Efficacy of dupilumab in patients with a history of prior sinus surgery for chronic rhinosinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease treated with sinus surgery when refractory to medical intervention. However, recurrence postsurgery is common. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor for interleukin 4 (IL-4) and IL-13, key and central drivers of type 2 inflammation. We report the efficacy of dupilumab in patients with CRSwNP from the SINUS-24/SINUS-52 trials (NCT02912468/NCT02898454), by number of prior surgeries and time since last surgery. METHODS: Patients were randomized to placebo or dupilumab 300 mg every 2 weeks. Post hoc subgroup analyses were performed for patients with 0, ≥1, 1/2, or ≥3 prior surgeries, and for patients who had surgery within <3, 3 to <5, 5 to <10, or ≥10 years. Efficacy outcomes at 24 weeks included co-primary endpoints nasal polyp score (NPS) and nasal congestion (NC), and Lund-Mackay (LMK), 22-item Sino-Nasal Outcome Test (SNOT-22), and smell scores. RESULTS: Of 724 patients randomized, 459 (63.4%) had ≥1 prior surgery. Baseline sinus disease (NPS, NC, LMK) and olfactory dysfunction (University of Pennsylvania Smell Identification Test [UPSIT] and loss of smell) scores were worse for patients with ≥3 prior surgeries vs no surgery. Baseline NPS and LMK were worse in patients with <3 years since last surgery than in patients with ≥5 years since last surgery. Dupilumab significantly improved all outcome measures vs placebo in all subgroups by number of surgeries and by time since last surgery. Improvements in NPS and LMK were greater in patients with <3 years since last surgery than patients with ≥5 years. Safety results were consistent with the known dupilumab safety profile. CONCLUSION: Dupilumab improved CRSwNP outcomes irrespective of surgery history, with greater improvements in endoscopic outcomes in patients with shorter duration since last surgery.

Morton's neuroma: diagnostic accuracy, effect on treatment time and costs of direct referral to ultrasound by primary care physicians.

BACKGROUND: The first-line treatment for symptomatic Morton's neuroma in our hospital is a perineural ultrasound-guided injection of corticosteroid and local anaesthetic (USI). The NHS has recently implemented 18-week referral-to-treatment targets. When GPs specifically suggest a diagnosis of Morton's neuroma there are two referral pathways in our hospital: direct referral to radiology for USI (limited slots) or referral to the specialist foot and ankle clinic. Patients with less specific referral letters are also evaluated in clinic and referred for USI as appropriate. METHODS: A retrospective audit was performed reviewing referral letters from general practitioners (GPs) in 2005-2006. A comparison was made between the referral pathways for time-to-treatment (TTT), accuracy of GP diagnosis, and cost implications. RESULTS: In the directly referred group, the median TTT was 99 days, compared to 206 days for patients who went via a foot and ankle clinic (P < 0.001). Of 57 patients with a GP diagnosis of Morton's neuroma, 40 (70%) had the diagnosis confirmed on USI compared to 44 of 64 (69%) patients referred by a foot and ankle surgeon, showing no significant difference between the groups (P = 0.87). CONCLUSION: For patients with features highly suggestive of a Morton's neuroma, direct referral from primary care for USI had a similar accuracy to referral from a specialist hospital clinic and the time-to-treatment was significantly shorter. The mean waiting time of this group was within the 18-week government target without any changes to our current radiology protocols.