Transcript Implementation of TTT in RA Through a Learning Collaborative

Implementation of Treat to Target
in RA Through a Learning
Collaborative
Daniel H. Solomon, MD, MPH
Chief, Section of Clinical Sciences
Professor of Medicine
Matthew H. Liang Distinguished Chair
Division of Rheumatology
Division of Pharmacoepidemiology
Brigham and Women’s Hospital
Harvard Medical School
NIH-P60-AR047782
Disclosures
•
•
•
•
NIH: NIAMS, NIA, NHLBI
PCORI
A&R Deputy Editor
Research grants: Amgen, Lilly, Pfizer, BMS,
Genentech, Astra Zeneca, CORRONA
• Pfizer, Executive Committee PRECISION trial (unpaid)
• UpToDate royalties
• No personal financial relationship with any
pharmaceutical company
Unsuspecting rheumatologists feeling confused
when considering TTT
What is TTT?
• Brigham Fellows:
– “The new paradigm in RA treatment is for early
diagnosis and treatment with goals of remission
and prevention of long-term sequelae.”
– “TTT for RA to me means to have the patient with
no significant morning stiffness, joint pain or
swelling.”
What is TTT?
• Brigham Attendings:
– “Using DAS < 2.6 as target for DMARD therapy.”
– “Treating with medications in order to meet a prespecified, quantitative target for disease activity.”
– “Change or add therapy to get to low disease
activity or remission.”
EULAR Recommendations for TTT
Overarching Principles:
A. The treatment of RA must be based on a shared decision
between patient and rheumatologist.
A.The
treatment
of RA
based
B. The
primary
goal of treating
the must
patientbe
with
RA is toon a
maximize
long-term
health-related
quality
of life through
shared
decision
between
patient
and
control of symptoms,
prevention of structural damage, and
rheumatologist.
normalization of function and social participation.
C. Abrogation of inflammation is the most important way to
achieve these goals.
D. Treatment to target by measuring disease activity and
adjusting therapy accordingly optimizes outcomes in RA.
Ref: Smolen et al, ARD, 2010
EULAR Recommendations for TTT
1. The primary target for treatment of rheumatoid arthritis
should be a state of clinical remission. (III)
2. Clinical remission is defined as the absence of signs and
symptoms of significant inflammatory disease activity.(IV)
3. While remission should be a clear target, based on available
evidence low disease activity may be an acceptable
1.The
primary
target goal,
for treatment
rheumatoid
alternative
therapeutic
particularlyof
in established
longstanding should
disease.(Ib)
arthritis
be a state of clinical remission.
4. Until the desired treatment target is reached, drug therapy
should be
least every 3months.(Ib)
2.Until
theadjusted
desiredattreatment
target is reached, drug
5.therapy
Measuresshould
of disease
activity must
obtained
be adjusted
at be
least
everyand
3months.
documented regularly, as frequently as monthly for patients
with high/moderate disease activity or less frequently (such
as every 3–6months) for patients in sustained low disease
activity or remission.(IV)
Ref: Smolen et al, ARD, 2010
6. The use of validated composite measures of disease activity, which include
joint assessments, is needed in routine clinical practice to guide treatment
decisions.(IV)
7. Structural changes and functional impairment should be considered when
making clinical decisions, in addition to assessing composite measures of
3. The
use of validated composite measures of
disease
activity.(IV)
8. Thedisease
desired treatment
should
be maintained
activity,target
which
include
jointthroughout the
remaining course of the disease.(III)
is needed
in routine
clinical
9. Theassessments,
choice of the (composite)
measure
of disease activity
and the level of
thepractice
target value
may
be influenced
by consideration
of co-morbidities,
to
guide
treatment
decisions.
patient factors and drug-related risks.(IV)
10.The patient has to be appropriately informed about the treatment target
and the strategy planned to reach this target under the supervision of the
4. The patient has to be appropriately
rheumatologist.(IV)
informed about the treatment
target and the
Ref: Smolen et al, ARD, 2010
strategy planned to reach this target under the
supervision of the rheumatologist.
Do you practice TTT?
• Brigham Fellows:
– “YES”
– “YES”
– “YES”
Do you practice TTT?
• Brigham Attendings:
– “Mostly”
– “No”
– “No, I don’t find that the concept provides for an
individualized balanced discussion about
tradeoffs between toxicity and disease control.”
– “Yes”
– “TTT is not viable in patients who have failed a
biologic-- lucky to see any response; TTT is most
helpful in new onset disease.”
Structured RA Disease Activity
• Which one? We cannot even agree how to
measure RA disease activity!
– With an APR or not?
– How important is the patient global and tender
joint count?
– Biomarker panel?
ACR Recommendations for RA Disease
Activity Measures
Measure
Scale
Remission Low
Moderate
High
Patient driven
PAS
0-10
0-0.25
0.26 – 3.7
3.71 – 7.9
8+
RAPID-3
0-10
0-1
1.1 - 2
2.1 - 4
>4
> 10 - 22
>22
Patient and provider
CDAI
0-76
≤ 2.8
> 2.8 – 10
Patient and provider with laboratory
DAS28
0-9.4
< 2.6
2.6 – 3.1
3.2 – 5.1
> 5.1
SDAI
0-86
≤ 3.3
> 3.3 - 11
> 11- 26
>26
Ref: Anderson et al, AC&R, 2012
Even if we can agree
on which target….
• Which is the best
“route” to achieve the
target?
TTT’s Attraction
• Establishing a Target allows for measurement
of a process associated with each visit.
• Targets are possible when many treatments
exist (many “routes”).
• Other well recognized targets:
– DM targets Hgba1c
– LDL targets
– BP targets
Selected Prior Trials Demonstrating Benefits of TTT
• At least 10 RCTs have found that TTT produces better
outcomes than usual care in RA, including reduced
pain, improved function, better DAS scores, and less
radiographic progression.
• The treatment algorithm used has varied and the
exact schedule of visits has varied.
• Most trials have occurred in Europe.
Why Rheumatologists Do Not Change
Treatment
• Patients with RA in
Australia with DAS28
• 584 were in MDA or HDA
and had no change in
DMARDs
• Rheumatologists
recorded barriers to
treatment change
Barriers to Treatment Change
%
Irreversible joint damage
20
Patient driven undertreatment
15
MD driven undertreatment
10
Non-inflammatory MSK pain
9
Waiting for DMARD response
9
Safety or contraindications
8
Comorbidities
7
DMARD resistant RA
6
Other*
16
*Logistics, reimbursement, pregnancy
Tymms, AC&R, 2014
Implementation of TTT in RA
Through a Learning Collaborative
DH Solomon, E Losina, B Lu, A Zak, C Corrigan, SB
Lee, J Agosti, A Bitton, LR Harrold, T Pincus, H
Radner, Z Yu, JS Smolen, L Fraenkel, JN Katz
Division of Rheumatology, Division of Pharmacoepidemiology, Department of
Orthopaedics, Brigham and Women’s Hospital, Harvard Medical School,
University of Massachusetts Medical School, Rush Medical School, Medical
University of Vienna, Yale School of Medicine
NIH-P60-AR047782
Acknowledgment
Practice Sites
Team Members
Cedars Sinai (Venturapali)
Venturapali, Gaggi, Uy, Bustos, Vasquez
Loyola
Tehrani, Ostrowski, Briones, Murphy
North Shore
Grober, Malik, Woodrick, Lynn, Sun, Drevlow, Zaacks, Bilbrey, Chavez,
Casey, Gan, Myers
Park Nicollet
Paisansinsup, Shousboe, Glickstein, Steele
University of Kansas
Lindsley, Schmidt, Colbert, Springer, Bhadbhade, Parker, Estephan,
McMillian, Heneghan
University of Kentucky
Lohr, Hanaoka, Lightfoot, Jenkins, Baker, Bisono, Wafford, Wiard, Lenert,
Howard
University of Houston
Scholz, McCray, Barnes, Tan, Homann
University of Vermont
Hynes, Bethina, Kennedy, Lau, Edwards, Libman, Farely
Univeristy of Virginia
Kimpel, Lewis, D’Souza, Potter, Carlson, Mosteanu, Khalique, Khurana,
Swamy
UTMB -- Galveston
Murthy, Musty, Rudrangi, Ganti, Gonzalez, McCullum
Vanderbilt
Annapureddy, Kroop, Hayden
Design
• Cluster randomized controlled trial
• Wait list control (step wedge design)
Intervention
• Learning Collaborative (LC)
–
–
–
–
Developed by Institute for Healthcare Improvement
Team learning with frequent measurement
Rapid cycle improvement (PDSA cycles)
Central team coaches with each team contributing to
the collaborative
– Central website for sharing PDSA cycles, results,
questions, resources
– Face-to-face meeting to start with monthly webinars
– Faculty developed a change package which guided LC
Change Package
Shared decision
making
Valid disease
Activity measure
Use a target and stick
to it
Site Recruitment
• E-mail contact with smaller academic programs plus other practices
• 25 rheumatology practices responded
• Telephone contact to describe program, assess interest, and whether practice
already implemented TTT
• 12 sites expressed interest and were randomized
• 1 site dropped out before start of first phase
Total
Providers
Patient Insurance (%)
Trainees
MidLevels
Total
Patients
Seen in 2014
Medicare
Medicaid
Commercial
None
Treatment Arm
Site location
Intervention
Chicago IL
3
No
No
1800-2000
31
16
49
4
Houston TX
5
Yes
No
1000
20
20
55
5
Suburban Chicago, IL
10
No
No
920
35
5
59
1
Louisville KY
9
Yes
Yes
1850
23
33
38
3
Burlington VT
5
Yes
Yes
NA
NA
NA
NA
NA
Minneapolis MN
6
No
No
2300
13
12
72
3
Los Angeles CA
2
No
Yes
350
60
1
35
4
Kansas City KS
10
Yes
Yes
500
40
10
45
5
Galveston TX
6
Yes
No
4000
40
15
40
5
UVA Rheumatology
5
No
Yes
550
25
10
50
5
Nashville TN
2
No
No
250
25
5
60
10
Control
Measurement of TTT Adherence
TTT Adherence: 4 components based on visit note
1.
2.
3.
4.
Treatment target
Disease activity measure
Follow TTT paradigm (or if not, document why not)
Shared-decision making if change in target or change in treatment
Implementation Score
1.
2.
Ordinal score using above 4 components
Converted into a percentage
Patient sampling
1.
2.
3.
Providers participating in at least one learning session
>40 patients/site with RA with a visit during periods of interest
Sampled visits in 3-months prior to intervention and last 3-months of
intervention period
Table 1: Baseline subject characteristics
Control
(n = 321)
Learning
Collaborative
(n = 320)
N (%) unless noted
Age*, years, mean
BMI*, kg/m2, mean
Female sex
RA duration*, years
≤2
2-5
6-10
>10
Serologic status*
Positive
Use of synthetic DMARDs
Use of biologic DMARDs
Comorbidity index, mean ( SD)
Joint erosion
Yes
Total medications
0
1-5
6-10
10+
60
30.1
78
60.
29.4
79
16
29
22
34
26
25
24
25
P-value
0.75
0.24
0.72
0.12
0.15
76
77
41
1.33
82
81
46
1.28
53
60
0.25
0.16
0.24
0.19
0.16
0
13
32
55
0.3
17
37
47
Figure 1: TTT Implementation
Control sites
70
Intervention sites
p <.0001
60
p =0.004
Percent adherence
50
40
30
20
p = 0.93
10
0
Baseline
Follow-up
Change in
implementation score
Table 2: TTT Implementation Components
100
100
Target
80
80
60
P = 0.065
40
20
20
0
0
Baseline
Follow-up
Change
Shared Decision Making
80
P < 0.001
40
20
20
0
0
Follow-up
Change
Follow-up
Change
Treatment Decision
60
40
Baseline
Baseline
100
80
60
P = 0.002
60
40
100
Disease Activity Measure
P = 0.064
Baseline
Follow-up
Change
Percentage of visits fully adherent with TTT
Figure 2: Full Adherence with TTT
100
Control
80
Learning collaborative
60
P = 0.045
40
25.9%
20
P = 0.25
0.0% 0.6%
Baseline
5.6%
Follow-up
Table 3: Resource use and adverse events
Control
(n = 321)
Learning
Collaborative
(n = 320)
P-value*
Number of tests or adverse events
(mean number per patient)
Monitoring laboratory tests (CBC, CMP)
2614 (8.14)
2591 (8.10)
0.67
CRP or ESR
788 (2.45)
607 (1.90)
0.66
Plain x-ray of musculoskeletal system
308 (0.96)
247 (0.77)
0.96
CT of musculoskeletal system
6 (0.019)
12 (0.038)
0.50
MRI of musculoskeletal system
14 (0.044)
16 (0.050)
0.77
Adverse events (GI, renal, liver, infxn, etc)
138 (0.43)
83 (0.26)
0.04
Table 4: Supplementary findings
Control
(n = 69)
Disease activity measure
Intervention
(n = 284)
N (%)
Remission
18 (26.1%) 115 (40.5%)
Low
19 (27.5%)
73 (25.7%)
Moderate
16 (23.2%)
59 (20.8%)
High
19 (23.2%)
37 (13.0%)
Visits w/ DMARD changes
Control Intervention
(n = 321)
(n = 320)
N (%)
0- 30%
198 (62%)
201 (63%)
>30 – 79%
101 (31%)
64 (20%)
22 (7%)
55 (17%)
80-100%
P-value
0.07
P-value
0.0001
Strengths/Limitations
• RCT across the US, but relatively small and
participants unblinded to treatment.
• Objective assessment tool to determine TTT
adherence with high reliability, but assessors
unblinded to treatment assignment.
• Complex intervention (Learning Collaborative)
but likely required for behavior change.
Conclusions
1. Baseline TTT implementation was very low.
– Even in these mostly academic programs.
2. A Learning Collaborative was an effective
intervention to improve implementation of TTT.
– But, few visits (25%) were fully adherent.
3. Explicit treatment target and following paradigm
were most common deficiencies.
4. No excess in resource use or adverse events
observed.
Implications regarding TTT
• More should be done to enhance adoption of
TTT in the US as baseline rates are low.
• A Learning Collaborative is a proven
intervention to enhance adoption of TTT, but
it requires investment of time by practices.
– Should professional societies promote TTT
Learning Collaboratives?
– How can practices be incentivized to participate in
Learning Collaboratives or other QI efforts?
Thanks ([email protected])