Spondylarthritis Patients Research Articles

Systemic lupus erythematosus induced by anti-tumor necrosis factor α therapy in inflammatory rheumatic diseases: a case series.

This case series aims to characterize the development of systemic lupus erythematosus (SLE) induced by anti-tumor necrosis factor α (anti-TNFα) therapy in patients with inflammatory rheumatic diseases, namely rheumatoid arthritis (RA), spondylarthritis (SpA), and psoriatic arthritis (PsA). Patients with a diagnosis of SLE induced by anti-TNFα therapy and registered on the Rheumatic Diseases Portuguese Register (Reuma.pt) who started their first anti-TNFα between 2001 and 2020 were included. Demographic, clinical, and laboratory data were obtained by consulting Reuma.pt. The diagnosis of SLE induced by anti-TNFα was considered if there was a temporal relationship between the onset of anti-TNFα therapy and manifestations (clinical and immunological) in accordance with the American College of Rheumatology/European League Against Rheumatism criteria (2019). A total of 607 patients with inflammatory rheumatic diseases and six cases of SLE induced by anti-TNF-α therapy were reviewed: two patients were affected by RA, three patients by SpA, and one by PsA. All these patients had articular and constitutional symptoms that improved after discontinuation of the anti-TNFα agent. After switching to a second anti-TNFα agent, there was no recurrence of SLE over time. The development of SLE secondary to anti-TNFα agents in inflammatory rheumatic patients is rare. In this case series, all patients had a mild disease that improved after therapy discontinuation without recurrence of the disease. SLE induced by anti-TNFα should be considered in the follow-up of RA, SpA, and PsA patients.

Inflammatory low back pain-associated malignancies mimicking spondylarthritis.

Inflammatory low back pain (IBP) is a typical feature of spondylarthritis (SpA). IBP can be caused by infections, drugs, and different malignancies. Among cancers, hematologic malignancies and solid tumors can cause IBD either paraneoplastically or through metastasis. In this study, we aimed to present the demographic and clinical characteristics of our patients who presented with IBP in the last 10years and whose final diagnosis was malignancy. Thirty-four patients who presented with inflammatory low back pain in the last 10years and were diagnosed with malignancy as the final diagnosis were included in the study. Thirty-six patients, diagnosed as axial SpA, with similar age-sex ratio of 1:1 from each center were included as the control group. Hematologic malignancies were multiple myeloma, acute leukemia, and lymphoma in descending order. Solid tumors were breast cancer, lung cancer, bone tumors, prostate, colon, embryonal carcinoma, and malignancy of unknown primary. In malignancy-related low back pain, the hematologic/solid ratio was similar (18/16), the interval between symptom and diagnosis was shorter, and biomarkers' results such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum lactate dehydrogenase (LDH) levels were significantly higher than the control group. Malignancy-related low back pain differs from SpA patients with a more severe clinical picture, higher acute phase reactants levels, and higher LDH values. Malignancies must be kept in mind in the differential diagnosis, and in order to validate our findings, the results of larger case series are needed, especially in terms of causative malignancies. Key Points • In malignancy-related inflammatory low back pain, the hematologic/solid ratio was similar, the interval between symptom and diagnosis was shorter, and acute phase reactant levels and LDH levels were significantly higher. • Malignancy-related inflammatory low back pain differs from axial SpA patients with a more severe clinical picture, higher acute phase reactants levels, and higher LDH values. • Malignancies must be kept in mind in the differential diagnosis of axial SpA.

Differences between radiographic and non-radiographic axial spondyloarthritis patients in a Mexican cohort

To compare the demographic, clinical, and laboratory characteristics, disease onset, and clinical features of radiographic axial Spondyloarthritis (r-axSpA) and non-radiographic axial Spondyloarthritis (nr-axSpA) patients. All patients who attended outpatient spondylarthritis (SpA) clinics at Hospital General de Mexico and the Instituto Nacional de la Nutrición from 1998 to 2005 and met the rheumatologist diagnostic criteria for SpA were selected. Then the SpA patients were classified by European Spondyloarthropathy Study Group criteria (ESSG). We selected SpA patients with axial presentation as axial SpA (axSpA), and they were classified as r-axSpA if they met modified New York (mNY) criteria for sacroiliitis and as nr-axSpA if they did not meet mNY criteria; to compared clinical, demographic, and laboratory test between the subgroups. It included 148 SpA patients; 55 (37.2%) patients had r-axSpA, and 70 (47.3%) had nr-axSpA. The nr-axSpA patients had a lower proportion of males (58.6% vs 78.2%, P < 0.05), lower HLA-B27 frequency (54.3%. vs. 92.7%, P < 0.05), were older at disease onset (21 vs 16 years; P < 0.01) and had a higher frequency of infections at disease onset (9.1% vs 32.9, P < 0.05) than r-axSpA. BASFI (2.9 vs 4.8; P < 0.0001), Dougados functional index (7 vs. 14; P < 0.05), and BASDAI (4.1 vs. 5.2; P < 0.001) were lower in patients with nr-axSpA than r-axSpA, respectively. The factors that most influenced the presentation of r-axSpA were history of uveitis (OR 14, 95% CI 2.3–85), HLA-B27 (OR 7.97, 95% CI, 2.96–122), male sex (OR 6.16, 95% CI, 1.47–25.7), axial enthesopathy count (OR 1.17 95% CI, 1.03–1.33). This study provides insight into the differences between nr-axSpA and r-axSpA in Mexico. Patients with r-axSpA were mainly male, with a younger presentation age, a higher prevalence of HLA-B27, more history of uveitis, fewer episodes of dactylitis, more axial enthesopathy, and higher disease activity than nr-axSpA.

Assessment of enthesopathy in conventional pelvis radiography: Another tool for spondyloarthritis diagnosis beyond sacroiliitis

Introduction/objectivesEnthesitis is a cardinal feature of spondylarthritis (SpA), and the pelvis is a common site of enthesitis. This study aimed to establish the association between pelvic enthesis involvement on pelvic X-ray and SpA diagnosis through a radiographic enthesis index (REI) and to assess the reliability and accuracy of this REI. Materials and methodsThe participants were SpA patients and a control group composed of patients with chronic lumbar pain without SpA. Three blinded observers assessed each pelvic radiography three times. Three zones were used: Zone I (ZI), the iliopubic ramus; Zone II (ZII), the pubic symphysis, and Zone III (ZIII), the ischiopubic ramus. A grading system was created from 0 to 3 [Grade 0, normal; Grade 1, minimal changes (subcortical bone demineralization and/or periosteal wishkering, seen as radiolucency and trabeculation of the cortical bone upon tendon insertion); Grade 2, destructive changes (Grade 1 findings and erosions at the enthesis site); and Grade 3, findings of Grade 2 plus >2 mm whiskering out of the cortical bone) for the REI. The sum of the results of the three zones was called the total REI. For statistical analysis, we used the weighted kappa statistic adjusted for prevalence and bias using Gwet's agreement coefficient. ResultsWe enrolled 161 patients, 111 of them with SpA (39.6 % with axial SpA and 47.7 % with peripheral SpA) and 50 without SpA. In the SpA group, 36.7 % and 25.7 % had REI Grades 2 and 3 in ZIII, respectively, while only 6 % of the controls had these grades. For ZI, the frequency of Grades 1 to 3 was 42.3 % in the SpA group (8.1 %, 14.4 %, and 19.8 %, respectively), compared to only 2 % in the controls. ZII was unaffected in most of the patients with SpA (82.9 %) and in the controls (98 %). In the control group, Grade 0 was the most common REI grade in all three zones. The agreement was almost perfect for each zone and between the independent readers. The ROC-curve analysis showed that the highest performance areas were the total REI, ZIII, and ZI. Most (75 %) of the SpA patients without sacroiliitis on X-ray were REI-positive. The sensitivity of the REI for SpA diagnosis was 82 %, while the sensitivity of sacroiliitis on X-ray was 38.7 %. ConclusionsThe assessment of pelvic enthesis using the REI on pelvic radiography may be useful for SpA diagnosis. Total REI, ZIII, and ZI had the highest accuracy and almost perfect reliability. The REI is especially helpful in patients without sacroiliitis on imaging.

Neutrophile to lymphocyte and platelet to lymphocyte ratios predict clinical response to bDMARD in naïve spondylarthritis patients.

Objective: We aim to study association between neutrophile to lymphocyte (NLR) and platelet to lymphocyte (PLR) ratios and disease activity, and their value to predict bDMARD response. Methods: A set of spondylarthritis (SpA) patients under bDMARD registered in the Reuma.pt registry was studied. Sociodemographic, clinical and laboratorial variables were assessed on bDMARD initiation, 6, 12, 18 and 24 months (M) thereafter. Univariable and multivariable generalized estimation equations models assessed associations with disease activity. The NLR and PLR predictive value was assessed using univariable and multivariable logistic regression models. Results: A total of 170 patients were included. Most were male (54.7%), with a predominantly axial phenotype (84.7%). Significant associations were observed between NLR [B=1.55, 95% confidence interval (CI) = (1.38; 1.74)] and PLR [(B=1.16, 95% CI = (1.09; 1.24)] with ASDAS-CRP (p < 0.001). Both baseline ratios predicted ∆ ASDAS-CRP ≥ 1.1 at 6 months [OR = 2.20, 95% CI = (1.21, 4.00) for NLR; OR = 1.02, 95% CI = (1.01, 1.04) for PLR, p < 0.01)]. PLR was a significant predictor of ∆ ASDAS-CRP ≥ 1.1 in all timepoints [OR (12 M) = 1.02, 95% CI = (1.00, 1.03), p < 0.05; OR (18M) = 1.02, 95% CI = (1.01, 1.03), p < 0.001; OR (24M) = 1.01, 95% CI = (1.01, 1.02), p < 0.01]. Conclusion: NLR and PLR were associated with disease activity during the follow up of these patients. They seem to be significant predictors of therapeutic response to bDMARD in naïve SpA patients.

P715 Multiparametric assessment of IBD and SpA-IBD patients to explore disease biomarkers and response predictors

Abstract Background Immune-mediated inflammatory diseases (IMID) are an emerging problem in Western world. Despite being traditionally considered nosologically distinct entities, two or more IMID can coexist within the same patient and their pathogenesis overlap to a certain extent. Two IMID, inflammatory bowel disease (IBD) and spondylarthritis (SpA), often associate, but their pathogenesis remains unknown and disease biomarkers are not fully characterized. This project aims to investigate pathogenic and predictor markers of response Methods A collaborative study, enrolling IMID patients (pts) starting a target therapy, was performed. We focused on 2 cohorts: IBD and IBD-SpA. At baseline, serum (to measure CRP, IL17A, TNFα, and TREM1), intestinal biopsy and stools were collected. Clinical response was assessed at 4 months. The exploratory outcome of this preliminary analysis was to investigate whether serum, immunohistochemical and microbiological markers correlate with each other and with response to therapy Results We enrolled 60 pts (36 IBD, 24 IBD-SpA): 61.7% were female, median age was 46 years (IQR 30-57.3). At 4 months, 52.8% and 41.7% of the IBD and IBD-SpA cohorts showed clinical response. A nearly significant correlation between increased intestinal CD68+ cell infiltrate and higher baseline CRP levels (R=0.52, p=0.06), and between increased CD21+ cell infiltrate and CRP drop at 4 months (R=0.47, p=0.09) was observed. Lower baseline TNFα levels correlated with CRP drop at 4 months (R=0.35, p=0.02); higher baseline TNFα levels correlated with a reduced intestinal infiltrate of CD20+ and CD21+ cells (R=0.67, p=0.04; R=0.69, p=0.04). In the IBD-SpA cohort, a trend towards higher mean TREM1 levels was observed in non-responders vs responders (389.0 pg/mL vs 276.4 pg/mL, p=0.09); ROC curve identified a cut-off of 361.0 pg/mL to predict nonresponse (sensitivity 66.6%, specificity 75.0%, p=0.09). IBD patients had a reduced α-diversity compared to healthy controls (HC) and SpA patients; IBD and SpA patients had an increased β-diversity compared to HC. IBD pts had increased Proteobacteria and decreased Bacteroidetes compared to HC. Agathobacteria, Bacteroides, Faecalibacteria and Prevotella genera were significantly decreased in IBD vs HC, whereas Streptococci and Escherichia-Shigella were significantly increased Conclusion Baseline TNFα may correlate with specific immune signatures of the intestinal infiltrate. Baseline TREM1 may help predicting response in the specific setting of concomitant IBD and SpA. Gut microbiome composition is altered in IBD pts compared to HC, comprising more pathogenic and fewer protective bacteria. Further analyses will be needed to confirm such observations and explore additional features and predictive biomarkers

Prevalence of positive tuberculin skin test in a Brazilian sample of rheumatoid arthritis and spondylarthritis patients.

Patients with rheumatic diseases have an increased risk of infections, especially tuberculosis. In this study, we aimed to recognize the positivity rate of tuberculosis skin test in patients with rheumatoid arthritis and spondyloarthritis and the characteristics of the patients with positive results. Retrospective study of tuberculosis skin test results in patients followed from 2004 to 2021 in a single rheumatology unit. Data related to clinical and epidemiological features, along with treatment information referring to the period in which the tuberculosis skin test was performed, were collected from patients' charts. A total of 723 tests were identified (448 tests in 269 rheumatoid arthritis patients and 275 in 174 spondyloarthritis patients). In the rheumatoid arthritis sample, 31/275 (11.5%) individuals had positive tests, and in the spondyloarthritis, 38/174 (21.8%) had positive tests. In the rheumatoid arthritis sample, patients with positive tuberculosis skin tests used a higher dose of methotrexate than those with negative results (median of 25 mg/week versus median of 20 mg/week respectively; p=0.02). In the spondyloarthritis sample, tuberculosis skin test positivity was associated with alcohol ingestion (13.1% versus 2.9% in users and non-users respectively; p=0.02) and sulfasalazine use (15.7% of positivity in users versus 5% in non-users; p=0.01). The tuberculosis skin test-positive prevalence in rheumatoid arthritis was lower than in the spondyloarthritis sample. Patients with rheumatoid arthritis using a higher dosage of methotrexate or with spondyloarthritis using sulfasalazine had more frequency of tuberculosis skin test positivity and should be carefully followed by the attending physician in order to avoid the appearance of full-blown tuberculosis.

Interplay between COVID-19 and Secukinumab treatment in Spondylarthritis patients during the omicron surge: a retrospective cohort study

The objective of this retrospective cohort study was to assess the relationship between Corona Disease 2019 (COVID-19) and Secukinumab treatment in patients with Spondylarthritis (SpA) in China during the omicron surge. Researchers retrieved 1018 medical records of Secukinumab-treated patients between January 2020 and January 2023 from the West China Hospital of Sichuan University. Out of these, 190 SpA patients from the rheumatology clinic were selected for the study. Guided phone questionnaires were administered by research staff to collect baseline characteristics, SpA disease status, and COVID-19 clinical outcomes. Cohabitants served as the control group and provided COVID-19 related data. Of the 190 potential SpA patients, 122 (66%) completed the questionnaire via phone, along with 259 cohabitants. 84.4% of SpA patients were diagnosed with Ankylosing Spondylitis (AS), and 15.6% were diagnosed with Psoriatic Arthritis (PsA). The rate of SARS-CoV-2 infection was 83.6% in the Secukinumab group and 88.8% in the cohabitants control group, with no significant difference (OR = 0.684, CI 0.366–1.275). One instance of severe COVID-19 was observed in the Secukinumab group, while two were identified in the cohabitants control group. Patients in the Secukinumab group had less time with fever caused by COVID-19 (p = 0.004). Discontinuing Secukinumab after SARS-CoV-2 infection did not significantly affect the course of COVID-19 or worsen SpA status according to our data. Our study suggests that administering Secukinumab to SpA patients does not increase their susceptibility to contracting SARS-CoV-2, and may have a positive effect on the course of SARS-CoV-2 infection.

Persistence of biological agents over an eight-year period in rheumatoid arthritis and spondylarthritis patients

ObjectiveTo calculate the persistence, over a period of eight years, the retention rate of first and second-line of treatment with biological agents in patients with rheumatoid arthritis, spondyloarthritis and psoriatic arthritis and to compare retention rates of the various drugs for each pathology. MethodRetrospective observational study that included patients affected by rheumatoid arthritis, spondyloarthritis and psoriatic arthritis, who started treatment with biological agents between January 2009 and December 2012 and followed until December 2016. Results132, 87 and 33 patients were included in rheumatoid arthritis, spondyloarthritis and psoriatic arthritis, respectively. The median retention duration of all biological agents for the first and second-line, was 30.9 months and 14.0 months, respectively for rheumatoid arthritis; 63.06 months and 25.6 months, respectively in spondyloarthritis. Psoriatic arthritis did not reach the median (> 70 months in first-line) (first line p = 0.002). Individual drug survival in first line: the median retention duration of tocilizumab was 58.3 months, followed by etanercept (p = 0.79) in rheumatoid arthritis. For spondyloarthritis, golimumab and etanercept had greater retention than the other drugs (they did not reach the median): adalimumab was 63.0 months and for infliximab was 50.1 months. In psoriatic arthritis, golimumab, infliximab and etanercept not reach the median and they had greater retention than adalimumab (59.4 months). Individual drug survival in second line: tocilizumab was the most persistent drug (median 22.1 months) in rheumatoid arthritis, and golimumab for spondyloarthritis and psoriatic arthritis. ConclusionsTocilizumab and etanercept in rheumatoid arthritis, and golimumab in spondyloarthritis and psoriatic arthritis also, were the most persistent drugs in first-line and second-line treatment.

Distinct long-term disease activity trajectories differentiate early on treatment with etanercept in both rheumatoid arthritis and spondylarthritis patients: a prospective cohort study

To characterize disease activity trajectories and compare long-term drug retention between rheumatoid (RA) and spondylarthritis (SpA) patients initiating tumor necrosis factor inhibitor (TNFi) treatment (etanercept). Prospective observational study of RA, axial (AxSpA) and peripheral SpA (PerSpA) patients initiating etanercept during 2004–2020. Kaplan–Meier plots were used for drug retention comparisons and multivariable Cox regression models for predictors of discontinuation. Long-term disease activity trajectories were identified by latent class growth models using DAS28-ESR or ASDAS-CRP as outcome for RA and AxSpA respectively. We assessed 711 patients (450 RA, 178 AxSpA and 83 PerSpA) with a median (IQR) follow-up of 12 (5–32) months. At 5 years, 22%, 30% and 21% of RA, AxSpA and PerSpA patients, respectively, remained on therapy. Etanercept discontinuation was independent of the diagnosis and was predicted by gender and obesity in both RA and SpA groups. Four disease activity (DA) trajectories were identified from 6th month of treatment in both RA and AxSpA. RA patients in remission-low DA groups (33.7%) were younger, had shorter disease duration, fewer comorbidities and lower baseline disease activity compared to moderate (40.6%) & high DA (25.7%) groups. In AxSpA 74% were in inactive-low DA and they were more often males, non-obese and had lower number of comorbidities compared to higher ASDAS-CRP trajectories. In RA and AxSpA patients, disease activity trajectories revealed heterogeneity of TNFi treatment responses and prognosis. Male gender, lower baseline disease activity and fewer comorbidities, characterize a favourable outcome in terms of disease burden accrual and TNFi survival.

Colonoscopy aspiration lavages for mucosal metataxonomic profiling of spondylarthritis-associated gastrointestinal tract alterations

The study of the GI-tract microbiota of spondylarthritis (SpA) patients has focused on the analysis of feces samples, that picture mostly the luminal microbiota. The aim of this study was to determine the contribution of mucosal and luminal microbiome to the gut dysbiosis in SpA, using colonoscopy aspiration lavages (CAL), a recent alternative for regional studies of the GI-tract. We analyzed 59 CAL (from sigmoid colon and distal ileum), and 41 feces samples, from 32 SpA patients and 7 healthy individuals, using 16S rRNA gene-targeted metataxonomic profiling. It was found high prevalence of GI-tract manifestations among SpA patients (65.3%). Metataxonomic profiling, confirmed CAL samples from the lower GI tract (colon or ileum) presented a distinctive and undifferentiated bacteriome and separate from that found in feces’ samples or in the beginning of the GI tract (oral cavity (OC)). Lower GI-tract samples and feces of SpA patients exhibited similar behavior to the microbiota of IBD group with reduced microbial richness and diversity, comparing to the healthy controls. Interestingly, it was found increase in proinflammatory taxa in SpA patients, such as Enterobacteriaceae family (mostly in the ileum), Succinivibrio spp. and Prevotella stercorea. Conversely, SpA patients presented significant decrease in the SCFA producers Coprococcus catus and Eubacterium biforme. Our data support the value of CAL samples for the regional study of GI-tract and contribute with information of potential “disruptor taxa” involved in the GI-tract associated disorders observed in SpA patients.

Interleukin 27 is a novel cytokine with anti-inflammatory effects against spondyloarthritis through the suppression of Th17 responses.

Spondylarthritis (SpA) development in HLA-B27/human β2-microglobulin transgenic rat (B27-rat) is correlated with altered conventional dendritic cell (cDC) function that promotes an inflammatory pattern of CD4+T cells, including a biased expansion of pro-inflammatory Th17 population and imbalance of regulatory T cells cytokine profile. Transcriptomic analysis revealed that cDCs from B27-rats under express IL-27, an anti-inflammatory cytokine which induces the differentiation of IL-10+ regulatory T cells and inhibits Th17 cells. Here, we first investigated whether in vitro addition of exogenous IL-27 could reverse the inflammatory pattern observed in CD4+ T cells. Next, we performed preclinical assay using IL-27 to investigate whether in vivo treatment could prevent SpA development in B27-rats. in vitro addition of IL-27 to cocultures of cDCs and CD4+ T cell subsets from B27-rats reduced IL-17 and enhanced IL-10 production by T cells. Likewise, IL-27 inhibited the production of IL-17 by CD4+ T cells from SpA patients. Interestingly, in vivo treatment with recombinant IL-27 starting before SpA onset, inhibited SpA development in B27-rats through the suppression of IL-17/TNF producing CD4+ T cells. Overall, our results reveal a potent inhibitory effect of IL-27 and highlight this cytokine as a promising new therapeutic target in SpA, especially for SpA patients non responders to currently approved biotherapies.

COVID-19 was not associated or trigger disease activity in spondylarthritis patients: ReumaCoV-Brasil cross-sectional data

ObjectivesTo evaluate the disease activity before and after COVID-19 and risk factors associated with outcomes, including hospitalization, intensive care unit (ICU) admission, mechanical ventilation (MV) and death in patients with spondylarthritis (SpA).MethodsReumaCoV Brazil is a multicenter prospective cohort of immune-mediated rheumatic diseases (IMRD) patients with COVID-19 (case group), compared to a control group of IMRD patients without COVID-19. SpA patients enrolled were grouped as axial SpA (axSpA), psoriatic arthritis (PsA) and enteropathic arthritis, according to usual classification criteria.Results353 SpA patients were included, of whom 229 (64.9%) were axSpA, 118 (33.4%) PsA and 6 enteropathic arthritis (1.7%). No significant difference was observed in disease activity before the study inclusion comparing cases and controls, as well no worsening of disease activity after COVID-19. The risk factors associated with hospitalization were age over 60 years (OR = 3.71; 95% CI 1.62–8.47, p = 0.001); one or more comorbidities (OR = 2.28; 95% CI 1.02–5.08, p = 0.001) and leflunomide treatment (OR = 4.46; 95% CI 1.33–24.9, p = 0.008). Not having comorbidities (OR = 0.11; 95% CI 0.02–0.50, p = 0.001) played a protective role for hospitalization. In multivariate analysis, leflunomide treatment (OR = 8.69; CI = 95% 1.41–53.64; p = 0.023) was associated with hospitalization; teleconsultation (OR = 0.14; CI = 95% 0.03–0.71; p = 0.01) and no comorbidities (OR = 0.14; CI = 95% 0.02–0.76; p = 0.02) remained at final model as protective factor.ConclusionsOur results showed no association between pre-COVID disease activity or that SARS-CoV-2 infection could trigger disease activity in patients with SpA. Teleconsultation and no comorbidities were associated with a lower hospitalization risk. Leflunomide remained significantly associated with higher risk of hospitalization after multiple adjustments.

Use of 18F FDG PET-CT to discriminate polymyalgia rheumatica and atypical spondylarthritis in clinical practice.

To evaluate the relevance of 18F-labeled fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET-CT) for discriminating polymyalgia rheumatica (PMR) and spondylarthritis (SpA) in atypical presentations. In 2 rheumatology departments, we identified PMR and atypical SpA patients who underwent 18F-FDG PET-CT and compared the 2 groups. The relevant 18F-FDG PET-CT findings identified on univariate analyses as discriminant for both groups were entered into a multivariable logistic regression model to derive a composite musculoskeletal score. Between September 2012 and August 2018, we enrolled 35 PMR and 27 SpA patients (median [interquartile range] age 71 years [63.5-74.5] and 54 years [41.5-63], P<0.001). 18F-FDG uptake in enthesis/bursae was more frequent in PMR than SpA (ischial tuberosities: 88.6% vs. 48.1%, P<0.001; interspinous processes: 91.4% vs. 51.9%, P<0.001). 18F-FDG uptake in sacroiliac joints was specific to SpA but rare (14.8% vs. 0 in PMR, P<0.05). The intensity of 18F-FDG uptake was similar in both conditions. The musculoskeletal score, including 18F-FDG uptake of the shoulders, ischial tuberosities and interspinous process, was higher for PMR than SpA patients (2.74 vs. 1.11, P<0.001). A score≥2 provided sensitivity and specificity of 74.1% and 77.1% for the diagnosis of PMR. 18F-FDG PET-CT patterns of atypical SpA and PMR widely overlap, so differentiating the conditions is challenging. The use of the proposed PET-CT composite score could improve the diagnostic performance of 18F-FDG PET-CT to discriminate these 2 entities in clinical practice.

P278 Baseline characteristics and treatment response to ixekizumab categorised by sex in radiographic and non-radiographic axial spondylarthritis patients through 52 weeks: data from three phase III, randomized, controlled trials

Abstract Background/Aims Axial spondyloarthritis (axSpA) is a chronic inflammatory disease of the axial skeleton comprising two subtypes within the same spectrum: radiographic (r-axSpA) and non-radiographic (nr-axSpA). Previous studies have shown that clinical presentation and treatment response of males and females may differ despite similar disease burden. Ixekizumab (IXE), a high-affinity monoclonal antibody that selectively targets interleukin-17A, has demonstrated superior efficacy to placebo in the treatment of patients with r-axSpA (COAST-V/W [bDMARD-naïve/TNFi-experienced]) and nr-axSpA (COAST-X [bDMARD-naïve]). Here we report baseline characteristics and treatment response to IXE categorised by sex in patients with r-axSpA and nr-axSpA for up to 52 weeks. Methods Patients fulfilled the ASAS classification criteria for r-axSpA or nr-axSpA. Patients were randomized to receive 80 mg subcutaneous IXE every two weeks (Q2W) or four weeks (Q4W), or to placebo (PBO; 16 weeks COAST-V/W; 52 weeks COAST-X). Baseline characteristics and treatment outcomes were assessed. Patients were categorised by sex; missing data were controlled for using non-responder imputation (NRI) and modified baseline observation carried forward (mBOCF) analysis was conducted on continuous efficacy variables. Results At baseline, females were older, with significantly higher pain and fatigue scores and peripheral joint symptoms. ASAS40 response rate with IXEQ4W was achieved in 39% of males with r-axSpA by week 16, and 44% by week 52. Females achieved 16.7% at week 16, and 33.3% at week 52. In nr-axSpA, 46% of IXEQ4W males achieved ASAS40 at week 16 and 30% at week 52. 23.9% of females achieved ASAS40 at week 16, increasing to 30.4% at week 52. Conclusion This analysis demonstrates that, for the axSpA disease spectrum, females present with higher disease burden as reflected by higher scores in fatigue/tiredness, and spinal pain at night. Our findings indicate that males and females respond to IXE; however, females experience this benefit later in their treatment course, with a more prolonged attainment of peak response. Disclosure A. Kiprianos: None. I.E. van der Horst-Bruinsma: None. R. Bolce: Shareholder/stock ownership; Eli Lilly and Company. T. Hunter: Shareholder/stock ownership; Eli Lilly and Company. D. Marcelino Sandoval Calderon: Shareholder/stock ownership; Eli Lilly and Company. D. Zhu: Shareholder/stock ownership; Eli Lilly and Company. V. Geneus: Shareholder/stock ownership; Eli Lilly and Company. J.R. Lisse: Shareholder/stock ownership; Eli Lilly and Company. S. Liu-Leage: Shareholder/stock ownership; Eli Lilly and Company. M. Magrey: None.

Assessment of pulmonary circulation unit during exercise in patients with ankylosing spondilitis and sporiatic arthritis

Abstract Funding Acknowledgements Type of funding sources: None. Background Ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are chronic multisystem inflammatory disorders that present with articular and extra-articular features. Cardiac dysfunction and pulmonary disease are well-known and commonly reported extra-articular manifestations of AS and PsA. The inflammatory process can induce respiratory complications, including chest wall restriction, significantly impacting patients" cardiorespiratory status. We aimed to assess pulmonary circulation and right ventricle behaviour during exercise in patients with AS and PsA and to detect the possible effect of chest wall restriction on right heart function. Methods A total of 45 spondylarthritis patients were enrolled in the study (age 51.5 ± 12.3 years, 82.2% men): 27 of them were diagnosed with AS (20 of them had ankylosis at the time of the study), while 18 had PsA (2 of them in ankylosis). According to a standardized protocol, all subjects underwent resting and exercise stress echocardiography on a semi-recumbent cycle ergometer with an incremental workload up to the maximal tolerated workload. Basic echocardiographic measurements were taken, focusing on the right and left ventricular functions and the systolic pulmonary artery pressure (PASP) at rest, at 50 watts workload, and maximal exercise. During the examination, non-invasive blood pressure measurements, transcutaneous capillary oxygen saturation and continuous ECG recording were performed. Results PASP did not differ between the AS and PsA patients at rest (15.6 ± 6.7 mmHg vs 13.7 ± 8.3 mmHg; p = ns); however, PASP measured at the maximal workload was significantly higher among AS patients (31.4 ± 15.9mmHg vs 21.6 ± 12.7mmHg; p &amp;lt; 0.05; Figure 1). PASP did not correlate with the age or the time that passed since the diagnosis. Parameters describing the left and right ventricular systolic and diastolic function did not differ significantly between AS and PsA patients at rest and peak stress. Comparing the LV diastolic parameters of ankylosing patients with non-ankylosing patients irrespective of the underlying disease showed significantly different values in peak E/e"ratio (8.9 ± 3 vs 7.4 ± 1.6; p &amp;lt; 0,05; Figure 2). Conclusion Exercise stress echocardiography is a promising diagnostic modality in autoimmune diseases. In AS patients, the chest wall restriction may results in elevation of PASP during the exercise. The noninvasive indice of left ventricular filling pressure increases significantly in patients with ankylosis in both groups, explaining the effect of the rigid chest wall on the left ventricular filling. Abstract Figure. Abstract Figure.

Efficacy of Probiotics in Rheumatoid Arthritis and Spondyloarthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: We aimed to provide a systematic review and meta-analysis of randomized controlled trials assessing the effect of probiotics supplementation on symptoms and disease activity in patients with chronic inflammatory rheumatic diseases (rheumatoid arthritis (RA), spondylarthritis (SpA), or psoriatic arthritis). Methods: A systematic literature review and meta-analysis from RA and SpA randomized controlled trials were conducted searching for articles in MEDLINE/PubMed and abstracts from recent international rheumatology meetings. The control group was a placebo or another dietary intervention. The risk of bias of the selected studies was evaluated using the Cochrane Collaboration tool and the Jadad scale. Results: The initial search yielded 173 articles. Of these, 13 studies were included in the qualitative synthesis, 8 concerning a total of 344 RA patients and 2 concerning a total of 197 SpA patients. Three meta-analyses were also analyzed. Probiotic strains and quantities used were different among trials (5 studies using Lactobacillus sp., 1 trial Bacillus coagulans and the others a mix of different probiotic strains). Time to assess response ranged from 8 weeks to one year. Two studies associated probiotic supplementation with a dietary intervention. Meta-analysis showed a statistically significant decrease of C-reactive protein (CRP) concentration (mean difference (MD)) −3.04 (95% CI −4.47, −1.62) mg/L, p < 0.001; I2 = 20%, n patients = 209) with probiotics in RA. However, after excluding high-risk-of-bias trials of meta-analysis, there was no difference between probiotics and placebo on DAS28 (standard MD −0.54; 95% CI −1.94 to 0.85, p = 0.45, I2 93%, n patients = 143). The two studies on SpA patients showed no efficacy of probiotics. Conclusions: Probiotic supplementation might decrease RA activity with a moderate decrease effect on CRP, but lack of evidence and studies’ heterogeneity do not allow us to propose them to patients with inflammatory arthritis to control their disease. Further RCTs are required in the future to determinate the efficacy of probiotics and the optimal administration design.

Treatment of rheumatoid arthritis and spondylarthritis with biologics

Biologika sind ein wichtiger Bestandteil moderner Therapiestrategien zur Behandlung von rheumatoider Arthritis (RA) und Spondyloarthritiden (SpA) inklusive der Psoriasisarthritis (PsA). Biologika sind biotechnologisch hergestellte Proteine, die inhibitorische Wirkungen auf humorale und zelluläre Komponenten der rheumatischen Entzündung haben. In der Rheumatologie eingesetzte Substanzklassen sind die gegen Zytokine gerichteten Tumor-Nekrose-Faktor(TNF)-α‑, Interleukin(IL)-1-, IL-6-, IL-12-, IL-17- und IL-23-Inhibitoren sowie der Hemmer der T‑Lymphozyten-Aktivierung Abatacept und das B‑Lymphozyten-depletierende Rituximab. Für den Einsatz von Biologika existieren Empfehlungen, die bei der RA das inadäquate Ansprechen auf ein oder mehrere konventionelle synthetische „disease-modifying antirheumatic drugs“ und bei der ankylosierenden Spondylitis und der nichtröntgenologischen axialen SpA das inadäquate Ansprechen auf mindestens 2 nichtsteroidale Antirheumatika vorsehen. Bei der PsA hängt der empfohlene Einsatz von der jeweiligen im Vordergrund stehenden Manifestation ab. Eine Biologikatherapie sollte nach dem Treat-to-target-Prinzip erfolgen, also mit einem definierten und validierten Therapieziel. Dies ist bei der RA und den SpA jeweils entweder die Remission oder aber die niedrige bzw. minimale Krankheitsaktivität. Die Sicherheit der Biologikatherapie wurde intensiv untersucht. Für die einzelnen Substanzklassen existieren sehr spezifische Kontraindikationen mit dem Fokus auf einem erhöhten Infektionsrisiko. Der Ausschluss einer latenten Tuberkulose wie auch einer Hepatitis B gehört zum Standard vor Beginn einer Biologikatherapie. TNF-α-Hemmer haben einen protektiven Effekt in Bezug auf Myokardinfarkt, Schlaganfall und venöse Thromboembolien.

Distinct Long-Term Disease Activity Trajectories Differentiate Early on Treatment with Etanercept in Both Rheumatoid Arthritis and Spondylarthritis Patients

Distinct Long-Term Disease Activity Trajectories Differentiate Early on Treatment with Etanercept in Both Rheumatoid Arthritis and Spondylarthritis Patients

Update: enterogenic spondylarthritis

Spondylarthritis (SpA) is one of the most frequent extraintestinal manifestations of chronic inflammatory bowel disease (IBD). Several arthritogenic enterobacterial infections can induce sequelae such as reactive SpA. Studies on the gut-synovium axis in view of genetic, immunological, clinical and therapeutic aspects has made enterogenic SpA amodel disease of all forms of SpA. The same applies for investigating IBD, as subclinical gut inflammation seen in SpA patients has provided significant evidence for a better understanding of mucosa-associated early immune events in Crohn's disease (CD). This article summarizes the pathognomonic clinical features, diagnostic steps, differential diagnosis and current pathogenetic models of enterogenic SpA. Knowledge of pathogenetic contexts leads to concrete treatment recommendations. These vary individually depending on the underlying IBD, on the inflammatory intestinal or rheumatic activity and on the rheumatological manifestation pattern.