Regarding the indications and timing of medication use

The 2023 European Position paper on Rhinosinusitis and Nasal Polyps (EPOS)/European Forum for Research and Education in Allergy and Respiratory Diseases (EUFOREA) guidelines state that for patients who have undergone endoscopic sinus surgery but still have bilateral nasal polyps CRSwNP patient,If any three of the following five criteria are met simultaneously, the use of biologics for treatment can be considered:

1. There is evidence of type 2 inflammation [blood eosinophil cells (BEC) ≥ 0.15 × 10 ⁹]/ L or IgE≥100IU/mL Or organize ≥ 10 eosinophils/ HPF]。

Regarding Blood Eos≥0.15 ×10⁹/ L As a type 2 inflammation marker， We have different opinions, believing that this value is too low and already lower than the normal population blood Eos The average value is worth discussing

2. Oral hormone therapy ≥ 2 courses/year or long-term (≥ 3 months) low-dose hormone therapy

3. Significant impairment in quality of life [nasal and sinus outcome test (SNOT-22) ≥ 40]

4. Significant loss of sense of smell (olfactory test indicates loss of sense of smell);

5. Combined asthma (requiring regular inhaled hormone therapy).

 

But if the following situations occur, we believe that priority can be given to using biologics for treatment:

1. Being too old and having poor physical fitness;

2. High disease severity: patients with serious cardiovascular and cerebrovascular diseases, poor control of hypertension and diabetes, high dependence on oral anticoagulants and other basic diseases;

3. Poor response to traditional treatment: For patients with refractory and severe chronic sinusitis accompanied by nasal polyps who have poor therapeutic effects of glucocorticoids and surgical treatment;

4. Patients with poor psychological resilience or psychogenic disorders who are unwilling to accept surgical risks or have no intention of undergoing surgery;

5. Existence of comorbidities: combined with asthma and requiring regular inhalation of glucocorticoids; Oral corticosteroids should be taken for at least 2 courses per year, or there may be contraindications for systemic corticosteroids;

6. Patients with bilateral nasal polyps who still experience disease recurrence after multiple standardized sinus surgeries;

7. Some patients with high risk of recurrence (such as those with surgical contraindications, polyps, and high inflammatory burden) may consider using biologics before and after surgery to improve surgical outcomes and reduce recurrence rates;

8. High net worth individuals.

 

Evaluation of the therapeutic effect of biologics therapy

1. Evaluation time: Efficacy evaluation should be conducted at 6 months and 12 months.

2. The efficacy is determined based on five specific criteria, including:

(1) Nasal polyp volume reduction ≥ 1 point;

(2) Reduced frequency of oral hormone use or surgical need;

(3) Improvement in quality of life (SNOT-22<40 and improvement exceeding minimal clinically important difference (MCID));

(4) Improvement in smell (through semi objective olfactory testing);

(5) Improvement in comorbidity control (achieved through specific comorbidity scores) MCID）。

If 4-5 criteria are met, it is considered a "superior response", 2-3 criteria are considered a "moderate response", and 0-1 criteria are considered an "ineffective response". If the therapeutic effect is poor, the diagnosis and treatable features need to be re evaluated, and consideration should be given to replacing the biological agent or performing salvage surgery.

 

Current research and evaluation of biologics

 

1. Dupilumab

Dupilumab is one of the most comprehensive and significant drugs in current research, especially suitable for refractory conditions CRS Or postoperative recurrence. Dupilumab can significantly reduce nasal polyp scores, improve nasal symptoms (including nasal congestion and reduced sense of smell), and control asthma levels, with efficacy lasting for up to 24 weeks and efficacy data up to two years.

It maintains stable control over the volume of nasal polyps and can maintain therapeutic efficacy regardless of dose reduction (increasing medication intervals). Individualized extended dosing intervals are safe and feasible in most patients, reducing treatment burden while ensuring efficacy. For some patients with unclear early reactions, continuous treatment for more than a year may still result in significant improvement.

2. Sprucubizumab monoclonal antibody

Sprucubizumab in the treatment of severe uncontrolled cases CRSwNP The improvement of nasal polyp volume and nasal congestion symptoms is significantly better than placebo, especially in patients with increased eosinophils.

3. Mabolizumab

Mabolizumab is suitable for patients with postoperative recurrence and eosinophilic inflammation, and has a certain effect in improving nasal congestion and olfaction.

4. Omalizumab

Omalizumab is mainly suitable for patients with poor control of inhaled steroids, which can significantly reduce the use of oral steroids and surgical needs, and the overall efficacy is moderate.

5. Trastuzumab

Tezepril monoclonal antibody as a novel antibody TSLP Biological agents have an early onset time (24 weeks) and a sustained therapeutic effect until 52 weeks, showing significant efficacy in improving nasal symptoms and quality of life. They are effective in treating low BEC（＜150 Cell/ μL） With high BEC（＞300 Cell/ μL） All patients showed better efficacy than placebo, with the latter having a response amplitude about twice that of the former.

6. Ultra long effect resistance IL-5 Preparation of Demochikumab monoclonal antibody

Demizumab can significantly improve nasal polyp scores and nasal obstruction symptoms by administering twice a year, and has good safety.

 

Overall, according to literature, resistance TSLP With resistance IL-4Ra Class of drugs have better therapeutic effects than antibiotics IL-5 Class and Resistance IgE Class of drugs, with a 95% confidence interval that does not overlap with other drugs in key clinical studies, suggest their ability to control CRSwNP There may be greater advantages in inflammation and symptom improvement.

 

In CRSwNP In patients with combined asthma, Dupilumab and Mabolizumab showed dual efficacy, not only improving nasal symptoms, but also helping to control asthma.

Dupilumab is effective against CRSwNP merge NSAID- NSAID aggravated respiratory disease (NERD) patients and non comorbidities NERD The overall therapeutic effect of patients is similar, but they have an advantage in nasal congestion. Mabolizumab is effective in various comorbidities, and nasal polyps are a sign of good response.

Tezepril monoclonal antibody can significantly reduce the frequency of acute exacerbations in asthma patients with nasal polyps, while omalizumab has a relatively stable efficacy in asthma control, regardless of whether it is combined or not CRSwNP influence. BEC The value as a predictive indicator of therapeutic efficacy is becoming increasingly prominent. Research shows that higher baselines BEC Level and treatment with Dupilumab and Mabolizumab SNOT-22 The improvement in ratings is positively correlated. In the study of extending the dosing interval of Dupilumab to 12 weeks, it was found that, BEC Higher frequency patients are more likely to lose disease control during the process of reducing frequency therapy BEC Lower values are more likely to maintain therapeutic efficacy.

From a safety perspective, potential side effects of monoclonal antibodies include:

1. Elevated blood eosinophilia is often a transient reaction, and rare patients may develop eosinophilic granulomatous polyangiitis or eosinophilic pneumonia. It is necessary to be vigilant in identifying and intervening in a timely manner.

2. Joint pain and hyperuricemia.

3. Risk of secondary parasitic infections.

Personalized combination therapy should be adopted for patients based on the intrinsic type of inflammation, comorbidities, and treatment response, including synchronous or sequential use of different biological agents, surgery, immunotherapy, and other methods. In clinical practice, multiple monoclonal antibodies used as perioperative adjuvant therapy can significantly improve nasal congestion and olfactory function, and may be combined with endoscopic sinus surgery (FESS) to improve efficacy.