Breakout Session C2 Christine Ho April 21, 2017

Transcription

1 3HP (12 dose Weekly INH and Rifapentine) Today and Tomorrow Christine S. Ho, M.D., M.P.H. CDC Division of Tuberculosis Elimination National Tuberculosis Conference TB Infection Breakout Session April 21, 2017 National Center for HIV/AIDS, Hepatitis, STD and Tuberculosis Prevention Division of Tuberculosis Elimination Financial Disclosure No financial interests to disclose 9 months of daily isoniazid Treatment Choices for LTBI 9 months of twice weekly isoniazid 6 months of daily isoniazid 4 months of daily rifampin labile 12 doses of weekly isoniazid and rifapentine up to 900 mg Isoniazid up to 900 mg Rifapentine Known as 12 dose INH RPT or 3HP DOT only 1

2 December 2011 A New Regimen is Born Sterling et al. Prevent TB study (TBTC Study 26) Multi site randomized control trial: INH RPT by DOT vs. 9H by SAT 7731 high risk persons enrolled Jun 01 Feb 08 INH RPT by DOT as effective as 9H in preventing TBhigher completion rate; less hepatotoxicity; more hypersensitivity Long term safety monitoring important CDC Recommendations: 12 dose INH RPT by DOT 12 weekly DOT doses of INH RPT an equal alternative to 9 months of daily self supervised INH for treating LTBI Use in otherwise healthy patients aged 12 years with a greater risk of developing TB Contacts Convertors Those with radiographic findings of healed TB HIV infected patients who are otherwise healthy and not taking antiretroviral medications For children aged 2 11 INH RPT can be considered on a case by case basis Vigilance for drug hypersensitivity reactions, particularly hypotension or thrombocytopenia MMWR Dec 9, 2011 Post marketing INH RPT Project Objectives Monitor for adverse events with 3 month INH RPT in nonresearch settings Track number of patients started on regimen Note if certain populations, risk factors or settings are associated with adverse effects (AE) more often Assess adherence and treatment completion Assess impact of INH RPT on programs Staffing Costs Conduct passive surveillance for TB after 2 years TB registry match Drug resistant TB 2

3 Post Marketing Surveillance Project Sites 16 sites using the regimen, 22 sites contributed to project design and forms DOT used for all sites Project period: June 2011 through December 2013 Bureau of Prisons Participated in study design Shared treatment results Participating Sites Represented Different Types of Programs State TB programs Entire state centralized programs Select counties decentralized programs County programs Health department (HD) partnered with community providers, student health clinics, correctional facilities Mandatory LTBI reporting in some sites Rifapentine access Some programs controlled access to RPT (authorization required) Some programs paid for RPT Some programs ordered and provided RPT Project Design Multiple volunteer sites implementing 3HP carry out postmarketing surveillance Modifiable data templates to record findings Core information collected by all sites Number of treatment starts Demographics Treatment reason Symptom review Treatment outcome Some sites collect additional information about patient characteristics or medical conditions 3

4 Template Forms Final Disposition: Completed INH RPT treatment Stopped INH RPT treatment Date / / Lost to follow up Died Other Adverse event Pending Completion of Alternate Regimen Recording Adverse Events 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 4

5 Results: Demographic Characteristics (n=3288) Patient Characteristics Total Number (%) No. completed 3HP (%) Sex Male 1759 (53.5) 1550 (88.1) Female 1529 (46.5) 1317 (86.1) Age (yrs.) 2 to (5.0) 155 (94.5) 18 to (31.5) 921 (89.1) 31 to (29.0) 834 ( 87.5) 45 to (28.6) 803 (85.3) (6.0) 154 (78.6) Race/ethnicity Hispanic 751 (22.8) 682 (90.8) Non Hispanic white 721 (21.9) 595 (82.5) Non Hispanic black 1195 (36.3) 1035 (86.6) Asian 540 (16.4) 481 (89.1) Other a 81 (2.5) 74 (91.4) Country of birth United States 1994 (60.6) 1699 (85.2) Foreign born 1294 (39.4) 1168 (90.3) Range of Treatment Completion Across 16 U.S. Sites, June 2011 December 2013 Treatment Completion Rate (%) * L E J A F D I N K H O P C B G M Participating Site * Proportion completing treatment among those eligible to complete at that site Number of participants at each site ranged from 14 to 1018 Completion ranged from % Discontinuation while reporting symptoms ranged from 0 16% Factors Associated with Treatment Discontinuation (n=3,288) Factor No. discontinued (%) Univariable Analysis RR (95% CI) Multivariable Analysis arr (95% CI) Male 208 (11.8) 0.85 ( ) ( ).041 Age 421 (12.8) 1.01 ( ) < ( ) <.001 Contact 70 (8.5) 0.60 ( ) < ( ).005 Corrections within past year 65 (12.6) 0.98 ( ) ( ).013 Homeless within past year 34 (18.8) 1.51 ( ) ( ).001 Student 7 (5.4) 0.41 ( ) ( ).044 Subgroup analysis for medical conditions and behavioral factors associated with Treatment discontinuation (n=2389) Current or past smoker 101 (18.9) 1.53 ( ) < ( )

6 Factor Factors Associated with Treatment Discontinuation (n=3,288) No. discontinued (%) Univariable Analysis RR (95% CI) Multivariable Analysis arr (95% CI) Male 208 (11.8) 0.85 ( ) ( ).041 Age 421 (12.8) 1.01 ( ) < ( ) <.001 Contact 70 (8.5) 0.60 ( ) < ( ).005 Corrections within past year 65 (12.6) 0.98 ( ) ( ).013 Homeless within past year 34 (18.8) 1.51 ( ) ( ).001 Student 7 (5.4) 0.41 ( ) ( ).044 Subgroup analysis for medical conditions and behavioral factors associated with Treatment discontinuation (n=2389) Current or past smoker 101 (18.9) 1.53 ( ) < ( ).002 Factor Factors Associated with Treatment Discontinuation (n=3,288) No. discontinued (%) Univariable Analysis RR (95% CI) Multivariable Analysis arr (95% CI) Male 208 (11.8) 0.85 ( ) ( ).041 Age 421 (12.8) 1.01 ( ) < ( ) <.001 Contact 70 (8.5) 0.60 ( ) < ( ).005 Corrections within past year 65 (12.6) 0.98 ( ) ( ).013 Homeless within past year 34 (18.8) 1.51 ( ) ( ).001 Student 7 (5.4) 0.41 ( ) ( ).044 Subgroup analysis for medical conditions and behavioral factors associated with Treatment discontinuation (n=2389) Current or past smoker 101 (18.9) 1.53 ( ) < ( ).002 Proportion of Patients on 3HP Who Stopped Treatment by Dose 11 doses counted as completion of therapy Y axis shows proportion of patient who had the dose as their last dose divided by total patients who received that dose 6

7 Number of patients that started 3HP reporting symptoms at least once, by treatment outcome (n=1174) % 400 5% 12% 3% 300 8% 7% 8% % 9% 3% 2% 5% 5% 6% 6% 6% 3% 2% 2% 5% 2% 4% 4% 1% 1% 4% 1% 3% 5% 3% 4% 4% 3% 3% 3% 3% 0.20% 0.40% 0.7% 0 Completed Tx Discontinued Tx Summary 3HP regimen is being used successfully in the United States Initial programmatic experience is similar to treatment trial experiences High completions rates, notably in difficult populations Nausea is the most common reason for stopping treatment, but the majority of patients with nausea completed the regimen No deaths or severe organ damage detected Next Steps Treatment completion manuscript accepted by CID Draft manuscript on adverse events and association with medical conditions and medications completed Analysis in search of possible syndromes using market basket analysis almost completed Cost effectiveness analysis poster accepted at ATS conference 3HP standard regimen in Bureau of Prisons system 7

8 Other rifapentine based projects TB Trials Consortium (TBTC) Study 33 3HP SAT vs. DOT manuscript awaiting acceptance TBTC Study 35 pharmokinetic studies of dispersible rifapentine in children 3HP performance in other settings: Indian Health Services Veterans Administration Iqaluit community in the arctic circle! Collaboration between TBTC and TBESC for 6 week daily rifapentine clinical trial INH RPT Post implementation Workgroup Naveen Patil, Leonard Mukasa Rose Sales Mike Holcombe, Risa Webb Shea Rabley Jon Warkentin Jane Moore Ann Davis, Carla Chee Mike Arbisi Dick Brostrom, Derrick Felix Diana Fortune, Marco Burgos Dean Tsukiyama, Deb Sodt Neha Shah, Charlie Crane, Julie Higashi, Marisa Moore, Kim Fields, Mark Lobato, Kelley Bemis Maria Galves Garrett Hunt Phil Griffin Krissie Guerguard, Dee Pritschet Acknowledgments Lorna Will Margaret Oxtoby Narita Masa Sara Burr, Sherri Wheeler Kevin Winthrop, Heidi Behm CDC Field Services and Evaluation Branch Amy Sandul Bunie Nwana Vern Green Gail Grant Mark Miner John Jereb, Sundari Mase, Terry Chorba Victor Balaban Vincent Fears, Regina Gore, Andy Heetderks, Dan Ruggiero, Dawn Tuckey, Awal Khan, Lakshmy Menon, Brandy Peterson, Judy Gibson Data Management and Surveillance Branch Jose Becerra Lon Gross Clinical Research Branch Andy Vernon Elsa Villarino Ruth Moro Andrey Borisov Stefan Goldberg Nigel Scott Surveillance, Epidemiology and Outbreak Branch Tom Navin Krista Powell Severe Adverse Events Severe Adverse Events (SAE): any patient who was hospitalized or died while receiving 3HP 34 hospitalizations reported, not necessarily attributed to 3HP 11 seen in the ED but not hospitalized No deaths No serious or permanent medical sequelae Hospitalizations investigated in coordination with national surveillance for LTBI SAE project under Krista Powell and Lilia Manangan 8