Performance of the Ankylosing Spondylitis Disease Activity Score based on a quick quantitative C-reactive protein assay in patients with axial spondyloarthritis.

OBJECTIVES: To evaluate the performance of the Ankylosing Spondylitis Disease Activity Score based on a validated quick quantitative C-reactive protein assay (ASDAS-qCRP) as compared to ASDAS based on a routine lab CRP assay (ASDAS-CRP) and ASDAS based on erythrocyte sedimentation rate (ASDAS-ESR). METHODS: Disease activity assessment was performed in 50 patients with axial spondyloarthritis (axSpA). Routine lab CRP was measured in the central lab while the quantitative quick-CRP assay and ESR measurements were performed locally. ASDAS-CRP, ASDAS-qCRP and ASDAS-ESR were subsequently calculated. RESULTS: The mean (±SD) serum level of the routine lab CRP (6.2±8.3mg/l) was lower than of the quick-CRP (7.4±8.4mg/l) (P<0.05). Whereat, there was no significant difference in the mean values of ASDAS-CRP and ASDAS-qCRP in axSpA patients (2.70±0.94 and 2.74±0.96, respectively, P=0.069), while the ASDAS-ESR (2.85±1.0) was significantly higher than ASDAS-CRP (P=0.036) and numerically higher than ASDAS-qCRP (P=0.125). In 47 of the 50 cases of axSpA (94%), patients were assigned to the same disease activity category according to ASDAS-CRP and ASDAS-qCRP. CONCLUSIONS: ASDAS-qCRP performed similarly well compared to ASDAS-CRP with the absolute agreement on the disease activity category according to the ASDAS of 94%. ASDAS-qCRP is, therefore, feasible for an immediate decision-making in clinical practice and trials aimed at treating to target.

Diagnostic accuracy of inflammatory back pain for axial spondyloarthritis in rheumatological care.

OBJECTIVE: Inflammatory back pain (IBP), the key symptom of axial spondyloarthritis (axSpA), including ankylosing spondylitis, has been proposed as a screening test for patients presenting with chronic back pain in primary care. The diagnostic accuracy of IBP in the rheumatology setting is unknown. METHODS: Six rheumatology centres, representing secondary and tertiary rheumatology care, included routinely referred patients with consecutive chronic back pain with suspicion of axSpA. IBP (diagnostic test) was assessed in each centre by an independent (blinded) rheumatologist; a second (unblinded) rheumatologist made the diagnosis (axSpA or no-axSpA), which served as reference standard. RESULTS: Of 461 routinely referred patients, 403 received a final diagnosis. IBP was present in 67.3%, and 44.6% (180/403) were diagnosed as axSpA. The sensitivity of IBP according to various definitions (global judgement, Calin, Berlin, Assessment of SpondyloArthritis international Society criteria for IBP) was 74.4%-81.1 % and comparable to published figures, whereas the specificity was unexpectedly low (25.1%-43.9%). The resulting positive likelihood ratios (LR+) were 1.1-1.4 and without major differences between sets of IBP criteria. The presence of IBP according to various definitions increased the probability of axSpA by 2.5%-8.4% only (from 44.6% to 47.1%-53.0%). CONCLUSIONS: The diagnostic utility of IBP in the rheumatology setting was smaller than expected. However, this was counterbalanced by a high prevalence of IBP among referred patients, demonstrating the effective usage of IBP in primary care as selection parameter for referral to rheumatology. Notably, this study illustrates potential shifts in specificity and LR+ of diagnostic tests if these tests are used to select patients for referral.

The frequency of non-radiographic axial spondyloarthritis in relation to symptom duration in patients referred because of chronic back pain: results from the Berlin early spondyloarthritis clinic.

OBJECTIVE: This study was aimed at investigating the frequencies of non-radiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS) diagnoses and their ratios in relation to symptom duration in patients referred because of chronic back pain and suspicion of axial SpA. METHODS: In this monocentre study, orthopaedists and primary care physicians were requested to refer patients with chronic low back pain (duration >3 months) and onset of back pain before 45 years of age to a SpA-specialised rheumatology outpatient clinic for further diagnostic investigation, if proposed screening parameters were present. The ratio of nr-axSpA to AS was analysed in relation to the duration of symptoms. RESULTS: A diagnosis of definite axial SpA was made in 43.7% of the referred patients (n=522). Axial SpA was diagnosed in a similar percentage of about 50% if back pain duration was <9 years but decreased to 36% if symptom duration was >9 years. Nr-axSpA represented the majority of patients (67.3%) only if duration of back pain was 1 year and less at the time of referral. Between 1 and 6 years of back pain duration the probability of nr-axSpA and AS was nearly equal (1-3 years: 52.5% and 47.5%, respectively; 3-6 years: 53.7% and 46.3%, respectively). In patients with back pain duration of 6-9 years, AS was more likely (61.1%) to be diagnosed than nr-axSpA (38.9%), and this increased further over time. CONCLUSIONS: Non-radiographic axial SpA represents an important differential diagnosis of back pain, especially in patients with recent symptom onset.

Evaluation of 2 screening strategies for early identification of patients with axial spondyloarthritis in primary care.

OBJECTIVE: To evaluate 2 referral strategies for axial spondyloarthritis (SpA) in patients with chronic low back pain at the primary care level. METHODS: Referral physicians (n = 259) were randomly assigned to either Strategy 1 or Strategy 2 in order to refer patients with chronic back pain (duration > 3 months), age at onset of back pain < 45 years, and no diagnosis of axial SpA, to a cooperating rheumatologist (n = 43). According to Strategy 1, suitable patients were referred if at least 1 of the following screening criteria was present: inflammatory back pain, HLA-B27, or sacroiliitis detected by imaging. According to Strategy 2, patients were referred if 2 out of 5 criteria were positive: the same 3 criteria from Strategy 1 and additionally a positive family history of ankylosing spondylitis (AS) or a good treatment response to nonsteroidal antiinflammatory drugs. The final diagnosis of the rheumatologist was used as the "gold standard." RESULTS: In total, 560 consecutively referred patients were included in the analysis. Among 318 patients referred by Strategy 1, 41.8% (95% CI 36.5%-47.3%) were diagnosed with definite axial SpA. Among 242 patients referred by the second strategy, definite axial SpA was diagnosed in 36.8% (95% CI 31.0%-43.0%) of the cases. CONCLUSION: Both referral strategies demonstrated comparable performance in identification of patients with axial SpA. Strategy 1 might be preferred as an easy and reliable screening method for axial SpA at the primary care level.

In vitro observations of T cell responsiveness to recall antigens during tumor necrosis factor-alpha-blocking therapy in patients with ankylosing spondylitis.

OBJECTIVE: Anti-tumor necrosis factor-alpha (TNF-alpha) therapy can induce reactivation of tuberculosis and an increase of other infections in patients with ankylosing spondylitis (AS). This raises the question if an alteration of T cell function can be detected by in vitro analysis to identify patients who might be more at risk of acquiring such infectious diseases. METHODS: We examined peripheral blood from AS patients without history of tuberculosis before and after 10-14 and 24-36 weeks of therapy with adalimumab (n = 8) or infliximab (n = 10). Fresh peripheral blood mononuclear cells were stimulated with cytomegalovirus antigens and with the Mycobacterium tuberculosis antigen purified protein derivative and early secretory antigen target 6. Interferon-gamma production of CD4+ T cells was assessed after in vitro antigen-specific stimulation by intracellular cytokine staining and flow cytometry. RESULTS: There was no significant change, either decrease or increase, of the T cell response to recall antigens during therapy compared to controls without treatment, if the mean values of all patients treated with adalimumab or infliximab were compared at the given timepoints. However, analysis on the individual patient level of such T cell responses revealed 1 adalimumab-treated patient and 2 infliximab-treated patients with a clear decrease of T cell response during therapy. Longterm analysis indicated that such a decrease of T cell responsiveness is generally transient and reconstituted at the latest after 52 weeks. CONCLUSION: Some patients treated with adalimumab or infliximab showed a decrease of T cell responsiveness, which seems to be transient. These patients in particular might be at risk for intracellular infections.

Performance of referral recommendations in patients with chronic back pain and suspected axial spondyloarthritis.

BACKGROUND: Ankylosing spondylitis (AS) and its early form account for up to 5% of all patients with chronic back pain. Interest has recently focused on shortening the delay of 5-10 years between the appearance of first symptoms and the diagnosis of AS, particularly because effective treatments have now become available. Referral parameters that are easy for doctors in primary care to apply to patients presenting with possible AS could contribute to earlier diagnosis. METHODS: Orthopaedists and primary-care doctors were requested to refer patients with (1) chronic low back pain (duration >3 months) and (2) onset of back pain before <45 years of age to a specialist rheumatology outpatient clinic for further diagnostic investigation if at least one of the following screening parameters was present: (1) inflammatory back pain, (2) positive human leucocyte antigen B27, and (3) sacroiliitis detected by imaging. The final diagnosis was made according to expert opinion. RESULTS: In total, 350 referred cases were analysed. A diagnosis of definite axial spondyloarthritis (axial SpA), comprising established AS and pre-radiographic axial SpA, could be made in 45.4% of all referred patients (of which 50.3% were classified as AS and 49.7% as preradiographic axial SpA), whereas 45.4% were classified as non-SpA and 9.1% as possible SpA. A diagnosis of definite axial SpA could be made in 34.2% if only one referral parameter was positive, and in 62.6% if there was >1 positive referral parameter. CONCLUSIONS: The proposed referral parameters have proven useful when applied in primary care in identifying patients with AS/pre-radiographic axial SpA among young to middle-aged patients with chronic low back pain.