Which outcome measures are typically used in axial SpA/AS trials?

An outcome measure, by definition, is a measure of the efficacy of an intervention (1), the standard against which the end result of the intervention is assessed. Multiple outcome measures have been described in axial spondyloarthritis, in order to better assess the efficacy and safety of medical intervention. Below we report the measures that are most commonly used in SpA clinical trials.

1. Binary/Disease activity measures:

Domains included in ASAS response criteria (Brandt 2004): Function: measured by BASFI (see function measures) Pain: measured by visual analogue scale (VAS) Inflammation: mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 (see BASDAI below) Patient global: measured by visual analogue scale (VAS)

• ASAS 20 (Brandt 2004):  In order to meet an ASAS 20 response, three of the four domains should improve by at least 20 % and by a minimum of one unit on a scale of 0 to 10. There should be no worsening in the potentially remaining domain (defined as deterioration of ≥20 % or ≥ 1 unit on a 0 to 10 scale).
• ASAS 40 (Brandt 2004): In order to meet an ASAS 40 response, three of the four domains should improve by at least 40% and a minimum of two units on a scale of 0 to 10. In the remaining domain, there should be no worsening of 20% and a minimum of 1 unit, on a 0 to 10 scale.
• ASAS 5/6 (Brandt 2004): In addition to the four domains listed above, acute phase reactant (CRP) and spinal mobility (assessed by lateral spinal flexion) are included. In order to meet an ASAS 5/6 improvement, there should be an improvement of at least 20 % in at least five of these six domains.
• ASAS partial remission (Anderson 2001): reflects very low disease activity. In order to fulfill an ASAS partial remission state, a value of 2 (on a 0 to 10 scale) or less should be present in each of the following domains: patient global, pain, function (BASFI), and inflammation (mean of BASDAI questions 5 and 6).
• The Ankylosing Spondylitis Disease Activity Score (ASDAS) (Lucas 2009): According to the ASDAS improvement criteria, a change in the score of at least 1.1 units is equivalent to a “clinically important improvement,” and a change of at least 2.0 units is called a “major improvement”.

Domains included in ASDAS: Back pain scale Peripheral pain/swelling Duration of morning stiffness Patient global Acute phase reactants (CRP or ESR)

• BASDAI 50 (Garrett 1994): improvement of at least 50 % in the BASDAI score or an absolute change of 2 units (on a 0 to 10 scale) after 3 months of treatment with TNFi.

Domains included in BASDAI: Fatigue/tiredness Level of AS neck, back or hip pain Level of pain/swelling in joints other than neck, back, or hips Level of discomfort from any areas tender to touch or pressure Level of comfort when waking up Duration of morning stiffness

2. Function measures:

• BASFI (Calin 1994): is based on 10 questions. The first 8 questions evaluate activities related to functional anatomical limitations due to the course of this inflammatory disease. The final 2 questions evaluate the patients’ ability to cope with everyday life. (link to questionnaire: http://basdai.com/BASFI.php)

3. Radiographic measurements:

• mSASSS (Creemers 2005): The mSASSS is a well-validated scoring method for quantifying chronic structural changes on conventional radiographs (x-rays). The methodology originally described by Creemers et al., recommended scoring each upper and lower vertebral edge as follows: 0 = no abnormality; 1 = erosion and/or sclerosis and/or squaring; 2 = syndesmophyte (non-bridging); 3 = total bony bridging between upper and lower vertebral edges (ankylosis), with the exception that the third cervical vertebra C3 is not scored for squaring. The total mSASSS (range: 0–72) is the sum of scores calculated for the 24 vertebral edges included in the lumbar and cervical scoring system, based on lateral radiographic views of the vertebrae. (descriptive slide below)
• Spondyloarthritis Research Consortium of Canada (SPARCC) MRI score (Maksymowych 2005): The entire spine is evaluated for inflammation, but only the 6 most severely affected discovertebral units are scored. (descriptive slide below)
  *Each SI joint is divided into 4 quadrants: upper and lower iliacs, upper and lower sacral. the presence of an increased signal on STIR is assigned a point, depending on intensity and depth of signal. The score is repeated in 6 consecutive slices. Score ranges from 0 to 72.

4. Enthesitis scores:

• Leeds Enthesitis index (LEI) (Wong 2012): sites evaluated: bilateral Achilles tendon insertions, medial femoral condyles, and lateral epicondyles of the humerus. Tenderness at each site is quantified on a dichotomous basis: 0 (nontender) and 1 (tender).
• Maastricht AS Enthesitis Score (MASES) (Heuft-Dorenbosch 2003): 13 different sites are assessed for tenderness, based on 6 bilateral sites and a single spinous process. Score ranges from 0–13. No grading of tenderness, so score is binary. (descriptive slide below)

5. Miscellaneous:

• FACIT fatigue: a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. (link to the questionnaire/pdf)
• Bath Ankylosing Spondylitis Metrology Index (BASMI) Metrology Index (Jenkinson 1994): a composite index of spinal mobility, the scale of the BASMI ranges from 0 to 10, where 0 is no mobility limitation and 10 is very severe

Domains included in BASMI: Tragus to wall distance Lumbar flexion (modified Schober test) Cervical rotation Lumbar side flexion Intermalleolar distance

• ASAS Health Index (Kiltz 2015): is a linear composite index with 17 items, which cover most aspects of the International Classification of Functioning, Disability and Health (ICF) core set. (link: https://www.asas-group.org/clinical-instruments/asas-health-index/)
• Patient Global Assessment (PGA): Visual analog scale (VAS), the score ranges from 0 (not active) to 10 (very active).

References

• Brandt et al. Development and preselection of criteria for short term improvement after anti-TNF alpha treatment in ankylosing spondylitis. Ann Rheum Dis. 2004 Nov;63(11):1438-44. Epub 2004 Mar 25.
• Anderson et al. Ankylosing spondylitis assessment group preliminary definition of short-term improvement in ankylosing spondylitis. Arthritis Rheum. 2001 Aug;44(8):1876-86.
• Garrett et al, A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol. 1994 Dec;21(12):2286-91.
• Calin et al. A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing Spondylitis Functional Index. J Rheumatol. 1994 Dec;21(12):2281-5.
• Creemers et al. Assessment of outcome in ankylosing spondylitis: an extended radiographic scoring system. Ann Rheum Dis. 2005 Jan;64(1):127-9. Epub 2004 Mar 29.
• Maksymowych et al. Spondyloarthritis Research Consortium of Canada magnetic resonance imaging index for assessment of spinal inflammation in ankylosing spondylitis. Arthritis Rheum. 2005 Aug 15;53(4):502-9.
• Heuft-Dorenbosch et al, Assessment of enthesitis in ankylosing spondylitis. Ann Rheum Dis. 2003 Feb;62(2):127-32.
• Jenkinson et al, Defining spinal mobility in ankylosing spondylitis (AS). The Bath AS Metrology Index. J Rheumatol. 1994 Sep;21(9):1694-8.
• Kiltz et al. Development of a health index in patients with ankylosing spondylitis (ASAS HI): final result of a global initiative based on the ICF guided by ASAS.

Web resources

• ASDAS calculator: https://www.asas-group.org/clinical-instruments/asdas-calculator/
• BASDAI calculator: https://qxmd.com/calculate/basdai

Author(s)

Mohamad Bittar, affiliation
Last modified 02/11/20