Two-year results of tapered dupilumab for CRSwNP demonstrates enduring efficacy established in the first 6 months.

BACKGROUND: Dupilumab is an anti-T2-inflammatory biological registered for chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), indicated by integrated CRS-care pathways when optimal medico-surgical treatment yields insufficient CRS control. This study aims to evaluate long-term results with focus on established therapeutic efficacy while tapering dupilumab. METHODS: Real-life, prospective observational cohort study in single tertiary referral center with add-on dupilumab as primary biological treatment in adult (≥18 years) biological-naïve CRSwNP patients per the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS)2020-indication with a 2-year follow-up. Tapering (increasing interdose interval) applied every 24 weeks, conditional to sufficient treatment response and CRS control. RESULTS: Mean scores (s.d.) of all co-primary outcomes improved significantly from baseline ( 228) to the 48 ( 214) and 96-weeks ( 99) timepoints: Nasal Polyp Score (0-8) improved from 5,3 (1,9) to 1,4 (1,8) and 1,3 (1,7); SinoNasal Outcome Test (SNOT)-22 (0-110) improved from 53,6 (19,6) to 20,2 (15,4) and 21,2 (15,6); Sniffin'Sticks-12 identification test (0-12; 0-6 anosmia, 7-10 hyposmia, 11-12 normosmia) improved from 3,7 (2,4) to 7,7 (2,9) and 7,3 (3,04); Asthma Control Test (5-25; >19 indicating well-controlled asthma) improved from 18,5 (4,8) to 21,8 (3,8) and 21,4 (3,9). Tapering was feasible in 79,5% of the patients at the 24-weeks timepoint, and in 93,7% and 95,8% at the 48- and 96-weeks timepoints, respectively. One-way repeated-measures ANOVA demonstrated no significant alterations of individual co-primary outcome mean-scores from 24 weeks onward. CONCLUSION: This first long-term real-life prospective observational cohort study shows high therapeutic efficacy of dupilumab for severe CRswNP in the first 2 years. Therapeutic efficacy is principally established within 24 weeks and endures while tapering dupilumab conditional to treatment response and CRS control.

Evaluation of switching or simultaneous use of biologic treatment in patients with severe chronic rhinosinusitis with nasal polyps and severe asthma. Considerations in clinical decision making.

INTRODUCTION: Type 2 targeting biologics have reached the market first for asthma and since 2019 also for CRSwNP. As clear guidelines and predictors for optimal biological choice are missing, patients are sometimes required to switch biologic therapy in order to find the optimal treatment result. In this paper, we evaluate reasons for switching biologics and the treatment effects after each sequential switch. MATERIALS AND METHODS: Ninety-four patients who switched from one biologic to another for their treatment of CRSwNP and asthma were evaluated. RESULTS: Twenty patients experienced satisfactory control of CRSwNP, but insufficient control of severe asthma. Fifty-one patients experienced satisfactory control of severe asthma, but insufficient control of CRSwNP/EOM. Twenty-eight patients experienced insufficient control of both upper and lower airways. Thirteen patients had to switch because of side effects. Furthermore, two cases are described to clarify clinical decision-making. DISCUSSION: For abovementioned patients, a multidisciplinary approach is mandatory to find the best suitable biologic. It seems ineffective to switch to a second anti-IL5 treatment if the first one is not successful. Most patients that failed omalizumab and/or an anti-IL-5 treatment are well controlled on dupilumab. Therefore, we suggest to use dupilumab as first choice when switching biologic agents.

Characteristics and Clinical Management Strategy of Petrous Apex Cholesterol Granulomas.

Purpose: To evaluate the clinical characteristics of petrous apex cholesterol granulomas (PACG) and assess outcomes after different treatment strategies. Method: A consecutive case series of 34 patients with a PACG. Main outcomes were PACG growth, symptoms, and the outcomes of different treatment strategies: wait-and-scan (WS) and surgical drainage. Results: Thirty-four patients were analyzed; mean follow-up time was 7.1 years. Twenty-one patients (61.7%) showed symptoms, mostly more than one. Most symptoms reported were cranial nerve palsy (58.8%) and headache (35.3%). Twenty-one patients (61.8%) received solely wait-and-scan (WS), and thirteen patients (38.2%) underwent surgery, five of whom (38.5%) after an initial WS period. In the solely WS group, one (4.8%) developed new symptoms, and two (9.5%) reported symptom progression despite a stable granuloma size. Two (9.5%) showed granuloma growth on follow-up scans without symptom progression. Surgery consisted of drainage. Eleven (84.6%) of these thirteen patients reported partial recovery; one (7.7%) reported no recovery; and one (7.7%) reported full recovery of reported symptoms related to PACG. Among the patients with cranial nerve involvement, 7.7% showed full recovery after surgery; 84.6% showed partial recovery; and 7.7% did not recover. Adverse events occurred in five out of 13 patients who underwent surgery, all with full recovery. Conclusions: This study confirms that PACG are slow-growing lesions with a low risk of adverse events. Solely using wait-and-scan strategy is a safe option for patients without symptoms, with acceptable symptoms without symptom progression, and with asymptomatic growth. Surgical treatment can be considered in patients with symptom progression or symptomatic growth.

The association between radiological spreading pattern and clinical outcomes in necrotizing external otitis.

Objectives: Necrotizing external otitis (NEO) is a rare infectious disease of the skull base. The purpose of this study was to determine whether clinical outcomes of NEO can be correlated to different infectious spread patterns. Methods: Retrospective chart review from 2010 to 2019 with NEO patients, who were divided into two cohorts: single spreading patterns (group A) or complex spreading patterns (group B) as diagnosed by CT. Clinical symptoms, diagnostic and treatment delay, course of disease, complications, and duration of antibiotic exposure were retrospectively collected from patient records. Results: 41 NEO patients were included, of which 27 patients belonged to group A (66%). The disease-related mortality rate was 12.2% among the entire cohort, no differences were found between group A and B. Higher rates of N.VII (42.9% vs 14.8% P = 0.047) and N. IX palsies were found in group B compared to group A (28.6% vs 3.7%, P = 0.039). The median duration of antibiotic use was significantly different for a complex spreading pattern, clinical recovery and hospitalizations. Complications were associated with higher diagnostic delay and with a complex spread pattern. The median duration of follow-up was 12.0 (IQR 6.0-19.5) months. Conclusion: NEO is a severe disease, with significant mortality and morbidity (cranial nerve palsies). The radiological spread pattern may assist in predicting clinical outcome. Furthermore, complex spread patterns are associated with higher rates of clinical nerve palsies (N. VII and N.IX), complications, surgery rates and longer duration of antibiotic use. Diagnostic delay was associated with mortality, complications and facial palsies. Level of evidence: Level IV.

Diagnosis, treatment and prognosis of otomastoiditis induced by Fusobacterium necrophorum: A retrospective multicentre cohort study.

OBJECTIVES: Otomastoiditis caused by the anaerobic Fusobacterium necrophorum (F. necrophorum) often induces severe complications, such as meningitis and sinus thrombosis. Early diagnosis is difficult, partly because little is known about specific early signs. Comprehensive research about clinically chosen antimicrobial therapy has not been done yet and prognostic information about otomastoiditis caused by F. necrophorum is scarce. More knowledge about this subject is required. METHODS: In this retrospective cohort study, we included all cases of otomastoiditis caused by F. necrophorum treated in two university medical centres in the Netherlands during the past 10 years. Data was gathered from patient records and analysed using independent sample T-tests and Chi2-tests. RESULTS: This study reveals that otomastoiditis caused by F. necrophorum potentially induces neurological sequelae. Thereby, 80% of all included patients (n = 16) needed readmission within six months due to recurrence or complications of otomastoiditis caused by F. necrophorum. Mean (range) of age, CRP and temperature were 4.5 years (0.9-29.3), 243 mg/L (113-423) and 40 °C (37-41). All patients were hospitalized and treated with antibiotics, mostly metronidazole (n = 13/16) and a ß -lactam (n = 15/16). Additional treatment contained low molecular weight heparin (83%, n = 10/12), dexamethasone (78%, n = 7/9) and/or surgery (80%, n = 12/16, whereof 9/12 mastoidectomy). CONCLUSIONS: Patients and/or their parents need to be informed about this potential unfortunate prognosis when otomastoiditis caused by F. necrophorum is diagnosed. To improve early diagnosis, otomastoiditis caused by F. necrophorum should be suspected and therefore immediately cultured when a) young children present with otomastoiditis, with b) high CRP values, and/or c) vomiting and decreased consciousness.