Overview. Topical Nasal Therapy: Distribution 11/13/14. Evidence for Topical Therapies in Chronic Rhinosinusitis. Nasal Saline Irrigation: Evidence

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1 Overview for Topical Therapies in Chronic Rhinosinusitis Jivianne T. Lee, MD November 14, 2014 Global Rhinology Web Symposium Essential principles Saline Steroids s Antifungals Additives Innovations in drug delivery Topical Nasal Therapies Delivery Techniques Topical Nasal Therapy: Distribution Nasal Saline Irrigation: Harvey R, et al. OTO-HNS 2008 FESS essential to allow for effective topical distribution to the sinuses Unoperated sinuses: distribution <2% with irrigation, <3% with nebulizers Harvey (2009) Variability in recommendations regarding method, frequency, and concentration (8s) QOE: Grade B & Saline vs. no peds rx or placebo; IS vs. HS Sx, imaging (IS vs HS) Saline irrigations recommended in medical management of routine Improve sx and QOL as sole or adjunct rx; No SS dif IS vs HS 1

2 11/13/14 Topical Nasal Steroids: for snp Topical Nasal Steroids: for wnp Snidvongs Kalish (2009) (9s) (10s) QOE: Grade A snp snp Intranasal steroids vs. Intranasal steroids vs. adverse efx QOL INS improved sx scores, safe INS improved sx but no change in QOL INS strongly recommended in medical management of routine snp Kalish (2013) Rudmik Joe (9s) (12s) (6s) QOE: Grade A wnp wnp wnp s s s NP size Symptoms NC, NP size SS symptoms, NP size with INS SS symptoms with INS SS NC & NP size with INS INS strongly recommended in medical management of routine wnp Rudmik L, IFAR 2012 Topical Budesonide Irrigations Potential alternative to systemic cs for refractory wnp No adverse efx on adrenal axis Welch K et al. (2010): No change in avg serum or 24 hr urine cortisol p 6 wks Bhalla R, et al. No change in am cortisol p 8 wks Snidvongs Rotenberg Prospective single arm (111) (60) Topical Budesonide Irrigations: Insufficient evidence to make definitive recommendations Additional investigation needed to determine clinical efficacy & long-term safety 4 post-ess Budesonide or betamethasone 1mg in 240ml NS qd x 3mo Samter s Saline (240ml), saline + separate budesonide spray (64µg qd), saline budesonide mix SNOT-22, NE SNOT-20, NE, CT SS improvement mean f/u 56 wks No ss difference among 3 groups after 1 year Topical Antimicrobials Tobramycin Ceftazidime Levofloxacin Mupirocin TMP-SMX Clarithromycin Vancomycin Meropenem Ceftriaxone Itraconazole Fosfomycin Theoretical advantage over systemic abx Act directly on site of infection Clindamycin Produce higher level of abx at target site Less systemic side efx (i.e. GI) Isaacs Sacks Topical Antifungals: (3 ; 266) (5 ; 206) vs. placebo vs. placebo NE, CT QOL, NE, CT QOE: Grade A No clinical benefit in all parameters in all parameters Topical antifungal irrigations are not currently recommended for use in routine 2

3 Nebulized Antibotics: Videler Desrosiers (2001) (14) (20) Bacitracin/colymycin 8ml (830/640 µg/ml) bid x 8 wks vs. saline Tobramycin tid x 4 wks vs. saline VAS symptoms, SF-36 NC, PND, rhinorrhea, mucosal edema Use of nebulized abx in routine is not currently recommended except worse NC in tobramycin arm Jervis- Bardy Wei Moss (1995) (25) (40) NR-PCT (51) SA+ recalcitrant snp Mupirocin vs. saline Pediatric Gentamycin, no h/ vs. saline o ESS, NP, CF 4 CF, recalcitrant SA cx, SNOT-20, VAS, NE Pre- & pos- Rx CT (LM), SN-5 QOL in SNOT-20 & VAS. Neg SA cx 0/13 (C) vs. 8/9 (MUP), SS improvement in NE at 1mo; lost with longer f/u (mean 89d) Tobramycin Need for SS in need for + surgery revision ESS revision ESS in Rx vs. surgery Lee JT and Chiu AG, (22%) AJRA vs. C 2013 (72%) Topical antibiotics are not currently recommended as first line therapy for routine, but can be a potential option for select patients with refractory who have failed traditional medical and surgical intervention. Red Oak: (Polyhydrated Ionogen) Topical Nasal Additives Manuka Honey: (Methylglyoxal) Xylitol Additional research required to determine clinical implications of microbiological relapse risk of systemic toxicity incidence of antibiotic resistance associated with prolonged use Lee JT and Chiu AG, AJRA 2014 Facilitates healing (i.e. diabetic foot ulcers) Enhances ciliated reepithelialization of sinonasal mucosa vs NS in rabbit model Inhibits Pseudomonas biofilm formation Antimicrobial efx Used to tx infected wounds/ ulcers Sugar alcohol Sweetener antimicrobial potency of endogenous factors Chiu Farag (2013) Weissman Thamboo Prospective single arm (18) SB- (40), pilot (15) SB- (34) Topical Additives: 4 Medically & recalcitrant undergoing ESS post-ess; intrapt Medically & refractory AFRS Additive (1% baby shampoo bid) x 4wks (1% baby shampoo tid) vs HS x13wks Xylitol (10mg/ 240 ml water) vs NSx10d Manuka honey (2 ml 50/50) vs NS qd x 30d UPSIT PEA, QOL (RSOM-31), side efx SNOT-20, VAS NE, cultures 47, 60, 53, 64% improvement in symptoms, mucus thickness, PND, smell in all parameters; 20% stopped rx due to side efx SS SNOT-20 no difference in VAS, no adverse efx in all parameters Lee JT and Chiu AG, AJRA 2013 No evidence-based recommendations have been made at this time Topical additives may have a role in the adjunctive treatment of refractory Additional studies are needed to investigate clinical efficacy & toxicity profiles which pts would derive the most benefit Lee JT and Chiu AG, AJRA

4 11/13/14 Innovations in Drug Delivery: Biomaterials Carboxymethylcellulose Plant-based polysaccharide Available as a net becomes lubricant gel when hydrated Rudmik Cote (2010) #Pts Formulation CMC + No ss difference LK/ dexamethasone NE scores p 3 mo (4ml; 4mg/ml) vs. CMC 36 CRsNP. Polyurethane Foam Polyactide Sinus Synthetic material Biologically inert Interconnected porous structure enables fluid absorption #Pts Formulation 19 Triamcinolone (2ml; 40mg/ml) impregnated PF vs. PF Improved early (pod 7/14) & late (3/6mo) NE scores Implant 370µg MF embedded in PLG polymer matrix x 30 days 5.2 x 23mm, 4 x 16mm Deployed using singlehanded delivery device into MM post-ess; spring-like expansion Murr AH, et al. IFAR 2011; 1: In-Office Steroid-eluting Ethmoid Implant S8 Steroid-eluting : #Pts Han Meta-analysis of 2 s 143 Marple Multi-center DB 105 Steroid-releasing SS LOA, ocs, & vs. non- NP pod30 drug eluting Murr Multi-center DB 38 Steroid-releasing SS adhesions, vs. non inflammation, drug-eluting NP pod30 Steroid-releasing SS in LOA, ocs, vs. non- MT lat, NP pod30 drug-eluting Pre-Implant 8-pronged, rounded tip to facilitate delivery Increased radial strength Releases 1350 µg MF over 90 days ed to dilate previously dissected ES re-obstructed by NP Day 0 Post-Implant Day 30 Day 90 6 Months 4

5 In-Office Steroid-eluting Ethmoid Implant S8 Multicenter SB-: (n=100 wnp, 18 sites) S8 one side, sham procedure on the other () SS polyp grade/eso in treatment vs. groups Change from baseline Day 7 Day 14 Day 30 Day 45 Day 60 Day Control Han JK, et al. IFAR 2014; In press Case 68 y/o M s/p 4 FESS (1995, 1998, 2001, 2006) for 2/2014 presented with 1yr h/o ltsided frontal HA Pt given 3-4 wks abx, oral steroids, budesonide irrigations w/o relief Sinus CT obtained Coronal/Sagittal CT Thank you! 5