Table 4 Round 2 of the modified Delphi process for the consensus statements for use of biologics in upper airway disease

1

Patients with symptoms of upper airway disease which include facial pressure/pain, nasal obstruction/congestion, nasal discharge or a loss of smell or uncontrolled asthma with persistent symptoms despite therapy should be evaluated for upper airway disease. Clinician(s) evaluating for upper airway disease should evaluate the nose with nasal endoscopy or in communities where no nasal endoscopy is available, anterior rhinoscopy is acceptable. If exam is unremarkable, a CT scan can be ordered to rule out sinus disease without polyps

Mean = 7 (Agree), Median = 8, Mode = 8

Total voters = 33

Revised and re-assessed in Round 3 of the Modified Delphi Process

2

All endotypes of CRSwNP confirmed by endoscopy or anterior rhinoscopy with a Nasal Polyp Score (NPS) of 5 and a biopsy confirming type 2 disease (eosinophilia > 10 HPF) are considered eligible for biologic therapy except for patients with antrochoanal polyp, primary ciliary dyskinesia, cystic fibrosis and vasculitis. CT reports indicating polyps are not sufficient to make the diagnosis of CRSwNP and/or starting on biologics

Mean = 5.84 (Neutral), Median = 7, Mode = 8

Total voters = 33

Revised and re-assessed in Round 3 of the Modified Delphi Process

3

Biologics should be principally considered for those who have undergone adequate sinus surgery within the past 5 years and failed even with compliant use of nasal steroids and saline irrigation. Patients unfit for surgery who have failed medical therapy may also be considered candidates for biologic therapy based on shared patient decision making. The adequacy of previous surgery matters in determining if subsequent surgical management is required versus initiation of biologic therapy. Adequate surgery should be evaluated with a CT scan to determine if each of the sinus cavities can receive appropriate drug delivery

Mean = 6.50 (Neutral), Median = 7.5, Mode = 8

Total voters = 33

Revised and re-assessed in Round 3 of the Modified Delphi Process

4

Statement 4 no vote

5

The severity of subjective CRSwNP symptoms needs to be moderate to severe based on the clinician’s choice of a validated patient reported outcome measure (PROM) for chronic sinus disease to warrant the use of biologics. There are a subgroup of patients that may score lower than moderate disease on a PROM due to acclimatization to their symptoms (i.e. allergic fungal rhinosinusitis and chronic prednisone users) and these cases should be considered for biologics on a case-by-case basis

Mean = 7.28 (Agree), Median = 8, Mode = 8

Total voters = 33

Revised and re-assessed in Round 3 of the Modified Delphi Process

6

All CRSwNP patients with lower respiratory symptoms who have not previously been evaluated for asthma should be evaluated for possible asthma and referred to a clinician who can provide a systematic evaluation. In a patient with CRSwNP qualifying for biologic therapy and severe asthma, a consultation with a specialist who can manage severe asthma is recommended before choosing the most appropriate biologic

Mean = 7.65 (Agree), Median = 8, Mode = 8

Total voters = 33

Revised and re-assessed in Round 3 of the Modified Delphi Process

7

There is insufficient evidence to make a recommendation for providing biologics to patients with CRSsNP

Mean = 7.31 (Agree), Median = 8, Mode = 8

Total voters = 33

Agreed upon; No vote required in Round 3 Modified Delphi Process

8

Patients with severe uncontrolled asthma or any other severe type 2 conditions in the setting of CRSsNP can be considered for biologics use outside of clinical research trials, for those conditions other than CRSsNP, if they meet eligibility criteria for biologic therapy for another severe type 2 condition based on their respective Canadian guidelines

Mean = 6.52 (Neutral), Median = 7, Mode = 7

Total voters = 33

Revised and re-assessed in Round 3 of the Modified Delphi Process

9

Biologics should not be provided to those with recurrent acute bacterial sinusitis without CRSwNP

25 REMOVE: 8 KEEP

(75.76%)

Removed based on majority vote

10

Where possible and there is no extended delay in assessment, if adequate surgery has been performed for a CRSwNP patient and the patient remains refractory, the patient should be evaluated by an individual who can perform extended surgical approaches. This is done in order to provide the patient comprehensive understanding of their options which include standard revision sinus surgery, extended surgical approaches or biologics

Mean = 5.78 (Neutral), Median = 6.5 Mode = 7

Total voters = 33

Revised and re-assessed in Round 3 of the Modified Delphi Process

11

Where possible, patients with Aspirin Exacerbated Respiratory Disease (AERD) should be preferentially managed in centres that can provide all aspects of care: advanced aeration surgery, severe asthma management, aspirin desensitization and biologic treatment in order to provide options to the patient and optimize multi-modal care for these complex patients

Mean = 6.78 (Neutral), Median = 8, Mode = 8

Total voters = 33

Revised and re-assessed in Round 3 of the Modified Delphi Process Revised and re-assessed in Round 3 of the Modified Delphi Process

12

Patients with CRSwNP who wait longer than 6 months for undergoing primary sinus surgery should be allowed to initiate biologic therapy as a bridge to surgical management. If a patient achieves desired symptom control on biologics prior to surgery, a patient may choose not to do surgery and continue with biologics

Mean = 6.48 (Neutral), Median = 7, Mode = 8

Total voters = 32

13

Biologics can be uniquely considered for hyposmic patients where their sense of smell function is required for safety reasons or for their job if they have a history CRSwNP treated with surgery with adequate control of their disease and no evidence of polyps on endoscopy. Objective testing must be performed (UPSIT \(\le 33\) or Sniffin’ Sticks Test \(\le\) 30)

24 REMOVE: 9 KEEP

(72.72%)

Removed based on majority vote

14

At the time of writing, there are no biological markers required to start CRSwNP patients on biologics nor any markers to indicate best biologic to use

Mean = 7.13 (Agree), Median = 7.5, Mode = 7

Total voters = 32

18 REMOVE: 13 KEEP

(56.25%)

Revised and re-assessed in Round 3 of the Modified Delphi Process

15

Response to biologics is based on subjective improvement by 24 weeks. Patients should experience an improvement to some or all of their major upper airway symptoms which include sense of smell, nasal obstruction, nasal discharge, and facial pain and achieve a documented minimal clinical important difference (MCID) using a validated disease specific questionnaire. Patients should be evaluated every 6 months in the first two years of biologic initiation and every 1 year thereafter

Mean = 6.83 (Neutral), Median = 7, Mode = 7

Fleiss’ Kappa = 0.520 (Moderate agreement)

Total voters = 30

Revised and re-assessed in Round 3 of the Modified Delphi Process

16

Patients who are prescribed biologics to manage co-existing CRSwNP and severe asthma should achieve the patient’s and physician’s goals of treatment for both the upper and lower airway respectively. If not, clinicians should discuss with one another if another biologic or treatment strategy is needed

Mean = 6.72 (Agree), Median = 7, Mode = 7

Total voters = 30

Revised and re-assessed in Round 3 of the Modified Delphi Process

17

A different biologic can be offered to a patient who fails to respond to one biologic or experiences side effects, but continues to meet inclusion criteria for another. Obtaining biologic markers such as serum IgE and eosinophils as well as FeNO (if available) may help a clinician pick the next appropriate biologic to use

Mean = 6.45 (Neutral), Median = 7, Mode = 7

Total voters = 30

Revised and re-assessed in Round 3 of the Modified Delphi Process

18

CRSwNP and asthma patients who have exhausted biologic switching and not achieved adequate response in either the upper or lower airways should be first evaluated for possible revision sinus surgery. If surgery is not indicated, the patient may be started on dual biologic therapy that is best suited for the sinuses and lungs independent of each other. These decisions may be best done in multidisciplinary clinics. Dual biologic response should be evaluated at 24 weeks. If there are subjective improvements achieved in the sinuses and lungs, dual biologic therapy may be continued and re-evaluated every 6 months

Mean = 5.24 (Neutral), Median = 5, Mode = 5

Total voters = 30

Revised and re-assessed in Round 3 of the Modified Delphi Process

19

The risk of side effects is low in the short-term use of biologics (12 months) in CRSwNP. However, there have been reports of adverse events with various biologics which include eosinophilic pneumonia, enthesitis/arthritis and serum sickness

Mean = 6.69 (Neutral), Median = 7, Mode = 7

Total voters = 30

Revised and re-assessed in Round 3 of the Modified Delphi Process

20

Cost and access to biologics matters in the decision making of the use of biologics for CRSwNP patients with or without another Type 2 inflammatory condition. Patient preference should also be considered when considering initiation of biologics

Mean = 6.69 (Neutral), Median = 7, Mode = 7

Total voters = 30

Revised and re-assessed in Round 3 of the Modified Delphi Process