• Humans
• Etanercept/therapeutic use
• Spondylitis, Ankylosing/drug therapy
• Spondylitis, Ankylosing/mortality
• Arthritis, Psoriatic/drug therapy
• Arthritis, Psoriatic/mortality
• Arthritis, Rheumatoid/drug therapy
• Arthritis, Rheumatoid/mortality
• Female
• Male
• Middle Aged
• Propensity Score
• Registries
• Tumor Necrosis Factor-alpha/antagonists & inhibitors
• Antirheumatic Agents/therapeutic use
• Adult
• Czech Republic
• Antibodies, Monoclonal/therapeutic use
• Aged
• Kaplan-Meier Estimate

• ankylosing spondylitis
• anti-TNF
• axial spondyloarthritis
• biological therapy
• drug survival

• Axial Spondyloarthritis
• Disease Activity
• Epidemiology

• Humans
• Male
• Female
• Registries
• Adult
• Middle Aged
• Europe/epidemiology
• Axial Spondyloarthritis/diagnosis
• Axial Spondyloarthritis/epidemiology
• Severity of Illness Index
• ROC Curve
• Rheumatology/standards
• Sex Factors
• Age Factors
• Tumor Necrosis Factor Inhibitors/therapeutic use

• Novartis Pharma

• biological DMARDs
• inefficacy
• psoriatic arthritis
• switching
• targeted synthetic DMARDs

• Instituto de Salud Carlos III (ISCIII), Ministry of Health, Spain, Red de Enfermedades Inflamatorias (REI)
• Fondo Europeo de Desarrollo Regional (FEDER)

• rheumatology
• spondyloarthritis
• ankylosing spondylitis
• biological therapy

• Female
• Humans
• Male
• Adalimumab/therapeutic use
• Antirheumatic Agents/therapeutic use
• Axial Spondyloarthritis
• Certolizumab Pegol/therapeutic use
• Etanercept/therapeutic use
• France
• Spondylarthritis/drug therapy
• Treatment Outcome
• Tumor Necrosis Factor Inhibitors/therapeutic use
• Tumor Necrosis Factor-alpha/therapeutic use
• Retrospective Studies

• MSD France

• Ankylosing spondylitis
• Biologics
• Psoriatic arthritis
• Recursive partitioning
• Rheumatoid arthritis
• Spondyloarthritis
• Treatment persistence
• Tumor necrosis factor-alpha inhibitors

• Adult
• Humans
• Female
• Infant
• Tumor Necrosis Factor Inhibitors/therapeutic use
• Arthritis, Psoriatic/drug therapy
• Arthritis, Rheumatoid/drug therapy
• Spondylarthritis
• Spondylitis, Ankylosing/drug therapy
• Antirheumatic Agents/therapeutic use
• Decision Trees
• Biological Products/therapeutic use

• Ankylosing spondylitis disease activity score
• Axial spondyloarthritis
• Predictors
• TNF-inhibitors

• Ankylosing spondylitis
• Axial spondyloarthritis
• Employment
• Female population
• Work productivity

• Eli Lilly and Company

The study objective was to explore differences in ankylosing spondylitis (AS) diagnosis experiences between men and women by examining the coding of health events over the 2 years preceding AS diagnosis.

Claims data (January 2006–April 2019) from the MarketScan databases were examined. Patients who had received two or more AS diagnoses at least 30 days apart and had at least 2 years of insurance enrollment before their first AS diagnosis were analyzed. Men were matched 1:1 to women by age, diagnosis date, insurance type, and enrollment duration. Health events (diagnosis and provider codes) were examined over 2 years before AS diagnosis and stratified by gender. Data were analyzed using univariate χ² tests.

Among 7744 patients, 274 of 1906 AS‐related codes showed statistically significant differences between men and women. Women received more diagnosis codes than men across diagnoses and providers; the largest difference in diagnosis codes among women versus men was in peripheral symptom coding (57.7% vs. 43.9%, respectively). More women than men received diagnosis codes for depression (21.2% vs. 9.8%) and other musculoskeletal symptoms (52.8% vs. 40.0%); only gout was more common in men (6.5%) than in women (2.2%). Among men, backache codes gradually increased 12 months before AS diagnosis, whereas axial and sacroiliitis coding increased sharply immediately before diagnosis. The greatest difference in physician types visited was for rheumatologists: 64.2% of women had visits compared with 45.1% of men.

Further investigation into the dissimilarities in diagnostic experiences between men and women is needed to determine whether differences are due to disease phenotype or potential cognitive bias influencing diagnostic decision‐making.

• Crohn’s disease
• extraintestinal manifestations
• methotrexate

Rheumatoid arthritis (RA) is a chronic inflammatory disease, affecting mostly women with a female/male ratio of 3:1. It is characterized by symmetrical polyarthritis, leading to progressive joint damage. Sex differences have been reported in terms of disease course and characteristics, influencing patients reported outcome measures (PROMs) and pain perception, ultimately leading to male–female disparities in treatment response. Notwithstanding, sex and gender discrepancies are still under-reported in clinical trials. Therefore, there is a consistent need for a precise reference of sex and gender issues in RA studies to improve treat-to-target achievement. This narrative review explores the above-mentioned aspects of RA disease, discussing the latest core principles of RA recommendations, from safety issues to early arthritis concept and management, treat-to-target and difficult-to-treat notions, up to the most recent debate on vaccination. Our final purpose is to evaluate how sex and gender can impact current management guidelines and how this issue can be integrated for effective disease control.

• Ankylosing spondylitis (AS)
• Biologics
• Disease activity
• Dose reduction
• Etanercept biosimilars

• Biosimilar Pharmaceuticals/therapeutic use
• Etanercept/therapeutic use
• Humans
• Retrospective Studies
• Severity of Illness Index
• Spondylitis, Ankylosing/drug therapy

• ankylosing spondylitis
• axial spondyloarthritis
• diagnosis
• inflammatory back pain
• primary care physicians

• Adult
• Humans
• Quality of Life
• Rheumatologists
• Sacroiliac Joint/diagnostic imaging
• Spine
• Spondylarthritis/diagnosis
• Spondylarthritis/therapy
• Spondylitis, Ankylosing

Despite of higher disease burden, lower efficacy to biologics has been reported in female compared to male patients with ankylosing spondylitis (AS). The aim of this study was to evaluate the efficacy and safety of secukinumab by sex in patients with active AS from five phase 3 studies (MEASURE 1–5) through 52 weeks.

Baseline demographics, disease characteristics and efficacy outcomes at Weeks 16 and 52 were summarized for males versus females. Baseline predictor analysis used multivariable logistic regression for binary outcome measures or generalized linear model for continuous outcome measures to assess the impact of sex as one of the independent variables on selected efficacy outcomes at Week 52.

Overall, 1031 males and 396 females were included in this analysis. Smoking status, hs-CRP, prior exposure to TNF inhibitors, BASMI occiput-to-wall and tragus-to-wall distance (cm) were higher in males, whereas MASES was higher in females. Efficacy outcomes i.e., ASAS40 responses and BASDAI change from baseline at Weeks 16 and 52 were generally comparable between males and females. Response rates were found to be significantly higher in male patients when compared with female patients only for ASDAS-CRP inactive disease (ID) at Week 52.

Comparable efficacy and safety outcomes were observed between male and female patients with active AS treated with secukinumab over 52 weeks. Further, sex was not an independent predictor of treatment response to secukinumab as assessed by ASAS40 responder rates and BASDAI change from baseline; association of ASDAS-CRP ID responder rates with sex warrants further exploration.

ClinicalTrials.gov; NCT01358175, NCT01649375, NCT02008916, NCT02159053, and NCT02896127.

The online version contains supplementary material available at 10.1007/s40744-021-00380-2.

• Ankylosing spondylitis
• Axial spondyloarthritis
• Biologics
• DMARDs
• Interleukins
• Quality of life
• Secukinumab
• Sex
• Spondyloarthropathies
• TNF inhibitors

• Biological therapy
• Disease activity
• Interleukins
• Psoriatic arthritis
• Survival analysis

Mounting evidence reveals evident sex differences in physiology, disease presentation and response to medication in axial SpA (axSpA). Unfortunately these data are often neglected in clinical practice and research. In this review, myths that still exist on diagnosis, disease manifestation and drug effectiveness were argued against data of the most recent literature. The aim is to increase awareness of sex differences in the clinical aspects of axSpA.

• biological therapies
• epidemiology
• inflammation
• patient reported outcomes
• sex differences
• spondyloarthritis

To assess the associations of the Assessment of Spondyloarthritis International Society Health Index (ASAS HI) with gender and other factors in patients with ankylosing spondylitis (AS).

From November 2017 to October 2018, we measured the Ankylosing Spondylitis Disease Activity Score (ASDAS), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and the ASAS HI score for AS patients at the Taichung Veterans General Hospital. After adjusting for disease activity (ASDAS-erythrocyte sedimentation rate [ESR], ASDAS- C-reactive protein [CRP], BASDAI+ESR or BASDAI+CRP), mSASSS and other potential confounders including medications, comorbidities, and laboratory data, any associations between gender and the sum score of ASDAS HI were assessed using multiple linear regression analysis, as well as any associations between gender and an ASAS HI score >5 using multivariable logistic regression analysis.

A total of 307 AS patients (62 [20.2%] females, mean age 46.4 years [S.D. 13.3], mean symptom duration 20.6 years [S.D. 12.1]) were included. Multiple linear regression analysis showed that the male gender was significantly associated with a lower ASAS HI (B = -1. 91, 95% confidence interval [CI], −2.82–−1.00, p <0.001). Multivariable logistic regression analysis revealed that males also had a lower risk of achieving scores of ASAS HI > 5 than females (odds ratio = 0.15, 95% CI, 0.07–0.36, p <0.001). Disease activity measures, including ASDAS-ESR, ASDAS-CRP and BASDAI, had positive correlations with ASAS HI.

This single-center, cross-sectional study revealed that a higher ASAS HI score was significantly associated with female gender and higher disease activity measures.

• Adult
• Blood Sedimentation
• C-Reactive Protein/analysis
• Cross-Sectional Studies
• Female
• Gender Identity
• Humans
• Linear Models
• Logistic Models
• Male
• Middle Aged
• Severity of Illness Index
• Sex Factors
• Spondylarthritis
• Spondylitis, Ankylosing
• Surveys and Questionnaires
• Taiwan

• Ankylosing spondylitis
• Nonradiographic axial spondyloarthritis
• Sex
• Sex differences
• Spondyloarthritis
• Women's health

• Autoimmunity
• CTLA-4
• Cancer
• Checkpoint therapy
• Influenza vaccine
• PD-1/PD-L1
• Rheumatoid arthritis
• Tumor necrosis factor (TNF) inhibitor

• Axial spondyloarthritis
• Burden of illness
• Cost of illness
• Delayed diagnosis
• Patient-reported outcome measures
• Quality of life
• Systematic review

• Novartis Pharmaceuticals Corporation

Objective: This prospective observational study investigated the efficacy of tumor necrosis factor inhibitors (TNFis) on disease activity, physical functionality, and mobility in patients with ankylosing spondylitis (AS) in a real-world setting.

Methods: The Chinese Ankylosing Spondylitis Prospective Imaging Cohort (CASPIC) is an ongoing cohort study. Patients with AS were included to one of two groups: the TNFi user group included those who received TNFi at any time point; the non-TNFi user group included those who did not receive TNFi. Disease activity, physical functionality, and mobility were assessed by AS Disease Activity Scores (ASDAS), Bath AS Functional Index (BASFI), and Bath AS Metrology Index (BASMI), respectively.

Results: A total of 804 patients with AS (241 TNFi users and 563 non-TNFi users) were recruited. For TNFi users, 83% received an etanercept biosimilar and 17.0% received adalimumab. Seventy-three TNFi users (30.3%) discontinued TNFis during the follow-up period; the mean duration of TNFi treatment was 6.9 ± 3.2 months. Reductions in ASDAS were significantly greater in TNFi users than in nonusers at 3, 6, and 12 months (differences in ASDAS reduction were 0.61, 0.56, and 0.46 units, respectively, all P < 0.05). Similarly, the improvement in BASFI was significantly greater in users than in nonusers at 3, 6, and 12 months (differences in BASFI improvement: 0.31, 0.75, and 0.74 units, respectively, all P < 0.05). BASMI increased in nonusers at 6 and 12 months (0.27, P = 0.47; 0.66, P < 0.001, respectively), but did not change in users (−0.16 and −0.13, respectively, both P > 0.05). At 12 months, changes in BASMI were significantly greater in nonusers than in users (−0.60, P = 0.47).

Conclusion: TNFis are effective against disease activity and improve the physical functionality of patients with AS, even in those who taper or discontinue TNFis. Thus, TNFis may retard the progression of spinal mobility dysfunction in AS patients. TNF may maintain spinal mobility as indicated by the BASMI.

• adalimumab
• ankylosing spondylitis disease activity
• biosimilar etanercept
• real-world study
• tumor necrosis factor

• Ankylosing spondylitis
• Persistence
• Treatment patterns

• Eli Lilly and Company

• Ankylosing spondylitis
• Observational
• Treatment
• Tumour necrosis factor inhibitor

• anti-TNF treatment
• genetics
• single nucleotide polymorphisms
• spondyloarthritis

We describe the journey to diagnosis of ankylosing spondylitis (AS) from the patient perspective and examine differences in this journey by sex.

US adults aged ≥ 18 years with a self-reported AS diagnosis were recruited online through CreakyJoints, a patient support community, and ArthritisPower, a patient research registry. Respondents completed a web-based survey on sociodemographics, disease burden, and diagnosis history. Results were stratified by sex and time to diagnosis using two-sample t tests and χ² tests, respectively, to observe differences across the groups; P < 0.05 was considered statistically significant.

Among 235 respondents, 174 (74.0%) were female. Mean (SD) ages of female and male respondents were 48.6 (10.6) and 53.1 (10.3) years, respectively. From the time respondents began seeking medical attention, 87 were diagnosed within ≤ 1 year, 71 in 2–9 years, and 77 after ≥ 10 years. Symptoms that led respondents to seek treatment were back pain (73.2%) and joint pain (63.8%); fatigue and difficulty sleeping were more common among respondents with longer times to diagnosis. During the diagnosis process, men with AS tended to receive quicker AS diagnosis compared with women. Overall, commonly reported initial diagnoses among respondents with longer time to AS diagnosis included back problems and psychosomatic disorders. Significantly more women reported misdiagnoses of fibromyalgia (20.7 vs. 6.6%) and psychosomatic disorders (40.8 vs. 23.0%) compared with men.

Diagnosis delays and misdiagnoses were common among respondents with AS. Increasing awareness about AS among referring providers may minimize diagnosis delay.

Novartis Pharmaceuticals Corporation.

Plain language summary available for this article.

The online version of this article (10.1007/s40744-019-0153-7) contains supplementary material, which is available to authorized users.

• Ankylosing spondylitis
• Diagnosis
• Misdiagnosis
• Patient experience
• Real-world study

This analysis explored the association of treatment adherence with beliefs about medication, patient demographic and disease characteristics and medication types in rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS) to develop adherence prediction models.

The population was a subset from ALIGN, a multicountry, cross-sectional, self-administered survey study in adult patients (n=7328) with six immune-mediated inflammatory diseases who were routinely receiving systemic therapy. Instruments included Beliefs about Medicines Questionnaire (BMQ) and 4-item Morisky Medication Adherence Scale (MMAS-4^©), which was used to define adherence.

A total of 3390 rheumatological patients were analysed (RA, n=1943; PsA, n=635; AS, n=812). Based on the strongest significant associations, the adherence prediction models included type of treatment, age, race (RA and AS) or disease duration (PsA) and medication beliefs (RA and PsA, BMQ-General Harm score; AS, BMQ-Specific Concerns score). The models had cross-validated areas under the receiver operating characteristic curve of 0.637 (RA), 0.641 (PsA) and 0.724 (AS). Predicted probabilities of full adherence (MMAS-4^©=4) ranged from 5% to 96%. Adherence was highest for tumour necrosis factor inhibitors versus other treatments, older patients and those with low treatment harm beliefs or concerns. Adherence was higher in white patients with RA and AS and in patients with PsA with duration of disease <9 years.

For the first time, simple medication adherence prediction models for patients with RA, PsA and AS are available, which may help identify patients at high risk of non-adherence to systemic therapies.

ACTRN12612000977875.

• adherence
• ankylosing spondylitis
• disease-modifying antirheumatic drugs
• psoriatic arthritis
• rheumatoid arthritis

• Ankylosing spondylitis
• Anti-TNF
• Co-medication
• Remission
• Switch

• Ankylosing spondylitis
• Biological therapy
• Registries
• Spondyloarthropathy
• Tumor necrosis factor inhibitors

To assess the impact of extra-articular spondyloarthritis (SpA) manifestations (anterior uveitis, psoriasis and inflammatory bowel disease (IBD)), and of comorbidities, on tumour necrosis factor alpha inhibitor (TNFi) drug retention in ankylosing spondylitis (AS).

We identified all bio-naïve patients with AS starting a first ever TNFi July 2006 to December 2015 from the Swedish Rheumatology Quality register and followed these from treatment start through December 2015. We determined the presence of extra-articular SpA-manifestations, comorbidities (cardiovascular disease, affective disease, diabetes, malignancies, chronic lung disease and kidney disease) and socioeconomic status before TNFi start, through linkage to five other national registers, and calculated, for each factor, crude and adjusted HRs for discontinuing the TNFi.

2577 patients with AS (71% men) started a first TNFi during the study period. 27% had a history of anterior uveitis, 6% psoriasis and 7% IBD. Anterior uveitis was associated with a superior TNFi drug retention (HR 0.72; 0.62 to 0.83), psoriasis with an inferior (HR 1.48; 1.18 to 1.86), whereas IBD did not affect TNFi drug retention. The effect of the SpA manifestations on TNFi drug retention was of a similar magnitude to that of the comorbidities.

In AS, anterior uveitis and psoriasis, but not IBD, affect TNFi drug retention. Possible explanations include differential effects of TNFi on these extra-articular SpA manifestations, or inherent differences in AS, associated with the inflammatory phenotype. Further, comorbidities and socioeconomy affect TNFi drug retention to a similar magnitude as the SpA manifestations, and should, as such, receive due attention in clinical practice.

• ankylosing spondylitis
• anti-TNF
• epidemiology
• treatment

• Ankylosing spondylitis
• Extra-articular manifestation
• Nationwide registry
• Peripheral arthritis
• Treatment duration

• Biologic DMARD
• Clinical outcomes
• Medication adherence
• Medication persistence
• Patient compliance
• Tumor necrosis factor inhibitors

• Age Factors
• Autoimmune Diseases/drug therapy
• Biological Products/administration & dosage
• Biological Products/adverse effects
• Biological Products/therapeutic use
• Biological Therapy/methods
• Body Mass Index
• Comorbidity
• Health Expenditures
• Humans
• Medication Adherence/statistics & numerical data
• Quality of Life
• Retrospective Studies
• Risk Factors
• Sex Factors
• Smoking/epidemiology
• Time Factors
• Treatment Outcome
• Tumor Necrosis Factor-alpha/antagonists & inhibitors

• UCB Pharma

• ankylosing spondylitis
• outcomes research
• spondyloarthritis

• Adult
• Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
• Antirheumatic Agents/therapeutic use
• Disease Progression
• Female
• Health Status Indicators
• Humans
• Male
• Middle Aged
• Psychometrics
• Reproducibility of Results
• Sensitivity and Specificity
• Severity of Illness Index
• Spondylarthritis/drug therapy
• Spondylarthritis/physiopathology
• Spondylarthritis/rehabilitation
• Translations
• Tumor Necrosis Factor-alpha/antagonists & inhibitors

To compare, in real‐life settings, the retention rates of initial anti‐tumor‐necrosis factor (TNF) treatments (etanercept [ETN], adalimumab [ADA] and infliximab [IFX]) used as first‐line biotherapy for axial spondyloarthritis (axSpA), and evaluate treatment switches to another anti‐TNF inhibitor in the event of treatment failure.

We analyzed the medical records of all SpA patients (Assessment in Ankylosing Spondylitis International Working Group axial criteria) treated with ETN, IFX or ADA between 2001 and February 2015. Drug retention rates were calculated using the Kaplan‐Meier method and compared by means of the Cox extended model. Sub‐analyses were performed according to discontinuation reasons.

Of the 249 SpA patients analyzed (135 radiographic cases, 114 non‐radiographic), 102 received ETN, 62 ADA, and 85 IFX. In total, 103 discontinued treatment. The retention rates of IFX, ADA and ETN were 67%, 59% and 56% after 3 years; 62%, 42% and 47% after 5 years; 55%, 42% and 24% after 8 years; 53%, 42% and 12% after 10 years, respectively. In multivariate analyses, the predictive factors for retention were: low BASDAI score (hazard ratio [HR]: 1.02 [1.01‐1.04]), high C‐reactive protein levels (HR: 0.98 [0.97‐0.99]), concomitant disease‐modifying therapy (HR: 0.4 [0.21‐0.75]), and radiographic SpA (HR: 1.5 [1.0‐2.52]). In total, 61 patients switched to another anti‐TNF therapy. No difference was observed among the three anti‐TNF therapies regarding median retention duration, although the retention rate proved higher for treatment switches from one monoclonal antibody to another.

The retention rate in SpA patients proved high, with retention for IFX superior to that of ETN.

• ankylosing spondylitis
• drug treatment

• Axial spondyloarthritis
• Disease manifestation
• Gender
• Radiological progression
• Sex
• TNF inhibitors