Disease activity measurements and monitoring in psoriatic arthritis and axial spondyloarthritis




Abstract


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.


Introduction


Spondyloarthritis (SpA) is a heterogeneous disease that can have either a predominantly axial or peripheral phenotype . 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 .


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 .


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 , 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?) .




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 divided into core sets to be applied in different settings ( Table 1 ) . 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 .



Table 1

Assessment of SpondyloArthritis International Society (ASAS) core sets .
































































Domain Instrument For SMARD and PT For CRK For DCART
Function BASFI X X X
Pain NRS/VAS (spine, at night, last week, due to AS)
NRS/VAS (spine, last week, due to AS)
X X X
Spinal mobility Chest expansion, modified Schober, occiput to wall distance, cervical rotation, lateral spinal flexion or BASMI X X X
Patient global NRS/VAS a (global disease activity, last week) X X X
Stiffness NRS/VAS a (spine, duration of morning stiffness, last week) X X X
Fatigue Fatigue question of BASDAI (NRS/VAS a ) X X X
Peripheral joints and entheses Number of swollen joints (44-joint count)
Validated entheses score
X X
Acute-phase reactants CRP or ESR X X
Radiograph of the spine Lateral lumbar and cervical spine X

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 (0–10); PT, physical therapy; SMARD, symptom modifying anti-rheumatic drugs; VAS, visual analog scale (0–10 cm).



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 .


The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) has been the most widely used disease activity composite index in axial SpA . 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 . For example, patients may give more value to subjective symptoms such as pain and fatigue, while doctors may give more value to objective signs such as the number of swollen joints or to laboratory findings such as the presence of elevated acute-phase reactants. Therefore, the correlation between patient and physician global assessments is typically weak in axial SpA and the same applies to the correlation between BASDAI and physician global assessment . Furthermore, BASDAI lacks specificity for inflammatory processes and does not take the redundancy and dependence of individual variables into account. A modified version of the BASDAI (mini-BASDAI) without the questions about tender areas and joint pain/swelling has also been tested and did not perform better than the BASDAI .



Table 2

Measures of disease activity in axial spondyloarthritis.






















Instrument Questions and calculation rules
BASDAI

  • 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 + Q2 + Q3 + Q4) + (Q5 + Q6) ÷ 2) ÷ 5

BAS-G

  • 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.

Spinal pain

  • 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.

Mini-BASDAI

  • 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 + Q2) + (Q3 + Q4) ÷ 2) ÷ 3

ASDAS

  • 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 + 0.07 × Q2 + 0.06 × Q3 + 0.11 × Q4 + 0.58 × Ln(CRP+1)



  • Calculation ASDAS-ESR: 0.08 × Q1 + 0.09 × Q2 + 0.07 × Q3 + 0.11 × Q4 + 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 <2 mg/L, the constant CRP value of 2 mg/L should be used to calculate ASDAS-CRP.


BASDAI questions relate to the past week, response is either on a 0–10 NRS or on 0–10 cm VAS, from “none” to “very severe”, except for the duration of morning stiffness in which the anchors are “zero hours” and “2 or more hours”. The same applies to mini-BASDAI and ASDAS questions extracted from the BASDAI. The anchors for the spinal pain questions are “no pain” and “most severe pain”.

ASDAS, Ankylosing Spondylitis Disease Activity Score; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BAS-G, Bath Ankylosing Spondylitis Patient Global Score; NRS, numerical rating scale; VAS, visual analog scale; √(ESR), square root of the erythrocyte sedimentation rate (mm/h); Ln(CRP + 1), natural logarithm of the C-reactive protein (mg/L) + 1.


BASDAI has served the SpA community well for many years, but its recognized limitations led the ASAS group to develop a new composite measure for disease activity in axial SpA: the Ankylosing Spondylitis Disease Activity Score (ASDAS). BASDAI, mini-BASDAI, Bath Ankylosing Spondylitis Patient Global Score (BAS-G) , spinal pain, and ASDAS questions and calculation rules are presented in Table 2 . The development process of the ASDAS and its cutoffs are summarized below.


Development of the ASDAS


Content validity of the ASDAS was ensured by the first development step, in which a group of experts agreed on a list of domains and individual variables reflecting disease activity that could potentially be included in a new composite index. This was done by a Delphi exercise conducted among ASAS members and resulted in the selection of the following variables: fatigue (BASDAI question 1), axial pain (BASDAI question 2), peripheral pain (BASDAI question 3), duration of morning stiffness (BASDAI question 6), acute-phase reactants (C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)), patient global assessment of disease activity, swollen joint count (SJC), tender enthesis count, spinal pain, and spinal pain at night .


These items were then tested in the International Study of Starting anti-tumor necrosis factor (TNF) agents in AS (ISSAS) database. In a similar process to the development of the disease activity score (DAS) in rheumatoid arthritis (RA), factor analysis and principle component analysis were used to evaluate the redundancy of items and to reduce the number of variables, and discriminant function analysis and linear regression analysis were used to investigate the optimal weights and combination of variables to be included in the ASDAS . These statistical processes ensured face and construct validity. Initially, four ASDAS formulas were proposed. These were later on reduced by consensus to two formulas, each one of them containing one acute-phase reactant. The preferred formula contains the CRP (ASDAS-CRP) and the alternative formula contains the ESR (ASDAS-ESR) ( Table 2 ). The other variables are shared between the two formulas (but with different weights) and include axial pain (BASDAI question 2), peripheral pain (BASDAI question 3), duration of morning stiffness (BASDAI question 6), and patient global assessment of disease activity.


The discriminative ability of the ASDAS was tested in multiple datasets, including the ISSAS database from where the formulas were developed (external construct: TNF-blocker treatment prescription by the rheumatologist), the Outcome in AS International Study (OASIS) database (external constructs: high and low levels of patient and physician global assessments), and the Norwegian disease-modifying antirheumatic drugs (NOR-DMARD) database (external constructs: high and low levels of physician global assessment, patient-acceptable symptom state, considerable improvement according to the patient, and impact of TNF-blocker vs. DMARD treatment). Overall, these studies have shown that ASDAS performs better than the BASDAI and better than any of the single-item variables, namely individual BASDAI questions, patient and physician global assessments, and acute-phase reactants alone . One of the great advantages of the ASDAS is that it provides a better balance between the patient’s and physician’s perspective, as compared to the BASDAI, which is a fully patient-driven index.


The discriminative ability and sensitivity to change in the ASDAS have also been tested in several clinical trial populations . Results have confirmed the validity of the ASDAS, its highly discriminative ability to detect differences between treatment groups (which has important implications in terms of sample size calculation), and its high sensitivity to change. Since its publication, the ASDAS has been further validated in various populations worldwide . Importantly, ASDAS has been shown to perform as well as or better than existing measures in the entire spectrum of axial SpA, including early and late disease, patients with radiographic and non-radiographic axial SpA , patients with and without peripheral arthritis , patients with and without elevated acute-phase reactants , patients with axial PsA and patients with concomitant fibromyalgia . Interestingly, ASDAS has also been shown to perform well in patients with peripheral SpA , suggesting that it may also be a useful and promising tool to measure and monitor disease activity in patients with peripheral SpA, an application for which it was not initially designed and that requires further scrutiny and validation.


Development of the ASDAS cutoffs and further validation of the ASDAS


Cutoffs are important because they give a meaning to a continuous index. Cutoffs can be defined for the level of disease activity at a single time point (“disease activity states”) or for changes in disease activity after therapeutic interventions (“response criteria”). “Disease activity states” help to decide about the need to change treatment, they can be used as selection criteria for patient participation in research studies, and they can also be used as therapeutic targets (e.g., aiming at remission/inactive disease). “Response criteria” allow measuring the impact of a treatment, namely if the treatment results in clinically relevant improvement. The use of standardized measures across different settings also allows combining results from different studies, for example, for meta-analysis, or to audit results and to define and improve the standards of care.


ASDAS cutoffs were determined in the NOR-DMARD database using receiver operating characteristic (ROC)-analysis. Four disease activity states were defined: inactive disease (a remission-like state), and moderate (although the term “moderate” was chosen, this represents a “low or moderate” disease activity state), high, and very high disease activity. Both the patient and physician global assessments of disease activity at predefined levels (<1, <3, and >6 on a 0–10 scale) were used as external anchors to define the three disease activity cutoffs: 1.3, separating “inactive disease” from “moderate disease activity”; 2.1, separating “moderate disease activity” from “high disease activity”; and 3.5, separating “high disease activity” from “very high disease activity” ( Fig. 1 ). The ASAS partial remission criteria were also used as an additional external anchor for “inactive disease.”




Fig. 1


Ankylosing Spondylitis Disease Activity Score (ASDAS) cut-offs for disease activity states (Fig. 1A) and response criteria (Fig. 1B). Cut-offs can be applied to both ASDAS-CRP and ASDAS-ESR; however, the two ASDAS formulas are not interchangeable. A. Disease activity states, B. Response criteria.


Regarding response criteria, the external anchor in ROC-curve analysis was a “global rating of change” after starting treatment, with the health change defined by the patient in five Likert-type categories: “much worse,” “worse,” “unchanged,” “better,” and “much better.” This resulted in the definition of two cutoffs for the magnitude of response: “clinically important improvement” (external construct: patients reporting to be “better” or “much better”), defined as a decrease in ASDAS ≥1.1, and “major improvement” (external construct: patients reporting to be “much better”), defined as a decrease in ASDAS ≥2.0 ( Fig. 1 ).


Validation aspects of the cutoffs were longitudinally tested in the NOR-DMARD database and in a clinical trial population, the AS Study for the Evaluation of Recombinant Infliximab Therapy (ASSERT). ASDAS cutoffs showed excellent psychometric properties, being more discriminative between treatment groups than classical response criteria (BASDAI50, BASDAI 2, ASAS 20, and ASAS 40) ( Table 3 ) . The two currently available remission-like states in axial SpA were also compared, ASDAS inactive disease being more discriminative than ASAS partial remission criteria .



Table 3

ASAS, BASDAI and ASDAS response criteria and remission-like states in axial SpA .






































ASAS response criteria
ASAS 20


  • Improvement of >20% and >1 unit in at least three out of four domains on a 0–10 scale.



  • No worsening of >20% and >1 unit in the remaining domain on a 0–10 scale.



  • 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


  • Improvement of >40% and >2 units in at least three out of four domains on a 0–10 scale.



  • No worsening at all in remaining domain.



  • 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


  • Improvement of >20% in at least five out of six domains.



  • 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


  • Improvement of ≥50% in BASDAI.

BASDAI 2


  • Improvement of ≥2 units (0-10 scale) in BASDAI.

ASDAS response criteria
Clinically important improvement


  • Improvement of ≥1.1 units is ASDAS.

Major improvement


  • Improvement of ≥2.0 units is ASDAS.

Remission-like states in axial SpA
ASDAS inactive disease


  • ASDAS score <1.3.

ASAS partial remission criteria


  • A value not above two units in each of four domains on a scale of 10.



  • The four domains are: 1) patient global, 2) spinal pain, 3) function (BASFI) and 4) inflammation (mean of BASDAI questions 5 and 6).


ASAS, Assessment of SpondyloArthritis International Society; ASDAS, Ankylosing Spondylitis Disease Activity Score; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BASFI, Bath Ankylosing Spondylitis Functional Index; SpA, SpondyloArthritis.


There have been two studies investigating the ASDAS patient-acceptable symptom state (PASS) cutoff. One study suggested cutoff values between 2.5 and 3.0 for ASDAS-CRP and between 2.8 and 3.5 for ASDAS-ESR, depending on the method used to determine the cutoff value . The other study suggested an ASDAS-PASS cutoff ≤2.3, for both ASDAS-CRP and ASDAS-ESR . It is not unexpected that the estimated ASDAS-PASS cutoff is greater that the cutoff between moderate and high disease activity as they represent different concepts and it has been shown that PASS can be associated with substantial levels of pain and disease activity in axial SpA .


The ASDAS and its cutoffs have now been applied in numerous clinical trials and observational studies, including long-term extension studies with TNF blockers, consistently showing good psychometric performance . ASDAS has also received the endorsement of both the ASAS and OMERACT study groups .


Evidence suggests that the ASDAS better reflects the inflammatory disease processes in axial SpA than the BASDAI, namely at the biological (correlation with biomarkers of inflammation, angiogenesis, cartilage, and bone turnover) and magnetic resonance imaging (MRI) level (correlation with MRI inflammation scores) . Furthermore, ASDAS high disease activity (ASDAS ≥2.1) might be a better threshold than the historically used BASDAI elevation cutoff level (BASDAI ≥4) for the selection of patients for treatment with TNF blockers, particularly because it selects a higher number of patients with characteristics predictive of a good response to these therapies .


A longitudinal relationship between disease activity and progression of radiographic damage in AS has recently been shown . This study included patients from the OASIS cohort clinically and radiographically evaluated every 2 years up to a period of 12 years. Several measures of disease activity (ASDAS, BASDAI, and CRP) were significantly associated with an increase in the modified Stoke AS Spine Score (mSASSS), but the ASDAS statistical model was the one that best fitted the data. Interestingly, the effect of ASDAS on mSASSS was higher in males and in patients with less symptom duration. These data add further validity (and predictive value in terms of progression of structural damage) to the ASDAS .


ASDAS feasibility


The ASDAS formula is complex, and it is not possible to mentally calculate the index. However, this is no different from the DAS that has been successfully implemented in RA and, in fact, compared to the DAS, the ASDAS benefits from not requiring a joint count. Rheumatologists are already familiarized with this type of indices and with the strategies that have been put in place to overcome their complexity: the availability of online, desktop, handheld, and smartphone calculators. The ASAS group has developed such tools (available at www.asas-group.org ) for the ASDAS as well as a “quick ASDAS calculation form,” a two-page form that provides the possibility of quickly calculating the ASDAS without the need of an electronic calculator. The availability of these instruments will facilitate the implementation of the ASDAS in clinical practice.


Further insights from clinical practice


In this section, we present two real-life clinical cases and explore the potential advantages of using the ASDAS in clinical practice.




Case scenario 1: A 32-year-old female diagnosed with axial SpA 2 years ago. Initially, the patient responded well to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). However, over the past 6 months, she developed persistent inflammatory back pain and prolonged morning stiffness in spite of continuous full-dose NSAID treatment. She already tried three different NSAIDs, without response, she wakes up frequently during the night due to back pain, and she has had to miss work due to her SpA symptoms. Her patient global assessment of disease activity was 7 (0–10 scale), the axial pain score was 7 (0–10), the duration of morning stiffness score was 7 (0–10 scale), and the CRP was 6 mg/l.



Given the above scenario, rheumatologists would unanimously agree that this patient should be treated with a TNF blocker. However, let us look at the patient’s BASDAI and ASDAS scores:




Case scenario 1 (continued): The patient’s responses to BASDAI questions (0–10 scale) were as follows: fatigue/tiredness = 1, axial pain = 7, pain/swelling in peripheral joints = 0, tender areas = 1, level of morning stiffness = 6, and duration of morning stiffness = 7. As mentioned above, the patient global assessment of disease activity was 7 (0–10 scale) and CRP was 6 mg/l. These scores resulted in a BASDAI of 3.1 and in an ASDAS of 3.2.



Interestingly, according to the BASDAI, the patient would not be eligible to start treatment with a TNF blocker, as the BASDAI cutoff of 4.0 is often recommended as the threshold to start this type of treatment . Conversely, according to the ASDAS, the patient has “high disease activity” and would be eligible to start treatment with a TNF blocker as the ASDAS cutoff of 2.1 has been suggested as an alternative to the BASDAI cutoff of 4.0 to start TNF-blocker treatment . Therefore, in the above case scenario, ASDAS better reflects disease activity than BASDAI, from both the patient’s and physician’s perspective. The main reason for the observed discrepancy between ASDAS and BASDAI is that the patient’s complaints are mainly axial (back pain and stiffness), which can be “underrepresented” by BASDAI.




Case scenario 2: A 56-year-old male with AS and disease duration of 21 years. The radiograph of the spine showed multiple syndesmophytes and several vertebral units with bridging syndesmophytes (ankylosis). After a long period of good response to NSAIDs, the disease flared, NSAIDs failed, and the patient had to be treated with a TNF blocker. The pretreatment assessment scores (0–10 scale) were as follows: BASDAI = 6.2, ASDAS = 4.0, patient global = 6, BASMI = 7.1, BASFI = 7.4, and CRP = 25 mg/l; an MRI was also performed for research purposes showing multiple bone marrow edema lesions in the sacroiliac joints. The posttreatment assessment scores were as follows: BASDAI = 0.8, ASDAS = 1.0, patient global = 1.0, BASMI = 5.7, BASFI = 4.6, and CRP = 3 mg/l. There were no posttreatment tender or swollen joints and no extra-articular manifestations, and the follow-up MRI showed no active lesions in the sacroiliac joints.



From a clinical perspective, when asked if this patient is in clinical remission/has inactive disease status under TNF-blocker treatment, rheumatologists would unanimously respond “yes” because disease symptoms are completely controlled and the only evidence of disease is the irreversible structural damage that is restricting spinal mobility and function independently of disease activity. However, looking at the two remission-like states that have been defined in axial SpA ( Table 3 ), this patient is only in clinical remission according to the ASDAS remission-like state (ASDAS <1.3, which represents inactive disease) but not according to the ASAS partial remission criteria, which also require a BASFI score <2 (0–10 scale), a goal that is often unrealistic in patients with extensive spinal structural damage. Therefore, for the purpose of defining a remission-like disease activity state, ASDAS is more appropriate than other currently available definitions as the definition of ASDAS inactive disease is independent of physical function.


Importantly, in a recent study reporting the outcomes of TNF-blocker treatment over a period of 2 years, achievement of ASDAS inactive disease or ASDAS major improvement was significantly associated with greater improvements in the 36-Item Short Form Survey (SF-36) physical and mental component scores as well as in work productivity compared to patients who did not meet these treatment targets . These data show that ASDAS response translates into improvements in health-related quality of life (QOL) and health economic outcomes, and suggest that achieving inactive disease should be considered a major treatment goal in patients with axial SpA .




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 divided into core sets to be applied in different settings ( Table 1 ) . 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 .



Table 1

Assessment of SpondyloArthritis International Society (ASAS) core sets .
































































Domain Instrument For SMARD and PT For CRK For DCART
Function BASFI X X X
Pain NRS/VAS (spine, at night, last week, due to AS)
NRS/VAS (spine, last week, due to AS)
X X X
Spinal mobility Chest expansion, modified Schober, occiput to wall distance, cervical rotation, lateral spinal flexion or BASMI X X X
Patient global NRS/VAS a (global disease activity, last week) X X X
Stiffness NRS/VAS a (spine, duration of morning stiffness, last week) X X X
Fatigue Fatigue question of BASDAI (NRS/VAS a ) X X X
Peripheral joints and entheses Number of swollen joints (44-joint count)
Validated entheses score
X X
Acute-phase reactants CRP or ESR X X
Radiograph of the spine Lateral lumbar and cervical spine X

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 (0–10); PT, physical therapy; SMARD, symptom modifying anti-rheumatic drugs; VAS, visual analog scale (0–10 cm).



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 .


The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) has been the most widely used disease activity composite index in axial SpA . 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 . For example, patients may give more value to subjective symptoms such as pain and fatigue, while doctors may give more value to objective signs such as the number of swollen joints or to laboratory findings such as the presence of elevated acute-phase reactants. Therefore, the correlation between patient and physician global assessments is typically weak in axial SpA and the same applies to the correlation between BASDAI and physician global assessment . Furthermore, BASDAI lacks specificity for inflammatory processes and does not take the redundancy and dependence of individual variables into account. A modified version of the BASDAI (mini-BASDAI) without the questions about tender areas and joint pain/swelling has also been tested and did not perform better than the BASDAI .



Table 2

Measures of disease activity in axial spondyloarthritis.






















Instrument Questions and calculation rules
BASDAI

  • 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 + Q2 + Q3 + Q4) + (Q5 + Q6) ÷ 2) ÷ 5

BAS-G

  • 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.

Spinal pain

  • 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.

Mini-BASDAI

  • 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 + Q2) + (Q3 + Q4) ÷ 2) ÷ 3

ASDAS

  • 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 + 0.07 × Q2 + 0.06 × Q3 + 0.11 × Q4 + 0.58 × Ln(CRP+1)



  • Calculation ASDAS-ESR: 0.08 × Q1 + 0.09 × Q2 + 0.07 × Q3 + 0.11 × Q4 + 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 <2 mg/L, the constant CRP value of 2 mg/L should be used to calculate ASDAS-CRP.

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Nov 10, 2017 | Posted by in RHEUMATOLOGY | Comments Off on Disease activity measurements and monitoring in psoriatic arthritis and axial spondyloarthritis

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