TNFα-inhibitors for ankylosing spondylitis and non-radiographic axial spondyloarthritis

SpA subtype classification and diagnosis

axSpA is characterised by inflammation of the sacroiliac joints and spine[6],[8], and patients with axSpA typically present with chronic back pain and spinal stiffness, as well as a reduction in mobility and quality of life (QoL). Over time, permanent damage to spinal mobility and function can occur owing to new bone formation in the spine[9]. According to current evidence, active inflammation in the sacroiliac joints and the spine is followed by bone repair, which leads to excessive new bone formation — a morphological substrate of structural damage in axSpA New bone formation/ankylosis in the sacroiliac joints has a diagnostic value without a significant impact on the patient’s functional status, whereas new bone formation in the spine (syndesmophytes, bridging syndesmophytes and ankylosis) has a clear correlation with reduction of spinal mobility and functional status in patients with axSpA

SpA are categorised into axSpA and phSpA on the basis of primary symptom localisation. According to the most recent ASAS definition, axSpA predominantly includes non-radiographic axSpA (nr-axSpA), radiographic axSpA and ankylosing spondylitis (AS), which is regarded as the most commonly known SpA type. Whereas phSpA predominantly includes psoriatic arthritis, reactive arthritis, enteropathic arthritis and undifferentiated SpA[12].

Several criteria are available for diagnosis of SpA, the earliest of which was the modified New York (mNY) criteria for AS (1984) that combined clinical and radiological criteria. In particular this classification distinguishes sacroiliitis using plain radiographs: grade 0: normal; grade I: some blurring of the joint margins — suspicious; grade II: minimal sclerosis with some erosion; grade III: definite sclerosis on both sides of the joint or severe erosions with widening of the joint space with or without ankylosis; and grade IV: complete ankyloses[13].

The Amor criteria for SpA (1990) and ESSG criteria (1991) were designed to capture the entire spectrum of SpA earlier in its disease course; this criteria has sensitivity and specificity of 87% and 90%, respectively, but their more general nature means they are unable to specifically identify early axSpA[14].

The introduction of tumour necrosis factor (TNF) inhibitors as an effective treatment resulted in a new classification criteria being proposed by ASAS that aimed to capture both early and established disease[6]. This highlighted the concept of axSpA that includes two groups: patients with mNY criteria for AS, and patients who do not meet the mNY criteria but have classifiable nr-axSpA (where definite structural changes are not evident in the sacroiliac joints on plain radiographs). When the ASAS axSpA criteria are compared with physician gold standard, they have a sensitivity and specificity of 83% and 84%, respectively. The imaging arm alone has a sensitivity of 66% and a specificity of 97%. This demonstrates that positive imaging with plain radiograph or magnetic resonance imaging (MRI) has high specificity but lacks sensitivity when assessed against physician gold standard[15].

Several biomarkers have demonstrated promise in differentiating axSpA from nr-axSpA, and identifying poor prognosis in patients with axSpA. These biomarkers include vascular endothelial growth factor, matrix metalloprotein 3, sclerostin, citrullinated vimentin, dikkopf-1 and antibodies to MHC class II-associated invariant chain[16].

MRI enables the diagnosis of axSpA at an early stage of disease and in patients who do not have erosive disease[17],[18],[19]. Research has demonstrated that T1 and short tau inversion recovery (STIR) sequences are the best indicators of axSpA and that gadolinium contrast does not add anything to the diagnosis[20],[21].

Definitions of a positive sacroiliac joint scan have been proposed as either two discrete STIR lesions on the same slice or one STIR lesion that is observed on more than one slice[22]. A positive spinal MRI is currently defined as three or more corner inflammatory lesions (osteitis), with each lesion being present on at least two slices[23]. Finally, research examining the value of scanning the entire spine, in addition to the sacroiliac joints for the diagnosis of nr-axSpA, indicates that there is little additional value in imaging the spine[24].

Current goals for SpA treatment are: reduction/remission of inflammatory signs and symptoms; improvement of functional performance; prevention, slowing or arrest of disease progression; avoidance of toxicities; and minimisation of co-morbidities[25].

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