Bevacizumab Nasal Spray for Frequent Epistaxis in HHT
Transcript of Bevacizumab Nasal Spray for Frequent Epistaxis in HHT
Bevacizumab (Avastin) Neus Spray voor Frequente Neusbloedingen bij ROW
Proefbehandeling
F.S. van der Meer, MDSt Antonius hospital Nieuwegein,, The Netherlands
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ROW en neusbloedingen (epistaxis)
- > 90% terugkerende epistaxis- Frequent ijzer and bloedtransfusies- Verstoort dagelijkse leven en werk
- Meeste behandelingen hebben tijdelijk effect of veel bijwerkingen- Laser, embolisation, surgery: Saunders- Estrogen (de pil),- Thalidomide
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Bevacizumab (Avastin)
Eerder onderzoek:- Patienten met ROW hebben verhoogde spiegels van VEGF
(oa Saddic et al, 2005)
-Menselijk antilichaam-Bind aan en remt VEGF activiteit
-Iremt vaatgroei
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Eerdere Bevacizumab publicaties, lokale toepassingDavidson TM, Olitsky SE, Wei JL. Hereditary hemorrhagic telangiectasia/avastin
Laryngoscope 2010:
- Case report, male 45 yrs, HHT, recurrent epistaxis
- Injection submucosal 100mg Bevacizumab• <1 wk epistaxis stopped• effect: 3-4 months
- Nasal spray 10mg/ml, 2wk, total 50mg• <1 wk epistaxis stopped• effect 3-4 months
- Nasal spray 25mg/ml, every 30min 1 spray till 25mg• effect 2.5 months
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Eerdere Bevacizumab publicaties, lokale toepassingKarnezis TT, Davidson TM. Efficacy of intranasal Bevacizumab (Avastin) treatment in patients with hereditary hemorrhagic telangiectasia-associated epistaxis
Laryngoscope 2011:
- 32 patients: • 17 topical, spray, 50-100mg, • 10 submucosal injection, 100mg (125mg), • 5 topical spray and submucosal injection, • 12/32 also KTP laser
•Follow-up:- ESS before treatment and 2-18 (mean 4.1) months after treatment
•Results: - ESS pre treatment 7.0, after treatment: 2.9 - ( 17 topical: 6.6- 3.6, 10 submucosal 8.1- 2.1)
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Eerdere Bevacizumab publicaties,lokale toepassing
VeiligheidChen S 4th, Karnezis T, Davidson TM. Safety of intranasal Bevacizumab (avastin) treatment in patients with hereditary hemorrhagic telangiectasia-associated epistaxis.
Laryngoscope 2010:
52 patients, treated with bevacizumab intranasally applied, some on mutiple occasions- Topical spray, 50-100mg Bevacizumab (26) KTP 0- Submucosal injection, 25-100mg bevacizumab, (34), also KTP (30)
•Follow-up 1.5-46 months after treatment:- 5 septal perforation (all combined submucosal injection and KTP laser)- No other common or serious event
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Proefbehandeling
Bevacizumab nasal spray- Solution 25mg/ml, dose 0.1ml (2.5mg)- Daily use: 2dd1 both sides (0.4ml=10mg)- Treatment duration: 1 week (70mg)
-Inclusion of 8 HHT patients with recurrent epistaxis-All signed informed consent
-Diary of epistaxis during 4 weeks before treatment and 4 weeks after treatment- Validated in previous studies-Hb, ferritin levels before and after treatment-Video of nasal mucosa before and after treatment
-June and August 2011:-2 and 4 months after treatment evaluation-4 weeks diary, hb/iron/ferritine levels
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Pilot treatment
Bevacizumab nasal spray- Solution 25mg/ml, dose 0.1ml (2.5mg)- Daily use: 2dd1 both sides (0.4ml=10mg)- Treatment duration: 1 week (70mg)
-Inclusion of 8 HHT patients with recurrent epistaxis-All signed informed consent
-Diary of epistaxis during 4 weeks before treatment and 4 weeks after treatment- Validated in previous studies-Hb, ferritin levels before and after treatment-Video of nasal mucosa before and after treatment
-June and August 2011:-2 and 4 months after treatment evaluation-4 weeks diary, hb/iron/ferritine levels
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Pilot treatment
Bevacizumab nasal spray- Solution 25mg/ml, dose 0.1ml (2.5mg)- Daily use: 2dd1 both sides (0.4ml=10mg)- Treatment duration: 1 week (70mg)
-Inclusion of 8 HHT patients with recurrent epistaxis-All signed informed consent
-Diary of epistaxis during 4 weeks before treatment and 4 weeks after treatment- Validated in previous studies-Hb, ferritin levels before and after treatment-Video of nasal mucosa before and after treatment
-June and August 2011:-2 and 4 months after treatment evaluation-4 weeks diary, hb/iron/ferritine levels
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Pilot treatment
Bevacizumab nasal spray- Solution 25mg/ml, dose 0.1ml (2.5mg)- Daily use: 2dd1 both sides (0.4ml=10mg)- Treatment duration: 1 week (70mg)
-Inclusion of 8 HHT patients with recurrent epistaxis-All signed informed consent
-Diary of epistaxis during 4 weeks before treatment and 4 weeks after treatment- Validated in previous studies-Hb, ferritin levels before and after treatment-Video of nasal mucosa before and after treatment
-June and August 2011:-2 and 4 months after treatment evaluation-4 weeks diary, hb/iron/ferritine levels
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InclusionPatients (8) Age (yrs) Sex (m/f) Type HHT Previous
treatmentsIron/bloodtransfusions
1 68 m HHT-1 LaserArgonlaser
Iron and blood iv every 3wks
2 68 f HHT-1 LaserArgonlaserSeptumbutton
Oral iron
3 68 m HHT-1 ArgonlaserSaundersThalidomide stopped 2009Sitaglyptine
Oral iron
4 60 f HHT-2 ArgonlaserSaundersEstrogen
Oral iron
5 68 f HHT-2 LaserEmbolisationThalidomide stopped 2-25-2011
Iron iv every week
6 51 f HHT-1 EmbolisationWeekly visit ENT
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7 72 m HHT-2 SaundersArgonlaser
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8 60 m HHT-2 LaserArgonlaserseptumbutton
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Mean 64.4 50% male 50% HHT-1
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ResultsFreq epistaxis/day Duration of
epistaxis min/daySeverity of epistaxis1-2-3
Patients opinion of bleeding
before
after diff before
after diff Before
after diff During treatment After treatment
1 2.9 2.6 -0.3 9.6 13 +3.4 1.3 1.6 +0.3 = Shorter
2 1.5 0.6 -0.9 77.0 33.9 -43.1 2.7 2.7 0 Heavy bleeding Less freq
3 3.0 2.1 -0.9 30.1 15.1 -15 2.6 2.4 -0.2 More bleeding Less freq less severe
4 1.3 1.0 -0.3 15.6 8.8 -6.8 1.0 1.1 +0.1 More bleeding =
5 0.9 0.9 0 12.6 80 +67.4 1.5 1.5 0 Severe bleeding Less severe, wholeday bleeding
6 3.7 0.9 -2.8 6.1 3.0 -3.1 1.1 1.1 0 More bleeding Less
7 0.5 0.2 -0.3 7.4 2.5 -4.9 1.6 1.5 -0.1 Some bleeding Less
8 1.6 1.1 -0.5 42.0 14.6 -27.4 1.3 1.2 -0.1 More bleeding Less
Median 1.55 0.95 14.1 13.0 1.64 1.63
-56%
-50%
-52%
-66%
-65%
+500%
p 0.757 / 0.065 p 0.049
Paired samples T-test
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ResultsHb level Ferritin Patients opinion of bleeding
patients before after Before after During treatment After
1 7.2 6.8 23 34 = shorter
2 6.7 6.6 27 21 Heavy bleeding Less freq
3 7.0 7.6 14 25 More bleeding Less freq en severe
4 8.8 7.9 16 9.7 More bleeding =
5 5.1 4.5 34 30 Severe bleeding, transfusion
Less severe, wholeday bleeding
6 9.1 9.0 23 163 More bleeding less Iron IV before last Hb/ferritin
7 7.9 7.8 15 13 Some bleeding Less
8 8.8 6.9 12 5.3 More bleeding Less
Mean 7.55 7.25 19.5 23 (21)
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Video before and after treatmentNo 4-5-8
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-Meer bloedneuzen tijdens gebruik neusspray(7)-Misselijkheid tijdens gebruik neusspray(1)-Moeheid(1)
-Ernstige bloeding warvoor opname en bloedtransfusie (1)
Ernstige bijwerkingen
Bijwerkingen
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Conclusies
•Mening van de patiënt:- Tijdens de behandeling ervaarden 7/8 patienten meer bloedingen - Na behandeling ervaarden 6/8 patientsen minder of minder ernstige bloedneuzen
•Dagboek evaluatie: - Overall minder vaak en kortere duur bloedneuzen- Geen verschil in ernst bloedarmoede en ijzervoorraad - Geen relatie tussen behandelresultaat en mutatie HHT1 of HHT2
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Discussion
Application of bevacizumab: - Competence/execution of spray- Spray type: lesions?
-Dose of Bevacizumab- Previous reports: 25-100mg- This report 70mg
-Follow up- Previous effects: after one week (case report), evaluation after 2-18 months- Extra follow-up planned after 2 and 4 months use
-Adverse events: - Patient 5 stopped using thalidomide 5 weeks before treatment
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Bevacizumab Nasal Spray for Frequent Epistaxis in HHT, a pilot treatment
•Previous reports: positive effect
•Our treatment:
- Some positive signs - Problems during application
- More research needed- Study group size- Effective dose- Application- RCT- Long term effects
NOSE:- Efficacy and safety
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