3HP A WAY TO DO IT INITIATION OF 3HP IN A STATEWIDE TB PROGRAM MISSISSIPPI STATE DEPARTMENT OF HEALTH NTCA April 2017, Atlanta GA TB Education and Training Projects: Updates from the Field August 10, 2017
I. Remind - 3hp study (ATS 5/2011, NEJM 12/2011 II. How our state piloted 3hp then moved to statewide use III. Issues/protocol to address when establishing and first starting a 3hp program AND HCW Education, Expertise, Settings?Missed doses?drug interactions?side effects IV. Completion Rates
ALREADY HAVE THE WHY DO 3HP- ATS 5/2011 3HP VS INH Self admin-reported 2011 7731 participants (Double blind randomized controlled trial) No statistical difference in TB disease outcomes 3HP higher completion rates versus INH (82% vs 69%) Less hepatotoxicity with 3HP(0.4% vs 2.4%) Treatment limiting adverse effects more common with 3HP (4.9 vs 3.7)
2017 High Rate of Treatment Completion in Program Settings with 12-Dose Weekly Isoniazid and Rifapentine (3HP) for Latent Mycobacterium tuberculosis Infection. Clin Infect Dis. May 2017; Multiple real life program settings with excellent completion rates over 2 year period
CID 5/17 RESULTS 3,327 persons started 3HP 3,288 eligible to complete treatment 39 stopped treatment for contraindication 421 (13%) discontinued treatment 2,867 (87%) completed treatment 246 (58%) discontinued with symptoms 175 (42%) discontinued for other reasons
MISSISSIPPI-2.9 MILLION POP Centralized agency 82 counties arranged in 9 districts governed by State Agency TB protocol (Now consolidated into 3 districts with budget cuts) County Health clinics do TB Infection testing (QFT or TST) for Contacts and any HIV patient identified by the health department We do not do testing for other reasons unless paid for by patient, but We offer TBI treatment to any with + QFT or TST if not considered a false positive Cost is to health department after any charges to insurance or Medicaid
Number of TBI Patients MISSISSIPPI TB INFECTION(TBI) PATIENTS 1991-2011 4000 3500 3hp pilot Started June 2011 3000 2500 2000 1500 1000 500 0 91 93 95 97 99 '01 '03 '05 '07 '09 '11 Year of Diagnosis
Completion Percentage MISSISSIPPI OVERALL COMPLETION OF TBI THERAPY 1988-2011(PRE 3HP) 100 90 3hp pilot Started 80 70 MS Goal 60 50 40 88 91 94 97 '00 '03 '06 '09 Year of Diagnosis Goal 85%
MISSISSIPPI STATE DEPARTMENT OF HEALTH Always the question what can we do better for patients and for program In 2011 - What will it take to try 3hp? Will nurses/clinicians/patients accept new regimen? Will we have adverse events? and then we will be the first to see?
3HP PILOT PROPOSED TO HEALTH DEPARTMENT ADMINISTRATION
PROS-2011 12 weeks vs. 9 months Promise of higher completion rates Non-inferior-possibly superior long-term protection
CONS-2011 Medication more expensive 3 months rifapentine apprx. $156.00 (Price now less $6 per week $70.92 for 12 doses Requires 12 vs. 9 nursing visits when compared to 9INH SA Possibly greater risk of hypersensitivity reaction due to intermittent dosing Not clear at that time
WHERE TO PILOT Proposed Pilot post CDC meeting and ATS presentation May 2011 Clinician Tuned in to TB/TBI patients Hinds County (Capitol City of Jackson) Most TB cases in state and with Homeless/0006 outbreak of past 4 years District 8 District Health Officer -Infectious Disease MD and actively involved with TB program
3HP ESTIMATED SAVINGS TO JUSTIFY PILOT MISSISSIPPI, JUNE 2011 The $ amounts for comparison assumed Fully compliant, non-complicated, hypothetical patients, Calculating minimal nursing/outreach time, and mid-range pricing for salary, Mid range pricing for laboratory testing and actual cost of drugs. Travel was based on a 10 mile round trip taking 15 minutes to complete. Nursing and outreach worker visits time based on 15 minutes per visit. Nursing visits based on $26.00 per hour (with travel to patient home) and outreach worker visits were based on $10.00 per hour. Testing for TBI, chest x-ray, HIV test, and physician visit are not included.
3HP Estimated Savings to Justify Pilot Consideration of $$ And Methods Proposal for 3hp Pilot Study- Reviewed three methods of Isoniazid-Rifapentine (3HP) administration; (1) 12 weeks of 3HP given by a nurse as directly observed therapy (3HP N) at patients home or workplace, (2) 12 weeks of 3HP given by a nurse/outreach worker team as directly observed therapy ((3HP O), and (3) 12 weeks of 3HP given by a nurse as directly observed therapy in clinic (3HP C).
3HP Estimated Savings to Justify Pilot Mississippi, June 2011 3HP C vs 9INH Self administered $159.56 (now $24.56) (including 45 minutes nursing time per patient) added by switching from 9 INH SA to 3HP C. 3HP increases lab ($5.56), drugs ($135.00 (now$55)), and nursing costs ($19.00). The benefit expected in this switch is in higher completion rates.
3HP CLINIC VS 9INH SELF ADMINISTERED The benefit expected in this switch is in higher completion rates. If an increase in completion from approximately 60% to greater than 80% then higher completion rates should translate into decreased morbidity and reduction in future transmission. By this estimate, switching to 3HP would increase cost $15,956.00 (Now $5456.00)per 100 patient completions but, would prevent two additional cases, 28 additional contacts, and 5.9 new infections (averaging 14 new contacts per case and a 21% reactor rate (MS Average) National average cost of treating a routine TB case is estimated at $20,000 to $25,000 dollars Est. $6927.00 as the minimal investigation cost Not calculated availability to focus on new contacts rather than keeping up with patients still on INH whether dot or SA
Only implement 3HP in the pilot areas prior to the release of CDC guidelines. Rifapentine usage was limited to the pilot physicians and the pilot areas by drugs at central HD pharmacy who only distributed to pilot clinician orders
Challenge 1 Approval done Challenge 2 Finding $$ Initial cost REAL $$ 2011 Cost RPT - $158.24 6/2011-10/2011 purchased 600 boxes with end of year money from MSDH field services to reduce nursing time 2017 Cost 340B pricing $ 0.96 for 150 mg tablet of rifapentine $5.76 for 900 mg dose rifapentine $0.15 for 900 mg INH 12 doses - $70.92 Challenge 3 Develop Policy with minimal information but we have more info now
CREATION OF POLICY/PROTOCOL/EDUCATION Who is eligible AGE > 18 years then > 12 years (now 2-12 years with approval of pediatric TB consultant)) years of age, Documented HIV- (now if HIV + and if not on meds), Non-pregnant or lactating, Not contact to INH or RIF resistant TB Not on drug that has unmanageable interaction-?warfarin, phenytoin, carbamazepine, methadone, etc.hormonal Contraception (must use other method) Comorbidities DM? HTN? RA on biologics? Who will review Drug interactions? Nurse, NP, Pharmacist, MD Who can do directly observed therapy? Where will DOT be? How often labs baseline and monthly? How often assessments-baseline and monthly? Minimal time between meds? > 72 hours no more than 5 doses in 28 days Maximal time What do we consider completion 11 or 12 doses? Within what time period? 12 doses in 16 weeks. If 3hp is stopped due to a reaction can other TBI be attempted?
CREATION OF POLICY/EDUCATION OF NURSES Who is eligible Clients >18 ( AGE then > 12 years (now 2-12 years with approval of pediatric TB consultant)) years of age, documented HIV- (now if not on meds), non-pregnant or lactating, not contact to INH or RIF resistant TB Not on drug that has unmanageable interaction-?warfarin, phenytoin, carbamazepine, methadone, etc.hormonal Contraception Who/How to review Co-morbidities, Drug interactions? Nurse, NP, Pharmacist, MD Who can do directly observed therapy? Where will DOT be? How often labs baseline and monthly? How often assessments-baseline and monthly? Minimal time between meds? > 72 hours no more than 5 doses in 28 days Maximal time What do we consider completion 11 or 12 doses? Within what time period? 12 doses in 16 weeks. If 3hp is stopped due to a reaction can other TBI be attempted?
CREATION OF POLICY/EDUCATION OF NURSES Who is eligible Clients >18 ( AGE then > 12 years (now 2-12 years with approval of pediatric TB consultant)) years of age, documented HIV- (now if not on meds), non-pregnant or lactating, not contact to INH or RIF resistant TB Who will review Drug interactions? Nurse, NP, Pharmacist, MD Who can do directly observed therapy? Where will DOT be? How often labs baseline and monthly? How often assessments-baseline and monthly? Minimal time between meds? > 72 hours no more than 5 doses in 28 days Maximal time What do we consider completion 11 or 12 doses? Within what time period? 12 doses in 16 weeks. If 3hp is stopped due to a reaction can other TBI be attempted?
CREATION OF POLICY/EDUCATION OF NURSES Who is eligible Clients >18 ( AGE then > 12 years (now 2-12 years with approval of pediatric TB consultant)) years of age, documented HIV- (now if not on meds), non-pregnant or lactating, not contact to INH or RIF resistant TB Who will review Drug interactions? Nurse, NP, Pharmacist, MD Who can do directly observed therapy? Where will DOT be? How often labs baseline and monthly? How often assessments and who does?-baseline and monthly? Minimal time between meds? > 72 hours no more than 5 doses in 28 days Maximal time What do we consider completion 11 or 12 doses? Within what time period? 12 doses in 16 weeks. If 3hp is stopped due to a reaction can other TBI be attempted?
CREATION OF POLICY/EDUCATION OF NURSES Who is eligible Clients >18 ( AGE then > 12 years (now 2-12 years with approval of pediatric TB consultant)) years of age, documented HIV- (now if not on meds), non-pregnant or lactating, not contact to INH or RIF resistant TB Who will review Drug interactions? Nurse, NP, Pharmacist, MD Who can do directly observed therapy? Where will DOT be? How often labs baseline and monthly? How often assessments-baseline and monthly? Minimal time between meds? > 72 hours no more than 5 doses in 28 days Maximal time What do we consider completion 11 or 12 doses? Within what time period? 12 doses in 16 weeks. If 3hp is stopped due to a reaction can other TBI be attempted?
CREATION OF POLICY/EDUCATION OF NURSES Who is eligible Clients >18 ( AGE then > 12 years (now 2-12 years with approval of pediatric TB consultant)) years of age, documented HIV- (now if not on meds), non-pregnant or lactating, not contact to INH or RIF resistant TB Who will review Drug interactions? Nurse, NP, Pharmacist, MD Who can do directly observed therapy? Where will DOT be? How often labs baseline and monthly? How often assessments-baseline and monthly? Minimal time between meds? > 72 hours no more than 5 doses in 28 days Maximal time What do we consider completion 11 or 12 doses? Within what time period? 12 doses in 16 weeks. If 3hp is stopped due to a reaction can other TBI be attempted?
PATIENT COUNSELING Number of Meds Need to report any change in other meds Report symptoms Who to call if issues Potential AEs Birth Control Food prior to meds
ADVERSE EVENTS Protocol?Automatic stop orders until labs can be checked; elevated liver tests; Or Who to Call? NP? MD? PCP? Symptomatic treatment - Ondansterone prior to 3hp; NSAIDs, etc.
3HP PILOT MISSISSIPPI Release of guidelines in Dec. 2011 Added HIV + if on no meds to pilot Added children > 12 years of age Added two additional districts (appr 18 counties ) Statewide policy completed March 2012 (approximately nine months after beginning pilot) to allow all districts and counties to utilize
TRAINING OF HCW By starting with a pilot Limited Area minimized number of HCW to train initially When set up statewide Informational piece in Statewide Mississippi Monthly Report directed to State MD s with emphasis on directly observed regimen The pilot directs expansion for what your nurses, ORW s and providers concerns and educational needs might be Also will recognize any unexpected issues with patients
ANECDOTAL CHALLENGES A little harder than we thought to complete Incentives of no benefit if patient had nausea or flu like symptoms usually refused to continue Enablers with bus tokens most helpful to come for dosing and blood work Patients sometimes balked at number of pills; chose longer regimenanecdotally older patients Most often nine pills Three 300 mg tabs INH Six 150 mg tables RFP What do you do with someone that has completed 6 weeks of 3hp and has worsening flu like symptoms not responsive to symptomatic treatment?
PATIENTS WHO STOPPED 3HP BUT COMPLETED ANOTHER REGIMEN 2011-2017 MISSISSIPPI 20 Chart Title 18 16 14 12 10 8 6 4 2 0 INH Rifampin I &RIF 3hp/rif 3hp/inh 2011 2012 2013 2014 2015 2016* 2017
ISSUES WITH SPECIFIC POPULATIONS
IF PATIENT HOSPITALIZED FOR REASON UNRELATED TO TBI TREATMENT - If admitted/transferred to hospital ensuring hospital understands regimen Few hospitals familiar with regimen
NURSING HOME PATIENTS Ensuring NH gives med/has familiarity with adverse reactions Ensuring f/u labs If transferred to hospital ensuring hospital understands regimen
HOMELESS Easier to search for once a week rather than twice a week for INH DOT. Stable housing more likely to complete all regimens
JAIL MSDH Nurses are currently distributing in Jails, In State Prison we have a TB nurse Frequent turnover with nurses Reeducation Issues with movement of prisoners and finding them if discharged Tried to utilize with patient we would know would be incarcerated at least 4-6 months CDC trial men with hx of incarceration less likely to complete any regimen
OTHERS HIV median CD4 500 2 Cases of TB in 3hp n = 206 (89%CR) group 6 cases in INH group n = 193 (64% CR) Work with primary HIV provider if delaying HIV meds Sterling et al, AIDS 2016 SOT 8 livers and 4 kidneys All completed 40 months no TB Knoll et al Infection, 2017
STILL CHALLENGES OF COST Will completion rates justify hard costs? 3HP consistently higher than INH completion rates; Is four months of rifampin better/cheaper than 3hp? Drug Costs have to be paid up front Consider Pilot with patients with third party payers 2017 Cost 340B pricing $ 0.96 for 150 mg tablet of rifapentine $5.76 for 900 mg dose rifapentine $0.15 for 900 mg INH 12 doses - $70.92 Nursing time saved is harder to measure and the payoff is slow in decrease in TB cases $$ actually saved
TRAINING NURSES Nurses have to become comfortable with medications and reactions Pilot gives them initial opportunity Once comfortable with new regimen then is preferred by nurses to nine months of treatment. Nursing Quotes It is the best new development for TB program Actually observe just once a week done in 12 weeks rather than uncertainty of 9 months Don t have to find patients and then start all over
Completion Percentage MISSISSIPPI OVERALL COMPLETION OF TBI THERAPY 100 90 80 70 60 50 40 30 20 10 MS Goal 0 '06 '09 '12 '15 Year of Diagnosis Goal 85%
% Completion COMPLETION OF TBI THERAPY 2002-2016 MISSISSIPPI STATE DEPT OF HEALTH 90 85 5 years of 3hp Program 80 75 70 65 60 Five years before starting 3hp program 55 2011 2012 2013 2014 2015 2016 Overall 76 77 77 81 81 3hp %Cpt 70 84.5 82.9 80.1 85 78.6 INH %CPLT 75 77.4 77 76 73 RIF %CPT 71 75 76 77 72 2002-2010 68 66 72 75 68 60
STARTING A PROGRAM Pilot Target an area AND target healthy group Greatest upfront cost from meds 340B pricing- Buy in from nurses and providers, administrators, pharmacy, outreach workers Establish protocol for assessments and labs, Standing orders for hold of meds for adverse reactions
STARTING A PROGRAM Ensure review of drug interactions and adverse reactions with patient and what to do if occur Cannot use with Coumadin or other drugs that might lead to variable levels Emphasize non hormonal birth control for all of cycle that includes any 3hp Decisions for HIV +, Pt to go on Biologics, Homeless, Pre and Post Transplant Develop expertise triage those patients to that expertise because often an individualized decision Guidelines for attempting other meds for completion