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

GRAPPA PsA Treatment Guidelines Establish Diagnosis of Psoriatic Arthritis Reassess Response to Therapy and Toxicity Initiate Therapy NSAID PT Biologics (anti-TNF) Axial Disease Peripheral Arthritis Initiate Therapy NSAIDs, IA steroids, DMARDs (MTX, CsA, SSZ, LEF), Biologics (anti-TNF) Skin and Nail Disease Initiate Therapy Topicals PUVA/UVB DMARDs (MTX,CsA,etc) Biologics (anti-TNF, etc) Dactylitis Initiate Therapy NSAID Injection Biologics (anti-TNF) Enthesitis Initiate Therapy NSAID Injection Biologics (anti-TNF)

Methods GRAPPA PsA Treatment Guidelines 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

Methods Principles of Systemic Review of Published Medical Literature 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 assessed 1 GRAPPA PsA Treatment Guidelines 1 Ann Intern Med 1997; 126:

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

Effect Size GRAPPA PsA Treatment Guidelines d = x 1 -x c s pooled d = Cohen’s d effect size x = Mean (average of treatment or comparison conditions) s = Standard deviation

Reporting Clinical Practice Guidelines (Conference on Guideline Standardization COGs) GRAPPA PsA Treatment Guidelines Overview material Focus Evidence Collection Goal Users/Setting Target Populations Developer Funding Source/Sponsor Recommended Grading Criteria Method for Synthesizing Evidence Prerelease Review Update Plan Definitions Recommendations, Rationale Potential Benefits, Harms Algorithm Implementation Considerations

GRAPPA PsA Treatment Guidelines

Evidence Presentations 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

GRAPPA PsA Treatment Guidelines Establish Diagnosis of Psoriatic Arthritis Reassess Response to Therapy and Toxicity Initiate Therapy NSAID PT Biologics (anti-TNF) Axial Disease Peripheral Arthritis Initiate Therapy NSAIDs, IA steroids, DMARDs (MTX, CsA, SSZ, LEF), Biologics (anti-TNF) Skin and Nail Disease Initiate Therapy Topicals PUVA/UVB DMARDs (MTX,CsA,etc) Biologics (anti-TNF, etc) Dactylitis Initiate Therapy NSAID Injection Biologics (anti-TNF) Enthesitis Initiate Therapy NSAID Injection Biologics (anti-TNF)

Combining the evidence into Guidelines: Values / Process Cost / Availability Patient Preference Political Combining: Decision analyses etc. GRAPPA PsA Treatment Guidelines

Evidence based? treatment algorithm for Peripheral PsA PolyarthritisOligoarthritisMonoarthritis Early DMARDs SSZ (A); LFN (A); MTX (B), CyA (B) NSAIDs (A) +/- IA corticosteroids (D) Respond Anti TNF alpha ? Positive Response Failed Response ? Adequate therapeutic trial of 2 DMARDs ?

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?