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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.

Additional file 1: Fig. S1. Study Design. Fig. S2. Mean change in SI joint bone marrow edema score by MRI in the overall population and in patients with baseline score >2 through week 104 (in patients with images available at all 4 time points). Table S1. Syndesmophyte status at screening by mNY status at screening based on single reader assessment and two reader agreement.

ObjectivesThe objective of COAST-Y was to evaluate the effect of continuing versus withdrawing ixekizumab (IXE) in patients with axial spondyloarthritis (axSpA) who had achieved remission.MethodsCOAST-Y is an ongoing, phase III, long-term extension study that included a double-blind, placebo (PBO)-controlled, randomised withdrawal-retreatment period (RWRP). Patients who completed the originating 52-week COAST-V, COAST-W or COAST-X studies entered a 24-week lead-in period and continued either 80 mg IXE every 2 (Q2W) or 4 weeks (Q4W). Patients who achieved remission (an Ankylosing Spondylitis Disease Activity Score (ASDAS)3.5 at any visit) after the 40-week RWRP, with time-to-flare as a major secondary endpoint.ResultsOf 773 enrolled patients, 741 completed the 24-week lead-in period and 155 entered the RWRP. Forty weeks after randomised withdrawal, 83.3% of patients in the combined IXE (85/102, pConclusionsPatients with axSpA who continued treatment with IXE were significantly less likely to flare and had significantly delayed time-to-flare compared with patients who withdrew to PBO.

Evidence suggests that immunogenicity to mRNA-based SARS-CoV-2 vaccination in immunosuppressed patients may be reduced. This study assessed the response to 2 doses of mRNA-based SARS-CoV-2 vaccine among 133 participants with underlying chronic inflammatory disease, many of whom were receiving glucocorticoids, B-cell depletion therapy, or other immunosuppressant therapy., Visual Abstract. Effect of Immunosuppression on Immunogenicity of mRNA SARS-CoV-2 Vaccines. Evidence suggests that immunogenicity to mRNA-based SARS-CoV-2 vaccination in immunosuppressed patients may be reduced. This study assessed the response to 2 doses of mRNA-based SARS-CoV-2 vaccine among 133 participants with underlying chronic inflammatory disease, many of whom were receiving glucocorticoids, B-cell depletion therapy, or other immunosuppressant therapy. Visual Abstract. Effect of Immunosuppression on Immunogenicity of mRNA SARS-CoV-2 Vaccines. Evidence suggests that immunogenicity to mRNA-based SARS-CoV-2 vaccination in immunosuppressed patients may be reduced. This study assessed the response to 2 doses of mRNA-based SARS-CoV-2 vaccine among 133 participants with underlying chronic inflammatory disease, many of whom were receiving glucocorticoids, B-cell depletion therapy, or other immunosuppressant therapy., Background: Patients with chronic inflammatory disease (CID) treated with immunosuppressive medications have increased risk for severe COVID-19. Although mRNA-based SARS-CoV-2 vaccination provides protection in immunocompetent persons, immunogenicity in immunosuppressed patients with CID is unclear. Objective: To determine the immunogenicity of mRNA-based SARS-CoV-2 vaccines in patients with CID. Design: Prospective observational cohort study. Setting: Two U.S. CID referral centers. Participants: Volunteer sample of adults with confirmed CID eligible for early COVID-19 vaccination, including hospital employees of any age and patients older than 65 years. Immunocompetent participants were recruited separately from hospital employees. All participants received 2 doses of mRNA vaccine against SARS-CoV-2 between 10 December 2020 and 20 March 2021. Participants were assessed within 2 weeks before vaccination and 20 days after final vaccination. Measurements: Anti–SARS-CoV-2 spike (S) IgG+ binding in all participants, and neutralizing antibody titers and circulating S-specific plasmablasts in a subset to assess humoral response after vaccination. Results: Most of the 133 participants with CID (88.7%) and all 53 immunocompetent participants developed antibodies in response to mRNA-based SARS-CoV-2 vaccination, although some with CID developed numerically lower titers of anti-S IgG. Anti-S IgG antibody titers after vaccination were lower in participants with CID receiving glucocorticoids (n = 17) than in those not receiving them; the geometric mean of anti-S IgG antibodies was 357 (95% CI, 96 to 1324) for participants receiving prednisone versus 2190 (CI, 1598 to 3002) for those not receiving it. Anti-S IgG antibody titers were also lower in those receiving B-cell depletion therapy (BCDT) (n = 10). Measures of immunogenicity differed numerically between those who were and those who were not receiving antimetabolites (n = 48), tumor necrosis factor inhibitors (n = 39), and Janus kinase inhibitors (n = 11); however, 95% CIs were wide and overlapped. Neutralization titers seemed generally consistent with anti-S IgG results. Results were not adjusted for differences in baseline clinical factors, including other immunosuppressant therapies. Limitations: Small sample that lacked demographic diversity, and residual confounding. Conclusion: Compared with nonusers, patients with CID treated with glucocorticoids and BCDT seem to have lower SARS-CoV-2 vaccine-induced antibody responses. These preliminary findings require confirmation in a larger study. Primary Funding Source: The Leona M. and Harry B. Helmsley Charitable Trust, Marcus Program in Precision Medicine Innovation, National Center for Advancing Translational Sciences, and National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Supplemental material, sj-docx-1-tab-10.1177_1759720X211057975 for Axial Involvement in Psoriatic Arthritis cohort (AXIS): the protocol of a joint project of the Assessment of SpondyloArthritis international Society (ASAS) and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) by Denis Poddubnyy, Xenofon Baraliakos, Filip Van den Bosch, J��rgen Braun, Laura C. Coates, Vinod Chandran, Torsten Diekhoff, Floris A. van Gaalen, Lianne S. Gensler, Niti Goel, Alice B. Gottlieb, D��sir��e van der Heijde, Philip S. Helliwell, Kay Geert A. Hermann, Deepak Jadon, Robert G. Lambert, Walter P. Maksymowych, Philip Mease, Peter Nash, Fabian Proft, Mikhail Protopopov, Joachim Sieper, Murat Torgutalp and Dafna D. Gladman in Therapeutic Advances in Musculoskeletal Disease

Additional file 1: Table S1. Number of patients in each subgroup. Table S2. Key efficacy endpoints by subgroups and by gender at screening analysed at Week 16. Table S3. Additional efficacy endpoints in the subgroups analysed at Week 16.

Supplemental material, sj-docx-2-tab-10.1177_1759720X211057975 for Axial Involvement in Psoriatic Arthritis cohort (AXIS): the protocol of a joint project of the Assessment of SpondyloArthritis international Society (ASAS) and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) by Denis Poddubnyy, Xenofon Baraliakos, Filip Van den Bosch, J��rgen Braun, Laura C. Coates, Vinod Chandran, Torsten Diekhoff, Floris A. van Gaalen, Lianne S. Gensler, Niti Goel, Alice B. Gottlieb, D��sir��e van der Heijde, Philip S. Helliwell, Kay Geert A. Hermann, Deepak Jadon, Robert G. Lambert, Walter P. Maksymowych, Philip Mease, Peter Nash, Fabian Proft, Mikhail Protopopov, Joachim Sieper, Murat Torgutalp and Dafna D. Gladman in Therapeutic Advances in Musculoskeletal Disease

Supplemental material, sj-docx-2-tab-10.1177_1759720X211057975 for Axial Involvement in Psoriatic Arthritis cohort (AXIS): the protocol of a joint project of the Assessment of SpondyloArthritis international Society (ASAS) and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) by Denis Poddubnyy, Xenofon Baraliakos, Filip Van den Bosch, J��rgen Braun, Laura C. Coates, Vinod Chandran, Torsten Diekhoff, Floris A. van Gaalen, Lianne S. Gensler, Niti Goel, Alice B. Gottlieb, D��sir��e van der Heijde, Philip S. Helliwell, Kay Geert A. Hermann, Deepak Jadon, Robert G. Lambert, Walter P. Maksymowych, Philip Mease, Peter Nash, Fabian Proft, Mikhail Protopopov, Joachim Sieper, Murat Torgutalp and Dafna D. Gladman in Therapeutic Advances in Musculoskeletal Disease

Additional file 1 : Table S1. List of ethical approval reference numbers for each participating center (MEASURE 1 study).

ObjectiveResponse to the coronavirus disease 2019 (COVID-19) pandemic has resulted in shelter-in-place orders and major changes to individuals' daily lives. The impact of such stressors on disease activity in individuals with axial spondyloarthritis (axSpA) is unclear. The aim of this study is to examine whether stress, anxiety, and depression are associated with patient-reported disease activity, after accounting for important factors.MethodsWe administered a survey to an axSpA cohort from a single center with well-defined demographic and disease characteristics. We included questions about job status changes, exercise, medication use, disease activity (by the Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]), and psychological factors (stress, depressive symptoms, and anxiety). Separate multivariable linear models examined the associations between perceived stress, anxiety, and depression with the BASDAI.ResultsAfter adjustment for potential confounders, those with higher levels of stress had a statistically significant 0.54-point higher BASDAI, on average, compared with those with lower levels of stress (95% confidence interval [CI]: 0.11, 0.97). Those with higher levels of anxiety also had a statistically significant higher BASDAI, on average, compared with those with lower levels of anxiety (β: 0.95, 95% CI: 0.18, 0.99). The association between depression and BASDAI was not statistically significant. We did not find differences in these associations among subgroups of age, job status, or county of residence.ConclusionIndividuals with axSpA with higher levels of stress and anxiety had significantly higher disease activity levels, although with a difference below clinical importance. Further planned studies will evaluate the trajectory of disease activity.

Supplemental material, AxSpA_review_Baraliakos_Appendix_TherAdvMuscDis_23Dec19 for Biologic therapy and spinal radiographic progression in patients with axial spondyloarthritis: A structured literature review by Xenofon Baraliakos, Lianne S. Gensler, Salvatore D’Angelo, Florenzo Iannone, Ennio G. Favalli, Natasha de Peyrecave, Simone E. Auteri and Roberto Caporali in Therapeutic Advances in Musculoskeletal Disease

Supplemental material, axSpA_SLR_tables_and_figures_13Feb20 for Biologic therapy and spinal radiographic progression in patients with axial spondyloarthritis: A structured literature review by Xenofon Baraliakos, Lianne S. Gensler, Salvatore D’Angelo, Florenzo Iannone, Ennio G. Favalli, Natasha de Peyrecave, Simone E. Auteri and Roberto Caporali in Therapeutic Advances in Musculoskeletal Disease

ObjectiveTo identify genetic associations with severity of radiographic damage in ankylosing spondylitis (AS).MethodWe studied 1537 AS cases of European descent; all fulfilled the modified New York Criteria. Radiographic severity was assessed from digitised lateral radiographs of the cervical and lumbar spine using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). A two-phase genotyping design was used. In phase 1, 498 single nucleotide polymorphisms (SNPs) were genotyped in 688 cases; these were selected to capture >90% of the common haplotypic variation in the exons, exon-intron boundaries, and 5 kb flanking DNA in the 5' and 3' UTR of 74 genes involved in anabolic or catabolic bone pathways. In phase 2, 15 SNPs exhibiting p

ObjectiveTo report population-based percentile reference values for selected spinal mobility measures in a nationally representative sample of 5,001 US adults ages 20-69 years who were examined in the 2009-2010 US National Health and Nutrition Examination Survey (NHANES).MethodsOcciput-to-wall distance (OWD), thoracic expansion (TE), and anterior lumbar flexion (ALF; by modified Schober test) were measured by trained examiners in a standardized manner. TE was measured at the xiphisternal level, while the lower reference point for ALF was a line marked at the level of the superior margin of the lateral iliac crests. We report reference values based on the 95th percentile for the OWD and the 5th percentile for TE and ALF, as well as other summary statistics for these measures, in the study population.ResultsAn OWD of >0 was present in 3.8% of the participants, while 8.8% of them had out-of-range values for TE based on the commonly used threshold of 2.5 cm. The 95th percentile of the OWD measurement was 0, while the 5th percentile for TE and ALF were 1.9 cm and 2 cm, respectively. The spinal measures were significantly associated with sex, age, ethnicity, height, and body mass index (BMI). Exclusion of individuals with severe obesity (BMI >35 kg/m(2) ) changed the proposed reference values for TE and ALF to 2.2 cm and 1.9 cm, respectively.ConclusionWe verified a reference value of 0 for the OWD in the general population. Using the reported population-based percentile values, new reference values for TE and ALF can be derived.

ObjectiveTo study the effect of tumor necrosis factor α (TNFα) inhibitors on progressive spinal damage in patients with ankylosing spondylitis (AS).MethodsAll AS patients meeting the modified New York criteria who had been monitored prospectively and had at least 2 sets of spinal radiographs a minimum of 1.5 years apart were included in the study (n=334). The patients received standard therapy, which included nonsteroidal antiinflammatory drugs and TNFα inhibitors. Radiographic severity was assessed by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Patients with a rate of AS progression that was ≥1 mSASSS unit/year were considered progressors. Univariable and multivariable regression analyses were done. Propensity score matching and sensitivity analysis were performed. A zero-inflated negative binomial (ZINB) model was used to analyze the effect of TNFα inhibitors on the change in the mSASSS with varying followup periods. Potential confounders, such as disease activity (as assessed by the Bath Ankylosing Spondylitis Disease Activity Index), the erythrocyte sedimentation rate, C-reactive protein level, HLA-B27 positivity, sex, age at onset, smoking burden (number of pack-years), and baseline damage, were included in the model.ResultsTNFα inhibitor treatment was associated with a 50% reduction in the odds of progression, with an odds ratio (OR) of 0.52 (95% confidence interval [95% CI] 0.30-0.88, P=0.02). Patients with a delay of >10 years in starting therapy were more likely to experience progression as compared to those who started earlier (OR 2.4 [95% CI 1.09-5.3], P=0.03). In the ZINB model, the use of TNFα inhibitors significantly reduced disease progression when the gap between radiographs was >3.9 years. The protective effect of TNFα inhibitors was stronger after propensity score matching.ConclusionTreatment with TNFα inhibitors appears to reduce radiographic progression in AS patients, especially with early initiation and with longer duration of followup.

ObjectiveWe sought to develop a list of 5 tests, treatments, or services commonly used in rheumatology practice whose necessity or value should be questioned and discussed by physicians and patients.MethodsWe used a multistage process combining consensus methodology and literature reviews to arrive at the American College of Rheumatology's (ACR) Top 5 list. Rheumatologists from diverse practice settings generated items using the Delphi method. Items with high content agreement and perceived high prevalence advanced to a survey of ACR members, who comprise >90% of the US rheumatology workforce. To increase the response rate, a nested random sample of 390 rheumatologists received more intensive survey followup. The samples were combined and weighting procedures were applied to ensure generalizability. Items with high ratings underwent literature review. Final items were then selected and formulated by the task force.ResultsOne hundred five unique items were proposed and narrowed down to 22 items during the Delphi rounds. A total of 1,052 rheumatologists (17% of those contacted) participated in the member-wide survey, whereas 33% of those in the nested random sample participated; respondent characteristics were similar in both samples. Based on survey results and available scientific evidence, 5 items (relating to antinuclear antibodies, Lyme disease, magnetic resonance imaging, bone absorptiometry, and biologic therapy for rheumatoid arthritis) were selected for inclusion.ConclusionThe ACR Top 5 list is intended to promote discussions between physicians and patients about health care practices in rheumatology whose use should be questioned and to assist rheumatologists in providing high-value care.

ObjectivesTo evaluate construct validity, interpretability, reliability and responsiveness as well as determination of cut-off points for good and poor health within the original English version and the 18 translations of the disease-specific Assessment of Spondyloarthritis international Society Health Index (ASAS HI) in 23 countries worldwide in patients with spondyloarthritis (SpA).MethodsA representative sample of patients with SpA fulfilling the ASAS classification criteria for axial (axSpA) or peripheral SpA was used. The construct validity of the ASAS HI was tested using Spearman correlation with several standard health outcomes for axSpA. Test–retest reliability was assessed by intraclass correlation coefficients (ICCs) in patients with stable disease (interval 4–7 days). In patients who required an escalation of therapy because of high disease activity, responsiveness was tested after 2–24weeks using standardised response mean (SRM).ResultsAmong the 1548 patients, 64.9% were men, with a mean (SD) age 42.0 (13.4) years. Construct validity ranged from low (age: 0.10) to high (Bath AnkylosingSpondylitisFunctioning Index: 0.71). Internal consistency was high (Cronbach’s α of 0.93). The reliability among 578 patients was good (ICC=0.87 (95% CI 0.84 to 0.89)). Responsiveness among 246 patients was moderate-large (SRM=−0.44 for non-steroidal anti-inflammatory drugs, −0.69 for conventional synthetic disease-modifying antirheumatic drug and −0.85 for tumour necrosis factor inhibitor). The smallest detectable change was 3.0. Values ≤5.0 have balanced specificity to distinguish good health as opposed to moderate health, and values ≥12.0 are specific to represent poor health as opposed to moderate health.ConclusionsThe ASAS HI proved to be valid, reliable and responsive. It can be used to evaluate the impact of SpA and its treatment on functioning and health. Furthermore, comparison of disease impact between populations is possible.