Biologics
In recent years, there has been significant progress in understanding the underlying immune mechanisms that drive CRSwNP leading to the development of targeted biologic therapies. For CRSwNP, biologics focus primarily on neutralising specific pro-inflammatory type-2 cytokines, such as interleukin (IL)-4/IL-13 (39, 40), or IL-5 (4, 41, 42)}, or mediators like IgE (43), which are central in promoting the recruitment and activation of inflammatory cells in CRSwNP. By blocking the activity of these mediators, biologics modulate the immune response and reduce the chronic inflammation associated with the disease (including comorbidities) (44). Biologics have been shown to reduce the size of nasal polyps, improve nasal obstruction, relieve symptoms, improve the sense of smell and improve the quality of life (45-49).
Based on EPOS 2020 (1) and the EPOS/EUFOREA update on biologics 2023 (9), the EUFOREA expert panels recommend biologics in CRSwNP patients that are uncontrolled despite appropriate medical treatment and appropriate sinus surgery and who fulfil 3 of 5 criteria (presence of Type 2 inflammation, regular need for SCS/contraindications to SCS, significant impact on QOL, loss of smell and comorbid asthma). Biologics are an effective treatment with an expected improvement in the short-term (16th week to 24th week), of at least one of the following symptom/scores: sense of smell, the Nasal Congestion Score (NCS), the Nasal Polyp Score (NPS), the Sino-Nasal Outcome Test (SNOT-22), and the Visual Analogue Scale (VAS)(49-53). For Dupilumab long term (up to 2 years) beneficial effects have been reported (46, 49). Beneficial effects on comorbidities may be confirmed at any point of the treatment, based on the aforementioned definitions and a reduction in the need for SCS and ESS can be observed (54, 55).
Biologics have a good safety profile but are contra-indicated in patients with hypersensitivity to the specific monoclonal antibodies or any drug components. Specific considerations should be taken in pregnancy since there is not yet enough data to rule out fetal harm or other side effects (56, 57). In this regard, the best data are available for omalizumab, where no increase in congenital anomalies has been demonstrated to date (57, 58. {Shakuntulla, 2022 #9).Therefore, the EUFOREA group advises to carefully counsel pregnant patients and female patients who wish to have children and to only continue the biologic if there are very strong reasons to do so (56-58). Two other reasons to closely monitor patients/discontinue a biologic are hypereosinophilia (mainly dupilumab(59-61)) and helminth infections if patients do not respond to anti-helminth treatment (62, 63).
Overall, biologics are a safe and effective treatment option in most severe uncontrolled CRSwNP patients, with the need to properly select the patient given the high direct costs and the necessity of repeated self-administration (46, 47, 49, 64)