Transcript GRAPPA PsA Treatment Guidelines Establish Diagnosis of Psoriatic

GRAPPA PsA Treatment Guidelines
Guidelines Mission Statement
“To develop guidelines, based upon the best
scientific evidence, for the optimal treatment
of patients with psoriatic arthritis (PsA).”
Guidelines: “Systematically developed
statements to assist practitioner and patient
decisions about appropriate health care for
specific clinical circumstances” IOM
GRAPPA PsA Treatment Guidelines
Considerations Relevant to
Guideline Creation in PsA
• PsA may follow heterogeneous, variable clinical course
• More research needed on important prognostic factors
(e.g. oligo vs poly) to allow optimal stratification
• PsA multifaceted (axial/periph joints, skin, etc): Work is
progressing on classification criteria (CASPAR)
• How appropriate is extrapolation of efficacy/safety data
from similar conditions (psoriasis, AS, RA, etc)?
• Determine most appropriate outcome measures
(signs/symptoms, structural integrity, QOL/functional
status)
• Guideline exigency driven by introduction of novel
immunomodulatory therapies
GRAPPA PsA Treatment Guidelines
If Guidelines Are Based on Best Available
Evidence, How Do We Handle:
• When “state of the art” outstrips peer-reviewed published
medical literature?
• That quality of newer studies is superior to older studies?
• The variable diagnostic criteria / outcomes in trials?
• The absence of studies for certain accepted therapies
(e.g. steroids)?
• The absence of head-to-head trials?
• Aphorism: “The absence of evidence of an effect is not
equivalent to evidence of absence of an effect”
When there is no data, what is the role of “expert” opinion?
GRAPPA PsA Treatment Guidelines
Methods
• Determine areas of interest for obtaining data (axial
disease, peripheral arthritis, skin, enthesitis, dactylitis)
• Formulate questions for the systematic review; for the
different manifestations (and based on disease
characteristics…)
– What is the effect of a given therapy on clinical
manifestations (including signs/symptoms, QOL/Fx,
structural integrity)? What is the effect size
– What is the effect of a given therapy as regards
safety? What is the effect size?
• Systematic literature review; excerpting data
• Identify key areas for research (i.e. lacking data)
• Re-assemble into unifying guideline
GRAPPA PsA Treatment Guidelines
Establish Diagnosis of Psoriatic Arthritis
Peripheral
Arthritis
Skin and
Nail Disease
Initiate
Therapy
Initiate
Therapy
NSAIDs,
IA steroids,
DMARDs
(MTX, CsA,
SSZ, LEF),
Biologics
(anti-TNF)
Topicals
PUVA/UVB
DMARDs
(MTX,CsA,etc)
Biologics
(anti-TNF, etc)
Axial
Disease
Dactylitis
Enthesitis
Initiate
Therapy
Initiate
Therapy
Initiate
Therapy
NSAID
PT
Biologics
(anti-TNF)
NSAID
Injection
Biologics
(anti-TNF)
NSAID
Injection
Biologics
(anti-TNF)
Reassess Response to
Therapy and Toxicity
GRAPPA PsA Treatment Guidelines
Methods
After considerations of relevant characteristics of PsA,
the best available evidence is collected, graded and
utilized to formulate recommendations. An important
task is the identification of areas lacking sufficient data
to support recommendations.
In an attempt to produce guidelines of the highest
quality, as guidelines are developed, we will adhere to
the Conference on Guideline Standardization
recommendations.1
1
Shiffman et al; Ann Intern Med 2003; 139:493
GRAPPA PsA Treatment Guidelines
Methods
Principles of Systemic Review of Published Medical Literature
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Review addresses a focused clinical question
Literature search strategy is explicit and reproducible
Literature review is comprehensive
Criteria for selection of articles for review are described
Criteria for selection of patients/patient groups w/in each article for
analysis are described
• Criteria for outcome assessments of patients/patient groups are
defined
• Articles and patients are assessed by multiple reviewers using a
standard form; differences of interpretation resolved by consensus
• Assembled data are quantitatively assessed1
1
Ann Intern Med 1997; 126: 376-80
GRAPPA PsA Treatment Guidelines
GRAPPA is using a systematic review of the literature, including languages
other than English, using established principles for such reviews.1
Retrieved articles are graded according to the categories of evidence
suggested by the Agency for Health Care Policy Research (AHCPR).
Categories Include:
1A Evidence from meta-analysis of randomized controlled trials (RCT)
1B Evidence from one or more RCTs
2A Evidence from 1 or more controlled trials (without randomization)
2B Evidence obtained through other well-designed studies (quasi-experimental)
3 Evidence from non-experimental studies (e.g. comparative, correlation or case-control)
4 Expert committee opinions, clinical experience
1
Cook et al; Ann Intern Med 1997: 126:376
GRAPPA PsA Treatment Guidelines
When the best evidence is extracted from published
literature, recommendations are graded accordingly:
Grade A: Based on category 1 evidence
Grade B: Category 2 evidence
Grade C: Category 3 evidence
Grade D: Category 4 evidence
GRAPPA PsA Treatment Guidelines
Effect Size
d=
x1-xc
spooled
d = Cohen’s d effect size
x = Mean (average of treatment or comparison
conditions)
s = Standard deviation
GRAPPA PsA Treatment Guidelines
Reporting Clinical Practice Guidelines
(Conference on Guideline Standardization COGs)
Overview material
Method for Synthesizing Evidence
Focus
Prerelease Review
Goal
Update Plan
Users/Setting
Definitions
Target Populations
Recommendations, Rationale
Developer
Potential Benefits, Harms
Funding Source/Sponsor
Algorithm
Evidence Collection
Implementation Considerations
Recommended Grading Criteria
GRAPPA PsA Treatment Guidelines
GRAPPA PsA Treatment Guidelines
Evidence Presentations
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Peripheral Arthritis– Enrique Soriano
Axial Involvement – Peter Nash
Skin – Souyma Reddy
Enthesitis – Chris Ritchlin
Dactylitis – Philip Helliwell
Questions – Discussion and Voting
GRAPPA PsA Treatment Guidelines
Establish Diagnosis of Psoriatic Arthritis
Peripheral
Arthritis
Skin and
Nail Disease
Initiate
Therapy
Initiate
Therapy
NSAIDs,
IA steroids,
DMARDs
(MTX, CsA,
SSZ, LEF),
Biologics
(anti-TNF)
Topicals
PUVA/UVB
DMARDs
(MTX,CsA,etc)
Biologics
(anti-TNF, etc)
Axial
Disease
Dactylitis
Enthesitis
Initiate
Therapy
Initiate
Therapy
Initiate
Therapy
NSAID
PT
Biologics
(anti-TNF)
NSAID
Injection
Biologics
(anti-TNF)
NSAID
Injection
Biologics
(anti-TNF)
Reassess Response to
Therapy and Toxicity
GRAPPA PsA Treatment Guidelines
Combining the evidence into
Guidelines: Values / Process
• Cost / Availability
• Patient Preference
• Political
Combining: Decision analyses etc.
Evidence based? treatment algorithm for Peripheral PsA
Polyarthritis
Oligoarthritis
Monoarthritis
?
Early DMARDs
SSZ (A); LFN (A); MTX
(B), CyA (B)
?
Adequate therapeutic
trial of 2 DMARDs ?
Anti TNF alpha
Positive Response
Failed Response
NSAIDs (A) +/- IA
corticosteroids (D)
Respond
1. Will GRAPPA guidelines be
focused on reimbursement or
treatment?
2. Can we “borrow” evidence from AS (or
other diseases, such as RA, Osteo or
Psoriasis) when there is an absence of
data in PsA? (what do we do when there
is no direct evidence from PsA? Look at
RCTs in RA/AS; look at eminence rather
than evidence data? Is level A evidence
from other diseases more relevant than
expert opinion in PsA when there is no
data for PsA?)
3. Do we only count skin data from PsA
clinical trials or can we include assessment
from psoriasis trials?
4. Given that PsA trials tend to be
few in number, is it appropriate to
borrow safety databases from
other diseases to help assess
safety of these compounds,
including effect size?
5. What influence, if any,
should the presence or severity
of bone and/or cartilage
damage as evidenced on X-ray
have concerning therapeutic
choices?
6. Should treatment guidelines be separate
for polyarticular vs. olioarticular? What if
only 1 or 2 joints are involved but the
involvement is severe (i.e., extensive
osteolysis or ankylosis)? What about
patients who have SAPHO?
7. What measures should we use to
assess Rx response (PsARC, modified
ACR, DAS28, or other measures)?
What data should be collected and what
outcome measures should be used in
the clinic and in clinical trials?
8. What are the holes in our evidence
that prevents us from addressing issues
of guidelines appropriately?