2.4.1 RA
A commonly used measure of disease activity in RA is the Disease Activity Score assessing 28 joints (DAS28) (Prevoo et al. 1995). It includes 28 tender and 28 swollen joint counts, the patient’s reported visual analogue scale (VAS) for global health (Patient Global Assessment; PGA), and the erythrocyte sedimentation rate (ESR) or sometimes C-reactive protein (CRP) instead of ESR. The DAS28 score is calculated by using these numbers in a complex mathematical formula. A result less than 2.6 implies remission, less than 3.2 low disease activity, and greater than 5.1 the active disease. High pain sensitization even in the absence of synovitis may have an impact on the patient’s reported components (tender joint count, VAS for global health), and thus cause a misleadingly high DAS28 score. On the other hand, in cases where RA affects mainly the feet (these are not included in the 28-joint count) or the blood inflammation markers are normal even if the disease is active, the DAS28 score may be misleadingly low.
Other disease activity indices include the simplified disease activity index (SDAI) and clinical disease activity index (CDAI). Both of these include 28 swollen and 28 tender joint counts as well as the patient’s and physician’s global health assessment (using a 100 mm VAS). SDAI also includes CRP. The values of all components are added together, thus the range of the CDAI is from 0 to 76, and that of SDAI from 0.1 to 86 (Anderson et al. 2011).
The valid definition of RA remission in clinical practice is the nonexistence of swollen (and tender) joints, normal inflammatory markers, and no radiological progression (Mäkinen et al. 2005).
The 1981 ACR criteria for remission require that the patient meets the following:
morning stiffness less than 15 minutes, no fatigue, no joint pain, no joint tenderness or pain in motion, no swelling in the joints or tendon sheaths, and a normal ESR for at least two months (Pinals et al. 1981). In the FIN-RACo study, a modified version of these 1981 ACR remission criteria were used; no swollen or tender joints were allowed, and the fatigue and the duration criteria were excluded (Möttönen et al.
1999).
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The latest ACR/EULAR remission criteria for clinical trials were created in 2011 (Felson et al. 2011). These criteria include a Boolean definition and an index-based definition for remission. The former requires a tender and swollen joint count ≤1, CRP ≤1 mg/dl, and PGA≤1 on a 0 to 10 scale. The latter requires SDAI to be ≤3.3 or CDAI to be ≤2.8.
Response measures for RA have been developed to better estimate changes in disease activity over time. These include the ACR20, ACR50, and ACR70 response criteria, with respective improvement levels of 20%, 50%, or 70%, in 5 out of the 7 core set variables (tender joint count, swollen joint count, acute phase reactant, patient’s assessment of pain, patient’s global assessment of disease activity, observer’s global assessment of disease activity, and patient’s assessment of physical disability). Of these core set variables, the first two are required and none are allowed to worsen. The EULAR response criteria are based on DAS28 change (van Gestel et al. 1996).
Plain radiographs show the radiological progression of RA, and different scoring methods for quantifying the damage (irreversible erosions typically in the small joints of the hands and feet) have been developed (Larsen et al. 1977, van der Heijde 2000).
Nowadays, ultrasound is a widely used tool in everyday clinical practice and allows the detection of synovitis more accurately than clinical examination. Ultrasound is also valuable, e.g. in demonstrating when arthralgia is not caused by inflammation.
However, targeting ultrasound remission instead of clinical remission has not been shown to improve remission rates of patients with early RA in a randomized study (Haavardsholm et al. 2016). The availability of MRI has also increased. Bone marrow oedema has proved to be an important MRI finding specific to RA and shown to predict future radiographic progression (e.g. new erosions in plain radiographs) in early RA (Olech et al. 2010, Hetland et al. 2009).
2.4.2 AxSpA
Disease monitoring in axSpA includes questionnaires for the AS Disease Activity Score (ASDAS), Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), and pain, as well as swollen joint counts, spinal mobility, and the assessment of extra-articular manifestations.
The ASDAS combines patient-reported outcomes and C-reactive protein (CRP) (or ESR) into an index to assess disease activity; the active disease is defined by an
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ASDAS of at least 2.1 and remission at <1.3 (van der Heijde et al. 2009, Machado et al. 2011). The BASDAI consists of a 0-10 scale measuring overall fatigue, spinal pain, arthralgia or joint swelling, overall pain of the body, and the duration and severity of morning stiffness; a BASDAI level of at least 4 is considered as the active disease (Garrett et al. 1994). BASFI is used to assess the degree of functional limitation in axSpA patients, and it consists of 10 questions that evaluate the patient’s ability to cope with activities related to functional anatomical limitations and everyday life (Calin et al. 1994).
Radiographs of the spine show the presence of syndesmophytes and thus may have prognostic value, but spinal radiographs are not used for monitoring (van der Heijde 2017). MRI is used to support the diagnosis of nr-axSpA, but it is not recommended for monitoring symptom-free patients (van der Heijde 2017). The main finding of active sacroiliitis is bone marrow oedema located periarticularly or on subchondral bone surfaces of the sacroiliac joints, usually symmetrically. Two or more of these lesions on the same image or one lesion on two consecutive images are considered as a positive MRI finding (Rudwaleit et al. 2009b). Also, the inflammation of ligaments, tendons, fascia, or capsules at the bone insertion sites are typical for axSpA (enthesitis). However, entesitis or synovitis alone (without oedema in the adjacent bone marrow) is not enough to make a diagnosis. In the spine, the active inflammation may show up in the bone marrow of the anterior or posterior vertebral corners (spondylitis), the cortical plates adjacent to the intervertebral discs (spondylodiscitis), the facet joints, or costovertebral joints. Chronic inflammatory lesions in axSpA include fat depositions, subchondral sclerosis, erosions, and ankylosis of the sacroiliac joints or spine, and also syndesmophyte formation in the spine (Canella et al. 2013). The interpretation of sacroiliac joint MRIs may be challenging: mechanical stress or degenerative changes may be hard to differentiate from inflammatory findings, which may lead to the over-diagnosis of axSpA in patients without inflammation (Jans et al. 2014, Eshed and Lidar 2017). In one study by de Winter et al., 23% of healthy individuals, 13% of frequent runners, 57% of women with postpartum back pain, and 92% of patients diagnosed with axSpA had MRI-positive sacroiliitis according to the ASAS definition (de Winter et al. 2018).
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