Page 88 - Recognizing axial spondyloarthritis - Janneke de Winter

CHAPTER FIVE
as a reference but also the combination of clinical diagnosis plus fulfilling the ASAS axSpA criteria to be even more stringent) would also be considered SpA in daily practice. Supporting our claim, the percentage of axSpA patients in SPACE (42% when using both clinical diagnosis and ASAS axSpA criteria) is similar to the percentage of 41.8% found by a multicenter study using a referral strategy consisting of the presence of either IBP or HLA-B27 or sacroiliitis on imaging (MRI and/or radiograph) (21) and not much higher than the 35.1% found in a study using IBP or a good NSAID response as referral symptom (22). So percentages around 40% are in line with what one would expect in such ‘diagnostic’ settings.
Furthermore, the meticulous collection of clinical and radiographic data enabled us to define axSpA in several ways and thus correct for potential biases. For example, an accurate clinical diagnosis of axSpA in an early phase remains challenging and the ASAS classification criteria are not appropriate for diagnostic use, questioning the validity of the ‘gold standard’ for assessment of a potential diagnostic biomarker. The SPACE cohort, however, allowed us to use more strict definitions of diagnosis, either by combining clinical diagnosis and classification criteria or by using clinical diagnosis confirmed at 1 year of follow-up. These analyses yielded very similar results as the primary analyses, indicating that it is unlikely that diagnostic biases explain the differences in anti-CD74 IgG between established AS and early axSpA, the relatively high prevalence of anti-CD74 IgG and IgA antibodies in CBP patients, or the limited PPV and NPV of anti-CD74 IgA in early back pain patients.
Similarly, the well-documented clinical and imaging data of the SPACE cohort also allowed us to explore if anti-CD74 IgA antibodies were associated with a specific sub-population of axSpA patients. These analyses showed that anti- CD74 IgA antibodies were not associated with HLA-B27, CRP, disease duration, sacroiliitis on X-ray, peripheral manifestations other than heel enthesitis or extra- articular disease manifestations, although they were associated with sacroiliitis on MRI and heel enthesitis. A longitudinal analysis may be more powerful than our cross-sectional approach to determine whether anti-CD74 antibodies are a useful biomarker for specific features of the disease, for example to predict radiographic damage.
Although the SPACE cohort is designed to simulate a real-life situation, the generalizability of findings in the SPACE cohort to the intended population could be questioned. First, the SPACE cohort includes patients with chronic back pain for ≥3 months but ≤2 years between 16-45 years in whom the diagnosis of AxSpA was considered. However, patients presenting for diagnostic work-up of potential AxSpA in clinical practice may have significantly longer symptom duration. Although we did not find any correlation between anti-CD74 IgG or IgA antibodies and disease duration in either of our cohorts, we cannot formally exclude a different relationship in patients with longer symptom duration. Second, SPACE includes patients in secondary and tertiary rheumatology practices, so this is the setting that we tested and our data are not applicable to a primary care or population-
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