Search

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., (© 2024. The Author(s).)

Objective: To assess how achievement of increasingly stringent clinical response criteria and disease activity states at week 52 translate into changes in core domains in patients with non-radiographic (nr-) and radiographic (r-) axial spondyloarthritis (axSpA)., Methods: Patients in BE MOBILE 1 and 2 achieving different levels of response or disease activity (Assessment of SpondyloArthritis International Society (ASAS) and Ankylosing Spondylitis Disease Activity Score (ASDAS) response criteria, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50)) at week 52 were pooled, regardless of treatment arm. Associations between achievement of these endpoints and change from baseline (CfB) in patient-reported outcomes (PROs) measuring core axSpA domains, including pain, fatigue, physical function, overall functioning and health, and work and employment, were assessed., Results: Achievement of increasingly stringent clinical efficacy endpoints at week 52 was generally associated with sequentially greater improvements from baseline in all PROs. Patients with nr-axSpA achieving ASAS40 demonstrated greater improvements (CfB) than patients who did not achieve ASAS40 but did achieve ASAS20, in total spinal pain (-5.3 vs -2.8, respectively), Functional Assessment of Chronic Illness-Fatigue subscale (12.7 vs 6.7), Bath Ankylosing Spondylitis Function Index (-3.9 vs -1.8), European Quality of Life 5-Dimension 3-Level Version (0.30 vs 0.16), Work Productivity and Activity Impairment-axSpA presenteeism (-35.4 vs -15.9), overall work impairment (-36.5 vs -12.9), activity impairment (-39.0 vs -21.0) and sleep (9.0 vs 3.9). Results were similar for ASDAS and BASDAI50. Similar amplitudes of improvement were observed between patients with nr-axSpA and r-axSpA., Conclusions: Patients treated with bimekizumab across the full axSpA disease spectrum, who achieved increasingly stringent clinical response criteria and lower disease activity at week 52, reported larger improvements in core axSpA domains., Competing Interests: Competing interests: 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; SR: Grants from AbbVie, Galapagos, MSD, Novartis, Pfizer and UCB Pharma; consultancy from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi and 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; PJM: Research grants from AbbVie, Acelyrin, Amgen, BMS, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sun Pharma, and UCB Pharma; consultancy fees from AbbVie, Acelyrin, Aclaris, Amgen, BMS, Boehringer Ingelheim, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Moonlake Pharma, Novartis, Pfizer, Sun Pharma, Takeda, UCB Pharma, and Ventyx; speakers’ bureau for AbbVie, Amgen, Eli Lilly, Janssen, 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; CdlL: Consultant to UCB Pharma; CF, VT: Employees and shareholders of UCB Pharma; MFM, UM: Employees of UCB Pharma; JK: Consulting fees from Alvotech Swiss AG, Boehringer Ingelheim GmbH, Organon, Ridgeline Discovery, Scipher Medicine, Samsung Bioepis, Sandoz and UCB Pharma; grant/research support paid to institution from Gilead and Novartis; MM: Consultancy fees from AbbVie, BMS, Eli Lilly, Novartis, Pfizer and UCB Pharma; research grants from AbbVie, BMS 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: 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., (© 2023 Pfizer Inc and The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: The objective is to update recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP) for patients with rheumatic or nonrheumatic conditions receiving >3 months treatment with glucocorticoids (GCs) ≥2.5 mg daily., Methods: An updated systematic literature review was performed for clinical questions on nonpharmacologic, pharmacologic treatments, discontinuation of medications, and sequential therapy. Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the certainty of evidence. A Voting Panel achieved ≥70% consensus on the direction (for or against) and strength (strong or conditional) of recommendations., Results: For adults beginning or continuing >3 months of GC treatment, we strongly recommend as soon as possible after initiation of GCs, initial assessment of fracture risks with clinical fracture assessment, bone mineral density with vertebral fracture assessment or spinal x-ray, and Fracture Risk Assessment Tool if ≥40 years old. For adults at medium, high, or very high fracture risk, we strongly recommend pharmacologic treatment. Choice of oral or intravenous bisphosphonates, denosumab, or parathyroid hormone analogs should be made by shared decision-making. Anabolic agents are conditionally recommended as initial therapy for those with high and very high fracture risk. Recommendations are made for special populations, including children, people with organ transplants, people who may become pregnant, and people receiving very high-dose GC treatment. New recommendations for both discontinuation of osteoporosis therapy and sequential therapies are included., Conclusion: This guideline provides direction for clinicians and patients making treatment decisions for management of GIOP. These recommendations should not be used to limit or deny access to therapies., (© 2023 American College of Rheumatology. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Introduction: Tofacitinib is an oral Janus kinase inhibitor for treatment of ankylosing spondylitis (AS). Using mediation modelling, we describe interrelationships between fatigue, pain, morning stiffness, C-reactive protein (CRP) and tofacitinib treatment in patients with AS., Methods: Data from phase 2 (NCT01786668)/phase 3 (NCT03502616) studies of patients receiving tofacitinib 5 mg twice daily (BID) or placebo were used. Initial models included treatment as the independent binary variable (tofacitinib 5 mg BID versus placebo); fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F; model A] or Bath AS Disease Activity Index [BASDAI] Q1 [model B]) as the dependent variable; and pain (total back pain/nocturnal spinal pain [model A] or pain measured by BASDAI Q2/3 [model B]), morning stiffness (BASDAI Q5/6) and CRP as mediator variables., Results: Pooled data from 370/371 patients were included in models A/B. Initial models demonstrated that tofacitinib treatment affects fatigue mainly indirectly via pain and morning stiffness. As a result, initial models were respecified to exclude direct treatment effect and the indirect effect via CRP. For respecified model A, 44.0% of the indirect effect of tofacitinib treatment on fatigue was mediated via back pain/morning stiffness, 40.0% via morning stiffness alone and 16.0% via back pain alone (all P < 0.05). For respecified model B, 80.8% of the indirect effect of tofacitinib treatment on fatigue was mediated via pain/morning stiffness and 19.2% via pain alone (both P < 0.05)., Conclusions: In tofacitinib-treated patients with AS, improvements in fatigue were collectively mediated through combined treatment effects on morning stiffness and pain., (© 2023. The Author(s).)

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., (© 2023 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: We aimed to characterize differences of clinical features, extra-musculoskeletal manifestations and treatment utilizations based on the patients' HLA-B*27 status in a global axSpA cohort and identify predictors of HLA-B*27 negativity in these patients., Methodology: In post-hoc analysis of the ASAS-PerSpA study, patients fulfilling the 2009 ASAS classification criteria for axSpA and typed for HLA-B*27 were included. The patient characteristics cwere compared between the HLA-B*27(+) and HLA-B*27(-) subgroups. Multivariablete logistic regression was conducted to identify predictors of HLA-B*27 negativity., Results: Of 2910 patients with axSpA from 24 countries, 2269 were tested for HLA-B*27 [1753 HLA-B*27(+) and 516 HLA-B*27(-)]. The proportion of males was higher in the HLA-B*27 (+) compared to the HLA-B*27 (-) subgroup (72.1 vs 54.3%). Patient population with HLA-B*27 (+) more often had positive family history for axSpA (29.8 vs 15.3%), and younger age at diagnosis, 31.6 years (SD 10.9) vs 37.7 years (SD 12.1). HLA-B*27 (-) patients had significantly higher peripheral arthritis (47.5 vs 42.1%, p<0.05), psoriasis (19.4 vs 10.2), enthesitis (56.6 vs 49.8%) and IBD (12.8 vs 3.4) (p<0.001). The exposure to csDMARDS in HLA-B*27 (-) patients was higher (61.2 vs 55.0%, p< 0.05). On multivariable analysis, HLA-B*27 (-) status was positively associated with enthesitis, psoriasis and IBD with an OR 1.27 (1.02-1.57), 1.84 (1.36-2.48) and 4.84 (3.23-7.30) respectively, and inversely associated with uveitis, OR 0.37 (0.27-0.50)., Conclusion: HLA-B*27 (-) axSpA patients had a longer delay in diagnosis, more frequently had peripheral arthritis, enthesitis, IBD, psoriasis, and were more often treated with csDMARDs compared to HLA-B*27 (+) subgroup., Competing Interests: Competing interests: HC, MAK, MD: none declared. MM: Consultant of Novartis, Abbvie, Pfizer, Janssen, Eli Lilly, UCB Pharma. CL-M: Consultant of Novartis, UCB and Eli Lilly., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Patients with ankylosing spondylitis (AS) have significant unmet treatment needs, despite advancements in biologic therapies. This study evaluated the impact of upadacitinib on clinically meaningful improvement in patient-reported outcomes (PROs) assessing disease activity, pain, fatigue, function, health-related quality of life (HRQoL), and work productivity in patients with AS with inadequate responses or intolerance to biologic disease-modifying antirheumatic drugs (bDMARD-IR)., Methods: Patients enrolled in the phase 3 SELECT-AXIS 2 AS bDMARD-IR study received blinded once-daily oral upadacitinib 15 mg or placebo for 14 weeks. The percentage of patients achieving improvements ≥ minimum clinically important differences (MCID) at week 14 were compared between treatment groups for disease activity (Bath Ankylosing Spondylitis Disease Activity Index, BASDAI), patient global assessment of disease activity (PtGA), total and nocturnal back pain, fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue, FACIT-F), physical function (Bath Ankylosing Spondylitis Functional Index, BASFI), HRQoL (Assessment of SpondyloArthritis international Society Health Index [ASAS HI], Ankylosing Spondylitis Quality of Life [ASQoL], Short form-36 [SF-36] physical [PCS] and mental [MCS] component summary scores), and work productivity (Work Productivity and Activity Impairment [WPAI] Questionnaire). Mean changes from baseline through week 14 in fatigue and HRQoL were compared between treatment groups., Results: A total of 420 patients with active AS who were bDMARD-IR were included. A higher proportion of patients reported MCIDs at week 14 across all PROs with upadacitinib compared with placebo (nominal p ≤ 0.05). Greater improvements in mean change from baseline through week 14 were reported with upadacitinib compared with placebo across FACIT-F, HRQoL, and WPAI, with improvements differentiated as early as week 1 for ASAS HI, ASQoL and SF-36 PCS and week 4 for SF-36 MCS., Conclusions: Upadacitinib 15 mg demonstrated rapid and clinically meaningful improvements in disease activity, pain, FACIT-F, function, HRQoL, and WPAI among bDMARD-IR patients with active AS., Trial Registry: Clinical Registration number: NCT04169373, SELECT-AXIS 2., (© 2023. The Author(s).)

Objective: Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that causes inflammation in the axial skeleton, resulting in structural damage and disability. We aimed to understand the effect of axSpA on work activity, day-to-day function, mental health, relationships, and quality of life and to examine barriers to early diagnosis., Methods: A 30-minute quantitative US version of the International Map of Axial Spondyloarthritis survey was administered online to US patients aged 18 years and older with a diagnosis of axSpA who were under the care of a health care provider from July 22 to November 10, 2021. This analysis describes demographics, clinical characteristics, journey to axSpA diagnosis, and disease burden., Results: We surveyed 228 US patients with axSpA. Patients had a mean diagnostic delay of 8.8 years, with a greater delay in women versus men (11.2 vs. 5.2 years), and 64.5% reported being misdiagnosed before receiving an axSpA diagnosis. Most patients (78.9%) had active disease (Bath Ankylosing Spondylitis Disease Activity Index score ≥4), reported psychological distress (57.0%; General Health Questionnaire 12 score ≥3), and experienced a high degree of impairment (81.6%; Assessment of Spondyloarthritis International Society Health Index score ≥6). Overall, 47% of patients had a medium or high limitation in activities of daily living, and 46% were not employed at survey completion., Conclusion: The majority of US patients with axSpA had active disease, reported psychological distress, and reported impaired function. US patients experienced a substantial delay in time to diagnosis of axSpA that was twice as long in women versus men., (© 2023 Novartis Pharmaceuticals Corporation. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

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., (© 2022. The Author(s).)

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., (© 2022. The Author(s).)

Background: Ankylosing spondylitis (AS) impacts quality of life. We assessed patient-reported outcomes (PROs), pain, fatigue, health-related quality of life (HRQoL) and work productivity in a phase III trial of tofacitinib., Methods: Adults with AS and with inadequate response/intolerance to ≥2 non-steroidal anti-inflammatory drugs received tofacitinib 5 mg twice daily or placebo for 16 weeks. Afterwards, all received open-label tofacitinib until week 48. Change from baseline to week 48 was determined for PROs: total back pain; nocturnal spinal pain; Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) overall spinal pain (Q2); Functional Assessment of Chronic Illness Therapy-Fatigue; BASDAI fatigue (Q1); AS Quality of Life (ASQoL); Short Form-36 Health Survey Version 2 (SF-36v2); EuroQoL-Five Dimension-Three Level health profile and Visual Analogue Scale; and the Work Productivity and Activity Impairment (WPAI) questionnaire. Improvements from baseline ≥minimum clinically important difference, and scores ≥normative values at week 16 were evaluated., Results: In 269 randomised and treated patients, at week 16, there were greater least squares mean improvements from baseline with tofacitinib 5 mg twice daily versus placebo in BASDAI overall spinal pain (-2.85 vs -1.34), BASDAI fatigue (-2.36 vs -1.08), ASQoL (-4.03 vs -2.01) and WPAI overall work impairment (-21.49 vs -7.64) (all p<0.001); improvements continued/increased to week 48. Improved spinal pain with tofacitinib was seen by week 2. Patients receiving tofacitinib reported clinically meaningful PRO improvements at week 16. Percentages with PRO scores ≥normative values at week 16 were greater with tofacitinib in SF-36v2 Physical Component Summary, physical functioning and bodily pain domains (p≤0.05)., Conclusions: In patients with AS, treatment with tofacitinib 5 mg twice daily resulted in clinically meaningful improvements in pain, fatigue, HRQoL and work productivity versus placebo to week 16, which were sustained to week 48., Trial Registration Number: NCT03502616., Competing Interests: Competing interests: VN-C has received research/grant support from AbbVie and Novartis, and is a member of the speakers’ bureaus for AbbVie, Eli Lilly, Janssen, Moonlake, MSD, Novartis, Pfizer Inc, and UCB. JC-CW has received research/grant support from AbbVie, Eli Lilly, Gilead Sciences, Janssen, MSD, Novartis, Pfizer Inc, and UCB, is a consultant for Eli Lilly, Novartis, and Pfizer Inc, and is a member of the speakers’ bureaus for Eli Lilly, Janssen, Novartis, and Pfizer Inc. FVdB has received consultancy and/or speaker fees from AbbVie, Celgene, Eli Lilly, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer Inc, and UCB. MM has received research/grant support from AbbVie and UCB, and has received consultancy fees from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer Inc, and UCB. VS has received consultancy fees from AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Eli Lilly, Genentech/Roche, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer Inc, Regeneron, Samsung, Sandoz, Sanofi, and UCB. LW, DF, JCC, CW, JW, OD, and LF are employees and shareholders of Pfizer Inc., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Abstract: Nonradiographic axial spondyloarthritis (nr-axSpA) represents a distinct phenotype within the spectrum of axial spondyloarthritis (axSpA), which is characterized by a range of clinical manifestations. Despite a high disease burden that is comparable to ankylosing spondylitis (also known as radiographic axSpA), there is an unmet need to recognize and effectively manage patients with active nr-axSpA.A targeted literature search was conducted in OVID (MEDLINE and Embase databases) to identify articles on nr-axSpA, including its definition, demographics, epidemiology, burden, diagnosis, clinical presentation, and treatment guidelines.The lack of adequate epidemiological data and incomplete understanding of nr-axSpA among rheumatologists and nonrheumatologists contributes to delayed referrals and diagnosis. This delay results in a substantial burden on patients, physically and psychologically, and the healthcare system. Targeted therapies, such as biologics, including inhibitors of tumor necrosis factor or interleukin-17A, have been approved and utilized for the management of nr-axSpA, and other novel therapeutics with different mechanisms of action are in development. Raising awareness among US internists regarding the prevalence of nr-axSpA, disease burden, clinical presentation, diagnostic tools, and available treatments is important for improved disease management.Future clinical investigations focusing on the development of markers that aid early diagnosis and predict treatment response may also improve the management of nr-axSpA. This review provides an overview of nr-axSpA with the aim of raising awareness of the disease among US internists, with an overarching goal to contribute toward the improved recognition and timely referral of these patients to rheumatologists for diagnosis and management., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Upadacitinib, a selective JAK1 inhibitor, has been evaluated for efficacy and safety in the treatment of psoriatic arthritis (PsA). Relevant literature using the terms 'upadacitinib' and 'PsA' were identified via PubMed and Google Scholar. Efficacy of upadacitinib in the treatment of PsA versus placebo was demonstrated in the SELECT-PsA I and II trials. SELECT-PsA1 also showed upadacitinib was noninferior to adalimumab in the treatment of PsA. The most common adverse events in patients treated with upadacitinib were infections, malignancies and thromboembolic events. Upadacitinib is an effective medication that can be used in the treatment of active PsA. Despite its proven efficacy and safety, upadacitinib does not yet have long-term safety data.

Objective: To identify clusters of peripheral involvement according to the specific location of peripheral manifestations (ie, arthritis, enthesitis and dactylitis) in patients with spondyloarthritis (SpA) including psoriatic arthritis (PsA), and to evaluate whether these clusters correspond with the clinical diagnosis of a rheumatologist., Methods: Cross-sectional study with 24 participating countries. Consecutive patients diagnosed by their rheumatologist as PsA, axial SpA or peripheral SpA were enrolled. Four different cluster analyses were conducted: one using information on the specific location from all the peripheral manifestations, and a cluster analysis for each peripheral manifestation, separately. Multiple correspondence analyses and k-means clustering methods were used. Distribution of peripheral manifestations and clinical characteristics were compared across the different clusters., Results: The different cluster analyses performed in the 4465 patients clearly distinguished a predominantly axial phenotype (cluster 1) and a predominantly peripheral phenotype (cluster 2). In the predominantly axial phenotype, hip involvement and lower limb large joint arthritis, heel enthesitis and lack of dactylitis were more prevalent. In the predominantly peripheral phenotype, different subgroups were distinguished based on the type and location of peripheral involvement: a predominantly involvement of upper versus lower limbs joints, a predominantly axial enthesitis versus peripheral enthesitis, and predominantly finger versus toe involvement in dactylitis. A poor agreement between the clusters and the rheumatologist's diagnosis as well as with the classification criteria was found., Conclusion: These results suggest the presence of two main phenotypes (predominantly axial and predominantly peripheral) based on the presence and location of the peripheral manifestations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In 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., Methods: Patients 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., Results: Consistent 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., Conclusion: Efficacy across various domains of PsA were maintained with upadacitinib 15 mg and 30 mg through week 56 with no new safety signals observed., Competing Interests: Competing interests: IBM: research grants and honoraria from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sanofi Regeneron and UCB Pharma. MM: research grants from AbbVie, Amgen and UCB Pharma; consulting fees from Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma. JFM: consultant and/or investigator for AbbVie, Arena, Avotres, Biogen, Bristol-Myers Squibb, Celgene, Dermavant, Eli Lilly, EMD Sorono, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma and UCB Pharma. MK: consulting fees and/or honoraria from AbbVie, AmgenAstellas BioPharma, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, Bristol-Myers Squibb, Chugai, DaiichiSankyo, Eisai, Eli Lilly, Gilead, Janssen, Kyowa Kirin, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, Teijin Pharma and UCB Pharma. CP-T: research grants and honoraria form AbbVie, AstraZeneca, Eli Lilly, Gilead, Janssen, Pfizer, Roche, R-Pharm, Sanofi Regeneron and UCB Pharma. DH: advisory board/speaker bureau or similar committee for AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Novartis, Pfizer, Roche, Sanofi Genzyme and Takeda; funded grant or clinical trials: AbbVie, Adiga Life-Sciences, Amgen, Bristol-Myers Squibb, Can-Fite Biopharma, Celgene, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Regeneron, Sanofi-Genzyme and UCB Pharma; honoraria or other fees from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi Genzyme, Takeda and UCB Pharma; not a part of/has not received payment from a commercial organisation (gifts or ‘in kind’ compensation); does not hold a patent for a product referred to in the CME/CPD program, or marketed by a commercial organisation; does not hold investments in a pharmaceutical organisation, medical devices company or communications firm. FB: research grants from Celgene, Chugai, Janssen, Pfizer and Roche; consultancies/speaker fees from AbbVie, Bristol-Myers Squibb, Boehringer, Celgene, Chugai, Eli Lilly, Genzyme, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi and UCB Pharma. KK, ALP, YD, LC, PZ, RL, JL: AbbVie employees and may own AbbVie stock or options., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To characterise peripheral musculoskeletal involvement in patients with spondyloarthritis (SpA) including psoriatic arthritis (PsA), across the world., Methods: Cross-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., Results: A 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%)., Conclusion: These 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Early diagnosis of ankylosing spondylitis (AS) remains challenging because of the high prevalence of chronic back pain in patients initially treated by nonrheumatology health care providers (HCPs). We assessed the patient pathway to rheumatology referral, including HCP recognition of inflammatory back pain (IBP) and other features suggestive of AS, diagnostic workup, treatment, and referral to a specialist with the goal of identifying barriers to patient referral to a rheumatologist., Methods: US HCPs from 10 specialties were invited to participate in a cross-sectional web-based survey on clinical characteristics and diagnostic measures leading to IBP suspicion and the subsequent referral process. Eligible HCPs were actively practicing and had referred a patient with suspected IBP or ocular findings (ophthalmology only) within 12 months. Data were analyzed descriptively., Results: Of 1690 HCPs, 61% identified morning stiffness lasting more than 30 minutes, 29% sleep disturbance due to back pain, and 28% pain that improves with activity as features suggestive of IBP. Nearly two-thirds of primary care HCPs reported that they were the first HCPs consulted by patients with suspected IBP. Among HCPs ordering diagnostic blood work, approximately 90% selected antinuclear antibody and rheumatoid factor, whereas 76% selected human leukocyte antigen B27. Almost 40% would treat patients with suspected IBP themselves. HCPs cited lack of adequate specialists nearby (35.1%), insurance restrictions (47.1%), and long wait time (77.0%) as barriers to early referral., Conclusion: Most HCPs had difficulty identifying features suggestive of IBP and indicated insurance restrictions and long wait times as barriers to early referral of patients with potential AS., (© 2020 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

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: This analysis assessed baseline predictors of remission in patients with non-radiographic axial spondyloarthritis (nr-axSpA) who received open-label adalimumab therapy., Methods: ABILITY-3 enrolled 673 adult patients with nr-axSpA who had objective evidence of inflammation by MRI or elevated high-sensitivity C reactive protein at screening, active disease and an inadequate response to two or more non-steroidal anti-inflammatory drugs. Patients received adalimumab 40 mg every other week during a 28-week open-label lead-in period. Clinical remission was defined as Ankylosing Spondylitis Disease Activity Score inactive disease (ASDAS ID; score <1.3) and Assessment of SpondyloArthritis international Society partial remission (ASAS PR; score <2/10 in each of the four ASAS domains). Stepwise logistic regression was used to identify baseline predictors of remission at week 12 and at final visit (last postbaseline visit up to week 28). Only patients without missing data were included., Results: Overall, 593 patients were included in the ASDAS ID and 596 in the ASAS PR analysis at week 12. Younger age (≤45 years), male sex, positive human leucocyte antigen (HLA)-B27 and higher Spondyloarthritis Research Consortium of Canada (SPARCC) MRI sacroiliac joint score were consistent predictors of remission by both ASAS ID and ASDAS PR at week 12. Results were generally similar in the final visit analysis. Other variables did not consistently predict remission., Conclusions: In ABILITY-3, consistent and strong baseline predictors of remission included younger age, male sex, HLA-B27 positivity and higher SPARCC MRI sacroiliac joint score among patients with active nr-axSpA receiving adalimumab therapy, similar to previous findings in ankylosing spondylitis., Competing Interests: Competing interests: JS has received consulting fees from AbbVie, Boehringer Ingelheim, Janssen, Lilly, Merck, Novartis, Pfizer, Sun Pharma, and UCB; and speaker fees from AbbVie, Janssen, Lilly, Merck, Novartis, Pfizer and UCB. RL has received consulting or advisory board fees from Abbott/AbbVie, Ablynx, Amgen, AstraZeneca, Bristol Myers Squibb, Celgene, Janssen, Galapagos, GlaxoSmithKline, Novartis, Novo Nordisk, Merck, Pfizer, Roche, Schering-Plough, TiGenix, UCB and Wyeth; research grants from Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB and Wyeth; speaker fees from Abbott/AbbVie, Amgen, Bristol Myers Squibb, Janssen, Merck, Pfizer, Roche, Schering-Plough, UCB and Wyeth; and is director of Rheumatology Consultancy BV, a registered Dutch company. MM has received research grants from Amgen, AbbVie and UCB Pharma and consulting fees from Novartis and Eli Lilly. SZ, XW, AL and JKA are full-time employees of AbbVie and may own AbbVie stock and/or stock options.

Purpose: This real-world study evaluated the feasibility of assessing patient-reported symptom improvement and treatment satisfaction using a web-based survey among patients with ankylosing spondylitis (AS) treated with secukinumab., Methods: This cross-sectional, web-based survey collected data on demographics, symptoms, treatment history, and treatment satisfaction from US patients with AS who were receiving secukinumab at survey participation. Patients reported AS symptoms experienced before and after secukinumab initiation, time to symptom improvement, and satisfaction with secukinumab treatment., Results: Of 2755 patients screened, 200 with AS were included in the analysis. The mean (SD) age of patients was 34.4 (10.6) years; 86.5% were biologic experienced. Most (74.0%) reported overall improvement ("a little," "moderately," or "much better") in AS symptoms since secukinumab initiation compared with before secukinumab initiation; a similar trend was observed for all the individual symptoms analyzed (pain disrupting sleep, fatigue, morning stiffness, pain and stiffness in lower back or neck, sore areas other than joints, and ankle or heel pain [indicating enthesitis]). Approximately 41.9% of patients reported overall symptom improvement within 4 weeks of secukinumab treatment. Most expressed overall satisfaction ("very," "mostly," or "somewhat satisfied") with secukinumab regarding symptom improvement (99.0%), speed of symptom improvement (97.0%), frequency and method of administration (96.0% and 91.5%, respectively), ease of use (93.5%), patient support services (97.0%), and side effects, if any (93.0%)., Conclusion: Most patients reported overall symptom improvement and satisfaction with treatment. Our study indicates that patient-reported perspectives may be feasibly collected using a web-based survey to provide insights into treatment experience and satisfaction.

Objective: To develop an evidence-based guideline for the pharmacologic and nonpharmacologic treatment of psoriatic arthritis (PsA), as a collaboration between the American College of Rheumatology (ACR) and the National Psoriasis Foundation (NPF)., Methods: We identified critical outcomes in PsA and clinically relevant PICO (population/intervention/comparator/outcomes) questions. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available pharmacologic and nonpharmacologic therapies for PsA. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of the evidence. A voting panel, including rheumatologists, dermatologists, other health professionals, and patients, achieved consensus on the direction and the strength of the recommendations., Results: The guideline covers the management of active PsA in patients who are treatment-naive and those who continue to have active PsA despite treatment, and addresses the use of oral small molecules, tumor necrosis factor inhibitors, interleukin-12/23 inhibitors (IL-12/23i), IL-17 inhibitors, CTLA4-Ig (abatacept), and a JAK inhibitor (tofacitinib). We also developed recommendations for psoriatic spondylitis, predominant enthesitis, and treatment in the presence of concomitant inflammatory bowel disease, diabetes, or serious infections. We formulated recommendations for a treat-to-target strategy, vaccinations, and nonpharmacologic therapies. Six percent of the recommendations were strong and 94% conditional, indicating the importance of active discussion between the health care provider and the patient to choose the optimal treatment., Conclusion: The 2018 ACR/NPF PsA guideline serves as a tool for health care providers and patients in the selection of appropriate therapy in common clinical scenarios. Best treatment decisions consider each individual patient situation. The guideline is not meant to be proscriptive and should not be used to limit treatment options for patients with PsA., (© 2018, American College of Rheumatology.)

Objective: To develop recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP)., Methods: We conducted a systematic review to synthesize the evidence for the benefits and harms of GIOP prevention and treatment options. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence. We used a group consensus process to determine the final recommendations and grade their strength. The guideline addresses initial assessment and reassessment in patients beginning or continuing long-term (≥3 months) glucocorticoid (GC) treatment, as well as the relative benefits and harms of lifestyle modification and of calcium, vitamin D, bisphosphonate, raloxifene, teriparatide, and denosumab treatment in the general adult population receiving long-term GC treatment, as well as in special populations of long-term GC users., Results: Because of limited evidence regarding the benefits and harms of interventions in GC users, most recommendations in this guideline are conditional (uncertain balance between benefits and harms). Recommendations include treating only with calcium and vitamin D in adults at low fracture risk, treating with calcium and vitamin D plus an additional osteoporosis medication (oral bisphosphonate preferred) in adults at moderate-to-high fracture risk, continuing calcium plus vitamin D but switching from an oral bisphosphonate to another antifracture medication in adults in whom oral bisphosphonate treatment is not appropriate, and continuing oral bisphosphonate treatment or switching to another antifracture medication in adults who complete a planned oral bisphosphonate regimen but continue to receive GC treatment. Recommendations for special populations, including children, people with organ transplants, women of childbearing potential, and people receiving very high-dose GC treatment, are also made., Conclusion: This guideline provides direction for clinicians and patients making treatment decisions. Clinicians and patients should use a shared decision-making process that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies., (© 2017, American College of Rheumatology.)

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.