Axial spondyloarthritis guidelines - aiming for maximum impact.

PURPOSE OF REVIEW: This review discusses international clinical practice guidelines (CPGs) for axial spondyloarthritis (axSpA) focusing on methodology, guideline quality, and implementation. RECENT FINDINGS: The Assessment of SpondyloArthritis International Society/European Alliance of Associations for Rheumatology (ASAS/EULAR) and Pan-American League of Associations for Rheumatology (PANLAR) recently published axSpA CPGs and updates of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network (ACR/SAA/SPARTAN) and Asia-Pacific League of Associations for Rheumatology (APLAR) CPGs are expected. GRADE has emerged as the dominant framework for CPG development and has been used by three of the four international axSpA guidelines. Notable differences exist among these guidelines in the way that the recommendations are presented. Two of the four acknowledge the need for implementation strategies, but little detail about this is provided. The few studies that have evaluated the implementation of axSpA CPGs have identified poor adherence to recommendations on physical therapy/exercise and disease activity monitoring. Implementation science has identified many barriers and facilitators affecting guideline uptake, including those related to healthcare professionals and to the guidelines themselves. Creation of a tailored implementation plan simultaneously with the CPG is recommended. SUMMARY: While methodological rigor in the creation of evidence-based recommendations is the focus of CPG development, recommendations must be presented in a user-friendly format that makes them easy to apply. 'Living guidelines' could facilitate keeping content up to date. Implementation is critical for the success of a CPG and should be emphasized in future axSpA guideline updates. Further research is needed to better understand the factors impacting the successful implementation of axSpA CPGs.

Association of clinical response criteria and disease activity levels with axial spondyloarthritis core domains: results from two phase 3 randomised studies, BE MOBILE 1 and 2.

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.

American College of Rheumatology (ACR) and Food and Drug Administration (FDA) Summit: Summary of the Meeting May 17-18, 2022.

On May 17-18, 2022, the ACR and the FDA co-sponsored a public meeting to address topics of mutual interest and importance in assessing long-term safety and clinical efficacy, as well as novel approaches to clinical trials in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). During the two-day consensus-building summit, rheumatologists, other health care professionals, and FDA staff provided a broad perspective on current clinical development challenges and potential approaches to address them. Key takeaways are summarized in this document, including issues related to innovative clinical trial designs, use of novel outcome measures such as magnetic resonance imaging (MRI) and patient-reported outcomes (PROs), and use of innovative approaches to collecting data including registries and digital health technology (DHT).

Treatment Persistence and Switching Patterns of Adalimumab Biosimilar ABP 501 in European Patients with Rheumatologic Diseases.

INTRODUCTION: ABP 501 was an adalimumab (ADA) biosimilar approved for treating immune-mediated inflammatory diseases (IMIDs) including rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). In this retrospective study, we aimed to examine the treatment patterns of ABP 501 among patients with these IMIDs using German and French pharmacy claims databases. METHODS: Patients with RA, PsA, or AS who initiated ABP 501 between October 2018 and March 2020 and were observed continuously for ≥ 365 days both before and after ABP 501 initiation were included. Descriptive analyses of persistence and switch after ABP 501 discontinuation were conducted and reported for each disease cohort by prior use of ADA products (patients naïve to ADA or patients experienced with ADA). RESULTS: Median (95% confidence interval) persistence on ABP 501 was 9.4 (8.6-10.3), 10.2 (9.0-11.7), and 12.1 (11.0-13.1) months in German patients, and 11.7 (9.9-13.3), 7.1 (5.8-8.4), and 10.8 (9.6-11.9) months in French patients for RA, PsA, and AS, respectively. For patients who switched from ABP 501 to another targeted therapy during the first 12 months of follow-up, switching patterns varied between patients naïve to ADA and patients experienced with ADA in both Germany and France, with patients naïve to ADA switching most frequently to other targeted therapies including non-ADA tumor necrosis factor inhibitor (TNFi), non-TNFi biologic, or Janus Kinase inhibitor (JAKi) and patients experienced with ADA switching most frequently back to ADA reference product (RP). CONCLUSIONS: Across three rheumatologic diseases, about half of patients persisted on ABP 501 at the end of 12 months after treatment initiation in both Germany and France. Patients experienced with ADA were more likely to switch back to ADA RP, regardless of indication and country, suggesting a possible nocebo effect. Future studies are warranted to understand reasons of discontinuation and switching.

Sex differences in time to initiate NSAIDs or bDMARDs among patients with axial spondyloarthritis.

OBJECTIVE: We evaluated sex differences in time to initiation of nonsteroidal anti-inflammatory agents (NSAIDs) or biologic disease modifying antirheumatic drugs (bDMARDs) among patients with axial spondyloarthritis (axSpA). METHODS: Using the 2013-2018 IBM® MarketScan® Database, we identified 174,632 axSpA patients aged ≥18 years. We evaluated the time between axSpA diagnosis and the first prescription NSAID dispensing (among those with no baseline NSAIDs use) or bDMARDs infusion/procedure claim (among those dispensed ≥ two different prescription NSAIDs in the baseline period). Adjusted hazard ratios (aHR) for time to initiation of NSAIDs or bDMARDs were computed using survival analyses. Cox proportional hazard models estimated associations between sex and predictors of treatment initiation. RESULTS: Average age at diagnosis was 48.2 years, 65.7% were females, and 37.8% had ≥ one NSAIDs dispensing before axSpA diagnosis. Of those without dispensing for ≥ two different prescription NSAIDs before diagnosis, NSAIDs were initiated earlier in females than males (NSAID initiators: Females (32.9%), Males (29.3%); aHR: 1.14, 95% CI: 1.11-1.16). Among those with ≥ two different prescription NSAIDs dispensations in the baseline period, 4.2% initiated a bDMARD while 77.9% continued NSAIDs use after diagnosis. Time to bDMARDs initiation was longer for females than males (aHR:0.61, 95% CI:0.52-0.72), but bDMARDs were initiated sooner among those with NSAIDs use in the baseline period. CONCLUSION: Prescription NSAID use was more common than initiation of bDMARDs among patients newly diagnosed with axSpA. Females appeared more likely to continue NSAIDs after diagnosis, and the time to initiation of bDMARDs was longer for females than males.

Modeling the Effects of Formulary Exclusions: How Many Patients Could Be Affected by a Specific Exclusion?

Background: Medication formularies, initially designed to promote the use of cost-effective generic drugs, are now designed to maximize financial benefits for the pharmacy benefit management companies that negotiate purchase prices. In the second-largest pharmacy benefit management formulary that is publicly available, 55% of mandated substitutions are not for generic or biosimilar versions of the same active ingredient and/or formulation and may not be medically or financially beneficial to patients. Methods: We modeled the effect of excluding novel agents for atrial fibrillation/venous thromboembolism, migraine prevention, and psoriasis, which all would require substitution with a different active ingredient. Using population data, market share of the 2 largest US formularies, and 2021 prescription data, we calculated how many people could be affected by such exclusions. Using data from the published literature, we calculated how many of those individuals are likely to discontinue treatment and/or have adverse events due to a formulary exclusion. Results: The number of people likely to have adverse events due to the exclusion could be as high as 1 million for atrial fibrillation/venous thromboembolism, 900 000 for migraine prevention, and 500 000 for psoriasis. The numbers likely to discontinue treatment for their condition are as high as 924 000 for atrial fibrillation/venous thromboembolism, 646 000 for migraine, and 138 000 for psoriasis. Conclusion: Substitution with a nonequivalent treatment is common in formularies currently in use and is not without substantial consequences for hundreds of thousands of patients. Forced medication substitution results in costly increases in morbidity and mortality and should be part of the cost-benefit analysis of any formulary exclusion.

Review of Adalimumab Biosimilar SB5 in Immune-Mediated Inflammatory Diseases.

SB5 is an approved biosimilar of adalimumab, a recombinant monoclonal anti-tumor necrosis factor (TNF) antibody. The approval of SB5 was based on the comparison with reference adalimumab in analytical studies, pharmacokinetic (PK) and immunogenicity assessments, and randomized controlled trials. Efficacy data was primarily obtained in patients with rheumatoid arthritis, and extended to include additional indications such as psoriasis, Crohn's disease, or ulcerative colitis by extrapolation. Following its approval, additional post-marketing data have been collected comparing SB5 with reference adalimumab. This review summarizes the clinical data on SB5 from randomized controlled trials and provides a comprehensive overview of the available post-approval data. In "real-world" settings, SB5 was as effective as its reference product across different indications and countries, treatment persistence was well maintained throughout studies, and no new safety concerns were identified. In both controlled and "real-world" settings, switching from reference adalimumab to SB5 was not associated with altered efficacy or clinical complications. In post-approval studies, the quality of SB5 was consistent over time, independent of the batch and process changes, and the SB5 autoinjector was preferred over other autoinjectors by both healthcare professionals and patients. Taken together, these data support the use of SB5 whenever reference adalimumab is appropriate and demonstrate that switching from reference adalimumab to SB5 is feasible.

Unmet need in rheumatology: reports from the Advances in Targeted Therapies meeting, 2023.

The Advances in Targeted Therapies meets annually, convening experts in the field of rheumatology to both provide scientific updates and identify existing scientific gaps within the field. To review the major unmet scientific needs in rheumatology. The 23rd annual Advances in Targeted Therapies meeting convened with more than 100 international basic scientists and clinical researchers in rheumatology, immunology, infectious diseases, epidemiology, molecular biology and other specialties relating to all aspects of immune-mediated inflammatory diseases. We held breakout sessions in five rheumatological disease-specific groups including: rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (axSpa), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and vasculitis, and osteoarthritis (OA). In each group, experts were asked to identify and prioritise current unmet needs in clinical and translational research. An overarching theme across all disease states is the continued need for clinical trial design innovation with regard to therapeutics, endpoint and disease endotypes. Within RA, unmet needs comprise molecular classification of disease pathogenesis and activity, pre-/early RA strategies, more refined pain profiling and innovative trials designs to deliver on precision medicine. Continued scientific questions within PsA include evaluating the genetic, immunophenotypic, clinical signatures that predict development of PsA in patients with psoriasis, and the evaluation of combination therapies for difficult-to-treat disease. For axSpA, there continues to be the need to understand the role of interleukin-23 (IL-23) in pathogenesis and the genetic relationship of the IL-23-receptor polymorphism with other related systemic inflammatory diseases (eg, inflammatory bowel disease). A major unmet need in the OA field remains the need to develop the ability to reliably phenotype and stratify patients for inclusion in clinical trials. SLE experts identified a number of unmet needs within clinical trial design including the need for allowing endpoints that reflect pharmacodynamic/functional outcomes (eg, inhibition of type I interferon pathway activation; changes in urine biomarkers). Lastly, within SSc and vasculitis, there is a lack of biomarkers that predict response or disease progression, and that allow patients to be stratified for therapies. There remains a strong need to innovate clinical trial design, to identify systemic and tissue-level biomarkers that predict progression or response to therapy, endotype disease, and to continue developing therapies and therapeutic strategies for those with treatment-refractory disease. This document, based on expert consensus, should provide a roadmap for prioritising scientific endeavour in the field of rheumatology.

Walter Bauer, Marian Wilkins Ropes, and the Massachusetts General Hospital.

Walter Bauer was instrumental in the development of rheumatology as a medical subspecialty, promoting careful clinical observation and description and bringing basic scientists and clinicians together to study the "anatomy, chemical composition, and metabolism of connective tissue" in the laboratory. Marian Wilkins Ropes was a pioneering woman in medicine: the first female medical resident at the Massachusetts General Hospital, the first woman appointed as an assistant professor of clinical medicine at Harvard Medical School, the first woman elected to membership in the American Society of Clinical Investigation, and the first woman elected president of the American Rheumatism Association.

Postpartum Depression in Reproductive-Age Women With and Without Rheumatic Disease: A Population-Based Matched Cohort Study.

OBJECTIVE: To examine postpartum depression (PPD) among women with axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), or rheumatoid arthritis (RA) in comparison with a matched population without rheumatic disease (RD). METHODS: A retrospective analysis using the 2013-2018 IBM MarketScan Commercial Claims and Encounters Database was conducted. Pregnant women with axSpA, PsA, or RA were identified, and the delivery date was used as the index date. We restricted the sample to women ≤ 55 years with continuous enrollment ≥ 6 months before date of last menstrual period and throughout pregnancy. Each patient was matched with 4 individuals without RD on: (1) maternal age at delivery, (2) prior history of depression, and (3) duration of depression before delivery. Cox frailty proportional hazards models estimated the crude and adjusted hazard ratios (aHR) and 95% CI of incident postpartum depression within 1 year among women with axSpA, PsA, or RA (axSpA/PsA/RA cohort) compared to the matched non-RD comparison group. RESULTS: Overall, 2667 women with axSpA, PsA, or RA and 10,668 patients without any RD were included. The median follow-up time in days was 256 (IQR 93-366) and 265 (IQR 99-366) for the axSpA/PsA/RA cohort and matched non-RD comparison group, respectively. Development of PPD was more common in the axSpA/PsA/RA cohort relative to the matched non-RD comparison group (axSpA/PsA/RA cohort: 17.2%; matched non-RD comparison group: 12.8%; aHR 1.22, 95% CI 1.09-1.36). CONCLUSION: Postpartum depression is significantly higher in women of reproductive age with axSpA/PsA/RA when compared to those without RD.

Comanagement with rheumatology and prescription biologics filled during pregnancy in women with rheumatic diseases: a retrospective analysis of US administrative claims data.

OBJECTIVES: To evaluate comanagement with rheumatology and biological prescriptions filled during pregnancy among women with axial spondyloarthritis (axSpA), rheumatoid arthritis (RA) or psoriatic arthritis (PsA) and to examine factors associated with receiving comanagement with rheumatology during pregnancy. DESIGN: A retrospective analysis of US claims data. SETTING: Commercially insured enrollees using data from the 2013-2018 IBM MarketScan Commercial Claims and Encounters Database. PARTICIPANTS: We identified 4131 pregnant women aged ≤55 years from the 2013-2018 IBM MarketScan Commercial Claims and Encounters Database with an International Classification of Disease, 9th Revision/10th Revision codes for RA, axSpA or PsA, with continuous enrolment at ≥3 months before the date of the last menstrual period (LMP) (index date) and throughout pregnancy. PRIMARY OUTCOMES: Filled biologics (prescriptions and infusions) claims were categorised by 90 days before the LMP and trimester, as were primary care, obstetrician and rheumatological claims. RESULTS: The prevalence of axSpA, RA and PsA was 0.7%, 0.2% and 0.04% among reproductive age women. The average maternal age was 32.7 years (SD 5.7). During pregnancy, 9.1% of those with axSpA (n=2,410) and 56.4% of those with RA/PsA (n=1,721) had a rheumatological claim. Biologics claims were less common among those with axSpA (90 days before LMP: 1.6%, during pregnancy: 1.1%) than those with RA/PsA (90 days before LMP: 11.9%, during pregnancy: 6.9%). Medications during pregnancy included corticosteroids (axSpA: 0.3%, RA/PsA: 2.2%), non-biological disease-modifying antirheumatic drugs (axSpA: 0.2%, RA/PsA: 1.7%), non-steroidal anti-inflammatory drugs (axSpA: 0.2%, RA/PsA: 1.3%) and opioids (axSpA: 0.2%, RA/PsA: 0.6%). Established rheumatological care and biologics claims during the 90 days before LMP showed good prediction accuracy for receiving comanagement with rheumatology during pregnancy (axSpA: area under the receiver operator curve (AUC) 0.73, RA/PsA: AUC 0.70). CONCLUSION: Comanagement with rheumatology during pregnancy occurs infrequently, especially for women with axSpA. Biologics claims during pregnancy may not align with published guidelines. Future research is warranted to improve comanagement with rheumatology during pregnancy.

The disparate impact of COVID-19 pandemic on walking and biking behaviors.

This study sought to assess changes in active transportation behaviors due to the COVID-19 pandemic, in addition to identifying the disparate impacts between sociodemographic groups. A survey was conducted in November 2020, which collected responses from 1,000 Michigan residents statewide regarding walking and biking behaviors before, during, and anticipated post-pandemic. The survey found that people who walked or biked frequently for recreation before the pandemic maintained or increased their activities during the pandemic. More importantly, the survey also revealed differing pandemic-related impacts on walking and biking behaviors between sociodemographic groups. Specifically, people from underprivileged sociodemographic groups, such as those who are older, have lower education or income level, or identify as a minority, were less active in general before the pandemic, and these walking and biking behavior gaps were exacerbated by the pandemic. Furthermore, the elevated negative impacts on these sociodemographic groups were anticipated to continue in the future.

The architecture of clonal expansions in morphologically normal tissue from cancerous and non-cancerous prostates.

BACKGROUND: Up to 80% of cases of prostate cancer present with multifocal independent tumour lesions leading to the concept of a field effect present in the normal prostate predisposing to cancer development. In the present study we applied Whole Genome DNA Sequencing (WGS) to a group of morphologically normal tissue (n = 51), including benign prostatic hyperplasia (BPH) and non-BPH samples, from men with and men without prostate cancer. We assess whether the observed genetic changes in morphologically normal tissue are linked to the development of cancer in the prostate. RESULTS: Single nucleotide variants (P = 7.0 × 10-03, Wilcoxon rank sum test) and small insertions and deletions (indels, P = 8.7 × 10-06) were significantly higher in morphologically normal samples, including BPH, from men with prostate cancer compared to those without. The presence of subclonal expansions under selective pressure, supported by a high level of mutations, were significantly associated with samples from men with prostate cancer (P = 0.035, Fisher exact test). The clonal cell fraction of normal clones was always higher than the proportion of the prostate estimated as epithelial (P = 5.94 × 10-05, paired Wilcoxon signed rank test) which, along with analysis of primary fibroblasts prepared from BPH specimens, suggests a stromal origin. Constructed phylogenies revealed lineages associated with benign tissue that were completely distinct from adjacent tumour clones, but a common lineage between BPH and non-BPH morphologically normal tissues was often observed. Compared to tumours, normal samples have significantly less single nucleotide variants (P = 3.72 × 10-09, paired Wilcoxon signed rank test), have very few rearrangements and a complete lack of copy number alterations. CONCLUSIONS: Cells within regions of morphologically normal tissue (both BPH and non-BPH) can expand under selective pressure by mechanisms that are distinct from those occurring in adjacent cancer, but that are allied to the presence of cancer. Expansions, which are probably stromal in origin, are characterised by lack of recurrent driver mutations, by almost complete absence of structural variants/copy number alterations, and mutational processes similar to malignant tissue. Our findings have implications for treatment (focal therapy) and early detection approaches.

Use of multibiomarker disease activity scores in biosimilarity studies for the treatment of patients with rheumatoid arthritis.

OBJECTIVES: This exploratory analysis investigated the potential use of the multibiomarker disease activity (MBDA) score to support biosimilarity assessments using data from two randomised controlled trials (RCTs) of biosimilar infliximab (IFX-qbtx) and biosimilar adalimumab (ADL-afzb) versus EU-sourced infliximab (Remicade; IFX-EU) and adalimumab (Humira; ADL-EU) reference products, respectively, both conducted in adult patients with active rheumatoid arthritis. METHODS: In one study, patients (N=650) were randomised 1:1 to IFX-qbtx or IFX-EU (3 mg/kg intravenous at weeks 0, 2 and 6, then every 8 weeks). In the other, patients (N=597) were randomised 1:1 to ADL-afzb or ADL-EU (40 mg subcutaneous every other week). All treatments were given with MTX. Mean values of MBDA scores were calculated at baseline (BL), based on the concentrations of 12 serum proteins using the Vectra disease activity algorithm, and at timepoints throughout treatment period 1 (TP1) of the IFX (weeks 6, 14, 30) and ADL (weeks 6, 12, 26) studies. Data were summarised using descriptive statistics for the intent-to-treat population, without imputation for missing data. RESULTS: At BL, mean (±SD) MBDA scores were 61.3 (±12.5) and 58.8 (±13.2) for IFX-qbtx (n=236) and IFX-EU (n=248), respectively, and 57.2 (±14.44) and 58.3 (±15.34) for ADL-afzb (n=292) and ADL-EU (n=293), respectively. Mean MBDA scores were highly comparable between IFX-qbtx and IFX-EU and between ADL-afzb and ADL-EU at all measured timepoints during TP1 in each study. CONCLUSIONS: These RCTs are the first to incorporate MBDA score as an exploratory assessment of biosimilarity. MBDA scores may provide objective, quantitative evidence of biosimilarity using an assessment of disease activity that is independent of the potential subjectivity inherent in joint counts, or in patient or physician global assessments. TRIAL REGISTRATION NUMBERS: NCT02222493 and NCT02480153.

The NALCN channel regulates metastasis and nonmalignant cell dissemination.

We identify the sodium leak channel non-selective protein (NALCN) as a key regulator of cancer metastasis and nonmalignant cell dissemination. Among 10,022 human cancers, NALCN loss-of-function mutations were enriched in gastric and colorectal cancers. Deletion of Nalcn from gastric, intestinal or pancreatic adenocarcinomas in mice did not alter tumor incidence, but markedly increased the number of circulating tumor cells (CTCs) and metastases. Treatment of these mice with gadolinium-a NALCN channel blocker-similarly increased CTCs and metastases. Deletion of Nalcn from mice that lacked oncogenic mutations and never developed cancer caused shedding of epithelial cells into the blood at levels equivalent to those seen in tumor-bearing animals. These cells trafficked to distant organs to form normal structures including lung epithelium, and kidney glomeruli and tubules. Thus, NALCN regulates cell shedding from solid tissues independent of cancer, divorcing this process from tumorigenesis and unmasking a potential new target for antimetastatic therapies.

Switching Between Adalimumab Reference Product and BI 695501 in Patients with Chronic Plaque Psoriasis (VOLTAIRE-X): A Randomized Controlled Trial.

BACKGROUND: BI 695501 is an FDA-approved biosimilar to adalimumab reference product (RP). VOLTAIRE-X was a randomized clinical trial to assess outcomes with a biosimilar monoclonal antibody in line with the FDA requirements for designation as an 'interchangeable' biosimilar. OBJECTIVE: The aim of this study was to assess whether multiple switches between adalimumab RP and BI 695501 lead to equivalent pharmacokinetics and a similar safety and immunogenicity profile compared with continuous adalimumab RP. METHODS: We conducted a phase III, double-blind, randomized controlled trial between July 19, 2017, and April 16, 2019. There were 49 investigational sites across Europe and North America. Of 323 screened patients with moderate-to-severe chronic plaque psoriasis, 259 were treated with adalimumab RP during the run-in period. Of these, 118 and 120 were randomized to the continuous or switching arms, respectively. Interventions consisted of a run-in period with adalimumab RP 80 mg subcutaneously (SC) on Day 1, then 40 mg SC every other week (EOW) Weeks 2-12. Patients were then randomized to receive adalimumab RP 40 mg EOW Weeks 14-48 (continuous arm) or BI 695501 40 mg Weeks 14 and 16, adalimumab RP 40 mg Weeks 18 and 20, and BI 695501 40 mg EOW Weeks 22 to 48 (switching arm); all interventions were given SC. Primary endpoints were pharmacokinetics parameters, area under the plasma concentration-time curve (AUCτ,30-32) and maximum observed drug plasma concentration (Cmax,30-32), measured after the third switch during the Week 30-32 dosing interval. RESULTS: 238 patients (mean [standard deviation] age 44.9 [13.8]; 66.0% male) were treated in the switching (n = 118) or continuous arms (n = 120). Adjusted mean Cmax,30-32 was 7.08 and 7.00 µg/mL in the switching and continuous treatment arms, respectively; adjusted mean AUCτ,30-32 was 2025.8 and 1925.9 µg h/mL. Point estimate for mean ratio for AUCτ,30-32 was 105.2% (90.2% confidence interval [CI] 96.6-114.6), and 101.1% (90.2% CI 93.3-109.7) for Cmax,30-32. Both CIs were within a predefined bioequivalence range of 80.0-125.0%. Treatment-emergent adverse events led to discontinuation in 0.8% and 1.7% of patients in the switching and continuous treatment arms, and Psoriasis Area and Severity Index (PASI) scores were highly similar in the two arms across the entire trial period. CONCLUSIONS: Pharmacokinetic equivalence was demonstrated, with highly similar efficacy and immunogenicity, and comparable safety observed in patients with chronic plaque psoriasis who received either adalimumab RP continuously or who switched between adalimumab RP and BI 695501. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03210259 (registered July 2017); Eudract.ema.europa.eu: 2016-002254-20.

Development and test-retest reliability of a screening tool for axial spondyloarthritis.

BACKGROUND: People with axial Spondyloarthritis (axSpA) suffer from lengthy diagnostic delays of ~7 years. The usage of screening tools to identify axSpA patients in primary care can reduce diagnostic delays by facilitating early referral to rheumatologic care. The purpose of this study was to examine the psychometric properties of a potential screening tool for patients with axSpA. METHOD: Content validity was evaluated by soliciting feedback from 7 rheumatologists regarding the relevance and content representativeness of the proposed screening questions. For the test-retest study, participants ≥18 years of age with chronic back pain (≥3 months) without a diagnosis of mechanical or inflammatory back pain (n = 91) were e-recruited through ResearchMatch. Participation included completing identical baseline and follow-up questionnaires ~14 days apart. Weighted quadratic kappa was used to measure test-retest reliability between the two ratings of the ordinal scales. Construct validity was examined using exploratory factor analysis (EFA) and items with factor loadings ≥0.6 were extracted. Scale dimensionality and simplified factorial solutions were measured using Kaiser's criteria (Eigenvalue >1). Cronbach's alpha was used to measure internal consistency. RESULTS: Most participants were women, non-Hispanic white, and had at least some college education, with a mean age of 45 years. On average, the age at onset of back pain was 31 years. Eleven questions yielded test-retest reliabilities ranging from 0.6 to 0.76. Results from EFA extracted two factors relating to: 1) how pain affects daily life functioning and 2) whether pain improves with movement. Internal consistency was high for questions evaluating how pain affects life, with a Cronbach's alpha of 0.81. Following assessment for validity and reliability, the questionnaire was revised to create the 6-item screening tool. CONCLUSIONS: The 6-item SpA-SED screening tool designed to identify potential cases of axSpA was found to have good test-retest reliability and high internal consistency.

Development of a screening tool to identify patients with axial spondyloarthritis: a cognitive interview study.

OBJECTIVE: To further refine the wording of screening questions and examine their face validity through cognitive interviews with axial spondyloarthritis (axSpA) and chronic mechanical back pain patients. METHODS: In-depth, semi-structured cognitive interviews were conducted with 30 patients (10 axSpA; 20 chronic mechanical back pain patients) to assess the face validity and comprehensibility of the screening questions. The interview protocol focused on 12 questions/domains including participants' feedback/thoughts on the duration of suffering from back pain, age at onset of back pain, pace of back pain development, improvement of pain with movement or rest, nocturnal back pain improving upon awakening, pain in other parts of the body, responsiveness of pain to nonsteroidal anti-inflammatory drug (NSAID) use, history of autoimmune conditions, and domains such as sleep, sitting, and stiffness. The Flesch-Kincaid grade level and Flesch reading ease scores were then analyzed for the revised versions of screening questions. RESULTS: Participants preferred questions that allowed them to provide more details regarding the frequency of their symptoms. Questions were refined for clarity and eliminated if participants considered them to be irrelevant (e.g., NSAIDs). Two sample screeners were derived from twelve questions each with an overall reading grade of 7.5 and reading ease of 65.7%. CONCLUSIONS: It is feasible to design a screening tool that is accessible to most (e.g., reading level) and clear to individuals with back pain. An evidence-based approach to demonstrate the validity of the screening tool will be critical for it to be implemented widely into clinical practice. Key Points • Our study developed two sample screeners that are clear to individuals with back pain and accessible to most with an overall Flesch-Kincaid reading grade of 7.5 and Flesch reading ease of 65.7%. • Questions that were considered irrelevant to participants were eliminated such as responsiveness of pain to nonsteroidal anti-inflammatory drug (NSAID). • It is feasible to design a screening tool that is accessible to most (e.g., reading level) and clear to individuals with back pain.

The disease burden of axial spondyloarthritis: through a gendered lens.

INTRODUCTION: Axial spondyloarthritis (axSpA) affects patients' health-related quality of life (HRQoL). Prior studies have documented gender differences in axSpA across the disease spectrum. Our study aims to assess gender differences on the effects of axSpA on patients' HRQoL. METHOD: A secondary qualitative thematic analysis was conducted using data from in-depth interviews (n = 24) of patients with a rheumatologist-confirmed axSpA diagnosis. This analysis focused on gender and HRQoL themes including activity, occupation, sleep, healthcare system, mental health, medication usage, and relationships. RESULTS: While men on average waited a year longer than women to tell healthcare providers about symptoms (2.5 years men versus 1.6 years women), the interval between first report of symptoms to diagnosis was ~ 2 years longer for women relative to men (7.5 women versus 9.3 years men). Women and men with axSpA shared more similarities than differences regarding the impact of disease on HRQoL including (1) physical health, (2) limited mobility, (3) occupation, (4) sleep, (5) healthcare system obstacles, (6) mental health, (7) medication usage, and (8) relationships. Some women reported being dismissed by doctors due to their gender, and some described the pain experienced during pregnancy and complications during birth. CONCLUSIONS: axSpA adversely impacts HRQoL regardless of gender, but women seeking care for axSpA may experience greater challenges reaching a diagnosis. It is essential that providers recognize impaired HRQoL among men and women with axSpA. Future studies with larger sample sizes are needed to identify aspects of HRQoL to adequately address people with axSpA. Key Points • While men waited on average a year longer to tell their healthcare provider about their symptoms, the diagnostic delay is 2 years longer for women. • Women and men with axSpA have similar experiences regarding impacts on their health-related quality of life. • Some women describe difficulty during pregnancy and being dismissed by doctors due to their gender.