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Background: 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.Methods: In this completed, randomised, double-blind, placebo-controlled, phase 2 trial, we enrolled adult patients from 30 sites in seven countries (Belgium, Bulgaria, Czech Republic, Estonia, Poland, Spain, and Ukraine). Eligible patients had active ankylosing spondylitis and an inadequate response or intolerance to two or more NSAIDs. Patients were randomly assigned (1:1) with an interactive web-based response system to receive filgotinib 200 mg or placebo orally once daily for 12 weeks. Randomisation was stratified by current use of conventional synthetic DMARDs and previous receipt of anti-tumour necrosis factor therapy. The patients, study team, and study sponsor were masked to treatment assignment. The primary endpoint was the change from baseline in ankylosing spondylitis disease activity score (ASDAS) at week 12, which was assessed in the full analysis set (ie, all randomised patients who received at least one dose of study drug). Safety was assessed according to actual treatment received. This trial is registered with ClinicalTrials.gov, number NCT03117270.Findings: Between March 7, 2017, and July 2, 2018, 263 patients were screened and 116 randomly assigned to filgotinib (n=58) or placebo (n=58). 55 (95%) patients in the filgotinib group and 52 (90%) in the placebo group completed the study; three (5%) patients in the filgotinib group and six (10%) in the placebo group discontinued treatment. The mean ASDAS change from baseline to week 12 was -1·47 (SD 1·04) in the filgotinib group and -0·57 (0·82) in the placebo group, with a least squares mean difference between groups of -0·85 (95% CI -1·17 to -0·53; p<0·0001). Treatment-emergent adverse events were reported in 18 patients in each group, the most common being nasopharyngitis (in two patients in the filgotinib group and in four patients in the placebo group). Treatment-emergent adverse events led to permanent treatment discontinuation in two patients (a case of grade 3 pneumonia in the filgotinib group and of high creatine kinase in the placebo group). No deaths were reported during the study.Interpretation: Filgotinib is efficacious and safe for the treatment of patients with active ankylosing spondylitis who have not responded to first-line pharmacological therapy with NSAIDs. Further investigation of filgotinib for ankylosing spondylitis is warranted.Funding: Galapagos and Gilead Sciences. [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinical response at week 52 in patients with ankylosing spondylitis (AS) who received secukinumab 300 vs 150 mg after inadequate response to 150 mg at week 16., Methods: ASLeap (NCT03350815) was a randomized, double-blind, parallel-group, multicentre, phase 4 trial. After 16 weeks of open-label secukinumab 150 mg (Treatment Period 1), patients who did not achieve inactive disease (Ankylosing Spondylitis Disease Activity Score [ASDAS] <1.3) at both Weeks 12 and 16 were considered to have an inadequate response and were randomized 1:1 to receive secukinumab 300 or 150 mg every 4 weeks until week 52 (Treatment Period 2). The primary efficacy variable was achievement of ASDAS <1.3 at week 52 using week 16 as baseline. Safety was evaluated by the incidence of treatment-emergent adverse events through week 52., Results: Of 322 patients treated with secukinumab in Treatment Period 1, 207 (64.3%) had inadequate response. Similar proportions of patients with inadequate response randomized to secukinumab 300 mg (n = 101) and 150 mg (n = 105) in Treatment Period 2 completed the study (83.8% and 84.3%, respectively). At week 52, 8.8% and 6.7% of patients receiving secukinumab 300 and 150 mg, respectively, achieved ASDAS <1.3. The incidence of treatment-emergent adverse events was similar in both groups through week 52. No new safety signals were observed., Conclusion: Patients with AS who did not achieve ASDAS <1.3 after receiving secukinumab 150 mg for 16 weeks experienced similar clinical response and safety through week 52 regardless of dose escalation., Trial Registration: ClinicalTrials.gov, NCT03350815., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: This 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)., Methods: Phase 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., Results: Overall, 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., Conclusion: Regardless 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., (Copyright © 2024 by the Journal of Rheumatology.)

Objectives: Acute anterior uveitis ('uveitis') is a common axial spondyloarthritis (axSpA) extramusculoskeletal manifestation. Interleukin (IL)-17 is implicated in its pathogenesis, however, there is conflicting evidence for IL-17A inhibition in uveitis management. We report pooled analyses of uveitis incidence in patients receiving bimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits IL-17F in addition to IL-17A, from phase 2b/3 trials., Methods: Data were pooled for patients receiving BKZ 160 mg or placebo in the double-blind treatment period of the phase 3 BE MOBILE 1 (NCT03928704; non-radiographic axSpA) and BE MOBILE 2 (NCT03928743; radiographic axSpA) trials. Data were separately pooled for patients treated with at least one BKZ dose in the BE MOBILE trials and their ongoing open-label extension (OLE; NCT04436640), and the phase 2b BE AGILE trial (NCT02963506; radiographic axSpA) and its ongoing OLE (NCT03355573). Uveitis rates and exposure-adjusted incidence rates (EAIR)/100 patient-years (PYs) are reported., Results: In the BE MOBILE 1 and 2 double-blind treatment period, 0.6% (2/349) of patients receiving BKZ experienced uveitis vs 4.6% (11/237) receiving placebo (nominal p=0.001; EAIR (95% CI): 1.8/100 PYs (0.2 to 6.7) vs 15.4/100 PYs (95% CI 7.7 to 27.5)). In patients with history of uveitis, EAIR was lower in patients receiving BKZ (6.2/100 PYs (95% CI 0.2 to 34.8); 1.9%) vs placebo (70.4/100 PYs (95% CI 32.2 to 133.7); 20.0%; nominal p=0.004). In the phase 2b/3 pool (N=848; BKZ exposure: 2034.4 PYs), EAIR remained low (1.2/100 PYs (95% CI 0.8 to 1.8))., Conclusions: Bimekizumab, a dual-IL-17A/F inhibitor, may confer protective effects for uveitis in patients with axSpA., Competing Interests: Competing interests: MAB: Grant/research support from UCB Pharma; consultant for Clementia, Grey Wolf Therapeutics, Incyte, Ipsen, Pfizer, Regeneron and Xinthera; speaker for Novartis and Pfizer; payment for expert testimony from Ipsen; participation on a Data Safety Monitoring Board or Advisory Board for Incyte, Ipsen and Regeneron. MR: Speakers bureau from AbbVie, Boehringer Ingelheim, Chugai, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma; consultant of AbbVie, Eli Lilly, Novartis and UCB Pharma. FAvG: Grants from Jacobus Stichting, Novartis, Stichting ASAS, Stichting Vrienden van Sole Mio and UCB Pharma; consultant for AbbVie, ASAS, BMS, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma. NH: Consultant for AbbVie, Eli Lilly, Janssen, Novartis and UCB Pharma. LSG: Consultant for Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma; grant/research support from Novartis and UCB Pharma paid to institution; participation on a Data Safety Monitoring Board or Advisory Board for Acelyrin; member of the Spondylitis Association of America Medical Scientific Advisory Board and ASAS Executive Committee. CF, KW: Employee and shareholder of UCB Pharma. AM, UM, TV, NdP: Employees of UCB Pharma. AD: Speaker for Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma; consultant for BMS, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer and UCB Pharma; grant/research support from BMS, Celgene, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer and UCB Pharma; support for attending meetings and/or travel from Eli Lilly; participation on a Data Safety Monitoring Board or Advisory Board for BMS, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer and UCB Pharma; member of the steering committee of GRAPPA. IvdH-B: Consultant for AbbVie, Eli Lilly, MSD, Novartis and UCB Pharma; unrestricted grants received for investigator-initiated studies from AbbVie, MSD, Pfizer and UCB Pharma; fees received for Lectures from AbbVie, BMS, MSD and Pfizer., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Objective: To assess the impact of bimekizumab on physical functioning, sleep, work productivity and overall health-related quality of life (HRQoL) in patients with non-radiographic (nr-) and radiographic (r-) axial spondyloarthritis (axSpA) in the phase 3 studies BE MOBILE 1 and 2., Methods: Patients were randomised to subcutaneous bimekizumab 160 mg or placebo every 4 weeks; from Week 16, all patients received bimekizumab 160 mg every 4 weeks. We report the following outcomes to Week 52: Bath Ankylosing Spondylitis Functional Index (BASFI), Medical Outcomes Study Sleep Scale Revised (MOS-Sleep-R) Index II, Work Productivity and Activity Impairment: axSpA (WPAI:axSpA), Short Form-36 Physical and Mental Component Summary (SF-36 PCS/MCS) and Ankylosing Spondylitis Quality of Life (ASQoL)., Results: At Week 16, bimekizumab-randomised patients demonstrated significantly greater improvement from baseline versus placebo in BASFI, SF-36 PCS and ASQoL (p<0.001), and numerically greater improvements in MOS-Sleep-R Index II and WPAI:axSpA scores. Higher proportions of bimekizumab-randomised versus placebo-randomised patients at Week 16 achieved increasingly stringent thresholds for improvements in BASFI (0 to ≤4), and thresholds for meaningful improvements in SF-36 PCS (≥5-point increase from baseline) and ASQoL (≥4-point decrease from baseline). Responses were sustained or further improved to Week 52, where 60%-70% of bimekizumab-treated patients achieved BASFI ≤4 and meaningful improvements in SF-36 PCS and ASQoL, regardless of whether originally randomised to bimekizumab or placebo., Conclusion: Bimekizumab treatment led to early improvements in physical function, sleep, work productivity and overall HRQoL at Week 16 in patients across the full axSpA disease spectrum. Improvements were sustained to Week 52., Trial Registration Numbers: NCT03928704; NCT03928743., Competing Interests: Competing interests: MD: Educational grant from Pfizer paid to institution; consulting fees (eg, advisory boards) from Amgen and UCB Pharma; VN-C: Speakers bureau for AbbVie, Eli Lilly, Fresenius Kabi, Janssen, MSD, Novartis, Pfizer and UCB Pharma; consultant for AbbVie, Eli Lilly, Galapagos, MoonLake, MSD, Novartis, Pfizer and UCB Pharma; grant/research support from AbbVie and Novartis; AB: Research grants from AbbVie; speakers honoraria and consultation fees from AbbVie, Galapagos, Pfizer, Novartis and UCB Pharma; KG: Speakers bureau for AbbVie, Eli Lilly, Novartis and UCB Pharma; consultant for AbbVie, Eli Lilly, Novartis and UCB Pharma; grant/research support from AbbVie, Gilead, Eli Lilly, Novartis and UCB Pharma; LSG: Grants from Novartis and UCB Pharma paid to institution; consulting fees from AbbVie, Acelyrin, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer and UCB Pharma; CdlL: Consultant to UCB Pharma; TV, UM and MFM: Employees of UCB Pharma; CF and VT: Employees and shareholders of UCB Pharma; AD: Speakers bureau for Janssen, Novartis, and Pfizer; consultant for AbbVie, BMS, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer and UCB Pharma; grant/research support from AbbVie, BMS, Celgene, Eli Lilly, MoonLake, Novartis, Pfizer and UCB Pharma; MR: Speakers bureau for AbbVie, Boehringer Ingelheim, Chugai, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma; consultant of AbbVie, Eli Lilly, Novartis and UCB Pharma., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Whether tumor necrosis factor inhibitor (TNFi) use is cardioprotective among individuals with radiographic axial spondyloarthritis (r-axSpA), who have heightened cardiovascular (CV) risk, is unclear. We tested the association of TNFi use with incident CV outcomes in r-axSpA., Methods: We identified a r-axSpA cohort within a Veterans Affairs database between 2002 and 2019 using novel phenotyping methods and secondarily using ICD codes. TNFi use was assessed as a time-varying exposure using pharmacy dispense records. The primary outcome was incident CV disease identified using ICD codes for coronary artery disease, myocardial infarction or stroke. We fit Cox models with inverse probability weights to estimate the risk of each outcome with TNFi use versus non-use. Analyses were performed in the overall cohort, and separately in two periods (2002-2010, 2011-2019) to account for secular trends., Results: Using phenotyping we identified 26,928 individuals with an r-axSpA diagnosis (mean age 63.4 years, 94 % male); at baseline 3633 were TNFi users and 23,295 were non-users. During follow-up of a mean 3.3 ± 4.2 years, 674 (18.6 %) TNFi users had incident CVD versus 11,838 (50.8 %) non-users. In adjusted analyses, TNFi use versus non-use was associated with lower risk of incident CVD (HR 0.34, 95 % CI 0.29-0.40) in the cohort overall, and in the two time periods separately., Conclusion: In this r-axSpA cohort identified using phenotyping methods, TNFi use versus non-use had a lower risk of incident CVD. These findings provide reassurance regarding the CV safety of TNFi agents for r-axSpA treatment. Replication of these results in other cohorts is needed., Competing Interests: Declaration of competing interest Jean Liew received grant/research support from Pfizer (over $10,000) for this work. All other authors have nothing to disclose. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To examine the association of multimorbidity phenotypes at baseline with disease activity and functional status over time in ankylosing spondylitis (AS)., Methods: Patient-reported AS morbidities (comorbidities, N = 28 and extra-musculoskeletal manifestations, EMMs, N = 3) within 3 years of enrollment with a prevalence ≥1 %, were included from the Prospective Study of Outcomes in Ankylosing Spondylitis (PSOAS) cohort. We defined multimorbidity as ≥2 morbidities (MM2+) and substantial multimorbidity as ≥5 morbidities (MM5+). Multimorbidity clusters or phenotypes were identified using K-median clustering. Disease activity (ASDAS-CRP) and functional status (BASFI) measures were collected every 6 months. Generalized estimating equation method was used to examine the associations of multimorbidity counts and multimorbidity clusters with measures of disease activity and functional status over time., Results: Among 1,270 AS patients (9,885 visits) with a median follow-up of 2.9 years (IQ range: 1.0-6.8 years), the prevalence of MM2+ and MM5+ was 49 % and 9 % respectively. We identified five multimorbidity clusters: depression (n = 321, 25 %), hypertension (n = 284, 22 %), uveitis (n = 274, 22 %), no morbidities (n = 238, 19 %), and miscellaneous (n = 153, 12 %). Patients in the depression cluster were more likely to be female and had significantly more morbidities and worse disease activity and functional status compared to those with no morbidities., Conclusion: Approximately 49 % of AS patients in the PSOAS cohort had multimorbidity and five distinct multimorbidity phenotypes were identified. In addition to the number of morbidities, the type of morbidity appears to be important to longitudinal outcomes in AS. The depression cluster was associated with worse disease activity and function., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Davis has received consulting fees and/or honoraria from Sanofi-Genzyme (less than $10,000 each), Girihlet (Rights to royalties for licensed technology; none received to date), and research support from Pfizer. Dr. Ogdie has received grant/research support from Amgen (to Forward), Novartis (to Penn) and Pfizer (to Penn) Inc, has been a consultant for AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Eli Lilly, Gilead, Janssen, Novartis, Pfizer Inc and UCB. Dr. Reveille has received consulting fees from Eli Lilly and Company (less than $5000). Dr. Weisman has received consulting fees from Eli Lilly and Company, UCB, and Novartis (less than $10,000 each). Dr. Gensler has received consulting fees from AbbVie, Acelyrin, Eli Lilly and Company, Fresenius Kabi, Janssen, Novartis, Pfizer, and UCB (less than $10,000 each) and has received grant support from UCB, Novartis, and Pfizer. Rest of the authors have no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Objectives: Bimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, has demonstrated superior efficacy versus placebo in patients with non-radiographic (nr-) and radiographic (r-) axial spondyloarthritis (axSpA) at Week 16. Here, the objective is to report the efficacy and safety of BKZ at Week 52., Methods: BE MOBILE 1 (nr-axSpA; NCT03928704) and BE MOBILE 2 (r-axSpA; NCT03928743) comprised a 16-week, double-blind, placebo-controlled period, then a 36-week maintenance period. From Week 16, all patients received subcutaneous BKZ 160 mg every 4 weeks., Results: Improvements versus placebo in Assessment of SpondyloArthritis International Society ≥40% response (primary endpoint), Ankylosing Spondylitis Disease Activity Score, high-sensitivity C-reactive protein levels and MRI inflammation of the sacroiliac joints/spine at Week 16 were sustained to Week 52 in BKZ-randomised patients. At Week 52, responses of patients switching from placebo to BKZ at Week 16 were comparable to BKZ-randomised patients. At Week 52, ≥1 treatment-emergent adverse events (TEAEs) were reported in 183 (75.0%) and 249 (75.5%) patients with nr-axSpA and r-axSpA, respectively. Serious TEAEs occurred in 9 (3.7%) patients with nr-axSpA and 20 (6.1%) patients with r-axSpA. Oral candidiasis was the most frequent fungal infection (nr-axSpA: 18 (7.4%); r-axSpA: 20 (6.1%)). Uveitis occurred in three (1.2%) and seven (2.1%) patients with nr-axSpA and r-axSpA, and inflammatory bowel disease in two (0.8%) and three (0.9%)., Conclusions: At Week 52, dual inhibition of IL-17A and IL-17F with BKZ resulted in sustained efficacy across the axSpA spectrum; the safety profile was consistent with the known safety of BKZ., Trial Registration Number: NCT03928704; NCT03928743., Competing Interests: Competing interests: XB: Speakers bureau for AbbVie, BMS, Chugai, Eli Lilly, Galapagos, MSD, Novartis, Pfizer and UCB Pharma; paid instructor for AbbVie, BMS, Chugai, Eli Lilly, Galapagos, MSD, Novartis, Pfizer and UCB Pharma; consultant of AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer and UCB Pharma; grant/research support from Novartis and UCB Pharma. AAD: Speakers bureau for Janssen, Novartis and Pfizer; consultant for AbbVie, Amgen, Aurinia, BMS, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer and UCB Pharma; grant/research support from AbbVie, BMS, Celgene, Eli Lilly, MoonLake, Novartis, Pfizer and UCB Pharma. DvdH: Consulting fees from AbbVie, Bayer, BMS, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer, Takeda and UCB Pharma; director of Imaging Rheumatology BV. MM: Consultancy fees from AbbVie, BMS, Eli Lilly, Novartis, Pfizer and UCB Pharma; research grants from AbbVie, BMS and UCB Pharma. WPM: Honoraria/consulting fees from AbbVie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma; research grants from AbbVie, Pfizer and UCB Pharma; educational grants from AbbVie, Janssen, Novartis, and Pfizer; Chief Medical Officer for CARE ARTHRITIS. TT: Consultancy fees from AbbVie, Eli Lilly, Gilead, Novartis and Pfizer; speaker fees from AbbVie, Astellas, Bristol-Myers Squibb, Eisai, Eli Lilly, Janssen, Kyowa Kirin, Mitsubishi-Tanabe, Novartis and Pfizer. HX: Speaker for AbbVie, Janssen, Novartis, Pfizer, and UCB Pharma; consultant for AbbVie, Beigene, BioMap, IASO, Pfizer and UCB Pharma; clinical investigator for Peking-Tsinghua Center for Life Sciences. UM, CF, AME, TV, JS-S, AM: Employees of UCB Pharma. LSG: Grants from Novartis and UCB Pharma paid to institution; consulting fees from AbbVie, Acelyrin, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer and UCB Pharma., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate the efficacy and safety of tofacitinib in patients with ankylosing spondylitis (AS) by prior biologic disease-modifying antirheumatic drug (bDMARD) use., Methods: Data from a placebo-controlled, double-blind study of patients with active AS were analyzed. Patients received tofacitinib 5 mg twice daily (BID) or placebo to week 16; all received open-label tofacitinib 5 mg BID to week 48 and were stratified by prior treatment (bDMARD-naive or tumor necrosis factor inhibitor [TNFi]-inadequate responder [IR], including bDMARD-experienced [non-IR]). Disease activity/safety were assessed throughout., Results: Of 269 patients, 207 (77%) were bDMARD-naive; 62 (23%) were in the TNFi-IR subgroup. TNFi-IR patients had higher baseline BMI (28.0 vs. 26.1 kg/m 2 ), longer symptom duration (14.4 vs. 13.2 years), and lower concomitant conventional synthetic DMARD use (14.5% vs. 30.9%) than bDMARD-naive patients. At week 16, for most outcomes, tofacitinib efficacy exceeded placebo for both subgroups and was sustained to week 48. At week 16, tofacitinib versus placebo differences were similar between bDMARD-naive and TNFi-IR patients (Assessment in Spondyloarthritis international Society 40 treatment difference [95% confidence interval]: 30.8% [19.1%-42.6%] vs. 19.4% [1.7%-37.0%]). Adverse event (AE) proportions were similar between tofacitinib-treated bDMARD-naive/TNFi-IR patients (77.5%/77.4%) at week 48 with no deaths. A numerically higher proportion of tofacitinib-treated TNFi-IR versus bDMARD-naive patients discontinued study drug (12.9% vs. 3.9%) or dose reduced/temporarily discontinued due to AEs (19.4% vs. 11.8%)., Conclusion: Tofacitinib efficacy exceeded placebo at week 16 for bDMARD-naive/TNFi-IR patients and was sustained to week 48. The absolute magnitude of responses was generally greater in bDMARD-naive patients versus TNFi-IR patients. More TNFi-IR versus bDMARD-naive patients discontinued or dose reduced/temporarily discontinued tofacitinib due to AEs. Small sample size and sample size differences between subgroups limited the interpretation., (© 2023 Pfizer Inc and The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Competing Interests: Conflicts of interest Tina Bhutani is a principal investigator for trials sponsored by Abbvie, Castle, CorEvitas, Dermavant, Galderma, Mindera, and Pfizer. She has received research grant funding from Novartis and Regeneron. She has been an advisor for Abbvie, Arcutis, Boehringer-Ingelheim, Bristol Myers Squibb, Janssen, Leo, Lilly, Novartis, Pfizer, Sun, and UCB. Wilson Liao has received research grant funding from Abbvie, Amgen, Janssen, Leo, Novartis, Pfizer, Regeneron, and TRex Bio. Lianne S. Gensler has received grant funding from Novartis, Pfizer and UCB and has been an advisor for AbbVie, Eli Lilly, Fresenius Kabi, Gilead, Janssen, MoonLake, Novartis, Pfizer and UCB. The remaining authors have nothing to disclose.

Objective: To determine if the efficacy of biologics differ based on magnetic resonance imaging (MRI) and C-reactive protein (CRP) findings., Methods: We compared four subgroups (MRI+/CRP+, MRI+/CRP-, MRI-/CRP+, MRI-/CRP-) from randomized controlled trials (RCTs). A comprehensive database search was performed to include axial spondylarthritis (axSpA; both radiographic axSpA [r-axSpA] and nonradiographic axSpA [nr-axSpA]) RCTs with treatment efficacy reported by different MRI and CRP subgroups. Study-specific disease activity scores (at 12-16 weeks) were pooled using a random-effects model and compared between the four subgroups., Results: Five trials (all nr-axSpA) were included: three with tumor necrosis factor inhibitors (TNFi, N = 729) and two with interleukin-17 inhibitors (IL-17i, N = 794). TNFi and IL-17i showed efficacy based on the Assessment of Spondyloarthritis International Society 40 (ASAS40) and Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50) in all MRI and CRP subgroups, except the CRP-/MRI- subgroup, which had a single study with only 39 patients. There was no statistically significant difference between the four subgroups in terms of patients achieving ASAS40 (P = 0.60, I 2 = 0%) or BASDAI50 (P = 0.27, I 2 = 23.9%). The number needed to treat was three for the CRP+/MRI+ and CRP+/MRI- subgroups and six for the CRP-/MRI+ and CRP-/MRI- subgroups. All trials had a low risk of bias. Between-study heterogeneity was low to moderate. Sensitivity analyses comparing TNFi or IL-17i versus placebo similarly showed no difference between subgroups in terms of ASAS40 (TNFi, P = 0.57; IL-17i, P = 0.28) and BASDAI50 (TNFi, P = 0.37; IL-17i, P = 0.18)., Conclusion: In this systematic review, there was no statistically significant difference between the four subgroups in terms of efficacy based on ASAS40 or BASDAI50., (© 2023 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Competing Interests: Dr Haemel reports serving as a consultant to CSL Behring and Guidepoint. Authors Gutierrez, Jacobson, Ghatnekar, Virji, Schwartz, Gensler, and Frangos have no conflicts of interest to declare.

Objective: 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., Methods: 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., Results: 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., Conclusion: 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., (© 2022 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

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., (© 2023. The Author(s).)

Objectives: Spondyloarthritis (SpA) results from the interplay between genetic and environmental factors. An emerging modifiable factor is the human intestinal microbiota, which multiple studies in children and adults have shown to be abnormal in SpA patients, including enthesitis related arthritis and ankylosing spondylitis (AS). However, HLA-B27 itself appears to impact the contents of the microbiota and is more common in SpA patients versus controls, thus serving as a confounding factor in most comparative studies., Methods: This was a cross-sectional study that evaluated the contents of the faecal microbiota among 29 patients with HLA-B27+ AS and 43 healthy adults who underwent 16S sequencing and genotyping as part of the TwinsUK Programme., Results: HLA-B27 positive+ patients and healthy controls demonstrated substantial clustering based upon diagnosis. Decreased richness was observed among the AS patients, although measures of evenness were similar. After correction for multiple comparisons, several taxa - including Faecalibacterium prausnitzii and Coprococcus - were elevated in AS patients compared to controls, even when restricted to female subjects, while Bacteroides fragilis, Ruminococcus, and Akkermansia muciniphila were depleted in AS patients., Conclusions: Consistent with some previous studies, our study demonstrates in patients with AS associations with Coprococcus, Bacteroides, and Ruminococcus. Other findings, including increased Faecalibacterium, are inconsistent with previous studies and thus potentially underscore the necessity of evaluating HLA-B27 positive controls in studies evaluating the impact of the intestinal microbiota on SpA.

Objective: 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., Methods: We used data from a prospective AS cohort with a median follow-up of 7 years. To determine the association of BMI (kg/m 2 ) 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., Results: 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/m 2 higher 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%)., Conclusion: 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., (© 2021 American College of Rheumatology.)

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.

Objective: 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., Methods: 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., Results: 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., Conclusion: 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., (© 2020, American College of Rheumatology.)

Objective: Response 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., Methods: We 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., Results: After 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., Conclusion: Individuals 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., (© 2020 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objectives: To compare the magnetic resonance imaging (MRI) morphology of inflammatory and chronic lesions in the sacroiliac joints (SIJs) and spine between patients with non-psoriatic and psoriatic non-radiographic axial spondyloarthritis (axSpA and p-axSpA, respectively)., Methods: Patients from the EMBARK trial (NCT01258738) with axSpA (n=179) and p-axSpA (n=24) who had MRI data available were compared in terms of baseline demographics, clinical characteristics, and the frequency (n/N [%]) and distribution of inflammatory and structural SIJ and spinal lesions., Results: Patients with p-axSpA were on average older (35.1 years vs. 31.7 years, p=0.047), had a higher occurrence of asymmetric sacroiliitis (54.2% vs. 29.6%, p=0.042), and a lower occurrence of human leukocyte antigen (HLA)-B27 positivity (41.7% vs. 73.7%, p=0.010) than patients with axSpA. There were no significant differences in the frequency of lesions in any of the SIJ or spinal quadrants between the two subgroups., Conclusions: These data suggest that differences between axSpA and p-axSpA extend beyond presence of psoriasis, and include age, SI symmetry, and HLAB27 status. These findings may help explain the morphotype-phenotype relationship across axSpA, similar to those described in older radiographic studies.

Objectives: To investigate the efficacy and safety of ixekizumab for up to 52 weeks in two phase 3 studies of patients with active radiographic axial spondyloarthritis (r-axSpA) who were biological disease-modifying antirheumatic drug (bDMARD)-naive (COAST-V) or tumour necrosis factor inhibitor (TNFi)-experienced (COAST-W)., Methods: Adults with active r-axSpA were randomised 1:1:1:1 (n=341) to 80 mg ixekizumab every 2 (IXE Q2W) or 4 weeks (IXE Q4W), placebo (PBO) or 40 mg adalimumab Q2W (ADA) in COAST-V and 1:1:1 (n=316) to IXE Q2W, IXE Q4W or PBO in COAST-W. At week 16, patients receiving ixekizumab continued their assigned treatment; patients receiving PBO or ADA were rerandomised 1:1 to IXE Q2W or IXE Q4W (PBO/IXE, ADA/IXE) through week 52., Results: In COAST-V, Assessment of SpondyloArthritis international Society 40 (ASAS40) responses rates (intent-to-treat population, non-responder imputation) at weeks 16 and 52 were 48% and 53% (IXE Q4W); 52% and 51% (IXE Q2W); 36% and 51% (ADA/IXE); 19% and 47% (PBO/IXE). Corresponding ASAS40 response rates in COAST-W were 25% and 34% (IXE Q4W); 31% and 31% (IXE Q2W); 14% and 39% (PBO/IXE). Both ixekizumab regimens sustained improvements in disease activity, physical function, objective markers of inflammation, QoL, health status and overall function up to 52 weeks. Safety through 52 weeks of ixekizumab was consistent with safety through 16 weeks., Conclusion: The significant efficacy demonstrated with ixekizumab at week 16 was sustained for up to 52 weeks in bDMARD-naive and TNFi-experienced patients. bDMARD-naive patients initially treated with ADA demonstrated further numerical improvements after switching to ixekizumab. Safety findings were consistent with the known safety profile of ixekizumab., Trial Registration Number: NCT02696785/NCT02696798., Competing Interests: Competing interests: MD has served as a consultant and received research grants from AbbVie, Eli Lilly and Company, Pfizer and UCB Pharma. JC-CW has served as a consultant and/or speaker and/or has received research grants from Abbott, Bristol-Myers Squibb, Celgene, Chugai, Eisai, Eli Lilly and Company, Janssen, Novartis, Pfizer, Sanofi-Aventis, TSH Taiwan and UCB Pharma. RL has served as a consultant and/or advisor and/or has received research grants from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Galapagos, Merck, Novartis, Pfizer and UCB Pharma. RL is the director of Rheumatology Consultancy BV, a company that was indirectly contracted by Eli Lilly and Company to perform read services for the COAST program. JS has served as a consultant and/or speaker for AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche and UCB Pharma. XB has served as a consultant and/or has received research grants from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, MSD, Novartis, Pfizer, Roche and UCB Pharma. FVdB has served as a consultant and/or speaker and/or has received research grants from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Sanofi and UCB Pharma. WPM has served as a consultant and/or received honoraria and/or research/educational grants from AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly and Company, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma, and is Chief Medical Officer of CARE Arthritis Limited. JE has served as a consultant and/or received research grants from AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Novartis, Pfizer, Takeda and UCB Pharma. JAW has been a consultant and/or received research grants from AbbVie, Amgen, Celgene, Eli Lilly and Company, Novartis, Pfizer and UCB Pharma. AD has been a consultant and/or received research support from AbbVie, Bristol-Myers Squibb, Eli Lilly and Company, Glaxo Smith & Klein, Janssen, Novartis, Pfizer and UCB Pharma. DvdH has been a consultant for AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi, Eli Lilly and Company, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda and UCB Pharma and is a Director of Imaging Rheumatology BV. TT has been a consultant and speaker for AbbVie, Astellas, Bristol-Myers Squibb, Eisai, Eli Lilly and Company, Janssen, Mitsubishi Tanabe, Novartis, Pfizer and Takeda. XL, FZ, CCB, GG and HC are current employees and shareholders of Eli Lilly and Company. LSG has been a consultant and/or received research grants/support from AbbVie, Amgen, Eli Lilly and Company, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.Funding: Novartis Pharmaceuticals Corporation.Plain Language Summary: Plain language summary available for this article.

Background: Patients with spondyloarthritis with radiographic sacroiliitis are traditionally classified according to the modified New York (mNY) criteria as ankylosing spondylitis (AS) and more recently according to the Assessment of SpondyloArthritis international Society (ASAS) criteria as radiographic axial spondyloarthritis (r-axSpA)., Objective: To investigate the agreement between the mNY criteria for AS and the ASAS criteria for r-axSpA and reasons for disagreement., Methods: Patients with back pain ≥3 months diagnosed as axSpA with radiographic sacroiliitis (mNY radiographic criterion) were selected from eight cohorts (ASAS, Esperanza, GESPIC, OASIS, Reuma.pt, SCQM, SPACE, UCSF). Subsequently, we calculated the percentage of patients who fulfilled the ASAS r-axSpA criteria within the group of patients who fulfilled the mNY criteria and vice versa in six cohorts with complete information., Results: Of the 3882 patients fulfilling the mNY criteria, 93% also fulfilled the ASAS r-axSpA criteria. Inversely, of the 3434 patients fulfilling the ASAS r-axSpA criteria, 96% also fulfilled the mNY criteria. The main cause for discrepancy between the two criteria sets was the reported age at onset of back pain., Conclusion: Almost all patients with axSpA with radiographic sacroiliitis fulfil both ASAS and mNY criteria, which supports the interchangeable use of the terms AS and r-axSpA., Competing Interests: Competing interests: AM reports grants and speaker/consultancy fees from AbbVie, Pfizer, BMS, UCB and Merck, outside the submitted work; DvdH reports speaker/consultancy fees from AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda and UCB outside the submitted work and is the Director of Imaging Rheumatology bv.; EDM reports grants and speaker/consultancy fees from AbbVie, BMS, MSD, Novartis, Pfizer, Roche and UCB outside the submitted work; DP reports grants and speaker/consultancy fees from AbbVie, MSD, Novartis and Pfizer and speaker/consultancy fees from BMS, Lilly, Roche, UCB and Celgene outside the submitted work; MR reports speaker/consultancy fees from AbbVie, BMS, Celgene, Chugai, Eli-Lily, Janssen, MSD, Novartis, Pfizer and UCB outside the submitted work; AvT reports grants from Pfizer, AbbVie, UCB and Biogen and grants and speaker/consultancy fees from Novartis outside the submitted work; FAvG reports grants from MSD, Novartis, AbbVie, the Dutch Arthritis Society, Stichting Vrienden van Sole Mio, UCB and Pfizer outside the submitted work; SR reports speaker/consultancy fees from AbbVie, Eli-Lilly, Novartis and Sanofi and grants and speaker/consultancy fees from MSD outside the submitted work. AB, AC, MD, LG and MJS have nothing to disclose. GESPIC has been financially supported by the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung—BMBF), as part of the German competence network in rheumatology (Kompetenznetz Rheuma). As funding by BMBF was reduced according to schedule in 2005 and stopped in 2007, complementary financial support has been obtained also from Abbott/Abbvie, Amgen, Centocor, Schering-Plough and Wyeth. Since 2010 GESPIC is supported by Abbvie, additional support has been obtained also from ArthroMark (grants number FKZ 01EC1401A) and METARTHROS (grant number FKZ 01EC1407A) projects funded by BMBF., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Evaluate the MR distribution of inflammatory sacroiliac joint changes in axial spondyloarthritis phenotypes, including Ankylosing Spondylitis (AS) and non-radiographic Axial Spondyloarthritis (nrAxSpA)., Methods: A retrospective review of 94 patients seen for treatment of axial spondyloarthritis (SpA) who underwent sacroiliac joint MRI between January 2011 and December 2015 was performed. MR images from 68 patients (20 with AS and 48 with nrAxSpA) were reviewed independently by two radiologists. Images were scored on presence of active inflammatory and chronic structural lesions. These lesions were further categorized as unilateral, bilateral and asymmetric, or bilateral and symmetric., Results: No statistically significant difference was found in the distribution (laterality or symmetry) of bone marrow edema or sclerosis between the AS and nr-axSpA groups. Osseous erosions were more commonly bilateral symmetric in AS than nr-axSpA (11/20 vs. 8/48, p = 0.01). No statistically significant difference was noted between bone marrow edema scores in the AS and nr-axSpA subgroups (2.6 vs 3.3, p = 0.514). Patients with AS had a significantly higher fat metaplasia score compared to patients with nr-axSpA (7.3 vs 1.1, p = 0.001). Patients with nr-axSpA had a higher mean score for erosions (11.6 vs 4.2, p = 0.001). Only patients classified as AS were found to have bony ankylosis. Inter-observer reliability was strong to excellent., Conclusion: Ankylosing spondylitis findings at the sacroiliac joints are classically described as bilateral and symmetric on radiographs. Our study demonstrates that distribution on MRI at an individual time point is variable. The variable distribution should be considered when radiologists evaluate MRI exams of AS patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Theoretical risks of biologic agents remain under study., Objective: The aim of this study was to integrate 1-year safety data from 12 ustekinumab registrational trials., Methods: Patients had moderate-to-severe plaque psoriasis, active psoriatic arthritis (PsA) (± methotrexate), or moderate-to-severe Crohn's disease (CD; failed/intolerant of immunomodulators/corticosteroids). Psoriatic patients received subcutaneous ustekinumab 45/90 mg or placebo, generally at week 0, week 4, then every 12 weeks thereafter, while those with CD received a single intravenous ustekinumab dose (130 mg or weight range-based dosing of approximately 6 mg/kg) or placebo induction dose at week 0, followed by subcutaneous ustekinumab 90 mg at week 8 and every 8/12 weeks thereafter. The incidence rates of a priori-defined safety events were integrated post hoc (adjusted for duration of follow-up, reported per 100 patient-years [PYs])., Results: Among 6280 enrolled patients, 5884 ustekinumab-treated patients (psoriasis: 3117; PsA: 1018; CD: 1749) contributed 4521 PYs versus 674 PYs in placebo-treated patients through year 1 (829 PYs and 385 PYs during 8- to 16-week controlled periods). Combined across diseases among ustekinumab- versus placebo-treated patients, respective incidences/100 PYs (95% confidence intervals) of infections were 125.4 (122.2-128.7) versus 129.4 (120.9-138.3) through year 1, and not meaningfully increased in patients who did versus those who did not receive methotrexate (92.5 [84.2-101.5] vs. 115.3 [109.9-121.0]), or significantly increased in patients who did versus those who did not receive corticosteroids (116.3 [107.3-125.9] vs. 107.3 [102.0-112.8]) at baseline. Major adverse cardiovascular events (0.5 [0.3-0.7] vs. 0.3 [0.0-1.1]), malignancies (0.4 [0.2-0.6] vs. 0.2 [0.0-0.8]), and deaths (0.1 [0.0-0.3] vs. 0.0 [0.0-0.4]) were rare across indications., Conclusions: Ustekinumab demonstrated a favorable and consistent safety profile across registrational trials in approved indications., Trial Registrations: ClinicalTrials.gov identifier: NCT00320216, NCT00267969, NCT00307437, NCT00454584, NCT00267956, NCT01009086, NCT01077362, NCT00265122, NCT00771667, NCT01369329, NCT01369342, and NCT01369355.

Objective: To evaluate the efficacy and safety of ustekinumab in 3 randomized, placebo-controlled studies in patients with axial spondyloarthritis (SpA). Studies 1 and 2 included patients with radiographic axial SpA (anti-tumor necrosis factor [anti-TNF]-naive patients and patients with inadequate response or intolerance to anti-TNF, respectively); study 3 patients had nonradiographic axial SpA., Methods: In all 3 studies, patients were randomly assigned (1:1:1) to receive subcutaneous ustekinumab at 45 mg or 90 mg or placebo up to 24 weeks, after which placebo-treated patients were rerandomized to receive ustekinumab at 45 mg or 90 mg. The primary end point in studies 1 and 2 was the proportion of patients who met the Assessment of SpondyloArthritis international Society criteria for 40% improvement in disease activity (achieved an ASAS40 response). The primary end point in study 3 was the proportion of patients who achieved an ASAS20 response. Other disease activity and safety measures were also evaluated. A week 24 analysis of study 1 was preplanned to determine continuation of studies 2 and 3., Results: For study 1, the primary and major secondary end points were not met, and the study was discontinued. As a result, studies 2 and 3 were prematurely discontinued before they were fully enrolled. For all 3 studies, neither ustekinumab dose group demonstrated clinically meaningful improvement over placebo on key efficacy end points. The proportion of patients experiencing adverse events in the ustekinumab groups was consistent with that in previous studies., Conclusion: In these 3 placebo-controlled trials, efficacy of ustekinumab in the treatment of axial SpA was not demonstrated. The safety profile was consistent with that of studies in other indications., (© 2018, American College of Rheumatology.)

Objective: To examine associations of HLA class I and class II alleles with ankylosing spondylitis (AS) in three cohorts of patients of European, Asian and African ancestry., Methods: HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 and HLA-DPB1 alleles were genotyped in 1948 unrelated white and 67 African-American patients with AS from the Prospective Study of Outcomes in Ankylosing Spondylitis cohort, the North American Spondylitis Consortium and Australo-Anglo-American Spondyloarthritis Consortium, 990 white and 245 African-American Controls and HLA-B alleles in 442 Han Chinese patients with AS and 346 controls from Shanghai and Gansu, China. In addition to the case:control analyses, HLA-B*27 -negative patients with AS were analysed separately, and logistic regression and 'relative predispositional effects' (RPE) analyses were carried out to control for the major effect of HLA-B*27 on disease susceptibility., Results: Although numerous associations were seen between HLA alleles and AS in whites, among HLA-B*27-negative patients with AS , positive associations were seen with HLA-A*29, B*38, B*49, B*52, DRB1*11 and DPB1*03:01 and negative associations with HLA-B*07, HLA-B*57, HLA-DRB1*15:01, HLA-DQB1*02:01 and HLA -DQB1*06:02 . Additional associations with HLA-B*14 and B*40 (B60) were observed via RPE analysis, which excludes the HLA-B*27 alleles. The increased frequency of HLA-B*40:01 and decreased frequency of HLA-B*07 was also seen in Han Chinese and African-Americans with AS. HLA-B*08 was decreased in whites with acute anterior uveitis., Conclusions: These data, analysing the largest number of patients with AS examined to date in three ethnic groups, confirm that other HLA class I and II alleles other than HLA-B*27 to be operative in AS predisposition., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Therapeutic targets have been defined for axial and peripheral spondyloarthritis (SpA) in 2012, but the evidence for these recommendations was only of indirect nature. These recommendations were re-evaluated in light of new insights. Based on the results of a systematic literature review and expert opinion, a task force of rheumatologists, dermatologists, patients and a health professional developed an update of the 2012 recommendations. These underwent intensive discussions, on site voting and subsequent anonymous electronic voting on levels of agreement with each item. A set of 5 overarching principles and 11 recommendations were developed and voted on. Some items were present in the previous recommendations, while others were significantly changed or newly formulated. The 2017 task force arrived at a single set of recommendations for axial and peripheral SpA, including psoriatic arthritis (PsA). The most exhaustive discussions related to whether PsA should be assessed using unidimensional composite scores for its different domains or multidimensional scores that comprise multiple domains. This question was not resolved and constitutes an important research agenda. There was broad agreement, now better supported by data than in 2012, that remission/inactive disease and, alternatively, low/minimal disease activity are the principal targets for the treatment of PsA. As instruments to assess the patients on the path to the target, the Ankylosing Spondylitis Disease Activity Score (ASDAS) for axial SpA and the Disease Activity index for PSoriatic Arthritis (DAPSA) and Minimal Disease Activity (MDA) for PsA were recommended, although not supported by all. Shared decision-making between the clinician and the patient was seen as pivotal to the process. The task force defined the treatment target for SpA as remission or low disease activity and developed a large research agenda to further advance the field., Competing Interests: Competing interests: DA served as a consultant and/or speaker for Abbvie, Astra-Zeneca, BMS, Janssen, Medac, MSD, Pfizer, Roche, UCB and received grant support from BMS. XB has served as consultant and/or speaker for Abbvie, BMS, Celgene, Chugai, Janssen, Novartis, Pfizer, UCB. NB has received consultancy fees for work commissioned by Grünenthal, Lilly, Janssen, PfizerLaura Coates has received research funding from Abbvie and Janssen and honoraria from Abbvie, Amgen, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Sun Pharma, UCBMaxime Dougados has participated as a speaker in symposia or as an advisor in boards organized by Pfizer, Abbvie, Ucb, Merck, Amgen, Novartis, Lilly, Bms, Roche and his department has received research grants from Pfizer, Abbvie, Ucb, Merck, Amgen, Novartis, Lilly, Bms, Roche. Laure Gossec has received honoraria or research funding from Abbvie, BMS, Celgene, Janseen, MSD, Novartis, Pfizer, Roche and UCB. PE has undertaken clinical trials and provided expert advice to Pfizer, MSD, Abbvie, BMS, UCB, Roche, Novartis, Samsung, Sandoz and Lilly. OF reports grants and personal fees from Novartis, personal fees from Pfizer, personal fees from Lilly, personal fees from Cellgene, grants and personal fees from Abbvie, personal fees from Janssen, personal fees from UCB, outside the submitted work. AK has served as consultant and/or performed clinical research for Abbvie, Amgen, Celgene, Janssen, Novartis, UCB. PMM has received consultancy/speaker’s fees from AbbVie, Centocor, Janssen, Merck, Novartis, Pfizer and UCB. AM has received honoraria from Abbvie, MSD and UCBDP has received Grant/research support from: AbbVie, MSD, Novartis, Pfizer, has honoraria/speaker fees from AbbVie, BMS, Boehringer, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, and UCB. MR has received honoraria/ consultancies from Abbvie, BMS, Celgene, Chugai/Roche, Janssen, MSD, Novartis, Pfizer, UCB. JS has received grant support from and/or provided expert advice to Abbvie, Amgen, Astra-Zeneca, BMS, Boehringer-Ingelheim, Celgene, Celltrion, Gilead, Glaxo, Iltoo, Janssen, Lilly, Pfizer, MSD, Roche, Samsung, Novartis-Sandoz, UCB. TS has received honoraria from Abbvie, Janssen, MSD, Novartis and Roche and grant support from Abbvie. FVB has received speaker and/or consultancy fees from AbbVie, Celgene, Janssen,Lilly, MSD, Novartis, Pfizer and UCB. DH has received consulting fees Afrom bbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB, and is Director of Imaging Rheumatology bv. MW has received consulting fees for lectures or advisory board meetings from Abbvie, BMS, Celgene, Eli Lilly, Novartis and Roche., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The purpose of this study is to compare disease severity in ankylosing spondylitis (AS) in three ethnic groups. We assessed 925 AS patients (57 Blacks, 805 Whites, 63 Latinos) enrolled in the longitudinal Prospective Study of Outcomes in AS (PSOAS) for functional impairment, disease activity, and radiographic severity. Comparisons of clinical characteristics and HLA-B27 frequency for each group were performed, in two multivariable regression models, we compared the baseline Bath Ankylosing Spondylitis Radiographic Index (BASRI) and modified Stokes Ankylosing Spondylitis Spine Score (mSASSS) by ethnicity, adjusting for covariates. Blacks had greater functional impairment (Bath Ankylosing Spondylitis Functional Index) (median 62.5 vs. 27.8 in Whites and 38.1 in Latinos; p < 0.0001); higher disease activity (Bath Ankylosing Spondylitis Disease Activity Index), (median 5.9 vs. 3.5 in Whites and 4.5 in Latinos; p < 0.0001), erythrocyte sedimentation rate (median 27.0 in Blacks vs. 10.0 in Whites and 17.0; p < 0.0001), and C-reactive protein levels (median 1.2 vs. 0.4 mg/dL in Whites and 0.9 in Latinos; p < 0.0001). Baseline BASRI and mSASSS were higher in Blacks (mean 9.5 and median 38.2, respectively) compared to Whites (7.3 and 6.4) and Latinos (7.3 and 8.1), (p = 0.004, 0.007), respectively, more significant as disease duration increased. HLA-B27 occurred in 62.5% of Blacks, 85.3% of Whites, and 86.7% of Latinos (p < 0.0001). On multivariable analysis, higher BASRI and mSASSS were associated with Black ethnicity, after adjusting for disease duration and gender as well as TNF inhibitor (TNFi) usage, smoking status, or education level. Blacks with AS have more severe disease compared to either Whites or Latinos.

Objective: The human major histocompatibility complex class I chain-related gene A (MICA) controls the immune process by balancing activities of  natural killer cells, γδ T cells and αβ CD8 T cells, and immunosuppressive CD4 T cells. MICA is located near HLA-B on chromosome 6. Recent genomewide association studies indicate that genes most strongly linked to ankylosing spondylitis (AS) susceptibility come from the region containing HLA-B and MICA. While HLA-B27 is a well-known risk genetic marker for AS, the potential effect of linkage disequilibrium (LD) shields any associations of genes around HLA-B with AS. The aim of this study was to investigate a novel independent genetic association of MICA to AS., Methods: We examined 1543 AS patients and 1539 controls from two ethnic populations by sequencing MICA and genotyping HLA-B alleles. Initially, 1070 AS patients and 1003 controls of European ancestry were used as a discovery cohort, followed by a confirmation cohort of 473 Han Chinese AS patients and 536 controls. We performed a stratified analysis based on HLA-B27 carrier status. We also conducted logistic regression with a formal interaction term., Results: Sequencing of MICA identified that MICA*007:01 is a significant risk allele for AS in both Caucasian and Han Chinese populations, and that MICA*019 is a major risk allele in Chinese AS patients. Conditional analysis of MICA alleles on HLA-B27 that unshielded LD effect confirmed associations of the MICA alleles with AS., Conclusions: Parallel with HLA-B27, MICA confers strong susceptibility to AS in US white and Han Chinese populations., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Glucocorticoids (GCs) are widely used for inflammatory and autoimmune diseases. Their mechanism of action is most commonly rooted in genomic effects that have both beneficial and adverse consequences. The purpose of this review is to discuss the potential complications and side effects that may occur with GC use. Many of these complications are related to the dose and duration of therapy used. Evidence-based preventative strategies are discussed. Many recommendations are based on expert opinion and not on strong evidence. A 54-year-old man presents with proximal upper and lower extremity weakness. There are no rashes. The antinuclear antibody is negative; the erythrocyte sedimentation rate and C reactive protein are 24 mm/h and 3 mg/dL, respectively. An electromyography displays myopathic motor unit potentials with fibrillation and a muscle biopsy confirms polymyositis. Prednisone of 60 mg/d is initiated. What are the risks associated with GC use? What other studies and interventions should occur in this patient starting long-term GC therapy?