Objective
To use high‐density genotyping to investigate the genetic associations of acute anterior uveitis (AAU) in patients with and those without ankylosing spondylitis (AS).
Methods
We genotyped ...samples from 1,711 patients with AAU (either primary or combined with AS), 2,339 AS patients without AAU, and 10,000 control subjects on an Illumina Immunochip Infinium microarray. We also used data for AS patients from previous genome‐wide association studies to investigate the AS risk locus ANTXR2 for its putative effect in AAU. ANTXR2 expression in mouse eyes was investigated by real‐time quantitative reverse transcription–polymerase chain reaction.
Results
A comparison between all patients with AAU and healthy control subjects showed strong association over HLA–B, corresponding to the HLA–B27 tag single‐nucleotide polymorphism rs116488202. The association of 3 non–major histocompatibility complex loci, IL23R, the intergenic region 2p15, and ERAP1, reached genome‐wide significance (P < 5 × 10−8). Five loci harboring the immune‐related genes IL10–IL19, IL18R1–IL1R1, IL6R, the chromosome 1q32 locus harboring KIF21B, as well as the eye‐related gene EYS, were also associated, reaching a suggestive level of significance (P < 5 × 10−6). Several previously confirmed AS associations demonstrated significant differences in effect size between AS patients with AAU and AS patients without AAU. ANTXR2 expression varied across eye compartments.
Conclusion
These findings of both novel AAU‐specific associations and associations shared with AS demonstrate overlapping but also distinct genetic susceptibility loci for AAU and AS. The associations in IL10 and IL18R1 are shared with inflammatory bowel disease, suggesting common etiologic pathways.
The Assessment of SpondyloArthritis international Society (ASAS) MRI working group (WG) was convened to generate a consensus update on standardised definitions for MRI lesions in the sacroiliac joint ...(SIJ) of patients with spondyloarthritis (SpA), and to conduct preliminary validation.
The literature pertaining to these MRI lesion definitions was discussed at three meetings of the group. 25 investigators (20 rheumatologists, 5 radiologists) determined which definitions should be retained or required revision, and which required a new definition. Lesion definitions were assessed in a multi-reader validation exercise using 278 MRI scans from the ASAS classification cohort by global assessment (lesion present/absent) and detailed scoring (inflammation and structural). Reliability of detection of lesions was analysed using kappa statistics and the intraclass correlation coefficient (ICC).
No revisions were made to the current ASAS definition of a positive SIJ MRI or definitions for subchondral inflammation and sclerosis. The following definitions were revised: capsulitis, enthesitis, fat lesion and erosion. New definitions were developed for joint space enhancement, joint space fluid, fat metaplasia in an erosion cavity, ankylosis and bone bud. The most frequently detected structural lesion, erosion, was detected almost as reliably as subchondral inflammation (κappa/ICC:0.61/0.54 and 0.60/0.83) . Fat metaplasia in an erosion cavity and ankylosis were also reliably detected despite their low frequency (κappa/ICC:0.50/0.37 and 0.58/0.97).
The ASAS-MRI WG concluded that several definitions required revision and some new definitions were necessary. Multi-reader validation demonstrated substantial reliability for the most frequently detected lesions and comparable reliability between active and structural lesions.
Objective
Women with psoriatic arthritis (PsA) may have reduced tumor necrosis factor inhibitor (TNFi) effectiveness compared to men. We examined sex differences in treatment response and retention ...rates during 24 months of follow‐up among patients with PsA initiating their first TNFi.
Methods
Data from patients with PsA across 13 European Spondyloarthritis Research Collaboration Network registries starting their first TNFi were pooled. Logistic regression was used to analyze the association between sex and treatment response using low disease activity (LDA) according to the Disease Activity Score in 28 joints using the C‐reactive protein level (DAS28‐CRP) (<3.2) at six months as the primary outcome. Analyses were adjusted for age, country, conventional synthetic disease‐modifying antirheumatic drug treatment, and TNFi start year. Retention rates were explored using the Kaplan–Meier estimator.
Results
We analyzed the treatment response of 7,679 patients with PsA (50% women) with available data on LDA at six months. At baseline, women and men had similar characteristics, including mean DAS28‐CRP (women vs men, 4.4 SD 1.2 vs 4.2 SD 1.2), though patient‐reported outcome measures were worse in women. At six months, 64% of women and 78% of men had LDA (relative risk RR 0.82; 95% confidence interval CI 0.80–0.84). This difference was similar after adjustment (RR 0.83; 95% CI 0.81–0.85). TNFi retention rates were evaluated in 17,842 patients with PsA. Women had significantly lower retention rates than men at all time points (women 79%, 64%, and 50% vs men 88%, 77%, and 64% at 6, 12, and 24 months, respectively).
Conclusion
Despite comparable disease characteristics at baseline, women with PsA have reduced treatment response and retention rates to their first TNFi, highlighting the need to consider sex differences in PsA research and management.
Mounting evidence reveals evident sex differences in physiology, disease presentation and response to medication in axial SpA (axSpA). Unfortunately these data are often neglected in clinical ...practice and research. In this review, myths that still exist on diagnosis, disease manifestation and drug effectiveness were argued against data of the most recent literature. The aim is to increase awareness of sex differences in the clinical aspects of axSpA.
Objective
Real‐world studies are needed to identify factors associated with response to biologic therapies in patients with axial spondyloarthritis (SpA). The objective was to assess sex differences ...in response to tumor necrosis factor inhibitors (TNFi) and to explore possible risk factors associated with TNFi efficacy.
Methods
A total of 969 patients with axial SpA (315 females, 654 males) enrolled in the BIOBADASER registry (2000–2019) who initiated a TNFi (first, second, or further lines) were studied. Statistical and artificial intelligence (AI)–based data analyses were used to explore the association of sex differences and other factors to TNFi response, using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), to calculate the BASDAI50, with an improvement of at least 50% of the BASDAI score, and using the Ankylosing Spondylitis Disease Activity Score, calculated using the C‐reactive protein level (ASDAS‐CRP).
Results
Females had a lower probability of reaching a BASDAI50 response with a first line TNFi treatment at the second year of follow‐up (P = 0.018) and a lesser reduction of the ASDAS‐CRP at this time point. The logistic regression model showed lower BASDAI50 responses to TNFi in females (P = 0.05). Other factors, such as older age (P = 0.004), were associated with unfavorable responses. The AI data analyses reinforced the idea that age at the beginning of the treatment was the main factor associated with an unfavorable response. The combination of age with other clinical characteristics (female sex or cardiovascular risk factors and events) potentially contributed to an unfavorable response to TNFi.
Conclusion
In this national multicenter registry, female sex was associated with less response to a first‐line TNFi by the second year of follow‐up. A higher age at the start of the TNFi was the main factor associated with an unfavorable response to TNFi.
Objective
As first‐degree relatives (FDRs) of HLA–B27–positive patients with axial spondyloarthritis (SpA) have an increased risk of developing axial SpA, the objectives were 1) to evaluate the ...presence of highly specific imaging features as well as clinical signs of SpA at baseline and after 1 year of follow‐up, and 2) to describe the evolution toward clinical disease within 1 year of follow‐up in a cohort of seemingly healthy FDRs of HLA–B27–positive axial SpA patients.
Methods
The Pre‐SpA cohort is a 5‐year prospective inception cohort of seemingly healthy FDRs of HLA–B27–positive axial SpA patients. Clinical and imaging features were collected and recorded.
Results
At baseline, 19% of the FDRs reported inflammatory back pain, 32% current arthralgia, 3% arthritis (ever), 5% enthesitis (ever), and 1% dactylitis (ever), and 3% had an extraarticular manifestation. C‐reactive protein level was elevated in 16%, and erythrocyte sedimentation rate was elevated in 7%. On magnetic resonance imaging (MRI) views of sacroiliac joints, 10% had a Spondyloarthritis Research Consortium of Canada score of ≥2, 4% had a score of ≥5, and 4% had deep lesions. In total, 1% fulfilled the modified New York criteria for radiographic sacroiliitis. Clinical, MRI, and acute phase findings were equally distributed between HLA–B27–positive and –negative FDRs. After 1 year of follow‐up, clinical parameters did not change on the group level, but 6% of the FDRs were clinically diagnosed with axial SpA, of whom 86% were HLA–B27–positive.
Conclusion
Features associated with SpA or imaging abnormalities were found in up to 32% of seemingly healthy FDRs, with an equal distribution between HLA–B27–positive and –negative FDRs. Progression to clinical axial SpA within 1 year of follow‐up was mainly observed in HLA–B27–positive FDRs.
Aim
To assess gender differences in ankylosing spondylitis (AS) patients in relation to tumor necrosis factor alpha inhibitor (TNFi) drug survival and occurrence of adverse events in daily practice ...in a large peripheral hospital.
Method
Retrospective data were collected from AS patients treated with etanercept, infliximab and adalimumab between January 2004 and January 2014. Kaplan–Meier survival curves were conducted to describe the drug survival and occurrence of adverse events in time.
Results
Overall, 122 AS patients (60.7% male) were included over a 10‐year time period, with a mean treatment period of 51 months (1–127 months). In total, 21 (17.2%) patients stopped the TNFi, mainly due to inefficacy (52.4%). Female patients showed a significant shorter treatment period compared to males (33.4 vs. 44.9 months). In addition, female patients switched more between TNFi compared to males (26.9% vs. 16.3%) and had a significantly higher risk at developing infections compared to male patients (26% vs.19%).
Conclusion
Females stayed on the same TNFi for a significantly shorter period compared to males (33.4 vs. 44.9 months) and the most important reason to stop or switch the drug was inefficacy. Moreover, females seemed to be more prone to infections during TNFi treatment than males.
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