Trial of Upadacitinib and Adalimumab for Psoriatic Arthritis.

BACKGROUND: The Janus kinase inhibitor upadacitinib is a potential treatment for psoriatic arthritis. The efficacy and safety of upadacitinib as compared with adalimumab, a tumor necrosis factor α inhibitor, in patients who have an inadequate response to nonbiologic disease-modifying antirheumatic drugs are unclear. METHODS: In a 24-week, phase 3 trial, we randomly assigned patients in a 1:1:1:1 ratio to receive oral upadacitinib at a dose of 15 mg or 30 mg once daily, placebo, or subcutaneous adalimumab (40 mg every other week). The primary end point was an American College of Rheumatology 20 (ACR20) response (≥20% decrease in the number of tender and swollen joints and ≥20% improvement in at least three of five other domains) at week 12 with upadacitinib as compared with placebo. Secondary end points included comparisons of upadacitinib with adalimumab. RESULTS: A total of 1704 patients received an active drug or placebo. The percentage of patients who had an ACR20 response at week 12 was 70.6% with 15-mg upadacitinib, 78.5% with 30-mg upadacitinib, 36.2% with placebo (P<0.001 for both upadacitinib doses vs. placebo), and 65.0% with adalimumab. The difference between groups for 15-mg upadacitinib as compared with adalimumab was 5.6 percentage points (95% confidence interval [CI], -0.6 to 11.8) and for 30-mg upadacitinib as compared with adalimumab was 13.5 percentage points (95% CI, 7.5 to 19.4). Both upadacitinib doses were noninferior to adalimumab for the ACR20 response at week 12; the 30-mg dose but not the 15-mg dose was superior to adalimumab. The incidence of adverse events through week 24 was 66.9% with 15-mg upadacitinib, 72.3% with 30-mg upadacitinib, 59.6% with placebo, and 64.8% with adalimumab. There were serious infections in 1.2%, 2.6%, 0.9%, and 0.7% of the patients, respectively. Hepatic disorders occurred in 9.1% of patients in the 15-mg upadacitinib group and 12.3% in the 30-mg upadacitinib group, but grade 3 increases in aminotransferase levels occurred in 2% of patients or fewer in all groups. CONCLUSIONS: The percentage of patients with psoriatic arthritis who had an ACR20 response at week 12 was significantly higher with 15-mg or 30-mg upadacitinib than with placebo. The 30-mg dose but not the 15-mg dose was superior to adalimumab. Adverse events were more frequent with upadacitinib than with placebo. (Funded by AbbVie; SELECT-PsA 1 ClinicalTrials.gov number, NCT03104400.).

Bimekizumab treatment in patients with active axial spondyloarthritis: 52-week efficacy and safety from the randomised parallel phase 3 BE MOBILE 1 and BE MOBILE 2 studies.

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.

Thresholds for unacceptable work state in radiographic axial Spondyloarthritis of four presenteeism and two clinical outcome measurement instruments.

OBJECTIVES: To a) identify threshold values of presenteeism measurement instruments that reflect unacceptable work state in employed r-axSpA patients; b) determine whether those thresholds accurately predict future adverse work outcomes (AWO) (sick leave or short/long-term disability); c) evaluate the performance of traditional health-outcomes for r-axSpA; d) explore whether thresholds are stable across contextual factors. METHODS: Data from the multinational AS-PROSE study was used. Thresholds to determine whether patients consider themselves in an 'unacceptable work state' were calculated at baseline for four instruments assessing presenteeism and two health-outcomes specific for r-axSpA. Different approaches derived from the receiver operating characteristic methodology were used. Validity of the optimal thresholds was tested across contextual factors and for predicting future AWO over 12 months. RESULTS: Of 366 working patients, 15% reported an unacceptable work state; 6% experienced at least one AWO in 12 months. Optimal thresholds were: WPAI-presenteeism ≥40 (AUC 0.85), QQ-method <97 (0.76), WALS ≥0.75 (AUC 0.87), WLQ-25 ≥ 29 (AUC 0.85). BASDAI and BASFI performed similarly to the presenteeism instruments: ≥4.7 (AUC 0.82) and ≥3.5 (AUC 0.79), respectively. Thresholds for WALS and WLQ-25 were stable across contextual factors, while for all other instruments they overestimated unacceptable work state in lower educated persons. Proposed thresholds could also predict future AWO, although with lower performance, especially for QQ-method, BASDAI and BASFI. CONCLUSIONS: Thresholds of measurement instruments for presenteeism and health status to identify unacceptable work state have been established. These thresholds can help in daily clinical practice to provide work related support to r-axSpA patients at risk for AWO.

Efficacy and Safety of Tofacitinib in Ankylosing Spondylitis by Baseline C-Reactive Protein Level: Post Hoc Analysis of Phase II and Phase III Clinical Trials.

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.

IL-17-producing cells in ankylosing spondylitis patients show gender-based differences in gene expression.

OBJECTIVES: Gender has been shown to impact disease expression in ankylosing spondylitis (AS) and Th17 cells play a key role in AS pathogenesis. To better understand what Th17-associated immune pathways are different between men and women, we compared the transcriptome of IL-17-enriched peripheral blood mononuclear cells (PBMCs) in male and female AS patients, with a particular focus on inflammatory cytokine genes. METHODS: PBMCs were collected from 10 female and 11 male AS patients at the Clinical Research Unit of MetroHealth Medical Center. IL-17-enriched PBMCs were isolated and stimulated with CytoStim. RNA-sequencing (RNA-seq) was performed on the samples, and the data were analysed using iPathwayGuide. Inflammatory markers and genes related to Th17 differentiation and function were identified based on previous studies. RESULTS: RNA-seq identified 12,893 genes with 2,851 genes with p-values <0.05 with distinct patterns of gene expression between male and female AS patients. TGF-ß, PGE2, and S100 proteins were significantly upregulated in males. Levels of IL-12B, a Th17 inducer, were lower in males compared to females. Additionally, receptors of IL-6, 12, 23, TGF-ß, and PGE2 were downregulated in males, except for IL-17RC, which was upregulated. Genes involved in Th17 differentiation showed differential expression between genders, with elevated expression of BATF, SOCS1, NKD2, and ARID5A in men and decreased expression of FOXO1. CONCLUSIONS: Transcriptomic analysis revealed that male AS patients exhibit distinct expression patterns of IL-17 pro-inflammatory genes, which may contribute to the phenotypic differences observed between genders in AS.

Dose Tapering and Discontinuation of Biologic DMARDs in Axial Spondyloarthritis: A Narrative Review (2023 SPARTAN Annual Meeting Proceedings).

PURPOSE OF REVIEW: Limited data is available for tapering or discontinuation of biologic therapy in patients with axSpA who are in disease remission. The current review concentrates on published studies regarding dose tapering or withdrawal of biologics in axSpA. RECENT FINDINGS: Recent evidence in light of randomized controlled trials suggests that tapering of b-DMARDs is a feasible strategy to maintain remission or low disease activity in axSpA patients. TNF inhibitors were the studied biologics in most of these trials. The disease flare rates were comparable to those maintained on standard dose in most of these studies, although with variable tapering strategies and follow-up. Additionally, the duration of disease in remission prior to tapering, studied primary outcome, and flare definitions were heterogeneous. Female sex, HLA-B*27 negativity, high physician global score, and high CRP were negative predictors of successful tapering, but not consistently reported in all the trials. Although designed to address efficacy, there were no safety concerns with b-DMARD tapering. Withdrawal or complete discontinuation of biologics met with increased risk of flares compared to standard dosing. Tapering of TNF inhibitors may be feasible in certain axSpA patients with an acceptable disease state; however, discontinuation is not currently recommended owing to increased risk of flare. Future studies with axSpA patients with longer remission duration prior to taper and different doses and types of b-DMARDs may provide more guidance.

Efficacy and safety of bimekizumab in axial spondyloarthritis: results of two parallel phase 3 randomised controlled trials.

OBJECTIVES: Axial spondyloarthritis (axSpA) is a complex disease with diverse manifestations, for which new treatment options are warranted. BE MOBILE 1 (non-radiographic (nr)-axSpA) and BE MOBILE 2 (radiographic axSpA (r-axSpA)) are double-blind, phase 3 trials designed to evaluate efficacy and safety of bimekizumab, a novel dual interleukin (IL)-17A and IL-17F inhibitor, across the axSpA spectrum. METHODS: In parallel 52-week trials, patients with active disease were randomised 1:1 (nr-axSpA) or 2:1 (r-axSpA) to bimekizumab 160 mg every 4 weeks:placebo. From week 16, all patients received bimekizumab 160 mg every 4 weeks. Primary (Assessment of SpondyloArthritis international Society ≥40% improvement (ASAS40)) and secondary endpoints were assessed at week 16. Here, efficacy and treatment-emergent adverse events (TEAEs) are reported up to week 24. RESULTS: 254 patients with nr-axSpA and 332 with r-axSpA were randomised. At week 16, primary (ASAS40, nr-axSpA: 47.7% bimekizumab vs 21.4% placebo; r-axSpA: 44.8% vs 22.5%; p<0.001) and all ranked secondary endpoints were met in both trials. ASAS40 responses were similar across TNFi-naïve and TNFi-inadequate responder patients. Improvements were observed in Ankylosing Spondylitis Disease Activity Score (ASDAS) states and objective measures of inflammation, including high-sensitivity C-reactive protein (hs-CRP) and MRI of the sacroiliac joints and spine. Most frequent TEAEs with bimekizumab (>3%) included nasopharyngitis, upper respiratory tract infection, pharyngitis, diarrhoea, headache and oral candidiasis. More fungal infections (all localised) were observed with bimekizumab vs placebo; no major adverse cardiovascular events (MACE) or active tuberculosis were reported. Incidence of uveitis and adjudicated inflammatory bowel disease was low. CONCLUSIONS: Dual inhibition of IL-17A and IL-17F with bimekizumab resulted in significant and rapid improvements in efficacy outcomes vs placebo and was well tolerated in patients with nr-axSpA and r-axSpA.

Axial Spondyloarthritis and Diagnostic Challenges: Over-diagnosis, Misdiagnosis, and Under-diagnosis.

PURPOSE OF REVIEW: This article aims to review the challenges in axial spondyloarthritis diagnosis and identify the possible contributing factors. RECENT FINDINGS: The inability to reach an accurate diagnosis in a timely fashion can lead to treatment delays and worse disease outcomes. The lack of validated diagnostic criteria and the misuse of the currently available classification criteria could be contributing. There is also significant inter-reader variability in interpreting images, and the radiologic definitions of axial spondyloarthritis continue to be re-defined to improve their positive predictive value. The role of inflammatory back pain features, serologic biomarkers, genetics, and their diagnostic contribution to axial spondyloarthritis continues to be investigated. There is still a significant amount of delay in the diagnosis of axial spondyloarthritis. Appreciating the factors that contribute to this delay is of utmost importance to close the gap. It is similarly important to recognize other conditions that may present with symptoms that mimic axial spondyloarthritis so that misdiagnosis and wrong treatment can be avoided.

Worldwide Differences in Clinical Phenotype of Axial Spondyloarthritis.

PURPOSE OF REVIEW: This review aims to describe the variations in the clinical presentation of axial spondyloarthritis (axSpA) across the globe. RECENT FINDINGS: We searched the PubMed database and screened more than 1360 articles; 60 of them were selected based on relevance to the topic being discussed and the goals of the review. Most of the clinical manifestations, including IBP, peripheral arthritis, and extra-articular involvement are seen in different regions of the world, but with appreciable clinical heterogeneity, possibly related to a smaller number of patients from some countries, and global variation in the prevalence of HLA-B27. For example, HLA-B27-positive patients have an earlier age of onset, higher prevalence of acute anterior uveitis, and greater familial occurrence. Peripheral arthritis and enthesitis are most commonly seen among axSpA patients from Latin America and Asia, whereas IBD appears to be slightly more common among Middle Eastern and North African patients. The main weakness encountered while reviewing these data is that some studies were small, and others were cross-sectional and retrospective; hence the inferences may have a selection bias. AxSpA is a very heterogenous disease with varied presentation across the globe, in part related to HLA-B27 positivity. It is imperative to further investigate the key regional differences as they impact timely disease recognition and initiation of early treatment. Therefore, there is a need for a large worldwide systematic study to capture the clinical picture of AxSpA in a more uniform manner.

Clinical Manifestations and Diagnosis of Axial Spondyloarthritis.

BACKGROUND: Axial spondyloarthritis (axSpA) is a chronic, rheumatic disease characterized by inflammation of the sacroiliac joint, spine, and entheses. Axial spondyloarthritis affects up to 1.4% of adults in the United States and is associated with decreased quality of life, increased mortality, and substantial health care-related costs, imposing a high burden on patients, their caregivers, and society. SUMMARY OF WORK: Diagnosing axSpA can be difficult. In this review, we seek to help rheumatologists in recognizing and diagnosing axSpA. MAJOR CONCLUSIONS: A discussion of challenges associated with diagnosis is presented, including use and interpretation of imaging, reasons for diagnostic delays, differences in disease presentation by sex, and differential diagnoses of axSpA. FUTURE RESEARCH DIRECTIONS: The early diagnosis of axSpA and advances in available therapeutic options have improved patient care and disease management, but delays in diagnosis and treatment remain common. Additional research and education are critical for recognizing diverse axSpA presentations and optimizing management early in the course of disease.

The American College of Rheumatology Fibromyalgia Criteria Are Useful in the Evaluation of Fibromyalgia Symptoms in Patients With Ankylosing Spondylitis: A Cross-Sectional Study.

BACKGROUND: Fibromyalgia (FM) is common among patients with ankylosing spondylitis (AS), and its coexistence is believed to interfere with the measurement of patient-reported outcomes of disease activity and function in AS because of overlapping symptoms between the 2 diseases. This can confound clinical assessment and treatment decisions. AIMS: The aim of this study was to assess the relationship between the Fibromyalgia Symptom Scale (FSS) and its components, the Widespread Pain Index (WPI), and System Severity Scale with measures of disease activity, function, and patient-reported outcomes in AS. METHODS: We recruited 63 AS patients (aged ≥18 years) meeting the modified New York criteria, and Bath Ankylosing Spondylitis Disease Activity Index, Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein, Routine Assessment of Patient Index Data 3, and Bath Ankylosing Spondylitis Functional Index questionnaires were administered to them. The presence of FM was determined using validated 2010 American College of Rheumatology diagnostic criteria for FM. RESULTS: Twenty-eight of 63 patients (44.4%) with AS and FM had higher disease activity and greater impairment of functional ability compared with AS patients without FM. Using multiple linear regression estimates, there was no significant relationship of FSS scores with Bath Ankylosing Spondylitis Disease Activity Index (p = 0.36), Routine Assessment of Patient Index Data 3 (p = 0.50), Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein (p = 0.24), Bath Ankylosing Spondylitis Functional Index (p = 0.42) scores, or erythrocyte sedimentation rate (p = 0.82) and C-reactive protein (p = 0.75). CONCLUSIONS: Despite a high prevalence of FM in our patients with the diagnosis of AS, there was no relationship between FSS and measures of disease activity or function in AS, suggesting that FSS and its components could be a useful tool to assess FM in AS patients. Also, FM impairs functional ability in patients with AS.

Measuring outcomes in ankylosing spondylitis: pearls and pitfalls.

PURPOSE OF REVIEW: Patients with ankylosing spondylitis (AS) warrant a comprehensive clinical assessment because of the lack of biomarkers of disease activity, prognosis and response to biologic therapy. Multiple AS-related questionnaires have been developed to assess the disease status accurately, but feasibility remains a problem in clinical practice. The purpose of this review is to assess the pearls and pitfalls of AS-related outcome measures. RECENT FINDINGS: Single-item questionnaires to measure pain, stiffness and fatigue in patients with AS are easily administrable but may lack a sufficient degree of responsiveness on an individual patient level. The Bath Ankylosing Disease Activity Index remains the gold standard for assessing disease activity in a routine practice, despite poor correlation with C-reactive protein (CRP) levels and MRI inflammation. The Ankylosing Spondylitis Disease Activity Score, a validated and highly discriminatory tool for assessing disease activity in AS, has been developed but lacks feasibility as erythrocytic sedimentation rate and CRP values are often not available during a clinic visit. RAPID-3 appears feasible to assess patients with AS quantitatively over time in busy clinical settings. SUMMARY: The assessment of disease status in AS is complex and is impacted by multiple factors. The biggest challenge in AS is to incorporate the disease-specific indices into a routine practice. VIDEO ABSTRACT: http://links.lww.com/COR/A42.

Mimics of axial spondyloarthritis.

PURPOSE OF REVIEW: Axial spondyloarthritis (AxSpA) is a distinct clinical entity with characteristic clinical and radiographic features; however, a multitude of other metabolic, infectious and inflammatory disorders mimic it both clinically and radiographically. RECENT FINDINGS: We present in this review article recent updates about the various disease entities and conditions that may mimic AxSpA and how to differentiate among them. The sensitivity and specificity of MRI in diagnosing AxSpA has limitations and needs to be interpreted in the context of the clinical picture. Interestingly, some recent studies have highlighted that a relatively high prevalence of bone marrow edema on pelvic MRIs in healthy volunteers which could even be categorized as having a 'positive MRI' as defined by Assessment of Spondyloarthritis International Society. Another study revealed that a substantial proportion of patients with suspected sacroiliitis were more commonly diagnosed with diseases other than inflammatory sacroiliitis. On the basis of these reports, it is prudent to request MRIs in the appropriate clinical context and interpreted with caution taking into considerations the wide differential diagnosis of such MRI changes. SUMMARY: Highlighting the clinical pearls that differentiate disorders suspected of having sacroiliitis will lead to earlier and correct diagnosis and management; however, one must always take into considerations the radiographic and MRI findings in addition to the clinical presentations in order to make the appropriate diagnosis.

Efficacy and safety of continuing versus withdrawing adalimumab therapy in maintaining remission in patients with non-radiographic axial spondyloarthritis (ABILITY-3): a multicentre, randomised, double-blind study.

BACKGROUND: Success of treatment withdrawal in patients with non-radiographic axial spondyloarthritis who are in remission remains unknown. The ABILITY-3 study explored the ability to withdraw adalimumab treatment in patients with non-radiographic axial spondyloarthritis who achieved sustained clinical remission after open-label treatment with adalimumab. METHODS: ABILITY-3 was a multicentre, two-period study done in 107 sites in 20 countries. We enrolled adult patients (≥18 years) diagnosed with non-radiographic axial spondyloarthritis, fulfilling Assessment of SpondyloArthritis international Society classification criteria but not the modified New York radiologic criterion, who had objective evidence of active inflammation, active disease, and inadequate response to at least two non-steroidal anti-inflammatory drugs. Patients who achieved Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease (<1·3) with open-label adalimumab (40 mg subcutaneously every other week for 28 weeks) at weeks 16, 20, 24, and 28 were randomly assigned (1:1) using an interactive voice or web response system to 40-week, double-blind treatment with adalimumab (continuation) or placebo (withdrawal). The primary efficacy endpoint was the proportion of patients who did not experience a flare (defined as ASDAS ≥2·1 at two consecutive visits) during the double-blind period. Patients who flared were rescued with open-label adalimumab. This study is registered with ClinicalTrials.gov, number NCT01808118. FINDINGS: Between June 27, 2013, and October 22, 2015, 673 patients were enrolled to the study. The trial completed on April 14, 2017. Of 673 enrolled patients, 305 (45%) achieved sustained remission and were randomly assigned to double-blind treatment (152 patients to adalimumab and 153 to placebo). A greater proportion of patients continuing adalimumab than those receiving placebo did not experience a flare (107 [70%] of 152 patients vs 72 [47%] of 153 patients; p<0·0001) up to and including week 68. Among 673 patients receiving adalimumab at any time, 516 (77%) patients reported an adverse event and 28 (4%) experienced a serious adverse event. The most common adverse events in both the adalimumab and placebo groups were nasopharyngitis (25 [16%] vs 20 [13%]), upper respiratory tract infection (20 [13%] vs 12 [8%]), and worsening of axial spondyloarthritis (ten [7%] vs 21 [14%]). INTERPRETATION: In patients with active non-radiographic axial spondyloarthritis who achieved sustained remission with adalimumab, continued therapy was associated with significantly fewer patients flaring than was treatment withdrawal. FUNDING: AbbVie.

The Paradox of Bone Formation and Bone Loss in Ankylosing Spondylitis: Evolving New Concepts of Bone Formation and Future Trends in Management.

PURPOSE OF REVIEW: The purpose of the study is to briefly review the molecular mechanisms that leads to structural damage in ankylosing spondylitis (AS), defined as new bone formation resulting in complete or incomplete ankylosis of the spine, and the impact of treatment with biologics to retard this process. RECENT FINDINGS: The understanding of molecular mechanisms leading to new bone formation in AS has significantly improved but is still incomplete. Availability of biologics has greatly enhanced the treatment of patients with AS, but its impact on slowing the structural damage is still a matter of debate, although a few observational studies have shown that long term use of TNF-α blockers may slow radiographic progression. The availability of newer biologics targeting IL-17/1L23 has shown some promising results in slowing radiographic progression in AS. Although the availability of TNF-inhibitors has greatly enhanced the treatment options for patients with AS, their impact on slowing the structural damage is still not clearly established. However, preliminary results using newer biologics targeting IL-17/1L23 axis are more encouraging but longer follow-up is needed.

Sacroiliitis mimics: a case report and review of the literature.

BACKGROUND: Radiographic sacroiliitis is the hallmark of ankylosing spondylitis (AS), and detection of acute sacroiliitis is pivotal for early diagnosis of AS. Although radiographic sacroiliitis is a distinguishing feature of AS, sacroiliitis can be seen in a variety of other disease entities. CASE PRESENTATION: We present an interesting case of sacroiliitis in a patient with Paget disease; the patient presented with inflammatory back pain which was treated with bisphosphonate. This case demonstrates comorbidity with Paget disease and possible ankylosing spondylitis. We also present a review of the literature for other cases of Paget involvement of the sacroiliac joint. CONCLUSIONS: In addition, we review radiographic changes to the sacroiliac joint in classical ankylosing spondylitis as well as other common diseases. We compare and contrast features of other diseases that mimic sacroiliitis on a pelvic radiograph including Paget disease, osteitis condensans ilii, diffuse idiopathic skeletal hyperostosis, infections and sarcoid sacroiliitis. There are some features in the pelvic radiographic findings which help distinguish among mimics, however, one must also rely heavily on extra-pelvic radiographic lesions. In addition to the clinical presentation, various nuances may incline a clinician to the correct diagnosis; rheumatologists should be familiar with the imaging differences among these diseases and classic spondylitis findings.

Screening and treatment of osteoporosis after hip fracture: comparison of sex and race.

Most patients with osteoporosis (OP) are untreated and remain so even after hip fracture. Outcomes after osteoporotic hip fractures are worse among men and non-Caucasians compared with Caucasian women. We hypothesized that screening and treatment of OP after hip fracture remains low in men and non-Caucasian women. We identified all patients aged 65 yr or older with a primary diagnosis of hip fracture (ICD9-DM code 820.xx) discharged from an urban public hospital between January 1, 2000 and December 31, 2010. Patients with active malignancy (1 yr before or after the fracture) and Paget's disease were excluded. Also, patients were excluded if they had less than 2 encounters for post-event care at the hospital. Patient charts were reviewed to obtain information on demographics, post-fracture OP screening status (dual-energy X-ray absorptiometry [DXA] ordered or resulted), OP treatment status (prescription for oral bisphosphonates, raloxifene, zoledronic acid, calcitonin, or teriparatide), and referral to rheumatology clinic. Data were captured using Research Electronic Data Capture. Differences in frequency of patients who had been evaluated by DXA and/or prescribed antiosteoporotic therapy after hip fractures overall and stratified by sex and race were evaluated using Chi-squared tests. The study was approved by our hospital institutional review board. There were a total of 596 patients discharged with a primary diagnosis of hip fracture during the study period. After exclusions, 417 patients remained and were included in the analyses. The median age was 80yr (range: 65-95), 113 (27%) were men, and 243 were White women (57.9%). Overall, 10.3% of the patients were ordered DXA after their hospital discharge, 5.4% of men and 12.1% of women (p=0.05). A total of 19% received treatment for OP, and women were nearly 3 times more likely to receive treatment than men (23.2% vs 8%, p=0.004). The rates of DXA, treatment, and referral to rheumatology did not differ by race. The frequency of OP screening using DXA scan and the initiation of OP treatment was low in all patients after fragility fractures of hip. Women were more likely than men to receive DXA and significantly more likely to receive OP treatment. Although representative of only 1 hospital, these data suggest that more attention should be paid to possible OP among elderly patients hospitalized for hip fracture, and especially among men.

Disease characteristics, pathogenesis, and treatment controversies of axial psoriatic arthritis.

Axial psoriatic arthritis (axPsA) has considerable overlap with axial spondyloarthritis (axSpA) but has some unique features that sometimes preclude classification into axSpA. It has some clinical and radiographic differences compared to axSpA. Imaging typically shows asymmetric syndesmophytes, mainly in the cervical spine, with less frequent sacroiliitis. It more commonly presents later in life and is associated with less severe inflammatory back pain than axSpA. The interleukin (IL) IL-23/IL-17 axis is central to the pathogenesis of both diseases. However, the response to therapies targeting these cytokines has been different. IL-23 inhibitors are ineffective in axSpA but may be effective in psoriatic arthritis (PsA). Recent post hoc analyses of clinical trial data with IL-23 inhibitors in PsA have raised the possibility of their efficacy in axPsA and need evaluation in future clinical trials. Moreover, there is a need for classification criteria for axPsA and better tools to assess therapeutic response.

Mortality and Ankylosing Spondylitis in the US population: leading causes and associated factors.

OBJECTIVE: Ankylosing Spondylitis (AS) is a chronic inflammatory condition that affects the axial skeleton. Recent studies have shown that mortality risk is higher in AS patients and that it is possibly related to disease activity and duration. Our aim was to investigate the leading causes and factors associated with mortality in hospitalized AS patients in the USA. METHODS: This is a case-control study using the Cerner Health Facts® database between 2015 and 2017. The search was done using ICD codes and administrative claims. Cases were hospitalized AS patients who died during that hospitalization, while controls were patients who survived. In addition to demographics, we collected data on the inpatient use of medications such as NSAIDs, as well as different comorbidities and systemic disease manifestations. The discharge diagnoses for deceased patients were collected to infer causes of mortality. Analysis of association was performed using chi-square tests, t-tests, Wilcoxon rank-sum tests, and logistic regression methods. RESULTS: The leading causes of death were cardiovascular, infectious, respiratory, and traumatic. The Elixhauser comorbidity index was the factor most associated with mortality (p-value < 0.0001), with congestive heart failure and renal disease the most contributing. Drug use disorder was associated with mortality (adjusted OR = 10.9; p = 0.001). Inpatient NSAIDs use was not associated with increased odds for mortality (p-value 0.33). CONCLUSION: Cardiovascular and renal comorbidities are associated with mortality and need to be targeted early on to lower the odds of mortality as patients age. Strategies to prevent opioid and drug abuse should be strengthened in the AS population. Key Points • Cardiovascular and renal comorbidities are associated with mortality and need to be screened for and targeted early on to lower the odds of mortality as patients age. • Drug use disorder including opioid dependence is associated with mortality, and strategies to prevent opioid and drug abuse should be strengthened in the AS population.

Relationships of Work Productivity and Activity Impairment With Patient-Reported Outcomes in Ankylosing Spondylitis: Results From Two Trials.

OBJECTIVE: We examined the relationships of work productivity and activity impairment with key patient-reported outcomes (PROs) assessing pain, disease activity, and health-related quality of life (HRQoL) in patients with ankylosing spondylitis (AS). METHODS: This post hoc analysis pooled available data from baseline to end of the double-blind phase of phase 2 and 3 placebo-controlled tofacitinib trials in patients with active AS. A repeated-measures longitudinal model assessed the relationships (linear or nonlinear) between Work Productivity and Activity Impairment questionnaire in Spondyloarthritis (WPAI:SpA) domains (absenteeism, activity impairment, presenteeism, and productivity loss) as outcomes and key PROs (total back pain, nocturnal spinal pain, Patient Global Assessment of Disease Activity, AS Quality of Life, EuroQol 5-Dimension 3-Level [EQ-5D-3L], and EQ-5D Visual Analog Scale [EQ-5D-VAS]) as predictors. RESULTS: Data from 330 to 475 patients were available, depending on the analysis. Relationships between WPAI:SpA domains and PROs were approximately linear. The worst PRO scores were associated with a decline in patients' work capacity (measured by activity impairment, presenteeism, and productivity loss [>65%]); the best scores were associated with improvements in WPAI:SpA domains (8%-23%). Incremental PRO improvements were associated with improvement of activity impairment, presenteeism, and productivity loss. Relationships between absenteeism and PROs were the weakest, owing to absenteeism being low in the study population. CONCLUSION: Evidence of linear relationships between work productivity and activity impairment with patient-reported pain, disease activity, and HRQoL was observed. Interventions to control pain and disease activity and improve HRQoL are therefore likely to improve work productivity and reduce activity impairment in patients with AS.