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In a trial comparing the JAK inhibitor upadacitinib (15 or 30 mg daily) with placebo and with the TNF-α inhibitor adalimumab, the percentage of patients with an ACR20 response at 12 weeks was 70.6% with the 15-mg dose, 78.5% with the 30-mg dose, 36.2% with placebo, and 65.0% with adalimumab. There were hepatic disorders with upadacitinib.

Axial spondyloarthritis (axSpA) is an important cause of chronic low back pain and affects approximately 1% of the US population. The back pain associated with axSpA has a characteristic pattern referred to as inflammatory back pain (IBP). Features of IBP include insidious onset before age 45 years, association with morning stiffness, improvement with exercise but not rest, alternating buttock pain, and good response to treatment with nonsteroidal anti-inflammatory drugs. In patients with IBP, it is essential to look for other features associated with spondyloarthritis (SpA), such as enthesitis, dactylitis, peripheral arthritis, extra-articular manifestations (eg, psoriasis, uveitis, or inflammatory bowel disease), human leukocyte antigen B27 positivity, and a family history of SpA. Axial SpA is underrecognized, and a delay of several years between symptom onset and diagnosis is common. However, with new and effective therapies available for the treatment of active axSpA, early recognition and diagnosis are of critical importance. For this narrative review, we conducted a literature search of English-language articles using PubMed. Individual searches were performed to identify potential articles of interest related to axSpA (search terms: [“axSpA” OR “axial SpA” OR “axial spondyloarthritis” OR “ankylosing spondylitis”]) in combination with terms related to IBP (“inflammatory back pain” OR “IBP” OR “chronic back pain” OR “CBP” OR “lower back pain” OR “LBP”), diagnosis ([“diagn∗” OR “classification”] AND [“criteria” OR “recommend∗” OR “guidelines”]), and referral (“refer∗”). No date range was formally selected, as we were interested in providing an overview of the evolution of these concepts in clinical practice. We supplemented the review with insights based on our clinical expertise. Patients with chronic back pain should be screened for IBP and other SpA features; suspicion for axSpA should trigger referral to a rheumatologist for further evaluation.

Axial spondyloarthritis (axSpA) is a chronic, immune‐mediated disease characterized by inflammatory axial skeleton involvement and extra‐musculoskeletal manifestations. The continuum of axSpA ranges from nonradiographic axSpA (nr‐axSpA) to ankylosing spondylitis, also known as radiographic axSpA; the latter is defined by definitive radiographic sacroiliitis. Human leukocyte antigen B27 (HLA‐B27) is a genetic marker strongly associated with axSpA; it aids in the diagnosis of axSpA, and its absence leads to delay in diagnosis. For HLA‐B27‐negative patients, disease pathogenesis is poorly understood, signs and symptoms are frequently underrecognized, and diagnosis and treatment are commonly delayed. The proportion of HLA‐B27‐negative patients may be higher among non‐White patients and those with nr‐axSpA, who can face additional diagnostic challenges related to lack of definitive radiographic sacroiliitis. In this narrative review, we discuss the role of HLA‐B27 in the diagnosis and pathogenesis of axSpA and highlight various pathways and genes that may be related to axSpA pathogenesis in HLA‐B27‐negative patients. We also emphasize the need to characterize gut microbial communities in these patients. Adequate understanding of clinical and pathological features underlying HLA‐B27‐negative patients with axSpA will improve diagnosis, treatment, and outcomes for this complex inflammatory disease.

Background Axial spondyloarthritis (axSpA) is a chronic inflammatory disease which mainly affects the spine and sacroiliac joints, causing longstanding back pain, stiffness, and limited mobility. AxSpA is an underrecognized disease in non-rheumatology practices because of its heterogeneous clinical features that may be difficult to identify. Main body Sports medicine practitioners are well positioned to suspect and recognize axSpA among their patients with chronic back pain and refer them to a rheumatologist. Early referral to a rheumatologist is important for timely diagnosis, prompt treatment, and improved long-term outcomes for patients with axSpA. Physical therapy and nonsteroidal anti-inflammatory drugs (NSAIDs) remain the first-line treatment for and the cornerstone of axSpA management. For patients with inadequate response to or intolerance of NSAIDs, biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic (ts) DMARDs are indicated. These drugs can reduce pain, inflammation, fatigue, and disability and can improve health-related quality of life. The goal of this review is to improve awareness of axSpA among sports medicine practitioners and other non-rheumatologists so that these providers ensure timely referral of patients with suspected axSpA to rheumatologists for appropriate treatment and better outcomes. We also provide an update on current treatment possibilities for axSpA and describe how rheumatologists use treatment guidelines and disease activity measures to identify and optimally treat patients with active axSpA. Conclusion Sports medicine practitioners have an excellent opportunity to identify patients with suspected axSpA and refer them to rheumatologists in a timely manner, as well as monitor symptoms among patients diagnosed with axSpA to identify inadequately controlled disease.

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.

BackgroundIn SELECT-PsA 1, a randomised double-blind phase 3 study, upadacitinib 15 mg and 30 mg were superior to placebo and non-inferior to adalimumab in ≥20% improvement in American College of Rheumatology (ACR) criteria at 12 weeks in patients with psoriatic arthritis (PsA). Here, we report 56-week efficacy and safety in patients from SELECT-PsA 1.MethodsPatients received upadacitinib 15 mg or 30 mg once daily, adalimumab 40 mg every other week for 56 weeks or placebo through week 24 switched thereafter to upadacitinib 15 mg or 30 mg until week 56. Efficacy endpoints included the proportion of patients achieving ≥20%/50%/70% improvement in ACR criteria (ACR20/50/70), ≥75%/90%/100% improvement in Psoriasis Area and Severity Index (PASI75/90/100), minimal disease activity (MDA) and change from baseline in modified total Sharp/van der Heijde Score. Treatment-emergent adverse events per 100 patient years (PY) were summarised.ResultsConsistent with results through week 24, ACR20/50/70, PASI75/90/100 and MDA responses were maintained with upadacitinib through week 56 and were generally numerically higher than with adalimumab; inhibition of radiographic progression was also maintained. Patients who switched from placebo to upadacitinib exhibited comparable improvements at week 56 as patients originally randomised to upadacitinib. The rates of serious adverse events were 9.1 events/100 PY with upadacitinib 15 mg and 12.3 events/100 PY with upadacitinib 30 mg. Two deaths were reported in each of the upadacitinib groups.ConclusionEfficacy across various domains of PsA were maintained with upadacitinib 15 mg and 30 mg through week 56 with no new safety signals observed.

Background Increased cancer-risk has been reported with rheumatoid arthritis and systemic lupus erythematosus, but the risk is poorly studied in ankylosing spondylitis (AS). Conflicting data in AS have been reported in Asia and Europe, with lack of US population-based studies. Our objective is to study the prevalence of cancer in patients with AS in the US. Methods Using the Explorys database, we performed a cross-sectional study. Data from AS patients and controls were stratified by 2 rheumatology visits, age groups, clinical characteristics, and frequency of cancers. The data were analyzed using a series of chi-square tests of independence as well as logistic regression to test for association between AS and cancer. Results 1410 AS patients (12.88%) had cancer. Female AS patients had a lower prevalence of cancer compared to controls (OR 0.840, 95% CI [0.769, 0.916]), while male AS patients had no statistically significant difference (OR 1.011, 95% CI [0.929, 1.099]). Among patients with AS, Skin cancers (squamous cell, malignant melanoma, and basal cell) and head and neck cancers were significantly increased. Conclusion Our study demonstrated that the prevalence of “any-type-cancer” was not increased in AS patients compared to controls with no rheumatic disease. Skin, head, and neck cancers were more frequently seen in AS patients.

Introduction Efficacy and safety of the Janus kinase (JAK) inhibitor upadacitinib (UPA) was evaluated in patients with psoriatic arthritis (PsA) through week 104 of the ongoing long-term extension of the phase 3 trial SELECT-PsA 1. Methods Exploratory analyses of all primary and secondary endpoints (non-responder imputation and as observed for binary endpoints; mixed-effect model repeated measures and as observed for continuous endpoints), and summary of treatment-emergent adverse events, in patients receiving UPA 15 mg (UPA15) or 30 mg (UPA30) once daily, or adalimumab 40 mg (ADA) every other week, through week 104 are reported. Results Of 1704 patients, 25.4% discontinued the study drug by week 104. Proportions of patients achieving ≥ 20%/50%/70% improvement in American College of Rheumatology criteria (ACR20/50/70), ≥ 75%/90%/100% improvement in Psoriasis Area and Severity Index (PASI75/90/100), or minimal disease activity (MDA) were maintained through week 104; greater responses by nominal P value were observed with UPA15 and UPA30 versus ADA for ACR20/50/70 and MDA. Mean change from baseline in modified total Sharp/van der Heijde Score (mTSS) was similar across groups and to week 56 results. The safety profile of UPA was generally comparable to ADA and not altered from week 56 data. Rates of serious infection, herpes zoster, anemia, neutropenia, lymphopenia, and elevated creatine phosphokinase remained numerically higher with UPA15 and/or UPA30 versus ADA. Rates of malignancies excluding non-melanoma skin cancer (NMSC), major adverse cardiovascular events, and venous thromboembolism were similar across groups; rates of NMSC were higher with UPA versus ADA. Two deaths were reported with UPA15, one with UPA30, and one with ADA. Conclusions In PsA patients, efficacy responses were similar or greater with UPA15 or UPA30 versus ADA through week 104, and inhibition of radiographic progression was maintained. No new safety risks were identified with exposure to UPA through 2 years (week 104). Clinical Trial Registration ClinicalTrials.gov, NCT03104400.

ObjectivesTo characterise peripheral musculoskeletal involvement in patients with spondyloarthritis (SpA) including psoriatic arthritis (PsA), across the world.MethodsCross-sectional study with 24 participating countries. Patients with a diagnosis of axial SpA (axSpA), peripheral SpA (pSpA) or PsA according to their rheumatologist were included. The investigators were asked which diagnosis out of a list of six (axSpA, PsA, pSpA, inflammatory bowel disease-associated SpA, reactive arthritis or juvenile SpA (Juv-SpA)) fitted the patient best. Peripheral manifestations (ie, peripheral joint disease, enthesitis, dactylitis and root joint disease), their localisation and treatments were evaluated.ResultsA total of 4465 patients were included (61% men, mean age 44.5 years) from four geographic areas: Latin America (n=538), Europe plus North America (n=1677), Asia (n=975) and the Middle East plus North Africa (n=1275). Of those, 78% had ever suffered from at least one peripheral musculoskeletal manifestation; 57% had peripheral joint disease, 44% had enthesitis and 15% had dactylitis. Latin American had far more often peripheral joint disease (80%) than patients from other areas. Patients with PsA had predominantly upper limb and small joint involvement (52%).Hip and shoulder involvement was found in 34% of patients. The prevalence of enthesitis ranged between 41% in patients with axSpA and 65% in patients with Juv-SpA. Dactylitis was most frequent among patients with PsA (37%).ConclusionThese results suggest that all peripheral features can be found in all subtypes of SpA, and that differences are quantitative rather than qualitative. In a high proportion of patients, axial and peripheral manifestations coincided. These findings reconfirm SpA clinical subtypes are descendants of the same underlying disease, called SpA.

At present, there are no studies that have established a microRNA (miRNA)-based signature profile in patients with radiographic axial spondyloarthritis (rad-axial SpA), and we hypothesized that these patients may have aberrantly expressed circulating miRNAs reflective of underlying disease and inflammation. This study aims to determine the expression profile of miRNAs in plasma of patients with rad-axial SpA and compare it with healthy, age, and sex-matched controls. Fifteen subjects with rad-axial SpA based on ASAS classification criteria and 5 controls were recruited from our local SpA registry. Demographic data were collected and disease activity was measured using Bath Ankylosing Spondylitis Disease Activity Index (BASDI). Peripheral blood samples (5 ml) were obtained from eligible consenting patients and controls. RNA from the plasma was prepared using miRNeasy kit (Qiagen) by a modified protocol. Expression of 175 miRNAs was screened in the plasma of all 15 patients and 5 controls using serum/plasma miRNA PCR arrays (Exiqon Inc. Woburn, MA) essentially following the manufacturer’s instructions. Real-time PCR was carried out on StepOne Plus (Applied Biosystems) and the data was extracted and analyzed using ExiGen Enterprise software (MultiD, Göteborg, Sweden). Potential miRNA targets were identified using bioinformatics. ESR and CRP levels were measured by standard laboratory methods. We identified 7 differentially expressed miRNAs (2 upregulated and 5 downregulated). miR-34a, which was overexpressed in patients with rad-axial SpA, was predicted to target BMP-3 mRNA by TargetscanS and PicTar miRNA target algorithms. miR-150 was downregulated in all of the samples analyzed by us using the TaqMan Gene Expression assay. The most repressed miRNA was miR-16 and is predicted to regulate the expression of activin A receptor (ACVR2B), a receptor for growth, and differentiation factor-5 (GDF-5). Our data indicates that (1) patients with axial SpA, as compared to controls, have dysregulated expression of selected miRNAs in the plasma; and (2) the differentially expressed miRNAs are predicted to target genes that play a role in bone morphogenesis, growth, and immune response.