Biologics for chronic rhinosinusitis

Abstract

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). To assess the effects of biologics for the treatment of chronic rhinosinusitis. 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Issue 9); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials.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. Randomised controlled trials (RCTs) with at least three months follow‐up comparing biologics (currently, monoclonal antibodies) against placebo/no treatment in patients with chronic rhinosinusitis. We used standard Cochrane methodological procedures. Our primary outcomes were disease‐specific health‐related quality of life (HRQL), disease severity and serious adverse events (SAEs). The secondary outcomes were avoidance of surgery, extent of disease (measured by endoscopic or computerised tomography (CT) score), generic HRQL and adverse events (nasopharyngitis, including sore throat). We used GRADE to assess the certainty of the evidence for each outcome. 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)  versus placebo/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)  versus placebo/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. 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. Biologics for people with chronic rhinosinusitis What is the aim of this review? 'Biologics' is the name given to a new type of drug. This type is increasingly being used to help people with diseases due to inflammation of body tissues. The aim of this review is to see if any of these drugs are effective in treating people with 'chronic rhinosinusitis'. These patients have long‐term problems with inflammation of the nose and sinuses. This leads to them having blocked, stuffy, runny noses and pain in their cheeks. They often need to use long‐term steroid nasal sprays. Some patients with chronic rhinosinusitis also get polyps in their nose. These can make their symptoms worse. Key message One of the new biologics – called dupilumab – helps people with severe chronic rhinosinusitis who also have nasal polyps. It makes their symptoms better and shrinks their polyps. It does not seem to cause any severe side effects. Another similar drug – called mepolizumab – may do the same but we are less certain about that. What was studied in the review? We looked for trials where patients with chronic rhinosinusitis had been given either one of the new biologic drugs or a placebo (dummy) treatment. They needed to have been treated for at least three months. We looked for studies that measured the effect of the drug on people's symptoms and their general health.  What are the main results of the review? Almost all the people studied in the trials had  severe  chronic rhinosinusitis with nasal polyps (so we can only draw conclusions about the effects of the drugs on people like this). We found eight studies, looking at three different drugs. Most of the information we have comes from two big trials (with nearly 800 patients) looking at the effect of one drug – dupilumab. Effect of dupilumab After 24 weeks of treatment, people taking dupilumab have a better quality of life than those who do not and their polyps have shrunk more. On average their symptoms are probably better too, and they do not have more severe side effects than those taking placebo. Effect of mepolizumab The effect of mepolizumab was studied in far fewer patients and so we are less certain about the results. We can say that this drug  may  have similar effects to dupilumab. Effect of omalizumab We found very little information about the use of this drug and cannot say whether it is effective or not. How up‐to‐date is this review? The evidence is up‐to‐date to September 2019.