Upload
others
View
2
Download
0
Embed Size (px)
Citation preview
Testing (the Who’s and How’s) and Treatment in 2013
Dr. Amy Morse FRCPC May 11, 2013
Faculty/Presenter Disclosure • Faculty: Dr. Amy Morse
• Relationships with commercial interests:
– Grants/Research Support: Fellowships in therapeutics from CIHR, Pentax and Olympus Canada
Disclosure of Commercial Support
• This program has received financial support from Abbvie,
Aptalis, Janssen, Olympus, Pendopharm and Takeda in the form of unrestricted educational grants.
• This program has not received in-kind support from any organizations.
• Potential for conflict(s) of interest: – Dr. Amy Morse has a fellowship in therapeutics from Olympus Canada – Olympus Canada manufactures endoscopic equipment, however their
products are not specifically addressed in the presentations.
Mitigating Potential Bias • All presentation content for this program has been
reviewed by the Course Program Committee for potential sources of bias
• Sessions presented by Dr. Amy Morse are not related to her receipt of research grant funding from sponsoring organizations
• All therapeutic recommendations provided at the conference, including those made by Dr. Morse, are based on evidence-based research that adheres to acceptable standards for the profession
Acknowledgements
• Dr S Van Zanten
Who to check for Hp infection?
• High risk populations • GI manifestations • Non-GI manifestations • Family members
Hp in Canada
• Populations at increased risk – Immigrants from high-risk areas
• (e.g., S America >50% Hp positive) – Aboriginal populations
• Recent work Van Zanten et al HP 70% in Northern hamlet of Aklavik NWT
• Old Crow YK, Ft MacPherson NT • Cf urban Canada approx 25%
– Elderly
GI Diseases Associated with Hp
• Malignancy – Gastric ca – Gastric MALT
• Peptic Ulcers • Duo>gastric
• Dyspepsia – More controversial
Dyspepsia • Rome III • One of
– Bothersome postprandial fullness – Early satiation – Epigastric pain – Epigastric burning
• Plus – No structural disease
• These criteria should be fulfilled for the last three months with symptom onset at least six months before diagnosis
Hp and Dyspepsia??? • Clear association not well established, conflicting evidence • Postulated mechanism
– H. pylori may cause altered smooth muscle dysfunction due to the induction of an inflammatory response or by the initiation of an antibody response
– The inflammatory response induced by H. pylori may lower the discomfort threshold to gastric distension by causing alterations in the enteric or central nervous system
• Meta-analysis concluded that there was evidence for a small benefit – at best, only a minority of patients with functional dyspepsia will benefit
from H. pylori eradication – AGA and ACG recommend test and treat for dyspepsia (NNT 17) for a
SHORT term benefit in symptoms (potential long-term benefit of decreasing gastric ca)
– In higher prevalent areas more effect seen
Non-GI Diseases Associated with HP
• Controversial • Likely benefit from Hp treatment
1. ITP • Studies have shown that plt return to normal in ITP
pts with HP who are treated for the infection • European guidelines reflect this
2. Unexplained iron deficiency anemia • Meta-analysis –treatment improved Hb levels
3. B12 deficiency
Non-GI Diseases Associated with HP
• Controversial • Postulated but unproven associations
1. DM2 • Negative association – with Hp treatment wt gain
seen worsening DM2 – Hp (decrease ghrelin and increase leptin) with Tx ghrelin
and hunger increase
• Positive association – Hp positive pts more likely to develop DM2, postulation is
that cytokines effect the insulin receptors phosphorylating them making them less sensitive
Non-GI Diseases Associated with HP
• Controversial • Postulated but unproven associations
2. Neurologic disorders 3. CAD 4. Allergy and asthma in children
• Positive US cohort, no association in European study
5. Impaired absorption of meds (thyroxin, levodopa)
What about family members of HP positivie pts?
• Hp postulated gastric-oral spread chronic infection acquired in childhood, therefore household contacts esp in childhood increased likely also +
• Symptomatic family members – test • Asymptomatic – possibly if family history
gastric ca from high prevalence area (e.g., Eastern Asian, Middle America, Eastern Europe, in Canada the Arctic)
HOW TO TEST FOR H PYLORI?
How to test? • Endoscopy
– Biopsy • Rapid urease test • Conventional histology +/-
Giemsa stain • Culture (rarely done, if
multiple treatment failures can aid by providing sensitivities)
– Usually what GI does as we are often seeing pts with complications of HP eg GIB with ulcer
How to test?
• Non-endoscopy – Serology – Urease-breath test – Stool Antigen testing – Salivary testing
(historical, oral reservior hp)
– PCR possible mostly in research settings
• On water sources, gastric biopsies etc
Serology
• Serum Ab to Hp measured • Does not let you know about active vs past
infection – Pts with documented eradication may have no
change in titer, a decrease in titer (but still read positive) or may be negative (confusing to follow this)
• Variable specificity and accuracy
UBT
• H pylori has urease • Urea containing
substance is ingested the h pylori releases carbon in the form of CO2 which is exhaled and measured in the exhaled gas
UBT
• 13C or 14C (associated with minimal radiation = day of background exposure)
• Sensitivity 88-95% Specificity 95-100% • Sensitivity decreased in situations where
the Hp load is decreased – Antibiotics (in the prior 4 weeks) – PPI (stop 2 weeks before, if PPI can be
stopped use antacid (or H2B) to bridge the patients symptoms)
Stool Ag Testing
• Polyclonal Ab based testing – EIA – Done in central lab – Sensitivity 87-95%, Specificity 67-83% (e.g.,
false pos with UGIB) • Monoclonal Ag testing
– 94% sensitivity, 97% specificity
HOW TO TREAT???
First-LineTreatment
– Conventional tx • PPI BID 7-14d • Antibiotic 7-14d: Clarithromycin 500mg po BID
plus either Flagyl 500 BID or Amoxil 1g BID • Eradication only about 80% (at best)
PPI-AC (CM)
• 7-14 days • PPI bid • Amoxicillin 1g BID (or metronidazole
500mg if pen allergic) • Clarithromycin 500mg po BID
What to do in cases of treatment failure?
Different regimen • Second line options
– QT (90%) (bismuth, PPI, tetracycline and flagyl for 14 days)
– ST (80-90%) • 10days: • all 10get bid PPI • 0-5 get amox, then 6-10 get clari and metro. • Bubble pack, I have pre-populated Rx
– Fluroquinolone based regimens (80%); PPI-AL(M)
• If failing second round of treatment, – think about what the treatment indication was for in the first
place, – Consider GI referral as
• biopsy with culture for sensitivity may be needed to guide treatment
Quadruple Therapy
• 7-14 days • PPI BID • Bismuth • Tetracycline • Metronidazole
Sequential Therapy
• PPI bid Amoxicillin 1 g bid • PPI bid Clarithromycin 500 mg bid x 5 days Metronidazole 500mg bid
x 5 days
Quinolone Based
• PPI bid • Amoxicillin 1g bid • Levofloxacin 500 mg once a day or bid
• In Italy > 80% • Elsewhere more variable results
Treatment regimen should be selected according to areas of low and high clarithromycin resistance (Clari-R).
Malfertheiner P et al. Gut 2012;61:646-664
Copyright © BMJ Publishing Group Ltd & British Society of Gastroenterology. All rights reserved.
Pre Primary treatment Resistance Over Time
0
5
10
15
20
25
NS 1995-96(MET NA)
NS 1997-98 NS 1999-01 NS 2002-04 Can 1999
Pe
rce
n
CLA MET
Nova Scotia Resistance 1999-06
25
15 1519
0 1
5256
22
50 0
0
10
20
30
40
50
60
70
80
90
100
Met Cla Azit Lev Amox Tetra
n. 253 n.245 n.43 n.157 n.157 n.175
Per
cent
Pre-treatment
Post-treatment
Confirmation of eradication
– Probably the most important overlooked step – 4-6 weeks later off abx and hold the PPI for
UBTs!! – Non-invasive test preferred unless indication
for a repeat scope, • e.g., gastric ulcer • If patients need to be on PPI and it can’t be
stopped biopsies can still be done to check for eradication (endoscopist needs to biopsy more proximal sites than just the antrum)
References: • Calvet et al. Diagnosis of Helicobacter pylori infection.
Helicobacter 15(Supp)1: 7-13. • O’Conner et al. Treatment of Helicobacter pylori
Infection 2010. Helicobacter 15(Supp)1:46-52 • Up to date 2011 Indications and diagnostic tests for
Helicobacter pylori infection. April 12/11. • Malfethheiner et al Management of H pylori infection –
the Maastricht IV/Florence Consensus Report. Gut 2012: 646-664
QUESTIONS??????
RCT Sequential vs PPI-CA • N = 300 • Results Sequential 89% PPI-CA 77% Sequential PPI-CA • Clari-R 8/9 (89%) 6/21 (29%) Clari-S 108/114 (95%) 86/91 (95%) Ann Intern Med 2007;556-563
Aklavik RCT
Treatment naïve • PPI-CA Triple 60% (29/48) • Sequential therapy 74% (29/39)
Previous treatment failure • Quadruple therapy
– 9 trial failures, 1 pre-trial failure 90% (9/10)