Search

ObjectiveThis post hoc analysis assessed the effect of baseline C-reactive protein (CRP) on the efficacy and safety of tofacitinib (TOF) use in ankylosing spondylitis (AS), as well as patient-reported outcomes (PROs).MethodsPhase II (ClinicalTrials.gov: NCT01786668) and phase III (ClinicalTrials.gov: NCT03502616) data from patients with active AS were used. Endpoints (weeks 12, 16, and 48), including 20% and 40% improvement in Assessment of SpondyloArthritis international Society (ASAS), AS Disease Activity Score with CRP low disease activity, 50% improvement in Bath AS Disease Activity Index (BASDAI50), and PROs (pain and fatigue), were stratified by baseline CRP (mg/L) as follows: < 5 (normal), ≥ 5 (elevated), < 10, and ≥ 10. Safety outcomes were evaluated between < 5 and ≥ 5 mg/L subgroups.ResultsOverall, 372 patients were included (69.6% ≥ 5mg/L; 50.8% ≥ 10 mg/L). At baseline in the < 5mg/L group, more placebo-treated than TOF-treated patients received concomitant nonsteroidal antiinflammatory drugs (NSAIDs) or sulfasalazine (SSZ). Week 12 efficacy and PRO responses were generally higher for TOF vs placebo, regardless of baseline CRP. The treatment effect (placebo-adjusted response) at week 12 was generally numerically higher in ≥ 5 mg/L and ≥ 10 mg/L vs < 5 mg/L and < 10 mg/L groups. Incidence rates for treatment-emergent adverse events (TEAEs) and “all infections” were numerically higher for TOF vs placebo in patients in the < 5 mg/L group, but similar for TOF vs placebo in patients in the ≥ 5 mg/L group.ConclusionRegardless of baseline CRP, TOF was more efficacious vs placebo at week 12. The placebo-adjusted efficacy and PRO responses were generally numerically higher in patients with CRP ≥ 5 mg/L and ≥ 10 mg/L vs < 5 mg/L and < 10 mg/L. The higher concomitant NSAID/SSZ exposure may have improved efficacy responses in the baseline < 5 mg/L placebo group, and ultimately affected the TOF treatment effect. Safety was consistent with previous studies of TOF use in AS, with numerically higher incidence rates for TEAEs and “all infections” for TOF vs placebo in patients with CRP < 5 mg/L.

Psoriatic arthritis, ankylosing spondylitis, and non-radiographic axial spondyloarthritis are a group of diseases that cause pain and inflammation of the joints and/or spine. Safety data were combined from five studies: two in psoriatic arthritis, two in ankylosing spondylitis, and one in non-radiographic axial spondyloarthritis. Patients were treated with upadacitinib or adalimumab for up to 5 years. Adalimumab was only used for patients participating in one of the two psoriatic arthritis studies. Side effects from treatment were more common in patients with psoriatic arthritis than those with ankylosing spondylitis and non-radiographic axial spondyloarthritis; more patients with psoriatic arthritis had side effects with upadacitinib than adalimumab. A similar number of patients across treatment groups and diseases had side effects that made them stop treatment. The number of cancer cases (except cancer of the upper layer of the skin), cardiovascular issues, and blood clots were similar between the upadacitinib and adalimumab groups in psoriatic arthritis and across diseases. Serious infections, painful rashes that cause blisters (herpes zoster, also commonly referred to as shingles), low levels of white blood cells, and cancer of the upper layer of the skin were more common with upadacitinib than adalimumab in patients with psoriatic arthritis; overall, these events occurred more often with upadacitinib in patients with psoriatic arthritis than with ankylosing spondylitis and non-radiographic axial spondyloarthritis. Our results showed that the safety of upadacitinib was generally similar across diseases, and patients could tolerate it well for up to 5 years. No new safety risks were found with upadacitinib treatment.

Immunocompromised patients with chronic inflammatory disease (CID) may have experienced additional psychosocial burden during the COVID‐19 pandemic due to their immunocompromised status. This study was undertaken to determine if vaccination would result in improved patient‐reported outcomes longitudinally among individuals with CID undergoing SARS–CoV‐2 vaccination regardless of baseline anxiety. Data are from a cohort of individuals with CID from 2 sites who underwent SARS–CoV‐2 vaccination. Participants completed 3 study visits before and after 2 messenger RNA vaccine doses in the initial vaccination series when clinical data were collected. Patient‐reported outcomes were measured using the Patient‐Reported Outcomes Measurement Information System 29‐item Health Profile and expressed as T scores, with 2 groups stratified by high and low baseline anxiety. Mixed‐effects models were used to examine longitudinal changes, adjusting for age, sex, and study site. A total of 72% of the cohort was female with a mean ± SD age of 48.1 ± 15.5 years. Overall, sleep disturbance improved following both doses of SARS–CoV‐2 vaccinations, and anxiety decreased after the second dose. Physical function scores worsened but did not meet the minimally important difference threshold. When stratifying by baseline anxiety, improvement in anxiety, fatigue, and social participation were greater in the high anxiety group. Physical function worsened slightly in both groups, and sleep disturbance improved significantly in the high anxiety group. Sleep disturbance decreased in a significant and meaningful way in patients with CID upon vaccination. In patients with higher baseline anxiety, social participation increased, and anxiety, fatigue, and sleep disturbance decreased. Overall, results suggest that SARS–CoV‐2 vaccination may improve mental health and well‐being, particularly among those with greater anxiety.

To address significant disruptions in didactic education precipitated by the COVID‐19 pandemic, a group of rheumatology program directors collaborated with the American College of Rheumatology to create a virtual fellows‐in‐training (V‐FIT) program. A working group was composed to develop the virtual didactic program comprising live virtual sessions of core curricular rheumatology topics that were recorded to permit asynchronous learning. Nationally recognized educators were invited to lead sessions to fill the void in didactic education occurring on a broad scale across US rheumatology fellowship training programs. Demographic information, live and asynchronous participation data, and feedback surveys were collected from participants in the program. There were 3 components to V‐FIT: the Virtual Rheumatology Learning (ViRL) series, the Virtual Rheumatology Practicum (ViP), and the Virtual Rheumatology Teaching Lessons (ViTLs). The ViRL program had global impact with more than 2,000 learners from more than 55 countries. ViP provided a standardized curriculum of rheumatology topics for incoming first‐year fellows. ViTLs addressed advanced and interdisciplinary rheumatic disease topics for learners at all stages. With collaboration, adaptation, and innovation, the V‐FIT program not only maintained but also enhanced education for rheumatology trainees, was enriched by national and international participation, and provided standardized, broadly accessible content with interdisciplinary learning.

ObjectiveTo assess test-retest reliability, construct validity, known groups discrimination, and responsiveness of the Assessment of the SpondyloArthritis international Society Health Index (ASAS HI) to evaluate functioning, disability, and health in patients with radiographic axial spondyloarthritis (r-axSpA).MethodsData were generated from 2 randomized, placebo-controlled, active-controlled phase III ixekizumab studies (COAST-V, N = 341; COAST-W, N = 316). Assessments included the following: test-retest reliability (ie, intraclass correlation coefficients [ICCs] between ASAS HI scores at screening and baseline), construct validity (ie, Spearman correlation with standard r-axSpA outcome measures), known groups discrimination (ie, 1-way ANOVA comparing the ASAS HI with different disease activity categories, measured by the Ankylosing Spondylitis Disease Activity Score [ASDAS]), and responsiveness (ie, Spearman correlation between changes in the ASAS HI and changes in the Bath Ankylosing Spondylitis Functional Index [BASFI], the Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], the ASDAS, and the Patient Global Assessment [PtGA] as well as ANOVA comparing changes in the ASAS HI with various responder categories).ResultsThe ICC for test-retest reliability was 0.78 for COAST-V and 0.76 for COAST-W, indicating adequate agreement. Moderate-to-large correlations (r= 0.40-0.61) were observed between the ASAS HI and the BASDAI. Statistically significant differences (all P< 0.001) between mean ASAS HI scores were observed for subgroups based on ASDAS-defined disease activity categories at baseline and week 16. Moderate-to-large correlations existed between changes in the ASAS HI and the BASFI, BASDAI, ASDAS, and PtGA from baseline to week 16. The ASAS HI differentiated statistically (P< 0.001) between ASAS, BASDAI, and ASDAS response groups.ConclusionThe ASAS HI demonstrated reliability, construct validity, known groups discrimination, and responsiveness in adults with r-axSpA in 2 clinical trials.

ObjectiveSacroiliac (SI) joint and spinal inflammation are characteristic of ankylosing spondylitis (AS), but some patients with AS have been identified who have discordant radiographic disease. We studied an AS subgroup with long-standing disease and fused SI joints. We identified factors associated with discrepant degrees of radiographic damage between the SI joints and spine.MethodsFrom the Prospective Study of Outcomes in AS (PSOAS) cohort, patients with a disease duration ≥ 20 years and fused SI joints were included in a nested case-control design. Patients with and without syndesmophytes were used as cases and controls for analysis. We used classification and regression tree (CART) analysis to determine risk factors for syndesmophytes presence and reexamined the validity of the risk factors using univariable logistic regression models.ResultsThere were 354 patients in the subgroup, 23 of whom lacked syndesmophytes. CART analysis showed females were less likely to have syndesmophytes. The next important predictor was age of symptom onset in males, with age of onset ≤ 16 years being less likely to have syndesmophytes. Univariable analysis confirmed females were less likely to have syndesmophytes (odds ratio [OR] 0.17, 95% CI 0.07-0.41). Syndesmophyte presence was associated with HLA-B27 positivity (P= 0.03) and age of symptom onset > 16 years old (OR 2.72, 95% CI 1.15-6.45). All 23 patients who lacked syndesmophytes were HLA-B27 positive.ConclusionUsing CART analysis and univariable modeling, women were less likely to have syndesmophytes despite advanced disease duration and SI joint disease. Patients with younger age of symptom onset were less likely to have syndesmophytes. All patients without syndesmophytes were HLA-B27 positive, indicating HLA-B27 positivity may be more associated with SI disease than spinal disease.

Little is known regarding the reactogenicity and related SARS–CoV‐2 vaccine response in patients with chronic inflammatory disease (CID). Our objective was to characterize the adverse event profile of CID patients following SARS–CoV‐2 vaccination and understand the relationship between reactogenicity and immunogenicity of SARS–CoV‐2 vaccines. CID patients and healthy controls eligible to receive messenger RNA (mRNA) SARS–CoV‐2 vaccines participated in 3 study visits (pre‐vaccine, after dose 1, and after dose 2) in which blood and clinical data were collected. Assessment of adverse events were solicited within 7 days of receiving each dose. Serum anti–SARS–CoV‐2 spike IgG ± antibody titers were quantified following vaccination. Statistical analysis was performed utilizing mixed models and tobit regressions, with adjustment for covariates. The present study included 441 participants (322 CID patients and 119 control subjects). Compared to controls, CID patients reported greater symptom severity after dose 1 (P= 0.0001), including more myalgia and fatigue (P< 0.05). For immunogenicity, a higher symptom severity after dose 1 and a higher number of symptoms after dose 2 was associated with higher antibody titers (P≤ 0.05). Each increase of 1 symptom was associated with a 15.1% increase in antibody titer. Symptom association was strongest with site pain after dose 1 (105%; P= 0.03) and fatigue after dose 2 (113%; P= 0.004). Patients with CID have a distinct reactogenicity profile following SARS–CoV‐2 vaccination compared to controls. Furthermore, there is an association between increased reactogenicity and increased vaccine response. This finding may speak to the more variable immunogenicity in CID patients and may be an important indicator of vaccine response to the novel SARS–CoV‐2 vaccines.

The rapid transmission of the highly infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), led to widespread infection throughout the world. Concerns and challenges regarding COVID-19 illness have emerged for patients with immune-mediated inflammatory diseases, such as spondyloarthritis (SpA), who receive treatment with biologic or targeted synthetic disease-modifying antirheumatic drugs (DMARDs), because this population is vulnerable to infections and has a high prevalence of risk factors associated with severe COVID-19 illness. Available data on COVID-19 indicate that patients with SpA who are treated with DMARDs have SARS-CoV-2 infection rates comparable with those in the general population, with similar increased risk associated with older age and comorbidities. Novel vaccines against SARS-CoV-2 are approved or authorized for emergency use by the US Food and Drug Administration, and others are in development to prevent infection and serious illness. This review provides an overview of SpA, the mechanism of action for the SARS-CoV-2 infection, the clinical course of COVID-19, and the vaccines approved for, or in development against, SARS-CoV-2. Detailed information on the use of established vaccines in patients with SpA receiving DMARDs is provided, along with recommendations for COVID-19 vaccination. Available evidence has shown COVID-19 vaccination in patients with SpA, among other rheumatic diseases, to be safe and effective with most DMARD use; however, there is evidence of potential interference with some therapies used in SpA. Healthcare providers should educate patients to provide the knowledge and confidence to receive a COVID-19 vaccine, since the potential benefit outweighs the low risk of vaccine-related adverse events.

Ankylosing spondylitis (AS) is associated with elevated cardiovascular risk, and obesity is a common, modifiable risk factor. Our aims were to assess the relationship of body mass index (BMI) with disease activity in AS patients and to assess the extent to which the effect is mediated through exercise. We used data from a prospective AS cohort with a median follow‐up of 7 years. To determine the association of BMI (kg/m2) with disease activity as measured by the Ankylosing Spondylitis Disease Activity Score (ASDAS), we used generalized estimating equations with inverse probability weighting to account for repeated measures per subject and time‐varying confounding. To estimate the direct effect of overweight/obese BMI on disease activity and the indirect effect through exercise, we performed a mediation analysis. There were 183 subjects with available BMI and disease activity data (77% male, 70% White, mean ± SD age 40.8 ± 13.3 years). Higher BMI was significantly associated with higher disease activity over time; on average, for a 1 kg/m2higher BMI, the ASDAS was 0.06 units higher (95% confidence interval 0.04–0.08) after adjustment for important confounders. The direct effect of an overweight/obese BMI accounted for most of the total effect on disease activity, with a smaller indirect effect mediated by exercise (7%). Higher BMI was associated with higher disease activity in a prospective AS cohort. We found that being overweight/obese largely influenced disease activity directly rather than indirectly through exercise. Other mechanisms, such as increased inflammation, may better explain the obesity–disease activity association.

To evaluate the effect of ixekizumab on self‐reported functioning and health in patients with active nonradiographic axial spondyloarthritis (SpA). COAST‐X was a randomized, controlled trial conducted in patients with nonradiographic axial SpA over 52 weeks. Participants were randomized at a ratio of 1:1:1 to receive 80 mg of ixekizumab subcutaneously every 4 weeks or 2 weeks or placebo for 52 weeks. Self‐reported functioning and health end points included the Medical Outcomes Study Short Form 36 (SF‐36) health survey, Assessment of Spondyloarthritis International Society (ASAS) health index, and European Quality of Life‐5 Dimensions‐5 Level (EQ‐5D‐5L) health‐utility descriptive system. Compared to placebo, ixekizumab treatment resulted in improvement of SF‐36 physical component summary scores from baseline, with a score of 4.7 improving to 8.9 with ixekizumab therapy every 4 weeks (P< 0.05) and a score of 9.3 with ixekizumab therapy every 2 weeks (P< 0.01); the greatest improvements were observed in the domains of physical functioning, role‐physical, and bodily pain at weeks 16 and 52. A higher proportion of patients receiving ixekizumab therapy every 2 weeks reported ≥3 improvements based on the ASAS health index from baseline to weeks 16 and 52 (P< 0.05). Significantly more patients receiving ixekizumab every 4 weeks reported improvements in “good health status” on the ASAS health index (ASAS score of ≤5) at weeks 16 and 52 (P< 0.05). Patients receiving ixekizumab reported improvements on the EQ‐5D‐5L compared to those who received placebo at week 16 (0.11 versus 0.17 for patients receiving treatment every 4 weeks and 0.19 for patients receiving treatment every 2 weeks; P< 0.05), which remained consistent at week 52. There were no clinical meaningful differences in responses based on the ixekizumab dosing regimen for patients who received ixekizumab therapy every 2 weeks or every 4 weeks. In patients with nonradiographic axial SpA, therapy with ixekizumab was superior to placebo in the improvement of self‐reported functioning and health at weeks 16 and 52.

ObjectiveIndividuals with ankylosing spondylitis (AS) have a greater cardiovascular (CV) risk than those in the general population. The effect of tumor necrosis factor inhibitors (TNFis) on CV risk, including on the development of hypertension (HTN), remains unclear, with some data suggesting higher risk. We assessed the association of TNFi use with incident HTN in a longitudinal AS cohort.MethodsAdults with AS enrolled in a prospective cohort in 2002–2018 were examined every 4–6 months. TNFi use during the preceding 6 months was ascertained at each study visit. We defined HTN by patient-reported HTN, antihypertensive medication use, or, on 2 consecutive visits, systolic blood pressure (BP) ≥ 140 mmHg or diastolic BP ≥ 90 mmHg. We evaluated the association between TNFi use and the development of HTN with marginal structural models, estimated by inverse probability-of-treatment weighting, to account for time-dependent confounders and informative censoring. Potential confounders included age, sex, race, site, nonsteroidal antiinflammatory drug use, and disease activity.ResultsWe included 630 patients without baseline HTN and with at least 1 year of follow-up. Of these, 72% were male, mean age was 39 ± 13 years, and 43% used TNFi at baseline. On follow-up (median 5 yrs), 129 developed incident HTN and 163 started on TNFi during follow-up. TNFi use was not associated with incident HTN (adjusted HR 1.10, 95% CI 0.83–1.37).ConclusionIn our prospective AS cohort, TNFi use was not significantly associated with incident HTN.

Introduction: Clinical remission in patients with ankylosing spondylitis (AS) has been determined using composite indices such as the AS Disease Activity Score inactive disease (ASDAS-ID), Assessment of SpondyloArthritis international Society criteria partial remission (ASAS-PR), and low Bath AS Disease Activity Index (BASDAI) scores. The objective of this exploratory analysis was to evaluate the proportion of secukinumab-treated patients with AS achieving remission defined based on the ASDAS-ID (score &lt; 1.3), ASAS-PR or BASDAI score ≤  2. Methods: The analysis pooled data from the MEASURE 1 and 2 studies over 3 years. The proportion of patients who achieved ASDAS-ID, ASAS-PR, or BASDAI ≤ 2 with secukinumab was compared with placebo at week 16; results for secukinumab-treated patients were summarized through week 156. Sustainability of each criterion was assessed from week 16 to 156 using shift analysis. The association between each of these criteria and specific patient-reported outcomes (PROs), such as health-related quality of life, function, fatigue, and work impairment, was also explored. Results: At week 16, a higher proportion of secukinumab-treated patients versus placebo achieved ASDAS-ID (17.6 vs. 3.5%), ASAS-PR (15.4 vs. 4.1%), or BASDAI ≤ 2 (22.3 vs. 6.4%) criteria (all P&lt; 0.0001), which were sustained through 156 weeks. Shift analysis showed that the majority of secukinumab-treated patients achieving remission at week 16 maintained their status at week 156 (ASDAS-ID, 57.1%; ASAS-PR, 68.0% and BASDAI ≤ 2, 74.3%). Remission was also associated with improved PROs over 156 weeks. Conclusions: Secukinumab-treated patients maintained ASDAS-ID, ASAS-PR, or BASDAI ≤ 2 from week 16 up to 3 years. Patients who achieved at least one of the three responses/states, reported improvement in PROs, which suggests an association of clinical remission/ID with PROs in patients with active AS. Trial registration: ClinicalTrials.gov: NCT01358175, NCT01863732, and NCT01649375

ObjectiveTo assess the efficacy of secukinumab on axial and peripheral enthesitis in patients with ankylosing spondylitis (AS) using pooled data from randomized controlled phase III studies.MethodsIn this posthoc analysis, data were pooled from patients originally randomized to secukinumab 150 mg, 300 mg, or placebo (PBO) from phase III MEASURE 1–4 studies (ClinicalTrials.gov: NCT01358175, NCT01649375, NCT02008916, and NCT02159053). Maastricht AS Enthesitis Score (MASES) was used for assessments of enthesitis through Week 52. Efficacy outcomes were mean change in MASES score and complete resolution (MASES = 0) of enthesitis in patients with baseline MASES > 0.ResultsA total of 693 (71.5%) patients had enthesitis at baseline in secukinumab 300 mg, 150 mg, and PBO groups (58 [76.3%], 355 [70.4%], and 280 [72%], respectively) out of 969 patients pooled in this analysis. At Week 16, mean changes from baseline for overall MASES and enthesitis at axial MASES sites, respectively, were as follows: –2.9 (P< 0.01) and –2.9 (P< 0.01) for secukinumab 300 mg; –2.4 (P< 0.015) and –2.3 (P< 0.05) for secukinumab 150 mg; and –1.9 and –1.8 for PBO, with improvements seen through Week 52. More than one-third of secukinumab-treated patients (300 mg: 36.2%; 150 mg: 40.8%) achieved complete resolution of enthesitis at Week 16.ConclusionSecukinumab improved enthesitis at overall MASES and axial sites in patients with AS.

Objective.Cardiovascular (CV) morbidity and mortality are increased in axial spondyloarthritis (axSpA).We conducted a cross-sectional study evaluating the 10-year atherosclerotic cardiovascular disease (ASCVD) risk in axSpA compared to the general US population.Methods.We included 211 adults, 40–75 years old with ankylosing spondylitis (AS) or nonradiographic axSpA from 2 sites, who had available data on comorbidities, medication use, blood pressure measures, and laboratory cholesterol values. General population comparators from the 2009–2014 National Health and Examination Survey (NHANES) cycles were matched 4:1 to subjects, on age, sex, and race. We estimated the prevalence ratio for a 10-year ASCVD risk score ≥ 7.5% comparing axSpA and matched NHANES comparators using conditional Poisson regression.Results.Overall, subjects were 53.9 ± 11.2 years old, 69% were male, and 74% were White. The mean 10-year ASCVD risk score was 6.7 ± 6.9% for those with axSpA, and 9.0 ± 10.5% for NHANES comparators. Compared to those with axSpA, the prevalence of current smoking and diabetes was higher among NHANES comparators. The estimated prevalence ratio for a 10-year ASCVD risk score ≥ 7.5% comparing those with axSpA and their age-, sex-, and race-matched comparators was 0.96 (95% CI 0.74–1.24).Conclusion.The prevalence of a 10-year ASCVD risk score ≥ 7.5% was not significantly different comparing axSpA patients and those drawn from the general population who were similar in terms of age, sex, and race. Future studies should focus on improved CV risk prediction in axSpA, because underestimation by a general population risk score may potentially explain these results.

Objective.This study evaluated the effect of ixekizumab (IXE) on self-reported functioning and health in patients with radiographic axial spondyloarthritis (r-axSpA) who were either biological disease-modifying antirheumatic drug (bDMARD)–nai¨ve or failed at least 1 tumor necrosis factor inhibitor (TNFi).Methods.In 2 multicenter, randomized, double-blind, placebo-controlled, and active-controlled (bDMARD-nai¨ve only) trials, patients with r-axSpA were randomly assigned to receive 80 mg of IXE [every 2 weeks (Q2W) or every 4 weeks (Q4W)], placebo (PBO), or adalimumab (ADA; bDMARD-nai¨ve only). After 16 weeks, patients who received PBO or ADA were rerandomized to receive IXE (Q2W or Q4W) up to Week 52. Functioning and health were measured by the generic 36-item Short Form Health Survey (SF-36) and the disease-specific Assessment of Spondyloarthritis international Society Health Index (ASAS HI). Societal health utility was assessed by the 5-level EuroQol-5 Dimension (EQ-5D-5L).Results.At Week 16, both doses of IXE in bDMARD-nai¨ve and TNFi-experienced patients resulted in larger improvement in SF-36, ASAS HI, and EQ-5D-5L versus placebo. For SF-36, the largest improvements were seen for the domains of bodily pain, physical function, and role physical. A larger proportion of patients reaching improvement in ASAS HI ≥ 3 as well as an achievement of ASAS HI good health status was reported in patients treated with IXE. Improvements were maintained through Week 52.Conclusion.IXE significantly improved functioning and health as assessed by both generic and disease-specific measures, as well as societal health utility values in patients with r-axSpA, as measured by SF-36, ASAS HI, and EQ-5D-5L at Week 16, and improvements were sustained through 52 weeks.

Nonsteroidal antiinflammatory drugs (NSAIDs) increase blood pressure and potentially cardiovascular burden, which may limit their use in ankylosing spondylitis (AS). Our objective was to determine the association of NSAID use with incident hypertension in a longitudinal AS cohort. Adults with AS were enrolled in a prospective cohort study of patient outcomes and examined every 4–6 months. Hypertension was defined by patient‐reported hypertension; antihypertensive medication use; or, on 2 consecutive visits, systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg. Continuous NSAID use was dichotomized based on the validated NSAID index. We assessed the association of NSAID use as a time‐varying exposure with the incidence of hypertension using Cox proportional hazards models. Of the 1,282 patients in the cohort, 628 patients without baseline hypertension had at least 1 year of follow‐up and were included in the analysis. Of these, 72% were male, the mean age at baseline was 39 ± 13 years, and 200 patients used NSAIDs continuously. On follow‐up, 129 developed incident hypertension. After controlling for other variables, continuous NSAID use was associated with a hazard ratio of 1.12 for incident hypertension (95% confidence interval 1.04–1.20), compared to noncontinuous or no use. The association did not differ in subgroups defined by age, body mass index, biologic use, or disease activity. In our prospective, longitudinal AS cohort, continuous NSAID use was associated with a 12% increased risk for the development of incident hypertension, as compared to noncontinuous or no NSAID use.

Introduction: Achievement of remission is a key treatment goal for patients with axial spondyloarthritis (axSpA). C-OPTIMISE assessed achievement of sustained clinical remission in patients with axSpA, including radiographic (r) and non-radiographic (nr) axSpA, during certolizumab pegol (CZP) treatment, and subsequent maintenance of remission following CZP dose continuation, dose reduction or withdrawal. Here, we report outcomes from the first 48 weeks (induction period) of C-OPTIMISE, during which patients received open-label CZP. Methods: C-OPTIMISE (NCT02505542) was a two-part, multicenter, phase 3b study in adult patients with early axSpA (r-/nr-axSpA), including a 48-week open-label induction period followed by a 48-week maintenance period. Patients with active adult-onset axSpA, &lt; 5 years’ symptom duration, and fulfilling Assessment of SpondyloArthritis international Society classification criteria, were included. During the induction period, patients received a loading dose of CZP 400 mg at weeks 0, 2, and 4, followed by CZP 200 mg every 2 weeks (Q2W) up to week 48. The main outcome of the 48-week induction period was the achievement of sustained clinical remission (defined as an Ankylosing Spondylitis Disease Activity Score [ASDAS] &lt; 1.3 at week 32 and &lt; 2.1 at week 36 [or vice versa], and &lt; 1.3 at week 48). Results: In total, 736 patients (407 with r-axSpA, 329 with nr-axSpA) were enrolled into the study. At week 48, 43.9% (323/736) of patients achieved sustained remission, including 42.8% (174/407) of patients with r-axSpA and 45.3% (149/329) with nr-axSpA. Patients also demonstrated substantial improvements in axSpA symptoms, MRI outcomes and quality of life measures. Adverse events occurred in 67.9% (500/736) of patients, of which 6.0% (44/736) were serious. Conclusions: Over 40% of patients with early axSpA achieved sustained remission during 48 weeks of open-label CZP treatment. Additionally, patients across the axSpA spectrum demonstrated substantial improvements in imaging outcomes and quality of life following treatment. No new safety signals were identified. Trial Registration: NCT02505542.

Ixekizumab, a high-affinity interleukin-17A (IL-17A) monoclonal antibody, has previously shown efficacy in radiographic axial spondyloarthritis (also known as ankylosing spondylitis). We aimed to evaluate the efficacy and safety of ixekizumab, an IL-17 inhibitor, in non-radiographic axial spondyloarthritis. Here, we report the primary results of COAST-X.

Patients with axial spondyloarthritis (axSpA) frequently report pain, stiffness, fatigue, and sleep problems, which may lead to impaired physical activity. The majority of reported-on measures evaluating physical activity and sleep disturbance in axSpA are self-reported questionnaires, which can be impacted by patient recall (reporting bias). One objective measure, polysomnography, has been employed to evaluate sleep in patients with axSpA; however, it is an intrusive measure and cannot be used over the long term. More convenient objective measures are therefore needed to allow for the long-term assessment of both sleep and physical activity in patients’ daily lives. Wearable technology that utilizes actigraphy is increasingly being used for the objective measurement of physical activity and sleep in various therapy areas, as it is unintrusive and suitable for continuous tracking to allow longitudinal assessment. Actigraphy characterizes sleep disruption as restless movement while sleeping, which is particularly useful when studying conditions such as axSpA in which chronic pain and discomfort due to stiffness may be evident. Studies have also shown that actigraphy can effectively assess the impact of disease on physical activity. More research is needed to establish the usefulness of objective monitoring of sleep and physical activity specifically in axSpA patients over time. This review summarizes the current perspectives on physical activity and sleep quality in patients with axSpA, and the possible role of actigraphy in the future to more accurately evaluate the impact of treatment interventions on sleep and physical activity in axSpA.

To update evidence‐based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). We conducted updated systematic literature reviews for 20 clinical questions on pharmacologic treatment addressed in the 2015 guidelines, and for 26 new questions on pharmacologic treatment, treat‐to‐target strategy, and use of imaging. New questions addressed the use of secukinumab, ixekizumab, tofacitinib, tumor necrosis factor inhibitor (TNFi) biosimilars, and biologic tapering/discontinuation, among others. We used the Grading of Recommendations, Assessment, Development and Evaluation methodology to assess the quality of evidence and formulate recommendations and required at least 70% agreement among the voting panel. Recommendations for ASand nonradiographic axial SpA are similar. TNFi are recommended over secukinumab or ixekizumab as the first biologic to be used. Secukinumab or ixekizumab is recommended over the use of a second TNFi in patients with primary nonresponse to the first TNFi. TNFi, secukinumab, and ixekizumab are favored over tofacitinib. Co‐administration of low‐dose methotrexate with TNFi is not recommended, nor is a strict treat‐to‐target strategy or discontinuation or tapering of biologics in patients with stable disease. Sulfasalazine is recommended only for persistent peripheral arthritis when TNFi are contraindicated. For patients with unclear disease activity, spine or pelvis magnetic resonance imaging could aid assessment. Routine monitoring of radiographic changes with serial spine radiographs is not recommended. These recommendations provide updated guidance regarding use of new medications and imaging of the axial skeleton in the management of ASand nonradiographic axial SpA.

Background: Radiographic progression and course of inflammation over 2 years in patients with non-radiographic axial spondyloarthritis (nr-axSpA) from the phase 3, randomized, PREVENT study are reported here. Methods: In the PREVENT study, adult patients fulfilling the Assessment of SpondyloArthritis International Society classification criteria for nr-axSpA with elevated CRP and/or MRI inflammation received secukinumab 150 mg or placebo. All patients received open-label secukinumab from week 52 onward. Sacroiliac (SI) joint and spinal radiographs were scored using the modified New York (mNY) grading (total sacroiliitis score; range, 0–8) and modified Stoke Ankylosing Spondylitis Spine Score (mSASSS; range, 0–72), respectively. SI joint bone marrow edema (BME) was assessed using the Berlin Active Inflammatory Lesions Scoring (0–24) and spinal MRI using the Berlin modification of the AS spine MRI (ASspiMRI) scoring (0–69). Results: Overall, 78.9% (438/555) of patients completed week 104 of the study. Over 2 years, minimal changes were observed in total radiographic SI joint scores (mean [SD] change, − 0.04 [0.49] and 0.04 [0.36]) and mSASSS scores (0.04 [0.47] and 0.07 [0.36]) in the secukinumab and placebo-secukinumab groups. Most of the patients showed no structural progression (increase ≤ smallest detectable change) in SI joint score (87.7% and 85.6%) and mSASSS score (97.5% and 97.1%) in the secukinumab and placebo-secukinumab groups. Only 3.3% (n= 7) and 2.9% (n= 3) of patients in the secukinumab and placebo-secukinumab groups, respectively, who were mNY-negative at baseline were scored as mNY-positive at week 104. Overall, 1.7% and 3.4% of patients with no syndesmophytes at baseline in the secukinumab and placebo-secukinumab group, respectively, developed ≥ 1 new syndesmophyte over 2 years. Reduction in SI joint BME observed at week 16 with secukinumab (mean [SD], − 1.23 [2.81] vs − 0.37 [1.90] with placebo) was sustained through week 104 (− 1.73 [3.49]). Spinal inflammation on MRI was low at baseline (mean score, 0.82 and 1.07 in the secukinumab and placebo groups, respectively) and remained low (mean score, 0.56 at week 104). Conclusion: Structural damage was low at baseline and most patients showed no radiographic progression in SI joints and spine over 2 years in the secukinumab and placebo-secukinumab groups. Secukinumab reduced SI joint inflammation, which was sustained over 2 years. Trial registration: ClinicalTrials.gov, NCT02696031.

At present, biological disease-modifying anti-rheumatic drugs (DMARDs) are the only treatment recommended for patients with ankylosing spondylitis who have not responded to first-line treatment with non-steroidal anti-inflammatory drugs (NSAIDs). The TORTUGA trial investigated the efficacy and safety of filgotinib, an oral selective Janus kinase 1 (JAK1) inhibitor, for the treatment of patients with active ankylosing spondylitis.

The cardiovascular burden in inflammatory rheumatic diseases is well recognized. Recently, this burden has been highlighted in ankylosing spondylitis (also known as radiographic axial spondyloarthritis) and psoriatic arthritis. We review the cardiovascular morbidity and mortality in these diseases, as well as the prevalence and incidence of traditional cardiovascular risk factors. We examine the contribution of anti-inflammatory therapy with nonsteroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs, and TNF inhibitors on the cardiovascular risk profile. Finally, we examine the available recommendations for the management of cardiovascular comorbidity, as they apply to the spondyloarthritis population.

Objective.Opioid analgesics may be prescribed to ankylosing spondylitis (AS) patients with pain that is unresponsive to antirheumatic treatment. Our study assessed factors associated with opioid usage in AS.Methods.A prospective cohort of 706 patients with AS meeting modified New York criteria followed at least 2 years underwent comprehensive clinical evaluation of disease activity and functional impairment. These were assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI). Radiographic severity was assessed by the Bath Ankylosing Spondylitis Radiology Index and modified Stokes Ankylosing Spondylitis Scoring System. Medications taken concurrently with opioids, as well as C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR), were determined at each study visit, performed every 6 months. Analyses were carried out at baseline, and longitudinal multivariable models were developed to identify factors independently associated with chronic and intermittent opioid usage over time.Results.Factors significantly associated with opioid usage, especially chronic opioid use, included longer disease duration, smoking, lack of exercise, higher disease activity (BASDAI) and functional impairment (BASFI), depression, radiographic severity, and cardiovascular disease. Patients taking opioids were more likely to be using anxiolytic, hypnotic, antidepressant, and muscle relaxant medications. Multivariable analysis underscored the association with smoking, older age, antitumor necrosis factor agent use, and psychoactive drugs, as well as with subjective but not objective determinants of disease activity.Conclusion.Opioid usage was more likely to be associated with subjective measures (depression, BASDAI, BASFI) than objective measures (CRP, ESR), suggesting that pain in AS may derive from sources other than spinal inflammation alone.

Non-radiographic axial spondyloarthritis (nr-axSpA) is a complex disease process that is part of the spectrum of axial spondyloarthritis (axSpA). This article reviews the current state of the literature as the understanding of this disease spectrum expands. The conceptual history and terminology, genetics, and epidemiology are reviewed. The clinical manifestations, diagnostic approach, and measures of disease activity are examined. Finally the current treatment modalities and recommendations and the research agenda for nr-axSpA are reviewed. With the advent of new criteria, the disease spectrum can be studied in a systematic manner. These data have enriched our knowledge that reflects an earlier or milder form of disease on a spectrum same as that of ankylosing spondylitis (or radiographic axSpA). We learned how patients present in this stage and that despite an unacceptable delay in diagnosis (regardless of the stage), the burden of disease is high and unremitting. nr-axSpA clinical trials have been somewhat heterogeneous (with variable inclusion criteria) but have nevertheless shown considerable efficacy with tumor necrosis factor inhibitors and flare on withdrawal of therapy.

Background: Patients with active axial spondyloarthritis (axSpA) exhibit more absences and lower levels of productivity in the workplace and household than the general population, which can improve upon treatment.Objectives: The objective of this study is to determine the long-term impact of achieving different levels of clinical response or disease activity on workplace and household productivity in patients with axSpA.Design: RAPID-axSpA (NCT01087762) was a 204-week phase III trial evaluating the safety and efficacy of certolizumab pegol (CZP) in adult patients with active axSpA.Methods: The impact of axSpA on workplace and household productivity was evaluated using the validated arthritis-specific Work Productivity Survey. Outcomes included the percentage of patients achieving Assessment of SpondyloArthritis International Society (ASAS) response and Ankylosing Spondylitis Disease Activity Score (ASDAS) thresholds. This post hoc study used a generalised estimating equations model to determine the association between the threshold of clinical response achieved and patient productivity.Results: Of 218 CZP-randomised patients, 65.1% completed week 204. At baseline, 72.0% were employed outside the home. Of the patients who were unemployed, 42.6% were unable to work due to arthritis. Achievement of higher treatment response thresholds, such as clinical remission, was associated with fewer days affected by workplace absenteeism (ASAS-partial remission: 4.0 days, ASAS40: 8.6 days, ASAS20 but not reaching ASAS40 response: 29.4 days, ASAS20 non-response: 69.2 days; ASDAS-inactive disease: 5.0 days, ASDAS-low disease activity: 15.6 days, ASDAS-high disease activity: 32.7 days, ASDAS-very high disease activity: 93.4 days). Similar associations were found for workplace presenteeism, and household absenteeism and presenteeism.Conclusions: Over 4 years, achievement of higher clinical response thresholds and lower levels of disease activity was associated with fewer cumulative days affected by absenteeism or presenteeism, with clinical remission associated with the greatest improvements in productivity. This highlights the importance of targeting these thresholds to limit the burden of axSpA on society and on patients’ daily lives.

Little data exist regarding mortality in ankylosing spondylitis (AS). We assessed diagnoses associated with in‐hospital mortality in AS using a population‐based inpatient data set. Data were abstracted from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample between 2007 and 2011. We identified AS admissions using International Classification of Diseases, Ninth Revision, Clinical Modification code 720.0. In‐hospital mortality was the primary outcome. Logistic regression was used to evaluate the association between top diagnoses and in‐hospital mortality. We performed a secondary analysis from the same years in all patients (with and without AS) with cervical spine (C‐spine) fracture to determine whether AS was an independent risk factor for mortality. Between 2007 and 2011, we identified 12,484 admissions and 267 deaths in AS patients. C‐spine fracture with spinal cord injury and sepsis had the highest odds of death, with odds ratios (ORs) of 13.43 (95% confidence interval [95% CI] 8.00–22.55, P< 0.0001) and 7.63 (95% CI 5.62–10.36, P< 0.0001), respectively. In the same time period, there were 53,606 C‐spine fracture admissions, of which 408 were coded with AS. Among all C‐spine fracture hospitalizations, an AS diagnosis was associated with inpatient death (OR 1.61 [95% CI 1.16–2.22], P= 0.004). In AS patients admitted to the hospital, C‐spine fracture is a leading cause of in‐hospital mortality. Other diagnoses associated with mortality include sepsis, pneumonia, cardiovascular disease, and comorbid illnesses. Among all hospitalizations with C‐spine fracture, AS was associated with increased odds of death. C‐spine fracture–associated mortality warrants further study to elucidate risk factors in order to prevent such devastating fractures in AS patients.

Lateral flow assays (LFA) are sensitive for detecting antibodies to SARS-CoV-2 proteins within weeks after infection. This study tested samples from immunocompetent adults, and those receiving treatments for chronic inflammatory diseases (CID), before and after mRNA SARS-CoV-2 vaccination.

To provide evidence‐based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). A core group led the development of the recommendations, starting with the treatment questions. A literature review group conducted systematic literature reviews of studies that addressed 57 specific treatment questions, based on searches conducted in OVID Medline (1946–2014), PubMed (1966–2014), and the Cochrane Library. We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. A separate voting group reviewed the evidence and voted on recommendations for each question using the GRADE framework. In patients with active AS, the strong recommendations included use of nonsteroidal antiinflammatory drugs (NSAIDs), use of tumor necrosis factor inhibitors (TNFi) when activity persists despite NSAID treatment, not to use systemic glucocorticoids, use of physical therapy, and use of hip arthroplasty for patients with advanced hip arthritis. Among the conditional recommendations was that no particular TNFi was preferred except in patients with concomitant inflammatory bowel disease or recurrent iritis, in whom TNFi monoclonal antibodies should be used. In patients with active nonradiographic axial SpA despite treatment with NSAIDs, we conditionally recommend treatment with TNFi. Other recommendations for patients with nonradiographic axial SpA were based on indirect evidence and were the same as for patients with AS. These recommendations provide guidance for the management of common clinical questions in AS and nonradiographic axial SpA. Additional research on optimal medication management over time, disease monitoring, and preventive care is needed to help establish best practices in these areas.

In spondyloarthritis (SpA), spontaneous remission is best described in reactive arthritis, a form of peripheral SpA. Prior SpA observational studies suggested that a significant percentage of patients reached spontaneous remission; however, these patients were followed up under older, broader European Spondyloarthropathy Study Group (ESSG) criteria or were not defined by specific criteria. In general, they were mixed populations of peripheral and axial disease, and the subsets were not differentiated when assessing end points such as remission. There are limited data on the natural history of axial SpA, in part because of the evolution of the criteria with the more recently developed Assessment of SpondyloArthritis International Society (ASAS) criteria, including the designation of non-radiographic axial SpA and peripheral SpA. Clinical trials have been conducted with various remission end points including withdrawal of therapy to determine remission maintenance. The following review addresses the potential for remission in axial and peripheral SpA based on the data from both observational studies and clinical trials.

Background: To investigate the efficacy of secukinumab in patients with active non-radiographic axial spondyloarthritis (nr-axSpA) grouped by disease activity as assessed by C-reactive protein (CRP) levels and/or magnetic resonance imaging (MRI) scores, human leukocyte antigen (HLA)-B27 status, and sex. Methods: The phase III PREVENT study randomized (1:1:1) 555 patients to receive subcutaneous secukinumab 150 mg with (LD) or without (NL) loading dose or placebo weekly, followed by every 4 weeks starting at week 4. Here, we report the results of a post hoc analysis reporting the efficacy outcomes (pooled secukinumab) to 16 weeks by CRP, MRI, HLA-B27, and sex. Results: Efficacy differences between the secukinumab and the placebo groups were highest in the CRP+, MRI+, HLA-B27+, and male subgroups, particularly for Ankylosing Spondylitis Disease Activity Score-CRP inactive disease and Assessment of SpondyloArthritis international Society (ASAS) partial remission outcomes. ASAS40 response rates in the CRP+/MRI+ subgroup was 52.3% (secukinumab) versus 21.8% (placebo; P&lt; 0.0001) at week 16. ASAS40 response rates (secukinumab versus placebo) were 43.9% versus 32.6% in HLA-B27+, 32.7% versus 16.4% in HLA-B27− subgroups, 51.2% versus 30.8% in male, and 31.7% versus 25.3% in female patients, respectively. Conclusions: Secukinumab improved the signs and symptoms of nr-axSpA across patients grouped by CRP (+/−) and/or MRI (+/−) status, HLA-B27 (+/−) status, and sex. The highest treatment differences between secukinumab and placebo were observed in patients with both elevated CRP and evidence of sacroiliitis on MRI. Treatment difference was minimal between HLA-B27 (+) and (−) subgroups. Male patients had higher relative responses than female patients. Trial registration: ClinicalTrials.gov, NCT02696031. Registered on 02 March 2016

Background: Involvement of the axial skeleton (sacroiliac joints and spine) is a relatively frequent manifestation associated with psoriatic skin disease, mostly along with involvement of peripheral musculoskeletal structures (peripheral arthritis, enthesitis, dactylitis), which are referred to as psoriatic arthritis (PsA). Data suggest that up to 30% of patients with psoriasis have PsA. Depending on the definition used, the prevalence of axial involvement varies from 25% to 70% of patients with PsA. However, there are currently no widely accepted criteria for axial involvement in PsA.Objective: The overarching aim of the Axial Involvement in Psoriatic Arthritis (AXIS) study is to systematically evaluate clinical and imaging manifestations indicative of axial involvement in patients with PsA and to develop classification criteria and a unified nomenclature for axial involvement in PsA that would allow defining a homogeneous subgroup of patients for research.Design: Prospective, multicenter, multinational, cross-sectional study.Methods and analyses: In this multicenter, multinational, cross-sectional study, eligible patients [adult patients diagnosed with PsA and fulfilling Classification Criteria for Psoriatic Arthritis (CASPAR) with musculoskeletal symptom duration of ⩽10 years not treated with biological or targeted synthetic disease-modifying anti-rheumatic drugs] will be recruited prospectively. They will undergo study-related clinical and imaging examinations. Imaging will include radiography and magnetic resonance imaging examinations of sacroiliac joints and spine. Local investigators will evaluate for the presence of axial involvement based on clinical and imaging information which will represent the primary outcome of the study. In addition, imaging will undergo evaluation by central review. Finally, the central clinical committee will determine the presence of axial involvement based on all available information.Ethics: The study will be performed according to the ethical principles of the Declaration of Helsinki and International Council for Harmonisation Good Clinical Practice guidelines. The study protocol will be approved by the individual Independent Ethics Committee / Institutional Review Board of participating centers. Written informed consent will be obtained from all included patients.Registration: ClinicalTrials.gov ID: NCT04434885.

We aimed to perform a structured literature review of spinal radiographic progression, as assessed by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), in patients with ankylosing spondylitis (AS) or nonradiographic axial spondyloarthritis (nr-axSpA) treated with biologic therapy. Searches were limited to English language manuscripts published in the 11 years prior to 9 July 2019. Randomized controlled trials, open-label extensions (OLEs) and observational studies reporting mSASSS progression in patients with AS or nr-axSpA treated with biologics were eligible for inclusion. Bias was assessed using the methodological index for nonrandomized studies (MINORS) tool. Among the 322 studies identified in the literature search, 23 (11 OLEs and 12 cohort studies) met the eligibility criteria and were selected for inclusion. Most studies reported mSASSS progression in patients with AS receiving tumor necrosis factor inhibitor (TNFi) treatment. One study reported mSASSS progression in patients with AS treated with secukinumab, an interleukin-17A inhibitor. The mean (range) MINORS score was 11.3 (7–15) for the 15 noncomparative studies and 15 (12–22) for the 8 comparative studies. Although results of the individual studies were variable, mSASSS progression in patients with AS was generally minimal and slow with long-term TNFi therapy. Moreover, odds ratios for the likelihood of mSASSS progression with/without TNFi favoured TNFi therapy in several of the cohort studies. The rate of mSASSS progression following continuous secukinumab treatment was low and remained stable over 4 years. Of two studies reporting progression in patients with nr-axSpA treated with TNFis, one showed no mSASSS progression; however, the lack of control limited comparative conclusions.