This living systematic review is one of several Cochrane Reviews evaluating the medical management of patients with chronic
rhinosinusitis. Chronic
rhinosinusitis is common. It is characterised by
inflammation of the nasal and sinus linings, nasal blockage, rhinorrhoea, facial pressure/
pain and loss of sense of smell. It occurs with or without
nasal polyps. 'Biologics' are medicinal products produced by a biological process. Monoclonal
antibodies are one type, already evaluated in related inflammatory conditions (e.g. asthma and
atopic dermatitis).
OBJECTIVES: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; CENTRAL (2019, Issue 9); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 16 September 2019.
SELECTION CRITERIA: We included eight RCTs. Of 986 adult participants, 984 had severe chronic
rhinosinusitis with
nasal polyps; 43% to 100% of participants also had
asthma. Three biologics, with different targets, were evaluated:
dupilumab,
mepolizumab and
omalizumab. All the studies were sponsored or supported by industry. Anti-IL-4Rα mAb (
dupilumab) versusplacebo/no treatment (all receiving intranasal
steroids) Three studies (784 participants) evaluated
dupilumab. Disease-specific HRQL was measured with the SNOT-22 (score 0 to 110; minimal clinically important difference (MCID) 8.9 points). At 24 weeks, the SNOT-22 score was 19.61 points lower (better) in participants receiving
dupilumab (mean difference (MD) -19.61, 95% confidence interval (CI) -22.54 to -16.69; 3 studies; 784 participants; high certainty). Symptom severity measured on a 0- to 10-point visual analogue scale (VAS) was 3.00 lower in those receiving dupilumab (95% CI -3.47 to -2.53; 3 studies; 784 participants; moderate certainty). The risk of serious adverse events may be lower in the
dupilumab group (risk ratio (RR) 0.45, 95% CI 0.28 to 0.75; 3 studies; 782 participants; low certainty). The number of participants requiring nasal polyp surgery (actual or planned) during the treatment period is probably lower in those receiving dupilumab (RR 0.17, 95% CI 0.05 to 0.52; 2 studies; 725 participants; moderate certainty). Change in the extent of disease using the Lund Mackay computerised tomography (CT) score (0 to 24, higher = worse) was -7.00 (95% CI -9.61 to -4.39; 3 studies; 784 participants; high certainty), a large effect favouring the
dupilumab group. The EQ-5D visual analogue scale (0 to 100, higher = better; MCID 8 points) was used to measure change in generic quality of life. The mean difference favouring dupilumab was 8.59 (95% CI 5.31 to 11.86; 2 studies; 706 participants; moderate certainty). There may be little or no difference in the risk of nasopharyngitis (RR 0.95, 95% CI 0.72 to 1.25; 3 studies; 783 participants; low certainty). Anti-IL-5 mAb (
mepolizumab) versusplacebo/no treatment (all receiving intranasal
steroids) Two studies (137 participants) evaluated
mepolizumab. Disease-specific HRQL measured with the SNOT-22 at 25 weeks was 13.26 points lower (better) in participants receiving mepolizumab (95%
CI -22.08 to -4.44; 1 study; 105 participants; low certainty; MCID 8.9). It is very uncertain whether there is a difference in s ymptom severity: on a 0- to 10-point VAS symptom severity was -2.03 lower in those receiving mepolizumab (95% CI -3.65 to -0.41; 1 study; 72 participants; very low certainty). It is very uncertain if there is difference in the risk of serious adverse events (RR 1.57, 95% CI 0.07 to 35.46; 2 studies; 135 participants, very low certainty). It is very uncertain whether or not the overall risk that patients still need surgery at trial end is lower in the
mepolizumab group (RR 0.78, 95% CI 0.64 to 0.94; 2 studies; 135 participants; very low certainty). It is very uncertain whether
mepolizumab reduces the extent of disease as measured by endoscopic
nasal polyps score (scale range 0 to 8). The mean difference was 1.23 points lower in the
mepolizumab group (MD -1.23, 95% -1.79 to -0.68; 2 studies; 137 participants; very low certainty). The difference in generic quality of life (EQ-5D) was 5.68 (95% CI -1.18 to 12.54; 1 study; 105 participants; low certainty), favouring the
mepolizumab group. This difference is smaller than the MCID of 8 points. There may be little or no difference in the risk of
nasopharyngitis (RR 0.73, 95% 0.36 to 1.47; 2 studies; 135 participants; low certainty).
Anti-IgE mAb (
omalizumab) versus placebo/no treatment (all receiving intranasal
steroids) Three very small studies (65 participants) evaluated
omalizumab. We are very uncertain about the effect of
omalizumab on disease-specific HRQL, severe adverse events, extent of disease (CT scan scores), generic HRQL and adverse effects.
AUTHORS' CONCLUSIONS: In adults with severe chronic
rhinosinusitis and
nasal polyps, using regular topical nasal
steroids,
dupilumab improves disease-specific HRQL compared to placebo, and reduces the extent of the disease as measured on a CT scan. It probably also improves symptoms and generic HRQL and there is no evidence of an increased risk of serious adverse events. It may reduce the need for further surgery. There may be little or no difference in the risk of
nasopharyngitis. In similar patients,
mepolizumab may improve both disease-specific and generic HRQL. It is uncertain whether it reduces the need for surgery or improves
nasal polyp scores. There may be little or no difference in the risk of
nasopharyngitis. It is uncertain if there is a difference in symptom severity and the risk of serious adverse events. We are uncertain about the effects of
omalizumab.