Validation%20of%20the%20OMERACT-OARSI%20Responder%20Index:%20Responders%20Have%20Better%20Overall%20Health%20Status%20than%20Non-responders

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Validation of the OMERACT-OARSI Responder
IndexResponders Have Better Overall Health
Status than Non-responders

• Marc C. Hochberg, Barker Bausell, Kevin Frick,
  Donald Steinwachs and Brian Berman
• University of Maryland School of Medicine and The
  Johns Hopkins Bloomberg School of Public Health,
  Baltimore, Maryland, USA

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Objective

• To validate the OMERACT-OARSI Responder Index
• Test the hypothesis that patients with knee OA
  participating in a clinical trial who fulfil the
  OMERACT-OARSI Responder Index will have better
  overall health status as measured by both
  arthritis-specific and general measures.

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Patient Cohort

• 570 patients with symptomatic knee OA enrolled in
  a randomized, 3-arm, 6-month, parallel group
  trial
• Traditional Chinese acupuncture
• Sham acupuncture
• Education/attention control

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Outcome Measures

• WOMAC Osteoarthritis Index
• Likert format
• Patient Global Assessment
• Health Assessment Questionnaire (HAQ)
• Medical Outcomes Study (MOS) SF-36
• European Quality of Life (EuroQoL)

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Data Analysis

• Data from all 3 treatment groups pooled for this
  analysis
• Responders identified using OMERACT-OARSI
  Responder Index
• Pham T et al J Rheumatol 2003301648-54
• Outcomes in responders compared to those in
  non-responders using Students t-test
• Analysis conducted on ITT population
• Sensitivity analysis on completers only

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Baseline Characteristics (N570)

• Age
• Mean (SD) 65.5 (8.6) years
• Sex
• Men (36), Women (64)
• Race
• White (69), Black (29), Other (2)
• Marital status Married (60)
• Education High-school graduates (91)

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Baseline Data (N570)

• WOMAC OA Index
• Pain 43.5 (17.0)
• Function 45.3 (17.6)
• Total 45.6 (16.6)
• HAQ
• Pain 1.4 (0.7)
• Disability 0.62 (0.41)
• EuroQoL
• EQ-5D 0.63 (0.22)
• EQ-VAS 75.9 (16.7)

• MOS SF-36
• Phys Funct 40.3 (22.3)
• Role Phys 44.3 (40.1)
• Bodily Pain 45.2 (19.9)
• Gen Health 70.6 (17.9)
• Role Emot 73.3 (37.5)
• Vitality 54.2 (20.8)
• Ment Heal 79.4 (14.2)
• Social Act 79.3 (23.0)

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Comparison of Outcomes by OMERACT-OARSI Response

• 236 (41.4) of 570 patients randomized achieved
  an OMERACT-OARSI Response at the end of study
• 61 of 386 completers

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WOMAC Scores by OMERACT-OARSI Response
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HAQ Scores by OMERACT-OARSI Response
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EuroQoL Scores by OMERACT-OARSI Response
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SF-36 Scores by OMERACT-OARSI Response
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Comparison of Outcomes by OMERACT-OARSI Response

• 234 (43) patients randomized achieved an
  OMERACT-OARSI Response at the end of study
• 61 of patients completing the study
• Responders had significantly better
  arthritis-specific and general health status than
  non-responders based on the WOMAC, HAQ, SF-36 and
  EuroQoL instruments (P lt 0.001 for all
  comparisons)

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Conclusion

• These data validate the OMERACT-OARSI Responder
  Index.
• Results unchanged when analysis performed only
  with completers (N 386)
• OMERACT-OARSI Responder Index should be
  considered as primary outcome for clinical trials
  of symptomatic therapies in patients with OA.

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State Measures - 2

• Minimal Clinically Important Improvement (MCII)
• Smallest change in measurement that signifies an
  important improvement in a patients symptom
• 75ile of distribution of change score among
  those who had good or excellent improvement with
  therapy
• Tubach F et al Ann Rheum Dis 20056429-33

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State Measures - 2

• Patient Acceptable Symptom State (PASS)
• Value in a measurement of a patients symptom
  beyond which the patient considers herself well
• 75ile of distribution of absolute score among
  those who are satisfied with their current state
  after therapy
• Tubach F et al Ann Rheum Dis 20056434-7

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State Measures in OA Patients

• MCII
• Pain 177 (33)
• Function 220 (41)
• Global 136 (25)

• PASS
• Pain 241 (44)
• Function 221 (41)
• Global 177 (33)

Highly significant association between achieving
an OMERACT-OARSI Response and having either an
MCII or a PASS for each of the 3 domains,
especially pain and function.
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Measurement of clinical outcomes

• WOMAC Osteoarthritis Index
• Lequesne Algofunctional Index
• Knee Injury and Osteoarthritis Outcome Score
  (KOOS)
• Roos EM, Lohmander LS HQLO 2003I64
• http//www.hqlo.com/content/1/1/64

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Knee Rating Scales for Athletic Patients

• Modified Lysholm Scale
• Cincinnati Knee Rating System
• AAOS Sports Knee Rating Scale
• ADL Scale of the Knee Outcome Survey
• Single Assessment Numeric Evaluation
• Knee Injury and OA Outcome Score
• QoL Outcome Measure for Chronic ACL Def
• International Knee Documentation Committee
• Marx RG Arthroscopy 2003191103-8

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KOOS

• Evaluates both short- and long-term consequences
  of knee injury
• 42 items in 5 separately scored domains
• Pain
• Other symptoms
• Function in daily living
• Function in sport and recreation
• Knee-related quality of life

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KOOS

• Validated in several populations
• Surgical reconstruction of ACL
• Knee arthroscopy
• Meniscectomy 16 years previously
• Total knee arthroplasty
• Autologous cartilage transplantation

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KOOS

• Reliable
• Responsive
• Effect sizes gt 1.0 for all 5 subscales in
  patients undergoing arthroplasty and tibial
  osteotomy
• Effect sizes gt 0.5 for all 5 subscales in
  patients undergoing ACL reconstruction and
  meniscectomy

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KOOS vs. WOMAC

• KOOS contains WOMAC pain, function and stiffness
  subscales (Likert v3.0)
• KOOS adds 18 questions covering sport and
  recreational function, knee-related quality of
  life and other symptoms
• Larger effect sizes with KOOS
• Younger subjects with knee injury
• Older subjects with total knee arthroplasty

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Summary

• There are numerous options for assessing
  clinically relevant outcomes in trials of
  products used for cartilage repair
• KOOS is the recommended self-report measure of
  pain, function and QoL
• http//www.koos.nu

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Other Potential Clinical Outcomes

• Time to joint replacement surgery
• Time to indication for joint replacement surgery
• Time to fulfil criteria for joint replacement
  surgery
• Time to failure of therapy
• Proportion of patients with success on Rx

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Clinically relevant outcomes

• Time to TJR
• TJR is a cost-effective procedure
• Recommended after failure of medical Rx
• Limitations
• Variability in decision to perform TJR
• Length of surgical waiting lists (queue)
• Patient related factors, including willingness
• Racial/ethnic and gender disparities

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Clinically relevant outcomes

• Time to decision to perform TJR
• Same limitations re surgeons variability
• Time to fulfil criteria to perform TJR
• Objective scoring based on pain, loss of function
  and health-related QoL
• Appropriateness criteria
• Subject of a SIG during OMERACT 7
• Maillefert JF et al J Rheumatol in press.
• Follow-up meeting was held in Paris 17/12/04

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Clinically relevant outcomes

• Time to treatment failure
• Prespecified amount of joint space loss
• Significant worsening of pain and/or function
• Proportion of patients with success
• Lack of loss of joint space by a prespecified
  amount
• Clinically relevant improvement in pain and/or
  function

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Prevention of the Occurrence of Incident OA

• Definition of incident OA
• Structural
• Arthroscopy
• Radiography
• MRI
• Symptomatic

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ACI Compared with Microfracture in the Knee

• RCT 80 patients followed for 2 years
• Similar clinical outcomes
• Lysholm and VAS pain score
• Significant difference in SF-36 PCS favoring
  microfracture group
• Similar structural outcomes
• Arthroscopy
• Histology of cartilage biopsies
• Knutsen et al J Bone Jt Surg 200486-A455-64

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Thank you for your time and attention.