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Chronic Rhinosinusitis With Nasal Polyps: Integrating Biologic
Therapies Into Practice and Defining Patient Response1
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
Chronic Rhinosinusitis With Nasal Polyps: Integrating Biologic
Therapies Into Practice and Defining Patient Response1
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 Treatment After 12 Months of Treatment
6 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
difference)
• VAS total symptoms: reduction
of ≥2 cm
Adequate response
(all of these definitions
are fulfilled)
• 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
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 Coordination6
Primary
care
Otolaryngology/
rhinology
Allergy-immunology/
pulmonology
Type 2 Biologic Therapies Approved for CRSwNP
Omalizumab4
• Humanized mAb directed against IgE
• Add-on maintenance treatment for nasal polyps
in adults with inadequate response to intranasal
corticosteroids
• Approved 2020
Dupilumab3
• Fully human mAb that inhibits signaling of IL-4
and IL-13
• Add-on maintenance treatment for adults with
inadequately controlled CRSwNP
• Approved 2019
Mepolizumab5
• Humanized mAb targets and binds to IL-5
• Add-on maintenance treatment of adults with
CRSwNP
• Approved 2021
CRSwNP Pathophysiology1,2
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
LTC4
PGD2
IL-25R
PGD2R
(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
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 CRSwNP1
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 CRSwNP1
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
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/NP2,3
Bilateral nasal polyps

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Biologics in CRSwNP: Putting a Paradigm Shift Into Practice

  • 1. Chronic Rhinosinusitis With Nasal Polyps: Integrating Biologic Therapies Into Practice and Defining Patient Response1 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 Response1 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 Treatment After 12 Months of Treatment 6 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 difference) • VAS total symptoms: reduction of ≥2 cm Adequate response (all of these definitions are fulfilled) • 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 Coordination6 Primary care Otolaryngology/ rhinology Allergy-immunology/ pulmonology Type 2 Biologic Therapies Approved for CRSwNP Omalizumab4 • Humanized mAb directed against IgE • Add-on maintenance treatment for nasal polyps in adults with inadequate response to intranasal corticosteroids • Approved 2020 Dupilumab3 • Fully human mAb that inhibits signaling of IL-4 and IL-13 • Add-on maintenance treatment for adults with inadequately controlled CRSwNP • Approved 2019 Mepolizumab5 • Humanized mAb targets and binds to IL-5 • Add-on maintenance treatment of adults with CRSwNP • Approved 2021 CRSwNP Pathophysiology1,2 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 LTC4 PGD2 IL-25R PGD2R (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 CRSwNP1
  • 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 CRSwNP1 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/NP2,3 Bilateral nasal polyps