Biologics in CRSwNP: Putting a Paradigm Shift Into Practice

Co-Chairs, Joseph K. Han, MD, and Seth J. Isaacs, MD, prepared useful Practice Aids pertaining to chronic rhinosinusitis with nasal polyps for this CME/MOC/CC/AAPA/IPCE activity titled “Biologics in CRSwNP: Putting a Paradigm Shift Into Practice.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/CC/AAPA/IPCE information, and to apply for credit, please visit us at https://bit.ly/3Tq6n1G. CME/MOC/CC/AAPA/IPCE credit will be available until May 6, 2025.

1. Chronic Rhinosinusitis With Nasal Polyps: Integrating Biologic
Therapies Into Practice and Defining Patient Response
1

Full abbreviations, accreditation, and disclosure information available at PeerView.com/AMJ40 Selection of a biologic drug and monitoring of its effectiveness
(Prediction of response in an individual patient is not possible today)
• Confirm diagnosis of uncontrolled, severe CRSwNP
• Check for comorbidity (asthma, N-ERD) and consequences
• Check that type 2 inflammation is highly likely
• Inform patient on treatment options, perspectives,
and risks
• Take decision on surgery or biologic drug with an informed
patient
• Select biologic drug
(note limitations applicable for specific drugs) 
CRSwNP and Asthma
Collaboration with
an asthma specialist
is essential for the
indication and
selection of biologics

2. Chronic Rhinosinusitis With Nasal Polyps: Integrating Biologic 
Therapies Into Practice and Defining Patient Response
1
 
Full abbreviations, accreditation, and disclosure information available at PeerView.com/AMJ40
1. Bachert C et al. J Allergy Clin Immunol. 2021;147:29 -36. After 6 Months of T reatment After 12 Months of T reatment6 12
Improvement of at least one 
symptom/score
•  Sense of smell: from anosmia to 
  hyposmia/normosmia, smell 
  score increase ≥0.5
•  NCS: decrease by ≥0.5 or 
  objective testing
•  NPS: decrease by ≥1 by nasal 
 endoscopy
•  SNOT-22: reduction of ≥8.9 
  (minimal clinically important 
 diference)
•  VAS total symptoms: reduction
  of ≥2 cm
Adequate response 
(all of these defnitions 
are fulflled)
•  NPS <4 (total of both 
 sides)
•  NCS <2
•  VAS total symptoms <5
•  SNOT-22 score <30
Further, there should be 
no current need for 
surgery or systemic GCS
No
No
Yes
Yes
Improvement not
acceptable to the patient
Salvage surgery
under biologic
protection
Stop – change to
surgery or another
biologic drug
Consider another
biologic drug
Surgery
Continue with
biologic treatment
Additional
short course of
systemic GCS
Improvement acceptable
to the patient
Continue with
biologic treatment
Please note that these are expert consensus statements, not guidelines

3. The Advent of Targeted Biologic Therapy for CRSwNP
Full abbreviations, accreditation, and disclosure information available at PeerView.com/AMJ40
1. Stevens WW et al. J Allergy Clin Immunol. 2016;4:565-572. 2. Patel GB et al. J Allergy Clin Immunol. 2020;8:1522-1531. 3. Dupixent (dupilumab) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761055s042lbl.pdf. 4. Xolair (omalizumab) Prescribing
Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/103976s5239lbl.pdf. 5. Nucala (mepolizumab) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761122s008,125526s019lbl.pdf. 6. Fokkens WJ et al. Allergy. 2019;74:2312-2319. Multidisciplinary Collaboration and Coordination
6
Primary
care
Otolaryngology/
rhinology
Allergy-immunology/
pulmonology
Type 2 Biologic Therapies Approved for CRSwNP
Omalizumab
4
• Humanized mAb directed against IgE
• Add-on maintenance treatment for nasal polyps
in adults with inadequate response to intranasal
corticosteroids
• Approved 2020
Dupilumab
3
• Fully human mAb that inhibits signaling of IL-4
and IL-13
• Add-on maintenance treatment for adults with
inadequately controlled CRSwNP
• Approved 2019
Mepolizumab
5
• Humanized mAb targets and binds to IL-5
• Add-on maintenance treatment of adults with
CRSwNP
• Approved 2021
CRSwNP Pathophysiology
1,2
Allergens
Particulates/
pollutants Viruses Proteases
Airway epithelium
Mast cell
Adaptive
response
DC Th2 cell
Eosinophilia
Basophil M2 Goblet
cell
Eosinophil
Cell recruitment
Mucus response
Remodeling
B cell
Th2 cell
B cell
IgE
Mast cell
LTC
4
PGD
2
IL-25R
PGD
2R
(CRTh2, DP2)
IL-33R (ST2)
ILC2 cell
IL-4
IL-5
IL-13
Type 2 cytokines
TSLPR
IL-25
IL-33
TSLP
Type 2
inducers

4. CRSwNP Management: Multidisciplinary Consensus
and EUFOREA Algorithms
Full abbreviations, accreditation, and disclosure information available at PeerView.com/AMJ40 Management Algorithm
Establish diagnosis and initial management
Document subjective symptom severity
Cardinal symptoms: Congestion, decrease in smell,
drainage, facial pressure, and QOL measures
Evidence of objective findings
(Anterior rhinoscopy,
nasal endoscopy, or CT)
Start with intranasal steroid
sprays ± consider short burst
of oral steroids if not
contraindicated
EDS-FLU
or
Consider repeat, short bursts of
oral steroids if not contraindicated
Reassess symptom
response and objective
evidence of disease with at
least 4 weeks of therapy
With persistence of symptoms
and evidence of disease, consider
allergy testing, ASA challenge,
CBC with differential, total IgE
Multidisciplinary Consensus on a Stepwise Treatment Algorithm
for Management of CRSwNP
1

5. CRSwNP Management: Multidisciplinary Consensus
and EUFOREA Algorithms
Full abbreviations, accreditation, and disclosure information available at PeerView.com/AMJ40 Escalation of Treatment (If Refractory)
Multidisciplinary Consensus on a Stepwise Treatment Algorithm
for Management of CRSwNP
1
Majority of patients
Sinus surgery
(Discuss extent of surgery)
Postoperative management
Saline irrigation, steroid irrigation, INS,
EDS-FLU, steroid sinus implant
Minority of patients
If symptoms persist or recur despite appropriate sinus surgery and
postoperative topical steroid therapy (steroid irrigation, EDS-FLU, INS),
consider comprehensive (multispecialty) approach for management
(Shared decision-making process)
Persistent disease
Contraindication to surgery
Poorly controlled asthma
despite standard therapy/
OCS-dependent asthma
Declined surgery
(Shared decision-making process)
Consider biologic
(eg, dupilumab, omalizumab)
Revision
sinus
surgery
Steroid
sinus
implant
Consider
short burst
of OCS
Biologics for
patients ± indicated
comorbidities
(eg, asthma)
ASA desensitization
for patients with AERD
(if not contraindicated)
Assess response
in 6 mo
Assess response
in 6 mo

6. CRSwNP Management: Multidisciplinary Consensus
and EUFOREA Algorithms
Full abbreviations, accreditation, and disclosure information available at PeerView.com/AMJ40
1. Han JK et al. Int Forum Allergy Rhinol. 2021;110:1407-1416. 2. Fokkens WJ et al. Allergy. 2019;74:2312-2319. 3. Fokkens WJ et al. Rhinology. 2023;61:194-202. • Evidence of T2 inflammation
• Need for systemic CS (≥2 courses in the past year)
or contraindication to systemic steroids
• Significantly impaired QOL
• Significant loss of smell
• Diagnosis of comorbid asthma
History of
surgery
No history
of surgery
3
Criteria
required
4
EUFOREA Indications for Biologic Treatment of CRS/NP
2,3
Bilateral nasal polyps