CCO HCV Frontline 2013 Downloadable

8/13/2019 CCO HCV Frontline 2013 Downloadable

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April G. Long, RN, MS, FNPFamily Nurse Practitioner

Liver Institute of Virginia

HoChong Gilles, RN, MS, FNPGI/Hepatology Department

Richmond Veterans Affairs Medical Center

Ensuring Treatment Success in

HCV: 10 Ways Frontline Providers

Can Improve Patient Outcomes

This program is supported by educational grants from


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clinicaloptions.com/hepatitis

Ensuring Treatment Success in HCV

About These Slides

Users are encouraged to use these slides in their ownnoncommercial presentations, but we ask that contentand attribution not be changed. Users are asked to honorthis intent

These slides may not be published or posted onlinewithout permission from Clinical Care Options(email [email protected])

Disclaimer

The materials published on the Clinical Care Options Web site reflect the views of the authors of the

CCO material, not those of Clinical Care Options, LLC, the CME providers, or the companies providing

educational grants. The materials may discuss uses and dosages for therapeutic products that have not

been approved by the United States Food and Drug Administration. A qualified healthcare professional

should be consulted before using any therapeutic product discussed. Readers should verify all information

and data before treating patients or using any therapies described in these materials.


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Faculty

April G. Long, RN, MS, FNPFamily Nurse PractitionerLiver Institute of VirginiaBon Secours Medical Group

Richmond, Virginia

HoChong Gilles, RN, MS, FNPGI/Hepatology DepartmentLiver Transplant Program

Richmond Veterans Affairs Medical CenterRichmond, Virginia


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Disclosures

April G. Long, RN, MS, FNP, has disclosed she hasreceived speakers fees from Gilead Sciences,GlaxoSmithKline, Kadmon Pharmaceuticals, Merck, SalixPharmaceuticals, and Vertex. She has also served as a paidadvisor to Gilead Sciences, GlaxoSmithKline, and JanssenTherapeutics.

HoChong Gilles, RN, MS, FNP, has no significant financialrelationships to disclose.


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Meet Early and Often

to Address Anemia


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Anemia During Pivotal Phase III Trials of

HCV Protease Inhibitor Therapy Adverse events in phase III trials evaluating

coadministration of PI vs placebo with pegIFN/RBV

Anemia, % PI Regimen Placebo Regimen

Boceprevir[1](previously untreated)

50 30

Boceprevir[1]

(previous treatment failures)45 20

Telaprevir[2] 36 17

1. Boceprevir [package insert]. July 2012. 2. Telaprevir [package insert]. April 2013.


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RBV Dose Reduction in Tx-Naive Pts Does

Not Reduce SVR Rates: Telaprevir Studies Randomized, multicenter

phase III ADVANCE andILLUMINATE studies inHCV treatment-naive pts

50% (446/885) receivedRBV dose reduction dueto anemia

In pooled subanalysis,no effect of RBV dosereduction on SVR

Sulkowski MS, et al. J Hepatol. 2012;56(suppl 2):S459-S460.

7974 75

0

20

40

60

80

100

No RBV

Reduction

RBV

600 mg/day

RBV 800-

1000 mg/day

SVR(%)

TVR + PegIFN/RBV

in Treatment-Naive Pts


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RBV Dose Reduction in Tx-Naive Pts Does

Not Reduce SVR Rates: Boceprevir Study Randomized, multicenter, open-label trial comparing RBV

dose reduction vs erythropoietin as anemia managementin treatment-naive pts receiving boceprevir + pegIFN/RBV(N = 500)

Similar overall SVR rates

71.5% with RBV dose reduction

70.9% with erythropoietin use

No impact of timing of either anemia intervention ormagnitude of RBV dose reduction

However, lower SVR in pts who received < 50% of theoriginally planned RBV dose

Poordad F, et al. Gastroenterology. 2013;[Epub ahead of print].


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RBV Dose Reduction in Tx-Experienced

Pts Does Not Reduce SVR Rates Phase III REALIZE study in

HCV treatmentexperienced pts

Pts requiring RBV dosereduction

Prior relapse: 39% (56/145)

Prior partial response: 31%(15/49)

Prior null response: 18%(13/72)

No effect of RBV dose reductionon SVR

Sulkowski MS, et al. J Hepatol. 2012;56(suppl 2):S459-S460.

TVR + PegIFN/RBV in

Treatment-Experienced Pts

Prior relapse Prior partial Prior null

100

80

60

40

20

0No RBV

Reduction

RBV 600

mg/d

RBV 800-

1000 mg/d

82

62

31

90

33

22

84

29

50


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Summary: Early Intervention for Anemia

Mitigates Effects Without Affecting SVR Anemia is the single most problematic adverse event of

current HCV therapy

When pts start HCV therapy, initially follow-up each wk

Intervene promptly and aggressively to manage anemia

Optimal initial management for anemia is RBV dosereduction


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Provide Practical Strategies to

Enhance Adherence


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Major Predictors of Poor Adherence to

MedicationPt and Treatment Factors

Treatment of asymptomaticdisease

Presence of psychologicalproblems, particularlydepression

Pts lack of belief in benefit

of treatment

Complexity of treatment

AEs of medication

Other Factors

Poor providerpt relationship

Inadequate follow-up ordischarge planning

Missed appointments

Cost of medication,

copayment, or both

Osterberg L, et al. N Engl J Med. 2005;353:487-497.


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Adherence Affected by Regimen

Complexity and Pill Burden Data from HIV field illustrates

virologic suppression as afunction of daily pill burden[1]

HCV triple therapy involvesmultiple daily pills plusinjection drug

BOC TID: 12 pills/day

TVR TID: 6 pills/day RBV BID: 4-6 pills/day

PegIFN: injection QW

Virologic Response by

Daily Pill Burden

Antiretroviral Pills

Prescribed/Day, n

HIV-1RNA

50copies/mL

at48Wks(%)

0

5

20

40

60

80

100

10 15 20

PI

NRTINNRTI

Bartlett JA, et al. AIDS. 2001;15:1369-1377.


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Treatment-Related Factors Affecting

Adherence to Current HCV Therapy Tolerability

AEs in nearly all pts

Moderately complex regimen Subcutaneous injections

Twice-daily oral administration

Frequent physician visits

Blood tests to monitor safety

Result: Not all pts complete treatment course

McHutchison JG, et al. Gastroenterology.2002;123:1061-1069.


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Motivating Pts to Complete HCV Treatment

Future HCV-related health problems most important factorencouraging therapy initiation

HCV therapy efficacy and safety also significant

Fear of adverse events most important factor limitinginitiation and completion of HCV therapy

Pt fears can be overcome with open communication andeducation

Emotional support (family, friends, support groups)important motivators for treatment initiation and adherence

Fusfeld L, et al. BMC Infect Dis. 2013;13:234.


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Strategies for Improving Adherence to a

Medication Regimen Identify risk factors for poor adherence early

Emphasize value of regimen and potential results to pts

Provide simple, clear instructions and simplified regimen Customize regimen to pt lifestyle when possible

Support from family members, friends, and community

Consider more forgiving medications Medications with long half-lives, sustained release, or depot

Encourage the use of medication-dispensing packaging

Osterberg L, et al. N Engl J Med. 2005;353:487-497.


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Summary: Adherence Support Strategies

Pill burden, regimen complexity, AEs adversely effectadherence

Common strategies for adherence support

Pt education

Scheduling alarms (eg, cell phone)

Pill boxes/organizers

Blister packs

Medication worksheets


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Use Care Contracts or

Statements of Understanding


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Care Contracts Form a Basis for

Successful Treatment Care contracts can help:

Gauge pt readiness to start therapy

Ensure all important information affecting therapy iscommunicated at each follow-up visit (eg, abstinence fromsubstance use)

Keep family members and friends informed

Encourage pts to be accountable for their own care


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Check HbA1c in Every Patient:

Diabetic or Otherwise


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Recommendations to Establish a Healthy

Baseline for Care Optimize glucose control before starting HCV therapy

Perform baseline eye exam in pts with diabetes orhypertension before therapy

Conduct cardiac stress test in pts with coronary arterydisease

Consider potential drugdrug interactions


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Give Patients the

Gift of (Your) Time

E i T t t S i HCV


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Effective Communication Reduces

Barriers to Adherence Effective providerpt communication associated with

2-fold improvement in adherence[1]

Interconnected interactions affecting adherence[2]

Provider-to-patient communication

Patient-to-healthcare system interactions

Physician-to-healthcare system interactions

1. Haskard Zolnierek KB, et al. Med Care. 2009;47:826-834.

2. Osterberg L, et al. N Engl J Med. 2005;353:487-497.

E i T t t S i HCV


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Effective Communication Requires Time

and Access Schedule in-office visits to ensure sufficient time for pts to

address all of their issues

Respond to pt phone calls in a timely manner

Ensure support staff understand the need for a promptresponse

Provide pts with contact numbers (pager and cell phone)for around-the-clock access


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Making Educated Partners

Out of Friends and Family

E i T t t S i HCV


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Leverage Existing Social Support

Networks Medication adherence may improve with family/friend

support[1]

Practical support for daily living requirements consistently

improves adherence

Social support helps pts cope with adverse events[2]

Fewer adverse events reported when pts experiencesatisfying social support

1. Scheurer D, et al. Am J Manag Care. 2012;18:e461-e467.

2. Evon DM, et al. J Psychosom Res. 2011;71:349-356.



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Social Contacts Are Important Factors for

Adherence and Communication Address the pts social support needs before starting

therapy

Educate caregivers on what to expect and look for as

treatment proceeds

Caregivers can be an important source of information onthe pts true experience of treatment


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Use HCVs Natural History

Against It and Build Hope



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Impact of HCV Subgenotype on SVR Rates

With Protease InhibitorBased Therapy In treatment-naive trials, SVR rates numerically lower in

pts with genotype 1a HCV vs genotype 1b[1,2]

Genotype 1a: 59% to 71%

Genotype 1b: 66% to 79%

Prevalence of resistance associated variants might explaindifferences in SVR[3]

Rates of resistance associated variants higher ingenotype 1a

1. Poordad F, et al. N Engl J Med. 2011;364:1195-1206. 2. Jacobson IM, et al. N Engl J Med.

2011;364:2405-2416. 3. Brass CA, et al. EASL 2011. Abstract 1194.



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IL28BGenotype Remains a Predictor of

SVR in the Direct-Acting Antiviral Era

Soriano V, et al. J Antimicrob Chemother. 2012;67:523-529.

40

20

0

100

80

60

SVR(%)

CC

PR

Non-CC

SPRINT-2(N = 938)

78

28

CC

BOC + PR

Non-CC

67

80

40

20

0

100

80

60

CC

PR

Non-CC

ADVANCE(N = 1088)

64

24

CC

TVR + PR

Non-CC

72

90



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Education Is Key to Successful Treatment

Inform pts about the improved efficacy of HCV therapyand that HCV disease is curable

Use positive predictors of response such as IL28Band

HCV genotype to motivate pts to commit to therapy


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Managing the Therapeutic

Betrayal of Stopping Rules



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Despite Pts Desires, Futility Rules Must

Be Followed All therapy should be discontinued in pts with the

following:

*Assay should have a lower limit of HCV RNA quantification of 25 IU/mL and a limit of HCVRNA detection of ~ 10-15 IU/mL.

Boceprevir[1]Time Point

Criteria*

Wk 12 HCV RNA 100 IU/mLWk 24 HCV RNA detectable

Telaprevir[2]Time Point Criteria*Wk 4 or 12 HCV RNA > 1000 IU/mLWk 24 HCV RNA detectable

1. Boceprevir [package insert]. July 2012. 2. Telaprevir [package insert]. April 2013.



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Retrospective Analysis of TVR Ph III Trials

Underscores Validity of TVR Futility Rules No pt with HCV RNA > 1000 IU/mL at Wk 4 attained SVR

HCV RNA already rebounding, not still decreasing

Jacobson I, et al. EASL 2012. Abstract 55.

Tx Experienced (n = 11)Tx Naive (n = 14)

Wks on Treatment

0 2 4 6 8 10 12

10

102

103

104

105

106

107

108

0 2 4 6 8 10 12

10

102

103

104

105

106

107

108

HCV

RNA(IU/mL)

Wks on Treatment

HCV

RNA(IU/mL)



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Treatment Milestones: Educate Pts Early

to Avoid Confusion Futility rules for HCV treatments define thresholds for

virologic response without which SVR is very unlikely tooccur

Stopping treatment for futility limits adverse events, cost,and the risk of resistance

Ensure pts understand futility rules before starting therapy


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Recommend or Provide

Treatments for Common Adverse

Events Before They Are Needed



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Pretreatment Considerations for

Telaprevir-Associated Rash Alert pt to risk of rash (56% of pts in phase III trials)[1]

Majority of cases was mild to moderate[1]

4% severe rash[1]

Can occur at any time during 12 wks of telaprevir[1]

Good skin hygiene[2]

Emollient creams and lipid-rich lotions

Sunscreen, avoid prolonged sun exposure

1. Telaprevir [package insert]. April 2013. 2. Cacoub P, et al. J Heptol. 2012;56:455-463.



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su g ea e Success C

Mild( 25% BSA)

Moderate(25% to 50% BSA)

Severe(> 50% BSA)

US Food and Drug Administration. FDA briefing on boceprevir and telaprevir. May 2011.

Mild

Rash

Moderate

Rash

Severe

Rash



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g

Management Recommendations for

Mild or Moderate Rash Due to Telaprevir Monitor for systemic symptoms

Continue all medicines

Do not dose reduce or discontinue TVR

Watch for progression

Continue good skin hygiene

Consider topical steroids

Systemic steroids not recommended

Consider oral antihistamines

Mild

Moderate

Telaprevir [package insert]. April 2013.

Telaprevir: a guide to help you assess and manage rash.



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g

Management Recommendations for

Severe Rash Associated With Telaprevir Generalized rash involving either

> 50% BSA or any of the following

Vesicles or bullae

Superficial ulceration of mucousmembranes

Epidermal detachment

Atypical or typicaltarget lesions

Palpable purpura,nonblanching

erythema

Recommendations

Discontinue telaprevir

If no better in 7 days (or early ifindicated), discontinue RBV and/or

pegIFN

Do not resume telaprevir

Remind pt that SVR is still possible

Good skin care practices

Oral antihistamines and/or topicalcorticosteroids

Consider referral to dermatologist

Cacoub P, et al. J Hepatol. 2012;56:455-463. Telaprevir [package insert]. April 2013.

Severe



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g

Severe Skin Reactions Are Rare but

Possible With Telaprevir Treatment In all pts with rash, monitor for:

Stevens-Johnson syndrome

Fever, target lesions, mucosal erosions, or ulcerations

Drug reaction eosinophilia and systemic symptoms (DRESS)

Fever, facial edema, organ involvement (nephritis, hepatitis)

Eosinophilia may or may not be present

Discontinue all medications immediately

Refer for urgent medical care

Telaprevir [package insert]. April 2013. Cacoub P, et al. J Hepatol. 2012;56:455-463.



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g

Managing Anorectal Symptoms Resulting

From Telaprevir Treatment Anorectal discomfort manifests in 29% pts as:

Burning

Itching

Hemorrhoids

Rarely leads to discontinuation of treatment

Treatment of intolerable symptoms

Perianal topical lidocaine

Zinc oxide

Pearlman BL. Lancet Infect Dis. 2012;12:717-728.



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Anticipate and Prevent Potential Problems

Skin care

Especially important in winter in drier environments

Use OTC moisturizers from the beginning

Emphasize need for hydration, staying out of the sun

Anorectal care

Encourage prophylactic use of mediated wipes from Day 1

to minimize itching and discomfort


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Find and Stick With

a Single Specialty Pharmacy



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Specialty Pharmacies Serve Multiple

Functions Especially helpful for pts with comorbidities

Allows re-evaluation and alignment of all treatments tominimize drugdrug interactions

Look for comprehensive services, such as a dedicated GIor HCV team

Services may provide pt home visits by a specialist staffnurse


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Go Online for Expert Faculty

Discussion of Practical StrategiesCME/CE-Certified Video in which expert providers review theirtop 10 actionable recommendations

Downloadable PowerPoint Slidesetsummarizing the supporting data

clinicaloptions.com/HCVTenWays
http://www.clinicaloptions.com/HCVTenWayshttp://www.clinicaloptions.com/HCVTenWays

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