Elevated DAS28-ESR in patients with rheumatoid arthritis who have comorbid fibromyalgia is associated more with tender joint counts than with patient global assessment or swollen joint counts: implications for assessment of inflammatory activity.

OBJECTIVES: More than 20% of rheumatoid arthritis (RA) patients have comorbid fibromyalgia (FM+), which may elevate DAS28-ESR (disease activity score 28-erythrocyte sedimentation rate) and other indices, resulting in challenges to assess inflammatory disease activity. Although several reports indicate that elevated patient global assessment (PATGL) may elevate DAS28 in the absence of inflammatory activity, less information is available concerning the other three components, tender joint count (TJC), swollen joint count (SJC), and erythrocyte sedimentation rate (ESR), to possibly elevate DAS28 in FM+ vs. FM- RA patients. METHODS: A PubMed search identified 14 reports which presented comparisons of DAS28-ESR and its four components in RA FM+ vs. FM- groups. Median DAS28, component arithmetic differences, pooled effect sizes and 95% confidence intervals were analysed in the FM+ vs. FM- groups. RESULTS: In FM+ vs. FM- groups, median DAS28 was 5.3 vs. 4.2, SJC 4.0 vs. 3.0, TJC 13.2 vs. 5.3, PATGL 61.6 vs. 39.9, ESR 26.3 vs. 26.5. DAS28-ESR was classified as "high" (>5.1) in 11/14 FM+ groups and "moderate" (3.2-5.1) in all 14 FM- groups. Effect sizes in FM+ vs. FM- groups for DAS28-ESR, SJC, TJC, PATGL, and ESR were large (≥0.8) in 10/14, 1/13, 12/13, 7/13, and 1/13 comparisons, respectively, and pooled effect sizes 0.84 (0.3, 1.4), 0.33 (-0.4, 1.0), 1.27 (0.01, 2.5), 0.91 (-0.6, 2.4), and 0.07 (-0.6, 0.7), respectively. CONCLUSIONS: DAS28-ESR is elevated significantly in FM+ vs. FM- RA patients; pooled effect sizes were highest for TJC, followed by PATGL, SJC and ESR. The findings appear relevant to response and remission criteria, treat-to-target, and general management of RA.

Small fibre pathology, small fibre symptoms and pain in fibromyalgia syndrome.

A proportion of people with fibromyalgia demonstrate small fibre pathology (SFP). However, it is unclear how SFP directly relates to pain phenomenology. Thirty-three individuals with FMS and ten healthy volunteers underwent assessment of SFP and sensory phenotyping using corneal confocal microscopy, validated questionnaires and quantitative sensory testing (QST). Corneal nerve fibre length was used to stratify participants with fibromyalgia into with SFP [SFP+] and without SFP [SFP-]. SFP was detected in 50% of the fibromyalgia cohort. Current pain score and QST parameters did not differ between SFP+ and SFP-. Mechanical pain sensitivity (MPS) demonstrated a significant gain-of-function in the SFP- cohort compared to healthy-volunteers (p = 0.014, F = 4.806, η2 = 0.22). Further stratification revealed a cohort without structural SFP but with symptoms compatible with small fibre neuropathy symptoms and a significant gain in function in MPS (p = 0.020 Chi-square). Additionally, this cohort reported higher scores for both depression (p = 0.039, H = 8.483, η2 = 0.312) and anxiety (p = 0.022, F = 3.587, η2 = 0.293). This study confirms that SFP is present in a proportion of people with fibromyalgia. We also show that in a proportion of people with fibromyalgia, small fibre neuropathy symptoms are present in the absence of structural SFP. Greater mechanical pain sensitivity, depression and anxiety are seen in these individuals.

Neutrophil function following treatment of psoriatic arthritis patients with secukinumab: altered cytokine signalling but no impairment of host defence.

OBJECTIVES: Identifying that dysfunction of the IL-23/17 axis underlies PsA has led to the development of effective targeted therapies such as the IL-17A inhibitor secukinumab. As IL-17A stimulates the secretion of neutrophil chemoattractants, such as CXCL8 (IL-8), we examined the effect of secukinumab on neutrophil function in PsA. METHODS: Nineteen patients with active PsA were treated with secukinumab. Clinical response [PsA Response Criteria (PsARC) and Psoriasis Area and Severity Index (PASI)] and peripheral blood neutrophil function (apoptosis, receptor expression, phagocytosis/killing, chemotaxis and RNA expression) were measured at 12 week intervals for 48 weeks and compared with age- and sex-matched healthy controls. RESULTS: At 12 weeks, 12/16 (75%) patients had a PsARC response (100% at 36 weeks) and 10/14 (71%) achieved a 90% PASI response. At baseline, there were no differences in PsA neutrophil reactive oxygen species generation, constitutive or cytokine-delayed apoptosis, chemotaxis or phagocytosis of opsonized Staphylococcus aureus compared with healthy controls. Similarly, there were no differences in these functions from baseline to 12 weeks of therapy. However, surface levels of CD11b/CD18 and CD63 increased and expression of CD16 decreased during therapy. In addition, in a subgroup of early (12 week) responders to secukinumab, RNA sequencing revealed transcriptome changes predicting down-regulation of cytokine signalling and chemotaxis pathways and up-regulation of de novo gene expression pathways, including translation initiation, mRNA catabolism and translation. CONCLUSION: Complex changes in the properties of circulating neutrophils occur with secukinumab treatment in PsA that may indicate altered responsiveness to changes in both local and systemic levels of pro-inflammatory cytokines. However, host defence processes of neutrophils were unaltered.

Inflammatory Bowel Disease Risk in Patients With Axial Spondyloarthritis Treated With Biologic Agents Determined Using the BSRBR-AS and a MetaAnalysis.

OBJECTIVE: To determine, among patients with axial spondyloarthritis (axSpA), whether the risk of inflammatory bowel disease (IBD) varies between patients treated with biologic therapies and those treated with other therapies and, specifically, whether the risk is higher in patients treated with etanercept (ETN). METHODS: The British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) was used to determine the incidence of IBD during follow-up and to calculate the incidence rate difference (IRD) per 1000 person-years (PY), between biologic treatment and other treatment groups. We then conducted a systematic review, involving observational studies and randomized controlled trials (RCTs), to perform a metaanalysis to quantify the difference in incidence of IBD between treatment groups. RESULTS: According to the BSRBR-AS, among people with axSpA, exposure to biologic therapy was associated with an increased incidence of IBD compared to those who were not exposed to biologic therapy (IRD 11.9, 95% CI 4.3-19.6). This finding was replicated across observational studies but was not seen in placebo-controlled RCTs (IRD 2.2, 95% CI -4.1 to 8.5). Data from the BSRBR-AS do not suggest that excess incidence of IBD is associated with exposure to ETN compared to other anti-tumor necrosis factor (TNF) therapies (IRD -6.5, 95% CI -21.3 to 8.5). RCTs and their extensions suggest a small-yet not statistically significant-absolute increased incidence associated with ETN of between 2.1 and 5.8 per 1000 PY compared to other anti-TNF therapies. CONCLUSION: There was an excess risk of IBD among persons treated with biologics in observational studies. Only evidence from RCTs suggested that ETN was associated with an increased risk compared to other anti-TNF therapies, albeit with considerable uncertainty.

The prevalence of comorbidity in rheumatoid arthritis: a systematic review and meta-analysis.

This systematic review and meta-analysis estimates the prevalence of common comorbid health disorders in adults with rheumatoid arthritis (RA). A multi-database search strategy was undertaken. Screening, data extraction and quality assessment were carried out by two independent reviewers. A meta-analysis and meta-regression were used to generate a pooled prevalence estimate and identify relevant moderators. After study selection, 33 studies (74633 participants) were included in the meta-analysis. Some 31 studies were judged to be of low risk of bias, and two studies were judged to be at moderate risk of bias. The three most common comorbidities in RA were anxiety disorders (62.1%, 95% Cl: 43.6%; 80.6%), hypertension (37.7%, 95% Cl: 29.2%; 46.2%) and depression (32.1%, 95% Cl: 21.6%; 42.7%). There was substantial statistically significant heterogeneity for all comorbidities (I2 ≥77%). Meta-regression identified that the covariate of mean age (unit increase) had a statistically significant effect on the prevalence of hypertension (+2.3%, 95% Cl: 0.4%; 4.2%), depression (-0.5%, 95% Cl: -0.6%; -0.4%) and cancer (0.5%, 95% Cl: 0.2%; 0.8%) in adults with RA. A country's income was identified to have a statistically significant effect on the prevalence of depression, with low-to moderate-income countries having 40% (95% Cl: 14.0%; 66.6%) higher prevalence than high-income countries. No studies consider health inequalities. It is concluded that comorbidities are prevalent among people with RA, particularly those associated with mental health and circulatory conditions. Provision of health services should reflect the importance of such multimorbidity and the consequences for quality and length of life.

Depression and anxiety symptoms at TNF inhibitor initiation are associated with impaired treatment response in axial spondyloarthritis.

OBJECTIVES: Depression and anxiety are associated with more severe disease in cross-sectional studies of axial spondyloarthritis (axSpA). We examined the association between baseline symptoms of depression or anxiety and response to TNF inhibitors (TNFi) in axSpA. METHODS: Biologic naïve participants from a national axSpA register completed the Hospital Anxiety and Depression Scale (HADS) before initiating TNFi. Symptoms of anxiety and depression were each categorized as moderate-severe (≥11), mild (8-10) and 'none' (≤7), and compared against change in disease indices [BASDAI and AS Disease Activity Score (ASDAS)] over time and time to treatment discontinuation using marginal structural models. Inverse-probability weights balanced baseline age, gender, BMI, deprivation, education and baseline values of respective disease indices. RESULTS: Of the 742 participants (67% male, mean age 45 years), 176 (24%) had moderate-severe and 26% mild depression; 295 (40%) had moderate-severe and 23% mild anxiety. Baseline disease activity was higher in higher HADS symptom categories for both depression and anxiety. Participants with moderate-severe depression had significantly poorer response compared with those with 'none' throughout follow-up. At 6 months, the difference was approximately 2.2 BASDAI and 0.8 ASDAS units after balancing their baseline values. Equivalent comparisons for anxiety were 1.7 BASDAI and 0.7 ASDAS units. Treatment discontinuation was 1.59-fold higher (hazard ratio 95% CI: 1.12, 2.26) in participants with moderate-severe anxiety compared with 'none'. CONCLUSIONS: Symptoms of depression and anxiety at TNFi initiation are associated with poorer treatment outcomes. Targeted interventions to optimize mental health have potential to substantially improve treatment response and persistence.

Diagnostic delay in axial spondyloarthritis: a systematic review and meta-analysis.

BACKGROUND: Delay to diagnosis in axial SpA (axSpA) is longer than in many other rheumatic diseases. Prolonged delay is associate with poorer outcomes, including functional impairment and quality of life. Our aims were to describe global variation in delay to diagnosis, factors associated with delay, and delay compared with PsA. METHODS: We searched MEDLINE, PubMed, Embase and Web of Science using a predefined protocol. Diagnostic delay was defined as years between the age at symptom onset and at diagnosis. We pooled the mean delay using random effects inverse variance meta-analysis. We examined variations in pooled estimates using prespecified subgroup analyses and sources of heterogeneity using meta-regression. RESULTS: A total of 64 studies reported the mean diagnostic delay in axSpA patients. The pooled mean delay was 6.7 years (95% CI 6.2, 7.2) with high levels of heterogeneity. Delay to diagnosis did not improve over time when stratifying results by year of publication. Studies from high-income countries (defined by the World Bank) reported longer delays than those from middle-income countries. Factors consistently reported to be associated with longer delays were lower education levels, younger age at symptom onset and absence of extra-articular manifestations (EAMs). The pooled estimate for diagnostic delay from 8 PsA studies was significantly shorter, at 2.6 years (95% CI 1.6, 3.6). CONCLUSION: For axSpA patients, delay to diagnosis remains unacceptably prolonged in many parts of the world. Patient factors (e.g. education) and disease presentation (onset age and EAMs) should inform campaigns to improve delay.

Association between comorbidities and disease activity in axial spondyloarthritis: results from the BSRBR-AS.

OBJECTIVE: Whether comorbidities influence disease activity assessment in axial SpA (axSpA) is unclear. Comorbidities inflate DAS28 in rheumatoid arthritis through the patient global score. We examined whether axSpA disease activity measures are differentially affected, and whether comorbidities inflate the AS disease activity score (ASDAS) through the patient global component. METHODS: We used baseline data from the British Society for Rheumatology Biologics Register for AS, including 14 physician diagnosed comorbidities. Linear models were used to compare disease activity (BASDAI, spinal pain, ASDAS) and ESR/CRP according to comorbidity count, adjusted for age, gender, BMI, smoking, socioeconomic status, and education. The same models were used to examine whether the patient global score was associated with comorbidities, additionally adjusting for other ASDAS components. RESULTS: The number of participants eligible for analysis was 2043 (67% male, mean age 49 years); 44% had at least one comorbidity. Each additional comorbidity was associated with higher BASDAI by 0.40 units (95% CI: 0.27, 0.52) and spinal pain by 0.53 (95% CI: 0.37, 0.68). Effect size for ASDAS (0.09 units; 95% CI: 0.03, 0.15) was not clinically significant. ESR and CRP were not associated with comorbidity count. Depression, heart failure and peptic ulcer were consistently associated with higher disease activity measures, but not CRP/ESR. Patient global was associated with comorbidity count, but not independently of other ASDAS components (P = 0.75). CONCLUSION: Comorbidities were associated with higher patient reported disease activity in axSpA. Clinicians should be mindful of the potential impact of comorbidities on patient reported outcome measures and consider additionally collecting ASDAS when comorbidities are present.

Comorbidity and response to TNF inhibitors in axial spondyloarthritis: longitudinal analysis of the BSRBR-AS.

OBJECTIVE: Comorbidities influence disease assessment in axial spondyloarthritis (axSpA), but their association with response to TNF inhibitors (TNFi) is unclear. We examined associations between comorbidity history at TNFi initiation and: (i) change in disease indices over time; (ii) binary response definitions; and (iii) time to treatment discontinuation. METHODS: We studied participants starting their first TNFi from a national axSpA register. Comorbidity categories were created from 14 physician-diagnosed conditions and compared against: change in disease indices over time using linear mixed effects models; BASDAI50/2 (50% or 2-unit reduction) and BASDAI < 4 at 6 months using logistic models; and time to treatment discontinuation using Cox models. Models were adjusted for age, gender, BMI, deprivation and education. RESULTS: In total, 994 were eligible for analysis (68% male, mean age 45 years); 21% had one comorbidity and 11% had ≥2. Baseline disease severity was higher in those with comorbidities across all indices, but absolute improvement over time was comparable for BASDAI and spinal pain. Participants with ≥2 comorbidities had smaller absolute improvement in BASFI and quality of life. This group also had numerically reduced odds of achieving BASDAI50/2 [odds ratio (OR) 0.81; 95% CI: 0.45, 1.45] and BASDAI < 4 (OR 0.57; 95% CI: 0.32, 1.04). Treatment discontinuation was increased in those with two comorbidities [hazard ratio (HR) 1.32; 95% CI: 0.88, 2.00] and ≥3 comorbidities (HR 2.18; 95% CI: 1.20, 3.93) compared with none. CONCLUSIONS: Participants with multiple comorbidities had poorer treatment outcomes, particularly increased treatment discontinuation and poorer improvements in function and quality of life. These results inform clinicians and educate patients about response to the first TNFi given comorbidity burden.

Smoking in spondyloarthritis: unravelling the complexities.

Tobacco smoking is a major threat to health. There is no doubt about the need to promote and support cessation at every opportunity. Smoking has a clear role in RA, but what evidence is there that the same relationship exists in SpA? In this review, we examine (the less cited) paradoxes and contradictions in the existing axial SpA (axSpA) and PsA literature; for example, smoking appears to be 'protective' for some axSpA manifestations. We also highlight findings from higher quality evidence: smoking is associated with increased risk of PsA and the risk of psoriasis in axSpA. The relationship between smoking and SpA is far from simple. Our aim is to highlight the harms of smoking in SpA and bring attention to inconsistencies in the literature to inform further research.

Biologic monotherapy in the biologic naïve patient with rheumatoid arthritis (RA): results from an observational study.

Approximately one-third of patients on biologic therapy for rheumatoid arthritis (RA) receive them as monotherapy. There are few head-to-head randomised control trials comparing biologics as monotherapy. Our aim was to compare the efficacy and persistence of multimodal biologic agents as monotherapy in biologic naïve patients with RA in the real-world setting. A multicentre retrospective observational study was carried out comparing TNF inhibitors (TNFi), IL6 receptor inhibitor (IL6Ri) and CTLA-4 inhibitor (CTLA-4i) monotherapy in biologic naïve RA patients. The primary study outcome was DAS28 score at 6, 12, and 18 months. 126 patients were enrolled; 98 patients (78%) were taking TNFi, 19 patients (15%) IL6Ri and 10 (8%) CTLA-4i with similar baseline characteristics of sex and age across groups. Patients in the CTLA-4i group were more often seropositive and had greater numbers of comorbidities. At 6 and 12 months, patients in the IL6Ri group had a lower DAS28 score compared to TNFi monotherapy. Those on CTLA-4i monotherapy also had a lower DAS28 score at 6 months than the TNFi group, although differences were lost by 12 months. Drug retention at 18 months was highest in the IL6Ri arm (68%) and CTLA-4i arm (80%) compared with only 55% in the TNFi group. Our findings support current guidance that IL6Ri should be considered in biologic naïve patients requiring biologic monotherapy, but also indicated that CTLA-4i could be an option.

Systematic review of mental health comorbidities in psoriatic arthritis.

OBJECTIVE: In this systematic review and meta-analysis of psoriatic arthritis (PsA) studies, we pooled data from existing literature to (1) estimate the prevalence of mental health disorders in PsA patients and (2) compare disease activity in PsA patients with and without these comorbidities. METHOD: We searched PubMED, Web of Science, Scopus, PsycINFO and the Cochrane Library using a predefined protocol in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Where possible, meta-analysis was performed using random effects model. Prevalence estimates were pooled according to the severity of mental health disorders. RESULTS: A total of 24 studies, amounting to 31,227 PsA patients, were included for review. Anxiety and depression were the only consistently reported mental health disorders, defined using a range of screening criteria/thresholds. Anxiety prevalence ranged from 4 to 61% with a pooled estimate of 33% (95%CI 17 to 53%) having at least mild anxiety and 21% (95%CI 14 to 29%) at least moderate. Depression prevalence ranged from 5 to 51%, with 20% (95%CI 8 to 35%) having at least mild and 14% (95%CI 8 to 21%) at least moderate. Only two studies compared disease activity according to the presence of mental health comorbidities; both reported higher disease activity and pain among those with comorbid anxiety and depression. CONCLUSIONS: Anxiety and depression are highly prevalent among PsA patients. Studies of other mental health disorders were scarce. More studies are needed on the impact of these comorbidities on disease activity and long-term outcomes.Key Points• One in three patients with psoriatic arthritis has at least mild anxiety, while 1 in 5 reported at least mild depression.• PsA patients with anxiety and/or depression reported greater disease activity.• More research is needed on other mental health comorbidities, particularly sleep, suicide/self-harm and substance misuse.

Impact of Smoking in Response to Tumor Necrosis Factor Inhibitors in Axial Spondyloarthritis: Methodologic Considerations for Longitudinal Observational Studies.

OBJECTIVE: Observational data facilitate examination of treatment-effect heterogeneity, but the risk of bias is substantial. The present study was undertaken to highlight methodologic considerations through an analysis of whether smoking affects response to tumor necrosis factor inhibitors (TNFi) in axial spondyloarthritis (SpA). METHODS: We used longitudinal data from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis. Participants fulfilling the Assessment of SpondyloArthritis international Society criteria for axial SpA who started their first TNFi were eligible for analysis. In comparing the impact of smoking status, weighted generalized estimating equations were used to examine changes in several continuous outcome measures, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS). Inverse probability weights were used to account for differences in baseline covariates and excluded participants. We separately assessed response in the first 3 months to account for nonrandom dropout. RESULTS: For 840 participants who started on TNFi, 1,641 assessments from 627 individuals were analyzed (69% male, mean age 46 years). A total of 33% were current smokers and 30% ex-smokers. Ex-smokers and current smokers had worse disease than never smokers at baseline. Accounting for these differences, response did not differ according to smoking status. Compared to never smokers, ex-smokers (ß = -0.6, 95% confidence interval [95% CI] -1.4, 0.3) and current smokers (ß = -0.4, 95% CI -1.1, 0.4) had a similar response according to the BASDAI and ASDAS (ex-smokers ß = -0.1, 95% CI -0.5, 0.3; current smokers ß = -0.01, 95% CI -0.4, 0.4) at 3 months. CONCLUSION: TNFi response did not differ according to baseline smoking status in this UK cohort. Conflicting results from previous studies were likely due to methodologic differences. This analysis highlights potential sources of bias that should be addressed in future studies.

The prevalence and impact of comorbid fibromyalgia in inflammatory arthritis.

Fibromyalgia (FM) is one of the most common conditions that rheumatologists encounter. It is characterised by chronic widespread pain, fatigue, sleep disturbances and impaired cognition. The prevalence of comorbid FM among populations with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) are considerably higher than among the general population, with pooled prevalence estimates of 18-24% in RA, 14-16% in axSpA and 18% in PsA. Prevalence estimates should be interpreted with care as the criteria for FM have not been validated for use in patients with inflammatory arthritis. Comorbid FM appears to affect assessment of disease severity in these conditions, particularly patient-reported outcome measures, and may influence response to treatment. There is a need for better identification, classification and management of FM in the context of inflammatory rheumatic diseases.

Smoking status and cause-specific discontinuation of tumour necrosis factor inhibitors in axial spondyloarthritis.

BACKGROUND: The impact of smoking on TNF inhibition (TNFi) therapy is unclear. We examined the effect of smoking on all-cause and cause-specific TNFi discontinuation in axial spondyloarthritis (axSpA). METHODS: We used longitudinal data from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS). Patients fulfilling the ASAS criteria for axSpA, who started their first TNFi, were eligible for analysis. Inverse-probability weights were used to balance differences in baseline disease severity and other confounders. We used marginal structural Cox proportional hazard models to estimate hazard ratios (HR) for TNFi discontinuation according to smoking status. In analyses of cause-specific discontinuation, competing risk events were considered as censoring, using inverse-probability weights. RESULTS: A total of 758 participants were included in the analysis (66% male, mean age 45 years), providing 954 patient-years of follow-up. TNFi was discontinued in 174 (23%) patients, among whom 26% stopped due to infections, 20% due to other adverse events and 44% due to inefficacy or other reasons. Thirty-four percent were current smokers and 30% ex-smokers. Compared to never smokers, current smokers' risk of TNFi discontinuation was HR 0.79 (95%CI 0.53 to 1.20) and ex-smokers HR 0.68 (95%CI 0.45 to 1.04). Our data did not show evidence that current smoking influenced discontinuation due to infections (HR 0.79, 95%CI 0.40 to 1.54), other adverse events (HR 0.86, 95%CI 0.41 to 1.78) or inefficacy/other causes (HR 1.44, 95%CI 0.86 to 2.41). CONCLUSION: Baseline smoking status did not impact TNFi discontinuation in this UK cohort of axSpA participants.

Comorbidity burden in axial spondyloarthritis: a cluster analysis.

OBJECTIVES: To examine how comorbidities cluster in axial spondyloarthritis (axSpA) and whether these clusters are associated with quality of life, global health and other outcome measures. METHODS: We conducted a cross-sectional study of consecutive patients meeting ASAS criteria for axSpA in Liverpool, UK. Outcome measures included quality of life (EQ5D), global health and disease activity (BASDAI). We used hierarchical cluster analysis to group patients according to 38 pre-specified comorbidities. In multivariable linear models, the associations between distinct comorbidity clusters and each outcome measure were compared, using axSpA patients with no comorbidities as the reference group. Analyses were adjusted for age, gender, symptom duration, BMI, deprivation, NSAID-use and smoking. RESULTS: We studied 419 patients (69% male, mean age 46 years). 255 patients (61%) had at least one comorbidity, among whom the median number was 1 (range 1-6). Common comorbidities were hypertension (19%) and depression (16%). Of 15 clusters identified, the most prevalent clusters were hypertension-coronary heart disease and depression-anxiety. Compared with patients with no comorbidities, the fibromyalgia-irritable bowel syndrome cluster was associated with adverse patient-reported outcome measures; these patients reported 1.5-unit poorer global health (95%CI 0.01, 2.9), reduced quality of life (0.25-unit lower EQ5D; 95%CI -0.37, -0.12) and 1.8-unit higher BASDAI (95% CI 0.4, 3.3). Similar effect estimates were found for patients in the depression-anxiety cluster. CONCLUSION: Comorbidity is common among axSpA patients. The two most common comorbidities were hypertension and depression. Patients in the depression-anxiety and fibromyalgia-IBS clusters reported poorer health and increased axSpA severity.

Association of Diverticulitis with Prolonged Spondyloarthritis: An Analysis of the ASAS-COMOSPA International Cohort.

This study examined the relationship between spondyloarthritis (SpA) duration and gastrointestinal comorbidities other than inflammatory bowel disease (IBD). We evaluated the association between SpA duration and upper gastrointestinal ulcers, hepatitis B (HBV), hepatitis C (HCV) and diverticulitis using data from a large international cross-sectional study. Binary regression models were created, adjusted for age, sex, body mass index (BMI), smoking, alcohol, non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), biologics, steroids, IBD history and country. Subgroup analysis was performed by disease phenotype. The data of 3923 participants were analysed. The prevalence of gastrointestinal conditions were 10.7% upper gastrointestinal ulcers; 4.7% viral hepatitis and 1.5% diverticulitis. While SpA duration was not associated with upper gastrointestinal ulcers, HBV or HCV, longer SpA duration was significantly associated with diverticulitis (odds ratios (OR) = 1.18, 95% confidence interval (CI): 1.03⁻1.34), reflecting an 18% increase for every five years of SpA duration. Other significant associations with diverticulitis were age and high alcohol intake but not medication history. In subgroup analyses, the association was strongest with those with axial SpA. The reasons for this association of increased diverticulitis with disease duration in SpA, especially those with axial disease, are unclear but may reflect shared underlying gut inflammation. Diverticulitis should be considered, in addition to IBD, when SpA patients present with lower gastrointestinal symptoms.

Associations between smoking and extra-axial manifestations and disease severity in axial spondyloarthritis: results from the BSR Biologics Register for Ankylosing Spondylitis (BSRBR-AS).

OBJECTIVE: The effects of smoking on disease manifestations in axial SpA are inadequately described. Utilizing a large and well-characterized cohort, we investigated the association between smoking and extra-axial manifestations, and smoking and disease severity measures. METHODS: Baseline data from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis were explored. Our analyses focused on extra-axial manifestations and other disease severity measures, including scales for fatigue, sleep, anxiety and depression. Logistic and linear models were used to quantify associations between disease characteristics according to smoking status (current/ex/never) and quantity (heavy/light), adjusting for age, gender, BMI, education, deprivation, comorbidities, symptom duration and alcohol status. RESULTS: A total of 2031 participants were eligible for the current analysis (68% male, mean age 49 years). Of these, 24% were current and 32% ex-smokers. When compared with non-smokers, current smokers had lower odds of uveitis [OR 0.7, 95% CI 0.5-0.9] and higher odds of psoriasis (ORadj 1.6, 95% CI 1.1-2.3). Ex- and current smokers had incrementally more severe disease than never smokers, with higher BASDAI (ß = 0.3, 95% CI 0.1-0.6; ß = 0.9, 95% CI 0.6-1.2) and BASFI (ß = 0.5, 95% CI 0.2-0.8; ß = 1.3, 95% CI 1.0-1.6); similar associations were observed for fatigue, sleep, anxiety and depression. CONCLUSION: In this large cross-sectional study, we observed that smoking is independently associated with an adverse disease profile in axial SpA, including worse fatigue, sleep, anxiety and depression, and higher odds of psoriasis. The paradoxical association between current smoking and reduced odds of uveitis is interesting and warrants further investigation.

Concomitant fibromyalgia complicating chronic inflammatory arthritis: a systematic review and meta-analysis.

Objectives: This systematic review and meta-analysis will describe the prevalence of concomitant FM in adults with inflammatory arthritis and quantify the impact of FM on DAS. Methods: Cochrane library, MEDLINE, Psychinfo, PubMed, Scopus and Web of Science were searched using key terms and predefined exclusion criteria. As appropriate, proportional and pairwise meta-analysis methods were used to pool results. Results: Forty articles were identified. In RA the prevalence of FM ranged from 4.9 to 52.4% (21% pooled). In axSpA the range was 4.11-25.2% (13% pooled in AS only). In PsA the range was 9.6-27.2% (18% pooled). The presence of concomitant FM was related to higher DAS in patients with RA and AS (DAS28 mean difference 1.24, 95% CI: 1.10, 1.37 in RA; BASDAI mean difference 2.22, 95% CI: 1.86, 2.58 in AS). Concomitant FM was also associated with higher DAS in existing PsA studies. Self-reported, rather than objective, components of DAS appear to be raised in the presence of FM (e.g. tender joint count and Visual Analogue Scale (VAS) pain scores). Conclusion: FM is common in RA, AxSpA and PsA. Comorbid FM appears to amplify DAS and could therefore influence management of these rheumatic conditions.