Idea Transcript
Targeted Immune Modulators for Rheumatoid Arthritis: Effectiveness & Value Draft Evidence Report January 20, 2017
Prepared for
©Institute for Clinical and Economic Review, 2017
ICER Staff/Consultants
University of Colorado School of Pharmacy (Anschutz Medical Campus) Modeling Group*
Daniel A. Ollendorf, PhD
Jonathan Campbell, PhD Associate Professor Department of Clinical Pharmacy Center for Pharmaceutical Outcomes Research
Chief Scientific Officer Institute for Clinical and Economic Review
Rick Chapman, PhD, MS Director of Health Economics Institute for Clinical and Economic Review
Steven D. Pearson, MD, MSc President Institute for Clinical and Economic Review
Varun Kumar, MBBS, MPH, MSc Health Economist Institute for Clinical and Economic Review
Melanie D. Whittington, PhD Professional Research Assistant Department of Clinical Pharmacy R. Brett McQueen, PhD Assistant Professor Department of Clinical Pharmacy Center for Pharmaceutical Outcomes Research
Foluso Agboola, MBBS, MPH Research Scientist Institute for Clinical and Economic Review
Patricia Synnott, MALD, MS Senior Research Associate Institute for Clinical and Economic Review
Shanshan Liu, MS, MPH Research Associate Institute for Clinical and Economic Review
Celia Segel, MPP Program Manager, New England CEPAC Institute for Clinical and Economic Review
Sonya Khan, MPH Program Director, Midwest CEPAC Institute for Clinical and Economic Review
DATE OF PUBLICATION:
*The role of the University of Colorado Skaggs School of Pharmacy Modeling Group is limited to the development of the cost-effectiveness model, and the resulting ICER reports do not necessarily represent the views of the UC.
JANUARY 20, 2017
We would also like to thank Margaret Webb, Noah Mwandha, and Erin Lawler of ICER for their contributions to this report. ©Institute for Clinical and Economic Review, 2017 Draft Evidence Report: Targeted Immune Modulators for Rheumatoid Arthritis
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About ICER The Institute for Clinical and Economic Review (ICER) is an independent non-profit research organization that evaluates medical evidence and convenes public deliberative bodies to help stakeholders interpret and apply evidence to improve patient outcomes and control costs. ICER receives funding from government grants, non-profit foundations, health plans, provider groups, and health industry manufacturers. For a complete list of funders, visit http://www.icerreview.org/about/support/. Through all its work, ICER seeks to help create a future in which collaborative efforts to move evidence into action provide the foundation for a more effective, efficient, and just health care system. More information about ICER is available at http://www.icerreview.org
About New England CEPAC The New England Comparative Effectiveness Public Advisory Council (New England CEPAC) – a core program of ICER – provides a public venue in which the evidence on the effectiveness and value of health care services can be discussed with the input of all stakeholders. New England CEPAC seeks to help patients, clinicians, insurers, and policymakers interpret and use evidence to improve the quality and value of health care. The New England CEPAC is an independent committee of medical evidence experts from across New England, with a mix of practicing clinicians, methodologists, and leaders in patient engagement and advocacy. All Council members meet strict conflict of interest guidelines and are convened to discuss the evidence summarized in ICER reports and vote on the comparative clinical effectiveness and value of medical interventions. More information about New England CEPAC is available at http://icer-review.org/programs/new-england-cepac/.
©Institute for Clinical and Economic Review, 2017 Draft Evidence Report: Targeted Immune Modulators for Rheumatoid Arthritis
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Expert Review In the development of this report, ICER’s researchers consulted with clinical experts, patients, manufacturers and other stakeholders. In addition, the Arthritis Foundation worked with ICER to deploy surveys of the Foundation’s membership on access to care issues, patient experience per type of treatment received, and other concerns. The results of these surveys are summarized in the report. The following experts provided input and
21
(tofacitinib or tasocitinib or tofacitinib citrate or Xeljanz).ti,ab.
22
(sarilumab or REGN88).ti,ab.
23
(baricitinib or LY3009104 or INCB028050).ti,ab.
24
21 or 22 or 23
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24 and 3
26
25 or 20
27
(animals not (humans and animals)).sh.
28
26 not 27
29
limit 28 to english language
30
(abstract or addresses or autobiography or bibliography or biography or clinical trial, phase I or case report or comment or congresses or consensus development conference or duplicate publication or editorial or guideline or in vitro or interview or lecture or legal cases or legislation or letter or news or newspaper article or patient education handout or periodical index or personal narratives or portraits or practice guideline or review or videoaudio media).pt.
31
cohort studies/ or longitudinal studies/ or prospective studies/ or retrospective studies/ or comparative study.pt
32
control Groups/ or (control* adj2 (clinical or group* or trial* or study or studies or design* or arm*)).ti,ab. or ("clinical trial" or "clinical trial, phase ii" or clinical trial, phase iii or clinical trial, phase iv or controlled clinical trial or "multicenter study" or "randomized controlled trial").pt. or (randomi?ed adj6 (study or trial* or (clinical adj2 trial*))).ti,ab. or ((single or doubl*) adj2 blind*).ti,ab.
33
31 or 32
34
29 not 30
35
34 and 33
36
Remove duplicates from 35
Table A3. Search Strategies of EMBASE on September 2, 2016 #1
'rheumatoid arthritis'/exp
#2
((rheumatoid OR rheumatic OR rheumat*) NEAR/3 (arthrit* OR diseas* OR condition*)):ab,ti
#3
#1 OR #2
#4
‘abatacept’/exp OR abatacept:ab,ti OR orencia:ab,ti
#5
‘rituximab’/exp OR rituximab:ab,ti OR rituxan:ab,ti OR mabthera:ab,ti
#6
'tocilizumab'/exp OR tocilizumab:ab,ti OR atlizumab:ab,ti OR actemra:ab,ti OR roactemra:ab,ti
#7
‘infliximab’/exp OR infliximab:ab,ti OR remicade:ab,ti
#8
'etanercept'/exp OR etanercept:ab,ti OR enbrel:ab,ti
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#9
'adalimumab'/exp OR adalimumab:ab,ti OR humira:ab,ti
#10
'certolizumab pegol'/exp OR 'certolizumab pegol':ab,ti OR cimzia:ab,ti
#11
'golimumab'/exp OR golimumab:ab,ti OR simponi:ab,ti
#12
#4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11
#13
#3 AND #12
#14
#13 AND [2010-2016]/py
#15
#14 AND ('chapter'/it OR 'conference abstract'/it OR 'conference paper'/it OR 'conference review'/it OR 'editorial'/it OR 'letter'/it OR 'note'/it OR 'review'/it OR 'short survey'/it)
#16
#14 NOT #15
#17
'tofacitinib'/exp OR tofacitinib:ab,ti OR tasocitinib:ab,ti OR 'tofacitinib citrate':ab,ti OR xeljanz:ab,ti
#18
'baricitinib'/exp OR baricitinib:ab,ti
#19
'sarilumab'/exp OR sarilumab:ab,ti
#20
#17 OR #18 OR #19
#21
#3 AND #20
#22
#21 AND ('chapter'/it OR 'conference review'/it OR 'editorial'/it OR 'letter'/it OR 'note'/it OR 'review'/it OR 'short survey'/it)
#23
#21 NOT #22
#24
#16 OR #23
#25
'animal'/exp OR 'nonhuman'/exp OR 'animal experiment'/exp
#26
'human'/exp
#27
#25 AND #26
#28
#25 NOT #27
#29
#24 NOT #28
#30
#29 AND [english]/lim
#31
#30 AND [medline]/lim
#32
#30 NOT #31
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Figure A1. PRISMA flow chart showing results of literature search for rheumatoid arthritis
3,588 potentially relevant references screened
747 references for full text review
2,841 citations excluded Population: 701 Intervention: 150 Comparator: 245 Outcomes: 268 Study design: 1,134 Duplicates: 343
636 citations excluded (posthoc analyses, placebo-controlled trials, sample size limitations, conference abstract duplicated peer-reviewed publication)
• 31 publications (published prior to 2010) identified from previous systematic reviews
142 TOTAL 68 RCTs o 108 publications o 18 conference abstracts 16 observational studies
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Appendix B. Public and Representative Private Insurer Coverage Policies Table B1: Coverage Policies for New England Commercial Payers Connecticut Anthem (Wellpoint Inc Group)
Connectica re
Maine Anthe m (Wellp HPHC oint Maine Inc Group)
TNFα inhibitors etanercept (Tradename: Enbrel; Manufacturer: Amgen) How many cDMARDs 1 1 1 How many TNFs 0 0 0 etanercept AND adalimumab? No No No No Preferred Agent Yes No Yes Yes infliximab (Tradename: Remicade; Manufacturer: Janssen) How many cDMARDs 1 1 1 NL How many TNFs 0 2 2 NL etanercept AND adalimumab? No No No NL Preferred Agent Yes No Yes NL adalimumab (Tradename: Humira; Manufacturer: AbbVie) How many cDMARDs 1 1 1 How many TNFs 0 0 0
Massachusetts BCBS of MA
Neighborhood Health Plan
Tufts Health Plan
Anthem (Wellpoint Inc Group)
HPHC New Hampshire
1 0
1 0
1 0
1 0
1 0
1 0 No Yes
No Yes
1 2 No No
1 0
New Hampshire
No Yes
1 0 No Yes
1 0
©Institute for Clinical and Economic Review, 2017 Draft Evidence Report: Targeted Immune Modulators for Rheumatoid Arthritis
No Yes
1 0 No Yes
1 0
No Yes
1 0 No Yes
1 0
1 0 No Yes
1 2 Yes No
1 0
Rhode Island Neigh borho BCBS od of RI Healt h Plan of RI
1 1
1 0
2 0 No Yes
1 0 No Yes
1 0
BCBS of VT
1 0 No Yes
No Yes
Vermont
2 2 Yes No
1 0
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2 0
Connecticut Anthem (Wellpoint Inc Group)
Connectica re
Maine Anthe m (Wellp HPHC oint Maine Inc Group)
Massachusetts BCBS of MA
etanercept AND adalimumab? No No No No No Preferred Agent Yes Yes Yes Yes Yes certolizumab pegol (Tradename: Cimzia; Manufacturer: UCB) How many cDMARDs 1 1 1 1 How many TNFs 2 2 2 1 etanercept AND adalimumab? No No No No Yes Preferred Agent No Yes No No No golimumab (Tradename: Simponi; Manufacturer: Janssen) How many cDMARDs 1 1 1 1 How many TNFs 0 2 2 1 etanercept AND adalimumab? No No No No Yes Preferred Agent Yes Yes Yes No No CD20- directed cytolytic antibodies rituximab (Tradename: Rituxan; Manufacturer: Genentech) How many cDMARDs 1 1 0 NL How many TNFs 1 2 1 NL etanercept AND adalimumab? No No No NL Yes Preferred Agent No Yes No NL No Tcell inhibitors abatacept (Tradename: Orencia; Manufacturer: Bristol Myers Squibb)
Neighborhood Health Plan
Tufts Health Plan
Anthem (Wellpoint Inc Group)
HPHC New Hampshire
No Yes
No Yes
No Yes
No Yes
1 2
1 0 No Yes
1 2
1 0 No Yes
1 0 No Yes
1 2
New Hampshire
©Institute for Clinical and Economic Review, 2017 Draft Evidence Report: Targeted Immune Modulators for Rheumatoid Arthritis
No Yes
1 0 No Yes
NL NL NL NL
1 2
1 0
1 1 No No
No Yes
No Yes
Yes No
No No
No Yes
Yes No
No No
2 2 Yes No
1 0 No Yes
1 2
BCBS of VT
1 0
1 2
1 2 No No
No Yes
1 2
1 1
1 1 No No
Vermont
1 1 No No
No Yes
Rhode Island Neigh borho BCBS od of RI Healt h Plan of RI
2 2 Yes No
NL NL NL NL
2 2 Yes No
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Connecticut Anthem (Wellpoint Inc Group)
Connectica re
Maine Anthe m (Wellp HPHC oint Maine Inc Group)
How many cDMARDs 1 1 1 How many TNFs 2 2 2 etanercept AND adalimumab? No No No No Preferred Agent No No No No IL-6 inhibitors tocilizumab (Tradename: Actemra; Manufacturer: Genentech) How many cDMARDs NF 1 1 How many TNFs NF 2 2 etanercept AND adalimumab? NF No No No Preferred Agent NF No No No JAK inhibitors tofacitinib (Tradename: Xeljanz; Manufacturer: Pfizer) How many cDMARDs 1 1 1 How many TNFs 2 2 2 etanercept AND adalimumab? No No No No Preferred Agent No No No Yes
Massachusetts
New Hampshire
BCBS of MA
Neighborhood Health Plan
Tufts Health Plan
Anthem (Wellpoint Inc Group)
HPHC New Hampshire
1 2
1 1
1 1
1 2
1 2
1 1 Yes No
1 1
0 No
1 2 Yes No
1 0
1 0 No Yes
1 2 Yes No
0 No
1 2 Yes No
1 0 No Yes
©Institute for Clinical and Economic Review, 2017 Draft Evidence Report: Targeted Immune Modulators for Rheumatoid Arthritis
No No
1 0 No Yes
No No
1 2
Rhode Island Neigh borho BCBS od of RI Healt h Plan of RI 1 2 No No
1 1
No No
No No
NL NL
NL NL
NL NL
NL NL
0
1 2
2 2 Yes No
1 0 No Yes
1 2 No No
BCBS of VT
1 1
No
No No
Vermont
2 2 Yes No
1 0 No No
2 2 Yes No
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Table B2. Coverage Policies for New England Medicaid Programs New England Medicaid Programs Connecticut
Maine
Massachusetts
New Hampshire
Rhode Island
Vermont
TNFα inhibitors adalimumab (Tradename: Humira; Manufacturer: AbbVie) Step Therapy
Yes
Yes
NL
Yes
NL
NL
PA
Yes
No
Yes
Yes
No
Yes
Preferred Agent
Yes
Yes
No
Yes
Yes
Yes
certolizumab pegol (Tradename: Cimzia; Manufacturer: UCB) Step Therapy
Yes
Yes
NL
Yes
NL
NL
PA
Yes
Yes
Yes
Yes
Yes
Yes
Preferred Agent
No
No
No
No
No
No
etanercept (Tradename: Enbrel; Manufacturer: Amgen) Step Therapy
Yes
Yes
NL
Yes
NL
NL
PA
Yes
No
Yes
Yes
No
Yes
Preferred Agent
Yes
Yes
No
Yes
Yes
Yes
golimumab (Tradename: Simponi; Manufacturer: Janssen) Step Therapy
Yes
Yes
NL
Yes
NL
NL
PA
Yes
Yes
Yes
Yes
Yes
Yes
Preferred Agent
No
No
No
No
No
No
infliximab (Tradename: Remicade; Manufacturer: Janssen) Step Therapy
Yes
Yes
NL
Yes
NL
NL
PA
Yes
No
Yes
Yes
Yes
Yes
Preferred Agent
No
No
No
No
No
No
CD20- directed cytolytic antibodies rituximab (Tradename: Rituxan; Manufacturer: Genentech) Step Therapy
NL
NL
Yes
NL
NL
NL
PA
Yes
NL
Yes
NL
NL
NL
Preferred Agent
NL
NL
No
NL
NL
NL
Tcell inhibitors abatacept (Tradename: Orencia; Manufacturer: Bristol Myers Squibb) Step Therapy
Yes
Yes
NL
Yes
NL
NL
PA
Yes
Yes
Yes
Yes
Yes
Yes
Preferred Agent
No
No
No
No
No
No
IL-6 inhibitors tocilizumab (Tradename: Actemra; Manufacturer: Genentech) Step Therapy
Yes
Yes
NL
Yes
NL
NL
PA
Yes
Yes
Yes
Yes
Yes
Yes
Preferred Agent
No
No
No
No
No
No
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New England Medicaid Programs Connecticut
Maine
Massachusetts
New Hampshire
Rhode Island
Vermont
JAK inhibitors tofacitinib (Tradename: Xeljanz; Manufacturer: Pfizer) Step Therapy
Yes
Yes
NL
Yes
NL
NL
PA
Yes
Yes
Yes
Yes
Yes
Yes
Preferred Agent
No
No
No
No
No
No
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Appendix C. Comparative Clinical Effectiveness Supplemental Information Methods: Supplemental Information We performed screening at both the abstract and full-text level. A single investigator screened all abstracts identified through electronic searches according to the inclusion and exclusion criteria described earlier. We did not exclude any study at abstract-level screening due to insufficient information. For example, an abstract that did not report an outcome of interest would be accepted for further review in full text. We retrieved the citations that were accepted during abstract-level screening for full text appraisal. One investigator reviewed full papers and provided justification for exclusion of each excluded study. We used criteria published by the US Preventive Services Task Force (USPSTF) to assess the quality of RCTs and comparative cohort studies, using the categories “good,” “fair,” or “poor” (see Appendix Table F)54 Guidance for quality ratings using these criteria is presented below, as is a description of any modifications we made to these ratings specific to the purposes of this review. Good: Meets all criteria: Comparable groups are assembled initially and maintained throughout the study; reliable and valid measurement instruments are used and applied equally to the groups; interventions are spelled out clearly; all important outcomes are considered; and appropriate attention is paid to confounders in analysis. In addition, intention to treat analysis is used for RCTs. Fair: Studies were graded "fair" if any or all of the following problems occur, without the fatal flaws noted in the "poor" category below: Generally comparable groups are assembled initially but some question remains whether some (although not major) differences occurred with follow-up; measurement instruments are acceptable (although not the best) and generally applied equally; some but not all important outcomes are considered; and some but not all potential confounders are addressed. Intention to treat analysis is done for RCTs. Poor: Studies were graded "poor" if any of the following fatal flaws exists: Groups assembled initially are not close to being comparable or maintained throughout the study; unreliable or invalid measurement instruments are used or not applied equally among groups (including not masking outcome assessment); and key confounders are given little or no attention. For RCTs, intention to treat analysis is lacking.
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Additional Comparative Clinical Effectiveness Results Table C1: DAS28-ESR measure and Number Needed Treated (NNT) in trials of TIMs versus conventional DMARDs DAS28-ESR remission rate Intervention Biologic Conventional DMARD TIMs plus conventional DMARD vs. conventional DMARD Biologic Naïve and Mixed Population Rituximab132 9 2 76 Abatacept 11 3 Tocilizumab133-136 30-38 2-4 82,137 Tofacitinib 6-9 1-3 84,138 Baricitinib 16-25 1-5 Adalimumab82,84 7-18 1-5 139,140 Certolizumab 17-26 0-6 Etanercept59,141 22-25 4-14 69,142 Golimumab 20-35 6-7 76 Infliximab 13 3 TIMs plus conventional DMARD vs. conventional Biologic Experienced Sarilumab†143,144 29-34 7-14 72 Baricitinib 9 3 TIMs monotherapy vs. conventional Tocilizumab65,66 43-59 1.6-3 67 Etanercept 34 19 145 Golimumab 12 6
P value
NNT
Number of trials (Total N)