5/4/2018. Outcome Measures in Spondyloarthritis. Learning Objectives. Outcome Measures Clinical Outcome Assessments

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1 Outcome Measures in Spondyloarthritis Marina N Magrey MD Associate Professor Case Western Reserve University School of Medicine at MetroHealth Medical Center Learning Objectives What are outcome measures and why do we measure them? What are the main outcome measures used in SpA clinical trials? How is improvement or response measured in SpA trials? What outcome measures are used in daily clinical Practice? The following report is proprietary information and constitutes trade secrets of The MetroHealth System and may not be disclosed in whole or part to any external parties without the express consent of The MetroHealth System. This document is intended to be used internally for MetroHealth System discussion. Outcome Measures Clinical Outcome Assessments Clinician-reported outcome (ClinRO) May not capture real patient experience of the disease completely (e.g, fatigue) Patient-reported outcome (PRO) Recorded without amendment of the patient's response by a clinician or other observer May not be limited to current SpA activity May incorporate other factors like depression Key component of efficacy endpoints in clinical trials Observer-reported outcome (ObsRO) Patient is unable to self-report (e.g., infants, young children) Cannot be validly used to directly assess symptoms (e.g., pain) or other unobservable concepts Courtesy of Dr. Dubreil Streiner DL. Norman GR. Health Measurement Scales: a Practical Guide to their Development and Use. Oxford University Press; 2008 Properties of an Ideal Outcome Measure when you can measure what you are speaking about, and express it in numbers, you know something about it; but when you cannot, your knowledge is of a meagre and unsatisfactory kind a) Measurable or Quantifiable b) Valid (measure what it intends to measure) c) Reproducible (reliable) d) Sensitive to change Disease Activity Outcome Measures in SpA Structural Damage Physical Function Disability/ Quality of Life BASDAI BASMI BASFI ASQoL ASDAS mssass HAQ-s ASASHI Enthesitis Index Peripheral Joint Count ESR/CRP Thomson W, Electrical units of measurement, Popular Lectures, vol. 1,

2 Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ASSESSING DISEASE ACTIVITY BASDAI Quick and simple index (takes about 30 sec to 2 minutes) Single summary score (mean of components) Good reliability ( r=0.93, p=<0.001) Following 3 weeks of physical therapy, it showed significant improvement (16 % improvement (p=.009), thereby demonstrating sensitivity to change) Limitations Patient-reported (no physician measures) Some redundancy No objective measures Garrett S, Jenkinson T, Kennedy LG, et al. J Rheumatol 1994;21: AS Disease Activity Scores: ASDAS ( az-dass ) Lukas C, Landewe R, Sieper J, et al. Ann Rheum Dis 2009;68:

3 Versions of ASDAS ASDAS-CRP 0.12 back pain duration of morning stiffness patient global peripheral pain/swelling ln(crp + 1) ASDAS-ESR (Alternate) 0.08 back pain duration of morning stiffness patient global peripheral pain/swelling (ESR) ASDAS Highly correlated with BASDAI, CRP, MRI inflammation scores, physician global Highly discriminatory between patients with different levels of disease, and levels of change in disease; better than BASDAI Better validity, enhanced discriminative capacity and improved sensitivity to change as compared to single-item variables Validated in observational cohort and trial van der Heijde D, Lie E, Kvien TK, et al. Ann Rheum Dis 2009;68(12): Disease activity ASDAS Cutoffs Between Disease States and Change in Scores for Monitoring Improvement Enthesitis Index 3

4 Acute Phase Reactants ESR and/or CRP elevated in 30-40% patients with axial SpA Normal values do not exclude the presence of active disease APR more likely to be increased in peripheral joint involvement or associated IBD ASSESSING STRUCTURAL DAMAGE Spoorenberg, A. van der Heijde D, de Klerk E et al. J. Rheumatol.1999;26, Spinal Mobility Measurements- Bath AS Metrology Index (BASMI) Five measurements of Axial Mobility Five measurements of axial mobility: tragus to wall cervical rotation lumbar flexion lumbar side flexion Inter- malleolar distance Jenkinson TR, Mallorie PA, Whitelock HC, et al. J Rheumatol 1994: 21: BASMI- 3 point Scale BASMI 11 Point Scale Mild (0) Moderate (1) Severe (2) Lateral Lumbar Flexion > 10 cm 5-10 cm < 5 cm Tragus to wall Distance < 15 cm cm > 30 cm Lumbar Flexion (modified Schober) >4 cm 2-4 cm < 2 cm Maximal Intermalleolar Distance > <70 Cervical Rotation (u) > <20 Jenkinson TR, Mallorie PA, Whitelock HC, et al. J Rheumatol 1994: 21:

5 BASMI Linear Function Sheet Psychometric Information of BASMI Reliability for each of the 5 responses r= (p<0.001) Sensitivity = 30% improvement in BASMI scores over a 3 week period of treatment. Validity= r=0.92(p=< 0.001) van der Heijde D, Landewe R, Feldtkeller E. Ann Rheum Dis 2008;67: Radiographic Damage of the Spine Modified Stoke AS Spine Score (msasss) 24 sites: Lumbar spine (below T12 to upper border of sacrum) Cervical spine (C2-7) Modified Stoke AS Spine score (msasss) Nominal scoring system: 0 = no abnormality 1 = squaring, or sclerosis, or erosion 2 = syndesmophyte 3 = total bony bridging at each site ASSESSING FUNCTIONAL CAPACITY 5

6 BASFI Quick and simple index (100 secs) Single summary score (mean of components) Good Reliability ( r=0.89, p=<0.001) Following 3 weeks of physical therapy, it showed significant improvement (p=.004 about 20 % improvement, thereby demonstrating sensitivity to change) Limitations Only patient-reported (no physician measures) Some redundancy Calin A, et al. J Rheumatol. 1994; 21: Psychometric Properties of HAQ-S Reliability is good ( r=0.92) Construct validity HAQ and HAQ s ( r= 0.98) Sensitivity to change- similar to HAQ Ward MM, Kuzis S. J Rheumatol 1999;26:4-6 Daltroy LH, et al. J Rheumatol. 1990;17(7): Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL) Doward LC, Spoorenberg A, Cook SA, Whalley D, Helliwell PS, et al.. Ann Rheum Dis 2003;62:

7 Psychometric Information for ASQOL Reliability is very good ( r= 0.92) Construct validity with BASFI = 0.72 Sensitivity and responsiveness to change- Future studies Garrett S, Jenkinson T, Kennedy LG, et al. J Rheumatol 1994:21: Clin Exp Rheumatol Sep-Oct;32(5 Suppl 85):S HOW TO MEASURE IMPROVEMENT ASAS Response Criteria (20/40/60) Other Outcome Measures Short Form- 36 (health survey with 36 questions that measures physical and mental components of health Work Productivity and Activity Impairment 7

8 Work Productivity & Activity Impairment (WPAI) Questionnaire WPAI yields four types of scores: 1. Absenteeism (work time missed) 2. Presenteeism (impairment at work / reduced onthe-job effectiveness) 3. Work productivity loss (overall work impairment / absenteeism + presenteeism) 4. Activity impairment Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work produc-vity and ac-vity impairment instrument. PharmacoEconomics 1993; 4: Courtesy of Dr. Kay ASSESSING DISEASE IN CLINICAL PRACTICE Van der Heijde DMFM, van der Linden SM, Dougados M, et al. J Rheumatol 1999;26: ASAS core set for Disease-Controlling Anti- Rheumatic Treatments What Clinical Measures Should Be Used in Clinical Practice Value Based Care ASQol BASDAI BASFI ASDAS Thoroughly Validated Sufficiently Reliable 50% improvement in BASDAI is deemed to be successful treatment Good correlation with CRP, MRI inflammation 8

9 Link to the Calculators Link to Link to the ASDAS Conclusion Link to HAQ Link to the enthesitis calculator Link to ASAS 9