Best Practice & Research Clinical Rheumatology 28 (2014) 711e728
Contents lists available at ScienceDirect
Best Practice & Research Clinical Rheumatology journal homepage: www.elsevierhealth.com/berh
5
Disease activity measurements and monitoring in psoriatic arthritis and axial spondyloarthritis Pedro M. Machado, MD a, *, Siba P. Raychaudhuri, MD b, ** a
MRC Centre for Neuromuscular Diseases, University College London, Box 102, 8-11 Queen Square, WC1N 3BG London, UK Division of Rheumatology, Allergy, Clinical Immunology, School of Medicine, UC Davis, 1911 Geneva Place, Davis, CA, USA
b
a b s t r a c t Keywords: Spondyloarthritis Psoriatic arthritis Disease activity Outcome measures Monitoring Validity
In addition to the critical need of measuring tools for drug development of spondyloarthritis (SpA), these tools are also valuable for patient management. An early diagnosis, determination of early therapeutic response, and monitoring therapeutic response have now become increasingly important because effective therapies are available, and therapies such as anti-tumor necrosis factor (TNF) drugs are even more effective if used in early disease stages. In this review, we focus on disease activity measurements and monitoring in axial SpA and psoriatic arthritis (PsA). Both axial SpA and PsA have heterogeneous clinical manifestations. Therefore, in addition to the measurement of each clinical domain, composite measures inclusive of all clinical domains can be very helpful and are more likely to give complete and reliable information about the disease activity. A major focus of this review is to describe the recently developed composite measures for axial SpA and PsA. © 2014 Elsevier Ltd. All rights reserved.
* Corresponding author. Tel.: þ44 2034488256; fax: þ44 2034483633. ** Corresponding author. E-mail addresses: [email protected] (P.M. Machado), [email protected] (S.P. Raychaudhuri).
http://dx.doi.org/10.1016/j.berh.2014.10.004 1521-6942/© 2014 Elsevier Ltd. All rights reserved.
712
P.M. Machado, S.P. Raychaudhuri / Best Practice & Research Clinical Rheumatology 28 (2014) 711e728
Introduction Spondyloarthritis (SpA) is a heterogeneous disease that can have either a predominantly axial or peripheral phenotype [1,2]. The range of clinical manifestations in SpA is broad and includes chronic (typically inflammatory) back pain, arthritis, enthesitis, dactylitis, and extra-articular features such as psoriasis, uveitis, inflammatory bowel disease, and fatigue. These manifestations may occur separately or simultaneously in the same patient or in their family members, and the disease is strongly linked to human leukocyte antigen B27 (HLA-B27) positivity [1,2]. Measuring and monitoring disease activity are of paramount importance in rheumatology and in medicine in general. Yet quantifying disease activity is a complex and challenging process. Composite scores can be particularly useful to measure disease activity because they integrate several different aspects of disease activity into one single numerical value, resulting in a more precise estimate of disease activity than the individual variables of the composite score. They also have the potential to increase the statistical power of clinical trials and observational studies. Furthermore, they improve the consistency of patient assessment and care across different clinical and research settings, and help patients and doctors better understand the disease and its impact. However, there may be times when measuring a specific disease feature may be more appropriate, because the therapeutic intervention may be directed primarily at a certain clinical manifestation and not necessarily aimed at generating a global change in disease activity [3,4]. In this review, we focus on disease activity measurements and monitoring in axial SpA and in the most prevalent form of peripheral SpA, psoriatic arthritis (PsA). All the instruments described for axial SpA were initially developed for ankylosing spondylitis (AS) but are currently applied in both radiographic (i.e., AS) and non-radiographic axial SpA. Several concepts addressed in this review relate to the Outcome Measures in Rheumatology (OMERACT) filter [5], a set of criteria that can serve as a guide to develop valid and meaningful indices. The OMERACT filter includes aspects of “truth” (Is the measure truthful? Does it measure what it intends to measure? Is the result unbiased and relevant?), “discrimination” (Does the measure discriminate between situations that are of interest? Does the measure have the ability to detect change?), and “feasibility” (Can the measure be applied easily, given constraints of time, money, and interpretability?) [5]. Disease activity measurements and monitoring in axial SpA The Assessment of SpondyloArthritis International Society (ASAS) has proposed several instruments to assess health outcomes in axial SpA. These instruments cover distinct domains and are Table 1 Assessment of SpondyloArthritis International Society (ASAS) core sets [2,6]. Domain
Instrument
For SMARD and PT
For CRK
For DCART
Function Pain
BASFI NRS/VAS (spine, at night, last week, due to AS) NRS/VAS (spine, last week, due to AS) Chest expansion, modified Schober, occiput to wall distance, cervical rotation, lateral spinal flexion or BASMI NRS/VASa (global disease activity, last week) NRS/VASa (spine, duration of morning stiffness, last week) Fatigue question of BASDAI (NRS/VASa) Number of swollen joints (44-joint count) Validated entheses score CRP or ESR Lateral lumbar and cervical spine
X X
X X
X X
X
X
X
X X X
X X X X
X X X X
X
X X
Spinal mobility Patient global Stiffness Fatigue Peripheral joints and entheses Acute-phase reactants Radiograph of the spine
a ASAS prefers the use of a NRS. AS, Ankylosing Spondylitis; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BASFI, Bath Ankylosing Spondylitis Functional Index; BASMI, Bath Ankylosing Spondylitis Metrology Index; CRK, clinical record keeping; CRP, C-reactive protein; DCART, disease-controlling anti-rheumatic treatments; ESR, erythrocyte sedimentation rate; NRS, numerical rating scale (0e10); PT, physical therapy; SMARD, symptom modifying anti-rheumatic drugs; VAS, visual analog scale (0e10 cm).
P.M. Machado, S.P. Raychaudhuri / Best Practice & Research Clinical Rheumatology 28 (2014) 711e728
713
divided into core sets to be applied in different settings (Table 1) [2,6]. These core sets include several disease activity variables such as the assessment of spinal pain, patient global assessment of disease activity, the number of swollen joints (with a 44-joint count being recommended), an enthesitis count (with a validated index), the duration of morning stiffness, and the level of fatigue [2,6]. Due to the phenotypic heterogeneity of axial SpA and the possibility of coexistence of a large number of clinical manifestations, the use of individual variables may lead to misrepresentation of disease activity. Therefore, composite indices can be very useful tools for the assessment of disease activity in axial SpA [7]. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) has been the most widely used disease activity composite index in axial SpA [8]. BASDAI combines six individual variables (fatigue, axial pain, joint pain and swelling, tender areas, and intensity and duration of morning stiffness) into one single score and is a fully patient-oriented measure (Table 2). However, it is well described that patients and doctors have different perspectives on disease activity in axial SpA [9]. For example, patients may give more value to subjective symptoms such as pain and fatigue, while doctors may give Table 2 Measures of disease activity in axial spondyloarthritis. Instrument
Questions and calculation rules
BASDAI [8]
1. How would you describe the overall level of fatigue/tiredness you have experienced? 2. How would you describe the overall level of AS neck, back or hip pain you have had? 3. How would you describe the overall level of pain/swelling in joints other than neck, back or hips you have had? 4. How would you describe the overall level of discomfort you have had from any areas tender to touch or pressure? 5. How would you describe the overall level of morning stiffness you have had from the time you wake up? 6. How long does your morning stiffness last from the time you wake up? Calculation: ((Q1 þ Q2 þ Q3 þ Q4) þ (Q5 þ Q6) ÷ 2) ÷ 5 1. Please place a mark on the scale below to indicate the effect your disease has had on your well-being over the last week. 2. Please place a mark on the scale below to indicate the effect your disease has had on your well-being over the last six months. Calculation: Each question represents a different timeframe and should be interpreted individually. 1. On average, last week, how much pain of your spine due to AS did you have? 2. On average, last week, how much pain of your spine due to AS did you have at night? Calculation: Each question is usually interpreted individually. 1. How would you describe the overall level of fatigue/tiredness you have experienced? 2. How would you describe the overall level of AS neck, back or hip pain you have had? 3. How would you describe the overall level of morning stiffness you have had from the time you wake up? 4. How long does your morning stiffness last from the time you wake up? Calculation: ((Q1 þ Q2) þ (Q3 þ Q4) ÷ 2) ÷ 3 1. How would you describe the overall level of AS neck, back or hip pain you have had? 2. How would you describe the overall level of pain/swelling in joints other than neck, back or hips you have had? 3. How would you describe the overall level of morning stiffness you have had from the time you wake up? 4. How active was your spondylitis on average during the last week? 5. C-reactive protein level (mg/L) or erythrocyte sedimentation rate level (mm/h) Calculation ASDAS-CRP: 0.12 Q1 þ 0.07 Q2 þ 0.06 Q3 þ 0.11 Q4 þ 0.58 Ln(CRPþ1) Calculation ASDAS-ESR: 0.08 Q1 þ 0.09 Q2 þ 0.07 Q3 þ 0.11 Q4 þ 0.29 √(ESR) Calculation of ASDAS-CRP for very low CRP values: When the conventional CRP is below the limit of detection or when the high sensitivity CRP is 1 unit in at least three out of four domains on a 0e10 scale. B No worsening of >20% and >1 unit in the remaining domain on a 0e10 scale. B The four domains are: 1) patient global, 2) spinal pain, 3) function (BASFI) and 4) inflammation (mean of BASDAI questions 5 and 6). ASAS 40 B Improvement of >40% and >2 units in at least three out of four domains on a 0e10 scale. B No worsening at all in remaining domain. B The four domains are: 1) patient global, 2) spinal pain, 3) function (BASFI) and 4) inflammation (mean of BASDAI questions 5 and 6). ASAS 5/6 B Improvement of >20% in at least five out of six domains. B The six domains are: 1) patient global; 2) spinal pain, 3) function (BASFI), 4) inflammation (mean of BASDAI questions 5 and 6), 5) CRP and 6) spinal mobility (lateral spinal flexion). BASDAI response criteria BASDAI 50 B Improvement of 50% in BASDAI. BASDAI 2 B Improvement of 2 units (0-10 scale) in BASDAI. ASDAS response criteria Clinically important improvement B Improvement of 1.1 units is ASDAS. Major improvement B Improvement of 2.0 units is ASDAS. Remission-like states in axial SpA ASDAS inactive disease B ASDAS score
Contents lists available at ScienceDirect
Best Practice & Research Clinical Rheumatology journal homepage: www.elsevierhealth.com/berh
5
Disease activity measurements and monitoring in psoriatic arthritis and axial spondyloarthritis Pedro M. Machado, MD a, *, Siba P. Raychaudhuri, MD b, ** a
MRC Centre for Neuromuscular Diseases, University College London, Box 102, 8-11 Queen Square, WC1N 3BG London, UK Division of Rheumatology, Allergy, Clinical Immunology, School of Medicine, UC Davis, 1911 Geneva Place, Davis, CA, USA
b
a b s t r a c t Keywords: Spondyloarthritis Psoriatic arthritis Disease activity Outcome measures Monitoring Validity
In addition to the critical need of measuring tools for drug development of spondyloarthritis (SpA), these tools are also valuable for patient management. An early diagnosis, determination of early therapeutic response, and monitoring therapeutic response have now become increasingly important because effective therapies are available, and therapies such as anti-tumor necrosis factor (TNF) drugs are even more effective if used in early disease stages. In this review, we focus on disease activity measurements and monitoring in axial SpA and psoriatic arthritis (PsA). Both axial SpA and PsA have heterogeneous clinical manifestations. Therefore, in addition to the measurement of each clinical domain, composite measures inclusive of all clinical domains can be very helpful and are more likely to give complete and reliable information about the disease activity. A major focus of this review is to describe the recently developed composite measures for axial SpA and PsA. © 2014 Elsevier Ltd. All rights reserved.
* Corresponding author. Tel.: þ44 2034488256; fax: þ44 2034483633. ** Corresponding author. E-mail addresses: [email protected] (P.M. Machado), [email protected] (S.P. Raychaudhuri).
http://dx.doi.org/10.1016/j.berh.2014.10.004 1521-6942/© 2014 Elsevier Ltd. All rights reserved.
712
P.M. Machado, S.P. Raychaudhuri / Best Practice & Research Clinical Rheumatology 28 (2014) 711e728
Introduction Spondyloarthritis (SpA) is a heterogeneous disease that can have either a predominantly axial or peripheral phenotype [1,2]. The range of clinical manifestations in SpA is broad and includes chronic (typically inflammatory) back pain, arthritis, enthesitis, dactylitis, and extra-articular features such as psoriasis, uveitis, inflammatory bowel disease, and fatigue. These manifestations may occur separately or simultaneously in the same patient or in their family members, and the disease is strongly linked to human leukocyte antigen B27 (HLA-B27) positivity [1,2]. Measuring and monitoring disease activity are of paramount importance in rheumatology and in medicine in general. Yet quantifying disease activity is a complex and challenging process. Composite scores can be particularly useful to measure disease activity because they integrate several different aspects of disease activity into one single numerical value, resulting in a more precise estimate of disease activity than the individual variables of the composite score. They also have the potential to increase the statistical power of clinical trials and observational studies. Furthermore, they improve the consistency of patient assessment and care across different clinical and research settings, and help patients and doctors better understand the disease and its impact. However, there may be times when measuring a specific disease feature may be more appropriate, because the therapeutic intervention may be directed primarily at a certain clinical manifestation and not necessarily aimed at generating a global change in disease activity [3,4]. In this review, we focus on disease activity measurements and monitoring in axial SpA and in the most prevalent form of peripheral SpA, psoriatic arthritis (PsA). All the instruments described for axial SpA were initially developed for ankylosing spondylitis (AS) but are currently applied in both radiographic (i.e., AS) and non-radiographic axial SpA. Several concepts addressed in this review relate to the Outcome Measures in Rheumatology (OMERACT) filter [5], a set of criteria that can serve as a guide to develop valid and meaningful indices. The OMERACT filter includes aspects of “truth” (Is the measure truthful? Does it measure what it intends to measure? Is the result unbiased and relevant?), “discrimination” (Does the measure discriminate between situations that are of interest? Does the measure have the ability to detect change?), and “feasibility” (Can the measure be applied easily, given constraints of time, money, and interpretability?) [5]. Disease activity measurements and monitoring in axial SpA The Assessment of SpondyloArthritis International Society (ASAS) has proposed several instruments to assess health outcomes in axial SpA. These instruments cover distinct domains and are Table 1 Assessment of SpondyloArthritis International Society (ASAS) core sets [2,6]. Domain
Instrument
For SMARD and PT
For CRK
For DCART
Function Pain
BASFI NRS/VAS (spine, at night, last week, due to AS) NRS/VAS (spine, last week, due to AS) Chest expansion, modified Schober, occiput to wall distance, cervical rotation, lateral spinal flexion or BASMI NRS/VASa (global disease activity, last week) NRS/VASa (spine, duration of morning stiffness, last week) Fatigue question of BASDAI (NRS/VASa) Number of swollen joints (44-joint count) Validated entheses score CRP or ESR Lateral lumbar and cervical spine
X X
X X
X X
X
X
X
X X X
X X X X
X X X X
X
X X
Spinal mobility Patient global Stiffness Fatigue Peripheral joints and entheses Acute-phase reactants Radiograph of the spine
a ASAS prefers the use of a NRS. AS, Ankylosing Spondylitis; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BASFI, Bath Ankylosing Spondylitis Functional Index; BASMI, Bath Ankylosing Spondylitis Metrology Index; CRK, clinical record keeping; CRP, C-reactive protein; DCART, disease-controlling anti-rheumatic treatments; ESR, erythrocyte sedimentation rate; NRS, numerical rating scale (0e10); PT, physical therapy; SMARD, symptom modifying anti-rheumatic drugs; VAS, visual analog scale (0e10 cm).
P.M. Machado, S.P. Raychaudhuri / Best Practice & Research Clinical Rheumatology 28 (2014) 711e728
713
divided into core sets to be applied in different settings (Table 1) [2,6]. These core sets include several disease activity variables such as the assessment of spinal pain, patient global assessment of disease activity, the number of swollen joints (with a 44-joint count being recommended), an enthesitis count (with a validated index), the duration of morning stiffness, and the level of fatigue [2,6]. Due to the phenotypic heterogeneity of axial SpA and the possibility of coexistence of a large number of clinical manifestations, the use of individual variables may lead to misrepresentation of disease activity. Therefore, composite indices can be very useful tools for the assessment of disease activity in axial SpA [7]. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) has been the most widely used disease activity composite index in axial SpA [8]. BASDAI combines six individual variables (fatigue, axial pain, joint pain and swelling, tender areas, and intensity and duration of morning stiffness) into one single score and is a fully patient-oriented measure (Table 2). However, it is well described that patients and doctors have different perspectives on disease activity in axial SpA [9]. For example, patients may give more value to subjective symptoms such as pain and fatigue, while doctors may give Table 2 Measures of disease activity in axial spondyloarthritis. Instrument
Questions and calculation rules
BASDAI [8]
1. How would you describe the overall level of fatigue/tiredness you have experienced? 2. How would you describe the overall level of AS neck, back or hip pain you have had? 3. How would you describe the overall level of pain/swelling in joints other than neck, back or hips you have had? 4. How would you describe the overall level of discomfort you have had from any areas tender to touch or pressure? 5. How would you describe the overall level of morning stiffness you have had from the time you wake up? 6. How long does your morning stiffness last from the time you wake up? Calculation: ((Q1 þ Q2 þ Q3 þ Q4) þ (Q5 þ Q6) ÷ 2) ÷ 5 1. Please place a mark on the scale below to indicate the effect your disease has had on your well-being over the last week. 2. Please place a mark on the scale below to indicate the effect your disease has had on your well-being over the last six months. Calculation: Each question represents a different timeframe and should be interpreted individually. 1. On average, last week, how much pain of your spine due to AS did you have? 2. On average, last week, how much pain of your spine due to AS did you have at night? Calculation: Each question is usually interpreted individually. 1. How would you describe the overall level of fatigue/tiredness you have experienced? 2. How would you describe the overall level of AS neck, back or hip pain you have had? 3. How would you describe the overall level of morning stiffness you have had from the time you wake up? 4. How long does your morning stiffness last from the time you wake up? Calculation: ((Q1 þ Q2) þ (Q3 þ Q4) ÷ 2) ÷ 3 1. How would you describe the overall level of AS neck, back or hip pain you have had? 2. How would you describe the overall level of pain/swelling in joints other than neck, back or hips you have had? 3. How would you describe the overall level of morning stiffness you have had from the time you wake up? 4. How active was your spondylitis on average during the last week? 5. C-reactive protein level (mg/L) or erythrocyte sedimentation rate level (mm/h) Calculation ASDAS-CRP: 0.12 Q1 þ 0.07 Q2 þ 0.06 Q3 þ 0.11 Q4 þ 0.58 Ln(CRPþ1) Calculation ASDAS-ESR: 0.08 Q1 þ 0.09 Q2 þ 0.07 Q3 þ 0.11 Q4 þ 0.29 √(ESR) Calculation of ASDAS-CRP for very low CRP values: When the conventional CRP is below the limit of detection or when the high sensitivity CRP is 1 unit in at least three out of four domains on a 0e10 scale. B No worsening of >20% and >1 unit in the remaining domain on a 0e10 scale. B The four domains are: 1) patient global, 2) spinal pain, 3) function (BASFI) and 4) inflammation (mean of BASDAI questions 5 and 6). ASAS 40 B Improvement of >40% and >2 units in at least three out of four domains on a 0e10 scale. B No worsening at all in remaining domain. B The four domains are: 1) patient global, 2) spinal pain, 3) function (BASFI) and 4) inflammation (mean of BASDAI questions 5 and 6). ASAS 5/6 B Improvement of >20% in at least five out of six domains. B The six domains are: 1) patient global; 2) spinal pain, 3) function (BASFI), 4) inflammation (mean of BASDAI questions 5 and 6), 5) CRP and 6) spinal mobility (lateral spinal flexion). BASDAI response criteria BASDAI 50 B Improvement of 50% in BASDAI. BASDAI 2 B Improvement of 2 units (0-10 scale) in BASDAI. ASDAS response criteria Clinically important improvement B Improvement of 1.1 units is ASDAS. Major improvement B Improvement of 2.0 units is ASDAS. Remission-like states in axial SpA ASDAS inactive disease B ASDAS score
