How to Screen for Axial Spondyloarthritis in Primary Care?
There are currently three investigations that used composite sets of parameters for referral. In the first of these investigations, which was performed as a prospective single center study in Berlin, Germany, orthopedists or primary care physicians were asked to send the patient to the rheumatologist in the presence of IBP or of a positive Human-Leukocyte-Antigen (HLA)-B27 test and/or in the presence of evidence of sacroiliitis in any imaging. These parameters could be present alone or in combination. Out of 350 patients referred, a diagnosis of axial SpA could be made in 45.4%; 50.3% of these 163 axial SpA patients were classified as AS and 49.7% as nr-axSpA. As a single parameter, either alone or in combination, HLA-B27 positivity performed best with a final diagnosis of axSpA in 45% of patients referred compared with 26 and 25% when IBP or sacroiliitis on imaging, respectively, were analyzed as referral parameter. IBP was used as a referral parameter in 53% of the patients. If combinations of referral parameters were looked at, a combination of HLA-B27 and evidence of sacroiliitis resulted in the highest percentage of an axSpA diagnosis in 85%, followed by a combination of HLA-B27 and IBP in 58%.
The second trial was conducted as a multicenter randomized study in Germany with 43 rheumatologists participating from all over the country, the Multicenter Ankylosing Spondylitis survey Trial to Evaluate and compare Referral parameters in early SpA. The just discussed set of referral parameters was compared with another set asking for two out of five offered parameters (IBP, HLA-B27, sacroiliitis on imaging, good response to NSAID treatment, and/or a positive family history) being positive for referral. In total, 560 consecutive patients were recruited for this study. Of the 318 patients referred via strategy 1, a diagnosis of axial SpA was made in 41.8 vs. 36.8% if strategy 2 was used, a small difference that was statistically not significant. IBP was used most frequently in 76.7% for referral in both strategies, followed by sacroiliitis on imaging in 55.7% and a positive HLA-B27-test in 44.7%. However, HLA-B27, alone or in combination, performed best with 57.7% of patients finally diagnosed as axial SpA, followed by sacroiliits on imaging in 50.3% and IBP in 41.8%.
Interestingly, out of 133 patients with axial SpA diagnosed by applying the whole strategy 1, a diagnosis of axial SpA would have been made in only 82 (out of these 133) patients (62%) if HLA-B27 had been used alone; if the most often used criterion IBP had been used alone such a diagnosis would have been made in only 102 patients (77%) referred by strategy 1, clearly indicating that the set of criteria used in strategy 1 results in a higher number of patients diagnosed as axSpA compared with a single referral criterium.
In the final and most recent investigation (the Recognizing and Diagnosing Ankylosing Spondylitis Reliably study), again two referral strategies were compared in a prospective randomized multicenter study with participating rheumatologists from 16 countries from all over the world. Strategy 1 was similar to that presented above, strategy 2 was modified by including a sixth SpAtypical parameter (presence of extraarticular manifestations), otherwise the study design was similar. Five hundred and four patients were referred via strategy 1 and 568 via strategy 2, resulting in a final diagnosis of axial SpA by the rheumatologist in 35.6 and 39.8%, respectively. Out of the 397 patients with axSpA, a diagnosis of AS was made by the local rheumatologist in 77% and of nr-axSpA in 23%. IBP was by far the most frequently used referral parameter in about 95% in both strategies. In contrast, HLA-B27 was only used in 17.2% and sacroiliitis on imaging in about 31.8% for referral.
Composite Sets of Referral Parameters
There are currently three investigations that used composite sets of parameters for referral. In the first of these investigations, which was performed as a prospective single center study in Berlin, Germany, orthopedists or primary care physicians were asked to send the patient to the rheumatologist in the presence of IBP or of a positive Human-Leukocyte-Antigen (HLA)-B27 test and/or in the presence of evidence of sacroiliitis in any imaging. These parameters could be present alone or in combination. Out of 350 patients referred, a diagnosis of axial SpA could be made in 45.4%; 50.3% of these 163 axial SpA patients were classified as AS and 49.7% as nr-axSpA. As a single parameter, either alone or in combination, HLA-B27 positivity performed best with a final diagnosis of axSpA in 45% of patients referred compared with 26 and 25% when IBP or sacroiliitis on imaging, respectively, were analyzed as referral parameter. IBP was used as a referral parameter in 53% of the patients. If combinations of referral parameters were looked at, a combination of HLA-B27 and evidence of sacroiliitis resulted in the highest percentage of an axSpA diagnosis in 85%, followed by a combination of HLA-B27 and IBP in 58%.
The second trial was conducted as a multicenter randomized study in Germany with 43 rheumatologists participating from all over the country, the Multicenter Ankylosing Spondylitis survey Trial to Evaluate and compare Referral parameters in early SpA. The just discussed set of referral parameters was compared with another set asking for two out of five offered parameters (IBP, HLA-B27, sacroiliitis on imaging, good response to NSAID treatment, and/or a positive family history) being positive for referral. In total, 560 consecutive patients were recruited for this study. Of the 318 patients referred via strategy 1, a diagnosis of axial SpA was made in 41.8 vs. 36.8% if strategy 2 was used, a small difference that was statistically not significant. IBP was used most frequently in 76.7% for referral in both strategies, followed by sacroiliitis on imaging in 55.7% and a positive HLA-B27-test in 44.7%. However, HLA-B27, alone or in combination, performed best with 57.7% of patients finally diagnosed as axial SpA, followed by sacroiliits on imaging in 50.3% and IBP in 41.8%.
Interestingly, out of 133 patients with axial SpA diagnosed by applying the whole strategy 1, a diagnosis of axial SpA would have been made in only 82 (out of these 133) patients (62%) if HLA-B27 had been used alone; if the most often used criterion IBP had been used alone such a diagnosis would have been made in only 102 patients (77%) referred by strategy 1, clearly indicating that the set of criteria used in strategy 1 results in a higher number of patients diagnosed as axSpA compared with a single referral criterium.
In the final and most recent investigation (the Recognizing and Diagnosing Ankylosing Spondylitis Reliably study), again two referral strategies were compared in a prospective randomized multicenter study with participating rheumatologists from 16 countries from all over the world. Strategy 1 was similar to that presented above, strategy 2 was modified by including a sixth SpAtypical parameter (presence of extraarticular manifestations), otherwise the study design was similar. Five hundred and four patients were referred via strategy 1 and 568 via strategy 2, resulting in a final diagnosis of axial SpA by the rheumatologist in 35.6 and 39.8%, respectively. Out of the 397 patients with axSpA, a diagnosis of AS was made by the local rheumatologist in 77% and of nr-axSpA in 23%. IBP was by far the most frequently used referral parameter in about 95% in both strategies. In contrast, HLA-B27 was only used in 17.2% and sacroiliitis on imaging in about 31.8% for referral.