-Exacerbated Respiratory Disease;&nbsp;NSAID, nonsteroidal antiinflammatory disease.

<h2 id="safety">Safety</h2>
<h5>ESTABLISHED SAFETY PROFILE WAS CONSISTENT THROUGH WEEK 521</h5>
DUPIXENT is a fully human monoclonal antibody with a safety profile comparable to placebo1,a

<table border="1" cellpadding="1" cellspacing="1" style="width:100%;border: 1px solid #fff;background: #d5eae5;">
 <tbody>
 <tr>
 <td colspan="3" style="border: 1px solid #fff;padding: 1rem;">
 <h4 style="font-size: 1.3rem;color: #0d9b83;">Adverse events in CRSwNP, asthma, and atopic dermatitis clinical trials1,a</h4></td>
 </tr>
 <tr>
 <td style="border: 1px solid #fff;padding: 1rem;">
 MedDRA System Organ Class</td>
 <td style="border: 1px solid #fff;padding: 1rem;">
 Frequencyb</td>
 <td style="border: 1px solid #fff;padding: 1rem;">
 Adverse reaction</td>
 </tr>
 <tr>
 <td style="border: 1px solid #fff;padding: 1rem;">
 Blood and lymphatic system disorder</td>
 <td style="border: 1px solid #fff;padding: 1rem;">
 Common</td>
 <td style="border: 1px solid #fff;padding: 1rem;">
 Eosinophilia</td>
 </tr>
 <tr>
 <td style="border: 1px solid #fff;padding: 1rem;">
 General disorders and administration site conditions</td>
 <td style="border: 1px solid #fff;padding: 1rem;">
 Common</td>
 <td style="border: 1px solid #fff;padding: 1rem;">
 Injection site reactions (includes erythema, edema, pruritus, pain, swelling, and bruising)d</td>
 </tr>
 <tr>
 <td style="border: 1px solid #fff;padding: 1rem;">
 Musculoskeletal and connective tissue disorders</td>
 <td style="border: 1px solid #fff;padding: 1rem;">
 Common</td>
 <td style="border: 1px solid #fff;padding: 1rem;">
 Arthralgiac</td>
 </tr>
 <tr>
 <td style="border: 1px solid #fff;padding: 1rem;">
 Immune system disorders</td>
 <td style="border: 1px solid #fff;padding: 1rem;">
 Uncommon
 Rare</td>
 <td style="border: 1px solid #fff;padding: 1rem;">
 Angioedemac
 Anaphylactic reaction Serum sickness reaction Serum sickness-like reaction</td>
 </tr>
 <tr>
 <td style="border: 1px solid #fff;padding: 1rem;">
 Skin and subcutaneous tissue disorders</td>
 <td style="border: 1px solid #fff;padding: 1rem;">
 Uncommon</td>
 <td style="border: 1px solid #fff;padding: 1rem;">
 Facial rashc</td>
 </tr>
 <tr>
 <td colspan="3" style="border: 1px solid #fff;padding: 1rem;">
 <h4 style="font-size: 1.3rem;color: #0d9b83;">Adverse events occurring predominantly in atopic dermatitis clinical trials</h4></td>
 </tr>
 <tr>
 <td style="border: 1px solid #fff;padding: 1rem;">
 Eye disorders</td>
 <td style="border: 1px solid #fff;padding: 1rem;">
 Common</td>
 <td style="border: 1px solid #fff;padding: 1rem;">
 Conjunctivitis allergic</td>
 </tr>
 <tr>
 <td style="border: 1px solid #fff;padding: 1rem;">
 Eye disorders</td>
 <td style="border: 1px solid #fff;padding: 1rem;">
 Uncommon</td>
 <td style="border: 1px solid #fff;padding: 1rem;">
 Blepharitisd 
 Dry eyed 
 Eye pruritusd 
 Keratitisc</td>
 </tr>
 <tr>
 <td style="border: 1px solid #fff;padding: 1rem;">
 Eye disorders</td>
 <td style="border: 1px solid #fff;padding: 1rem;">
 Rare</td>
 <td style="border: 1px solid #fff;padding: 1rem;">
 Ulcerative keratitisc,d</td>
 </tr>
 <tr>
 <td style="border: 1px solid #fff;padding: 1rem;">
 Infections and infestations</td>
 <td style="border: 1px solid #fff;padding: 1rem;">
 Common</td>
 <td style="border: 1px solid #fff;padding: 1rem;">
 Conjunctivitis 
 Oral herpes</td>
 </tr>
 </tbody>
</table>

<h4>In the safety pool, the proportion of patients who discontinued treatment due to adverse events:1</h4>
2.0% of the DUPIXENT group
4.6% of the placebo group

DUPIXENT IS NOT AN IMMUNOSUPPRESSANT1

a&nbsp;DUPIXENT was studied in 12 randomized, placebo-controlled trials, including atopic dermatitis, asthma, and CRSwNP patients. The pivotal controlled studies involved 4,206 patients receiving dupilumab and 2,326 patients receiving placebo during the controlled period. b&nbsp;Common (≥1/100 to &lt;1/10); uncommon (≥1/1,000 to &lt;1/100); rare (≥1/10,000 to &lt;1/1,000). c&nbsp;From postmarketing reporting. d&nbsp;The frequencies for eye pruritus, blepharitis, and dry eye were common and ulcerative keratitis was uncommon in atopic dermatitis studies.
MedDRA, Medical Dictionary for Regulatory Activities.

<h2 id="legacy">Legacy</h2>
<h5>7-YEAR OF LEGACY ACROSS INDICATIONS DRIVEN BY TYPE 2 INFLAMMATION1,a</h5>
Approved across 6 indications driven by type 2 inflammation1

Atopic dermatitis 
 uncontrolled severeb

Asthma 
 severe type 2 asthma or OCS-dependentc

CRS with nasal polyps 
 severe inadequately controlled

Prurigo nodularis 
 uncontrolled moderate to severe

Eosinophilic esophagitis 
 inadequately controlled

COPD 
 uncontrolled while on optimized inhaled therapyd

INDICATION STATEMENTS1

<h2 id="dosing">Dosing</h2>
<h5>DUPIXENT OFFERS THE CHOICE OF AT-HOME OR IN-OFFICE ADMINISTRATION1</h5>
Recommended dosing for patients with uncontrolled CRS with nasal polyps1

<table border="1" cellpadding="1" cellspacing="1" style="width:100%;border: 1px solid #fff;background: #d5eae5;">
 <tbody>
 <tr>
 <td style="border: 1px solid #fff;padding: 1rem;">
 18+ YEARS</td>
 <td style="border: 1px solid #fff;padding: 1rem;">
 300 mga</td>
 <td style="border: 1px solid #fff;padding: 1rem;">
 every-other-week</td>
 <td style="border: 1px solid #fff;padding: 1rem;">
 NO LOADING DOSE</td>
 </tr>
 </tbody>
</table>

DUPIXENT is intended for use under the guidance of a healthcare provider. A patient may self-inject DUPIXENT after training in subcutaneous injection technique using the pre-filled syringe or the pre-filled pen. Provide proper training to patients and/or caregivers on the preparation and administration of DUPIXENT prior to use according to the Instructions for Use.1
DUPIXENT can be administered in the office under the guidance of a healthcare provider if the patient is not an appropriate candidate for self-administration.1
a&nbsp;300 mg/2 mL solution.

<h2>References</h2>
1. DUPIXENT Summary of Product Characteristics, 2024.
2. Gandhi NA, Bennet BL, Graham NMH, Pirozzi G, Stahl N, Yancopoulos GD. Targeting key proximal drivers of type 2 inflammation in disease. Nat Rev Drug Discov. 2016;15(1):35-50. doi:10.1038/nrd4624
3. Schleimer RP. Immunopathogenesis of chronic rhinosinusitis and nasal polyposis. Annu Rev Pathol. 2017;12:331-357. doi:10.1146/annurev-pathol- 052016-100401
4. Stevens WW, Peters AT, Tan BK, et al. Associations between inflammatory endotypes and clinical presentations in chronic rhinosinusitis. J Allergy Clin Immunol Pract. 2019;7(8):2812-2820.e3. doi:10.1016/j.jaip.2019.05.009
5. Maspero J, Adir Y, Al-Ahmad M, et al. Type 2 inflammation in asthma and other airway diseases. ERJ Open Res. 2022;8(3):00576-2021. doi:10.1183/23120541.00576-2021
6. Dietz de Loos DA, Hopkins C, Fokkens WJ. Symptoms in chronic rhinosinusitis with and without nasal polyps. Laryngoscope. 2013;123(1):57-63. doi:10.1002/lary.23671
7. Tsunemi Y, Nakayama T, Kashiwagi T, Akutsu M, Saito S, Haruna S. Long-term efficacy of dupilumab for eosinophilic chronic rhinosinusitis. Am J Rhinol Allergy. 2024;38(1):14-22. doi:10.1177/19458924231204128
8. Han JK, Bosso JV, Cho SH, et al. Multidisciplinary consensus on a stepwise treatment algorithm for management of chronic rhinosinusitis with nasal polyps. Int Forum Allergy Rhinol. 2021;11(10):1407-1416. doi:10.1002/alr.22851
9. De Corso E, Baroni S, Settimi S, et al. Sinonasal biomarkers defining type 2-high and type 2-low inflammation in chronic rhinosinusitis with nasal polyps. J Pers Med. 2022;12(8):1251. doi:10.3390/jpm12081251
10. Amirapu S, Biswas K, Radcliff FJ, Wagner Mackenzie B, Ball S, Douglas RG. Sinonasal tissue remodelling during chronic rhinosinusitis. Int J Otolaryngol. 2021;2021:7428955. doi:10.1155/2021/7428955
11. Ferguson BJ, Rizk H, Ramakrishnan J, Pant H. Categorization of nasal polyps. In: Önerci TM, Ferguson BJ, eds. Nasal Polyposis. Springer-Verlag; 2010:103-110.
12. Hellings PW, Peters AT, Chaker AM, et al. Rapid and sustained effects of dupilumab in severe chronic rhinosinusitis with nasal polyps. Int Forum Allergy Rhinol. 2022;12(7):958-962. doi:10.1002/alr.22944
13. Bachert C, Han JK, Desrosiers M, et al. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallelgroup phase 3 trials. Lancet. 2019;394(10209):1638-1650. doi:10.1016/S0140- 6736(19)31881-1
14. Canonica GW, Bourdin A, Peters AT, et al. Dupilumab demonstrates rapid onset of response across three type 2 inflammatory diseases. J Allergy Clin Immunol Pract. 2022;10(6):1515-1526. doi:10.1016/j.jaip.2022.02.026
15. Yan X, Whitcroft LK, Hummel T. Olfaction: sensitive indicator of inflammatory burden in chronic rhinosinusitis. Laryngoscope Investig Otolaryngol. 2020;5(6):992-1002. doi:10.1002/lio2.485
16. Chen M, Reed RR, Lane AP. Chronic inflammation directs an olfactory stem cell functional switch from neuroregeneration to immune defense. Cell Stem Cell. 2019;25(4):501-513.e5. doi:10.1016/j.stem.2019.08.011
17. Rouyar A, Classe M, Gorski R, et al. Type 2/Th2-driven inflammation impairs olfactory sensory neurogenesis in mouse chronic rhinosinusitis model. Allergy. 2019;74(3):549-559. doi:10.1111/all.13559
18. Mullol J, Mariño-Sánchez F, Valls M, Alobid I, Marin C. The sense of smell in chronic rhinosinusitis. J Allergy Clin Immunol. 2020;145(3):773-776. doi:10.1016/j.jaci.2020.01.024
19. Bachert C, Bahattacharyya N, Desrosiers M, Khan AH. Burden of disease in chronic rhinosinusitis with nasal polyps. J Asthma Allergy. 2021;14:127-134. doi:10.2147/JAA.S290424
20. DeConde AS, Mace JC, Levy JM, Rudmik L, Alt JA, Smith TL. Prevalence of polyp recurrence after endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis. Laryngoscope. 2017;127(3):550-555. doi:10.1002/lary.26391
21. De Corso E, Settimi S, Montuori C, et al. How to manage recurrences after surgery in CRSwNP patients in the biologic era: a narrative review. Acta Otorhinolaryngol Ital. 2023;43(2)(suppl 1):S3-S13. doi:10.14639/0392-100X-suppl.1-43-2023-01
22. Fokkens WJ, Viskens AS, Backer V, et al. EPOS/EUFOREA update on indication and evaluation of biologics in chronic rhinosinusitis with nasal polyps 2023. Rhinology. 2023;61(3):194-202. doi:10.4193/Rhin22.489
23. Hellings PW, Alobid I, Anselmo-Lima WT, Bernal- Sprekelsen M, Bjermer L, Caulley L, Chaker A, Constantinidis J, Conti DM, De Corso E, Desrosiers M. EUFOREA/EPOS2020 statement on the clinical considerations for chronic rhinosinusitis with nasal polyps care. Allergy. 2024 May;79(5):1123-33.
24. Hox V, Lourijsen E, Jordens A, et al. Benefits and harm of systemic steroids for short- and long-term use in rhinitis and rhinosinusitis: an EAACI position paper. Clin Transl Allergy. 2020;10:1. doi:10.1186/s13601-019-0303-6
25. XOLAIR Summary of Product Characteristics, 2020.
26. NUCALA Summary of Product Characteristics, 2021.
27. Han JK, Bachert C, Lee SE, et al. Estimating clinically meaningful change of efficacy outcomes in inadequately controlled chronic rhinosinusitis with nasal polyposis. Laryngoscope. 2022;132(2):265-271. doi:10.1002/lary.29888
28. Gelardi M, Bocciolini C, Notargiacomo M, et al. Chronic rhinosinusitis with nasal polyps: how to identify eligible patients for biologics in clinical practice. Acta Otorhinolaryngol Ital. 2022;42(1):75-81. doi:10.14639/0392-100X-N1699
29. Asiri M, Alokby G. Validation and cross-cultural adaptation of the Sinonasal Outcome Test (SNOT)-22 for the Arabian patient population. Cureus. 2019;11(4):e4447.doi:10.7759/cureus.4447
30. Mullol J, Bachert C, Amin N, et al. Olfactory outcomes with dupilumab in chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol Pract. 2022:1086-1095.e5. doi:10.1016/j.jaip.2021.09.037

Dupixent® CRSwNP

Rhinosinusitis is een ontsteking van de neusbijholten; als dit langer dan 12 weken duurt, spreekt men van chronische rhinosinusitis. Dit kan de kans op neuspoliepen vergroten: er is dan sprake van chronische rhinosinusitis met neuspoliepen (CRSwNP). De aandoening kenmerkt zich door symptomen van neusblokkade (‘verstopte neus’), neusafscheiding/slijm in de keel, en pijn/drukkend gevoel in het gezicht. Soms hebben patiënten ook een verminderd reukvermogen of ervaren ze verlies van reukvermogen.

<h2>Wat is chronische rhinosinusitis met neuspoliepen (CRSwNP)?</h2>

<ul>
 <li>Chronische rhinosinusitis met neuspoliepen (CRSwNP) is de combinatie van neusbijholteontsteking die ondanks behandeling langer duurt dan 12 weken en neuspoliepen 
 &nbsp;</li>
 <li>Door bijholteontsteking zwelt het slijmvlies in de bijholten op waardoor de neus verstopt kan raken en er slijmophopingen kunnen ontstaan 
 &nbsp;</li>
 <li>Neuspoliepen zijn goedaardige zwellingen van het neusslijmvlies 
 &nbsp;</li>
 <li>Neuspoliepen geven vaak klachten van neusverstopping en een verminderd reuk- en smaakgevoel; ook hebben patiënten vaak het gevoel dat ze verkouden zijn 
 &nbsp;</li>
 <li>Neuspoliepen kunnen door hun ligging in de neus de afvoer van slijm uit de neusbijholten belemmeren1,2</li>
</ul>

<h2>Hoe ontstaat chronische rhinosinusitis met neuspoliepen (CRSwNP)?</h2>
CRSwNP kan voortkomen uit Type 2-inflammatie, gekarakteriseerd door interleukine 4 (IL-4), IL-5 en IL-13, en een nasale infiltratie van eosinofielen, mastcellen, basofielen en T-helper 2 (Th2) cellen; evenals mogelijke comorbiditeit met astma en allergische ziekten.[1-5]
<h5>Referenties</h5>
<ol>
 <li>
 Akdis CA, Bachert C, Cingi C, et al. Endotypes and phenotypes of chronic rhinosinusitis: a PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma &amp; Immunology. J Allergy Clin lmmunol. 2013;131(6):1479-1490.</li>
 <li>
 Gandhi NA, Bennett BL, Graham NMH, Pirozzi G, Stahl N, Yancopoulos GD. Targeting key proximal drivers of type 2 inflammation in disease. Nat Rev Drug Discov. 2016;15(1):35-50.</li>
 <li>
 Robinson D, Humbert M, Buhl R, et al. Revisiting type 2-high and type 2-low airway inflammation in asthma: current knowledge and therapeutic implications. Clin Exp Allergy. 2017;47(2):161-175.</li>
 <li>
 Stevens WW, Schleimer RP, Kern RC. Chronic rhinosinusitis with nasal polyps. J Allergy Clin lmmunol Pract. 2016;4(4):565-572.</li>
 <li>
 Kato A. lmmunopathology of chronic rhinosinusitis. Allergol Int. 2015;64(2):121-130.</li>
</ol>

<h2>Symptomen</h2>
<ul>
 <li>Verstopte neus</li>
 <li>Neusafscheiding/slijm in de keel</li>
 <li>Pijn/drukkend gevoel in het gezicht</li>
 <li>Een verminderde/verlies van reuk- en smaakvermogen</li>
</ul>

<h2>Diagnose</h2>
De diagnose chronische rhinosinusitis wordt gesteld aan de hand van de klachten van de patiënt en op basis van lichamelijk onderzoek.
De diagnose neuspoliepen wordt vaak makkelijk gesteld met het blote oog (grotere en voor in de neus gelegen poliepen zullen makkelijk zichtbaar zijn) of met een neusendoscopie waarbij verder in de neus kan worden gekeken.1

<h2>Soorten behandelingen</h2>
<ul>
 <li>De behandeling van chronische rhinosinusitis bestaat uit (lokale) corticosteroiden en neusspoelingen.2 
 &nbsp;</li>
 <li>Operatieve verwijdering van de neuspoliep(en) onder plaatselijke verdoving (dan verwijdert de KNO-arts het zichtbare deel uit de neus) of onder plaatselijke/algehele verdoving waarbij de KNO-arts de poliepen uit zowel de neus als de neusbijholten verwijdert.1,2 
 &nbsp;</li>
 <li>Ongecontroleerde neuspoliepen, die na verwijdering terugkomen en waarbij behandeling met systemische corticosteroïden en/of operatieve verwijdering onvoldoende helpt, kunnen worden behandeld met een biological. Momenteel zijn er 3 biologicals beschikbaar voor chronische rhinosinusitis met neuspoliepen, namelijk dupilumab, omalizumab en mepolizumab.</li>
</ul>

<h2>Producten en chronische rhinosinusitis met neuspoliepen (CRSwNP)</h2>
Bij chronische rhinosinusitis met neuspoliepen (CRSwNP) worden de volgende producten ter behandeling en ondersteuning gebruikt:
<ul>
 <li>(Lokale) corticosteroiden en neusspoelingen 
 &nbsp;</li>
 <li>Operatieve verwijdering 
 &nbsp;</li>
 <li>Biologicals 
 &nbsp;</li>
</ul>

Op deze pagina vindt u uitgebreide informatie over chronische rhinosinusitis met neuspoliepen (CRSwNP). Ook kunt u diverse handige materialen voor uzelf en uw patiënt aanvragen die u kunnen ondersteunen in uw zorg en aandacht voor uw patiënt met CRSwNP.

Algemene informatie chronische rhinosinusitis met neuspoliepen (CRSwNP)

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