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Disclosure Consultant for IntersectENT Minor Stockholder Off label - - PDF document

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STEROIDS AND STENTS Pacific Rim Otolaryngology Update February 16, 2013 Andrew H. Murr, MD FACS Professor and Interim Chairman Roger Boles, MD Endowed Chair in Otolaryngology Education Department of Otolaryngology-Head and Neck Surgery

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SLIDE 1

STEROIDS AND STENTS

Pacific Rim Otolaryngology Update

February 16, 2013 Roger Boles, MD Endowed Chair in Otolaryngology Education Department of Otolaryngology-Head and Neck Surgery University of California, San Francisco School of Medicine Chief of Service Otolaryngology-Head and Neck Surgery San Francisco General Hospital

Andrew H. Murr, MD FACS

Professor and Interim Chairman

Disclosure

  • Consultant for IntersectENT

– Minor Stockholder

  • Off label discussion

– Fluticasone – Budesonide

  • Many members of the rhinology community have

contributed to the stent technology that I will discuss: Team Effort!

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SLIDE 2

Treatment of Nasal Polyps

  • Antibiotics
  • Antifungals
  • Corticosteroids
  • Anti-Leukotrienes
  • Antihistamines
  • Mast cell stabilizers
  • Parasympathetic blockade

drugs

  • Surgery

Corticosteroid Delivery: What is the Evidence?

  • Topical

– Spray – Irrigation

  • Systemic
  • Direct injection
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SLIDE 3

Evidence:Topical Delivery

Joe SA, Thambi R, Huang J. A systematic review of the use of intranasal steroids in the treatment of chronic rhinosinusitis. Otolaryngol Head Neck Surg. 2008 Sep;139(3):340-7. Review. PubMed PMID: 18722209.

  • “This systematic

review showed that intranasal steroids decrease polyp size, which we believe would provide some relief of nasal

  • bstruction.”
  • “Th

revi intra decr whic wou relie

  • bst

Evidence: Topical Steroids Larger Dose

[100 micrograms] Jankowski R, Klossek JM, Attali V, Coste A, Serrano E. Long-term study of fluticasone propionate aqueous nasal spray in acute and maintenance therapy of nasal polyposis. Allergy. 2009 Jun;64(6):944-50. Epub 2009 Mar 3. PMID:19298572.

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SLIDE 4

Evidence: Topical Steroids Larger Dose

[100 micrograms] Jankowski R, Klossek JM, Attali V, Coste A, Serrano E. Long-term study of fluticasone propionate aqueous nasal spray in acute and maintenance therapy of nasal polyposis. Allergy. 2009 Jun;64(6):944-50. Epub 2009 Mar 3. PMID:19298572.

Evidence: Budesonide (Pulmicort) Respules

Kanowitz SJ, Batra PS, Citardi MJ. Topical budesonide via mucosal atomization device in refractory postoperative chronic rhinosinusitis. Otolaryngol Head Neck

  • Surg. 2008 Jul;139(1):131-6. PubMed PMID: 18585575.
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SLIDE 5

Evidence: Budesonide (Pulmicort) Respules

Kanowitz SJ, Batra PS, Citardi MJ. Topical budesonide via mucosal atomization device in refractory postoperative chronic rhinosinusitis. Otolaryngol Head Neck

  • Surg. 2008 Jul;139(1):131-6. PubMed PMID: 18585575.

Does Budesonide in Respule Nasal Washes cause Adrenal Cortex Suppression?

Sachanandani NS, Piccirillo JF, Kramper MA, Thawley SE, Vlahiotis A. The effect of nasally administered budesonide respules on adrenal cortex function in patients with chronic rhinosinusitis. Arch Otolaryngol Head Neck Surg. 2009 Mar;135(3):303-7. PubMed PMID: 19289711.

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SLIDE 6

Systemic Steroid Delivery

  • Cochrane Database 2011 Jul6;(7):CD005232
  • “The authors found three randomised controlled trials [166

patients], albeit of moderate to poor quality, that suggest a short-term benefit of oral steroids in patients with multiple nasal polyps. To address the issue more thoroughly well- designed, prospective, randomised controlled trials are still needed.”

  • Parameters:

– Polyp size (endoscopic) – Symptom questionnaires – QOL

Bioabsorbable Steroid Eluting Stent

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SLIDE 7

Causes of FESS Failure

  • Recurrent inflammation
  • Recurrent polyps
  • Adhesion/synechiae

formation

  • Middle turbinate

lateralization

  • Stenosis of surgically

created ostia

Septum MT

Bioabsorbable Steroid-Eluting Stent Device

FDA Approval: August, 2011 FDA Approval for mini stent: December, 2012

  • Stent

– Spring-like design – Polylactide-co-glycolide

  • Mometasone Furoate

– Gradually released over approximately 30 days – 370 micrograms – FDA approved – Spray

  • 100 micrograms/day

A.R.

  • 200 micrograms/day

Polyps

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SLIDE 8

Example of Stent Placement

International Forum of Allergy & Rhinology Vol. 1 No.1 January/February 2011

  • Prospective, multi-center, randomized, double

blind, controlled clinical trial

– Patients undergoing FESS for CRS refractory to medical management of 3 months duration or more – With or without Nasal Polyps – Primary or revision surgery – Intra-patient control design – Oral steroids not permitted in a 14 day run-in – IV steroids given perioperatively

  • 4mg – 20 mg

– No post operative steroids until Day 30 – 14 Day course of Amoxicillin with Clavulonic Acid begun one day preoperatively – Saline spray permitted throughout

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SLIDE 9

Follow-up Paradigm

  • POD

– 7 – 14 – 21 – 30

  • Steroid prescription allowed at this juncture if necessary by clinical opinion of

treating physician – 45 – 60

Efficacy Assessment Form

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SLIDE 10

SAFETY

  • No evidence of systemic steroid absorption
  • No evidence of adrenal-pituitary axis suppression

INFLAMMATION:

  • Day 21 p = .0032
  • Day 30 p = .0011
  • Day 45 p = .0022
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SLIDE 11

Bioabsorbability Polyp/Inflammation Assessment

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SLIDE 12

Polypoid Change, Adhesion, Middle Turbinate Position

How the Coated Stent Works…

  • Function of the Stent

– Mechanical function

  • Spring like mechanical function
  • Placement of drug in key location
  • Patency of ethmoid cavity

– Pharmacological function

  • Systemic steroid side effects obviated
  • Decreased polyp formation and inflammation
  • Improves mechanical function of stent

– Adhesions/stenosis

– Bioabsorbable

  • Li, Downie, Hwang, AJR, 2009;23:591-596

PMID 19958608

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SLIDE 13

Benefit of Steroid Elution: Historical Comparison

  • Current Stent Study:

– Adhesion rate with steroid: 5.3% – Adhesion rate without steroid: 21.1% – P=0.0313

  • Historical Comparison:

– Wormald et al., AJR, 2006 Jan-Feb; 20(1):7-10 PMID 16539287

  • Hyaluronic Acid (HA) Packs to No packing
  • HA adhesion rate 21%

– Miller and Steward, Oto-HNS, 2003;128:862-869 PMID 12825038

  • HA to non absorbable packing: 35% overall with adhesions, each

group similar (~25%)

  • 19% required surgical (in office) intervention
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SLIDE 14
  • 120 videos

– 14,30,45 days post FESS

  • Comparison b/t onsite raters and

the panel: strong agreement Categoric variables:

  • MT position

– Kappa = .499, prevalence index =0.925

  • Adhesions

– Kappa=.364, prevalence index=0.829 Continuous variables:

  • Inflammation

– Reliability coefficient=0.554

  • Crusting

– Reliability coefficient=0.620

Bland-Altman Plots

Smith et. al., Laryngoscope, 122:230-236, January 2012

  • The results suggest that the

endoscopic scoring parameters have acceptable interexaminer reproducibility for both categoric and continuous data elements and that parameters are suitable for evaluating the middle meatal and ethmoid sinus anatomy in postsurgical patients.

  • Green Line: 95% agreement b/t

real time and panel

  • Red Line: mean difference b/t
  • n site and panel scores
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SLIDE 15

Expanded Clinical Data: Advance II

Marple BF, Smith TL, Han JK, Gould AR, Jampel HD, Stambaugh JW, Mugglin AS. Advance II: A Prospective, Randomized Study Assessing Safety and Efficacy of Bioabsorbable Steroid-Releasing Sinus Implants. Otolaryngol Head Neck Surg. 2012 Jun;146(6):1004-11. Epub 2012 Feb 1. PubMed PMID: 22301107.

  • 105 Patients
  • Intra-patient control

design

  • Panel raters and on-

site raters

Intervention

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SLIDE 16

POST-OPERATIVE INTERVENTION Steroid Prescription or Surgical Adhesion Lysis

Figure 4. Frequency of postoperative interventions by treatment group at day 30, as judged by the independent panel and in real time by on-site clinical investigators. Postoperative intervention is a composite of either surgical adhesion intervention and/or

  • ral steroid intervention. Arrows with percentages indicate

relative reductions.

3 Prospective Clinical Trials

Studied in > 200 patients

Pilot Study1

n=38 4 sites

ADVANCE Study2

n=50 7 sites

ADVANCE II Pivotal Trial3

n=105 11 sites

Broad Patient Populations

  • > 60% polyps at baseline
  • > 30% prior sinus/nasal surgery
  • > 12 Mean Lund-Mackay CT stage

Randomized Controlled Double Blind Intra-patient Control Non-Randomized Single Arm Safety / Symptoms to 6 months Randomized Controlled Double Blind Intra-patient Control

1. Murr AH, Smith TL, Hwang PH, et al. Int Forum Allergy Rhinol. 2011;1:23–32. 2. Forwith KD, Chandra RK, Yun PT, Miller SK, Jampel HD. Laryngoscope. 2011;121:2473–2480. 3. Marple BF, Smith TL, Han JK et al. Otolaryngol Head Neck Surg. 2012; 146(6) 1004–1011.

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SLIDE 17

PubMed PMID: 22550039.

Meta Analysis: 2 Double Blind, Randomized Controlled Trials

  • 143 patients
  • Bioabsorbable Steroid

Eluting Stent: Improves post-op healing

  • Reduction in need for oral

steroids & surgical adhesion lysis

PMID: 22550039

Panel grading

Relative Reduction p value Need for Medical / Surgical Tx 35% 0.0008 Need for Oral Steroids 40% 0.0023 Polyposis 46% <0.0001

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SLIDE 18

Propel: Bioabsorbable Steroid Eluting Stent

  • LEVEL 1A EVIDENCE
  • Reduction in:

– adhesions – polyposis – inflammation – middle turbinate lateralization – oral steroid Rx and surgical adhesion lysis

FUTURE DEVELOPMENT

  • 1. OFFICE BASED

PRODUCT

  • 2. OTHER SINUSES

– FRONTAL

  • 3. DRUGS
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SLIDE 19

Conclusion

  • Sinusitis is an

inflammatory disease and steroids can be effective

  • Novel methods of

steroid delivery have promise for treatment effectiveness and for decreased morbidity