Efficacy of secukinumab on dactylitis in patients with active psoriatic arthritis from the FUTURE 5 study.

OBJECTIVES: Dactylitis is an important clinical domain of psoriatic arthritis (PsA) associated with significant burden of disease and impaired function. Post-hoc analysis of the FUTURE 5 study was performed to evaluate the efficacy of secukinumab in patients with dactylitis at baseline over 2 years. METHODS: Randomised patients received secukinumab 300mg with loading dose (LD)/150mg LD/150mg without loading dose/placebo. Assessment of dactylitis was based on Leeds Dactylitis Index. Exploratory analyses included resolution of dactylitis based on severity, time to first resolution of dactylitis (Kaplan-Meier estimate) and resolution of dactylitis (heatmap analysis). Clinical efficacy outcomes, composite domains of disease activity, health-related quality of life (HRQoL) and radiographic progression using van der Heijde-modified total Sharp score were assessed in patients with/without dactylitis at baseline. RESULTS: Overall, 389/996 (39%) patients presented with dactylitis at baseline, had more active clinical disease and greater disease activity than those without dactylitis at baseline. Resolution of dactylitis was observed across all treatment groups at Week 104. Improvement in joints, enthesitis, skin psoriasis, nail outcomes, physical function and HRQoL were sustained over 2 years in patients with dactylitis at baseline. With secukinumab treatment, >80% of patients did not show structural radiographic progression. The proportion of non-structural radiographic progressors were comparable across patients with/without dactylitis at baseline with secukinumab treatment over 2 years. CONCLUSIONS: Patients with dactylitis at baseline were associated with higher burden of disease. Secukinumab provided sustained improvements across all clinical outcomes, QoL and inhibition of radiographic progression in PsA patients with dactylitis at baseline over 2 years.

Disease control in patients with ankylosing spondylitis in real clinical practice in Spain: Results of the MIDAS study.

INTRODUCTION AND OBJECTIVES: Understanding the disease activity is fundamental to improve patient prognosis and patients' quality of life. MiDAS study described disease activity in ankylosing spondylitis (AS) Spanish patients and the proportion of them with controlled disease. METHODS: Observational, cross-sectional, multicenter study carried out under conditions of routine clinical practice. Adult (≥18 years) patients with ≥6 months since AS diagnosis treated ≥3 months prior to inclusion. The primary endpoint was the percentage of patients with low disease activity assessed through BASDAI (primary endpoint) and ASDAS-CRP (secondary endpoint). RESULTS: 313 AS patients included: 75.7% male; 78.5% HLA-B*27 positive; mean (SD) baseline age of 50.4 (12.0) years; mean (SD) disease duration of 15.5 (11.6) years; 73.5% were treated with biological disease-modifying antirheumatic drugs (DMARDs), 22.4% with non-biological DMARDs and 53.7% with non-steroidal anti-inflammatory drugs, alone or in combination. Monotherapy with biologics and non-biologics was used by 29.7% and 26.8% of patients, respectively. According to BASDAI, 38.0% were in remission (BASDAI≤2) and 64.5% showed adequate disease control (BASDAI<4). According to ASDAS-CRP, 29.4% achieved remission (ASDAS-CRP<1.3) and 28.1% low disease activity (1.3≤ASDAS-CRP<2.1). CONCLUSIONS: Almost two thirds of the AS patients recruited had low disease activity, with about one third of them being in remission (BASDAI≤2, ASDAS-CRP<1.3). These results highlight the existing room for improvement in treating AS patients in clinical practice.

Patients with Axial Spondyloarthritis are Great Consumers of Healthcare Resources, Especially Young and Women: Results from the Spanish Atlas.

INTRODUCTION: This study aimed to assess high healthcare utilization over 1 year in patients with axial spondyloarthritis (axSpA) and factors associated with increased healthcare utilization. METHODS: A total of 530 unselected patients with axSpA from the Atlas of Axial Spondyloarthritis in Spain-who had used at least one healthcare resource-were included in the present study. Total health care utilization was obtained from the total number of healthcare visits, medical tests, hospital admissions and emergency visits, during the 12 months prior to the survey. Linear regression was used to analyse possible factors associated with higher healthcare utilization. RESULTS: A total of 530 patients with axSpA participated in this study: mean age was 45.3 years and 51.1% were female. In the previous 12 months, 77.9% (n = 530) used at least one healthcare resource, with the median healthcare utilization at 25. In the multiple linear regression, the only categorical factor associated with higher healthcare utilization was female gender (ß = 12.854), while the continuous factors associated with higher healthcare utilization were higher disease activity (ß = 3.378), longer diagnostic delay (ß = 0.959), younger age (ß = - 0.737) and greater functional limitation (ß = 0.576). CONCLUSION: Half of patients with axSpA used 25 or more healthcare resources during 1 year. Higher healthcare utilization was associated with younger age, female gender, greater disease activity, higher functional limitation and longer diagnostic delay. Optimal monitoring of patients with axSpA may help to reduce their healthcare utilization.

Disease control in patients with psoriatic arthritis in real clinical practice in Spain: MiDAS study.

OBJECTIVE: MiDAS study assessed the percentage of psoriatic arthritis (PsA) patients treated in routine clinical practice who achieved control of disease activity according to Disease Activity in Psoriatic Arthritis (DAPSA) and Minimal Disease Activity (MDA). METHODS: Observational, non-interventional, cross-sectional, multicenter study conducted under conditions of routine clinical practice in 36 centers with outpatient rheumatology clinics in Spanish public hospitals. Patients included were adults (≥18 years) with ≥6 months PsA diagnosis according to classification for PsA (CASPAR) criteria and undergoing treatment ≥3 months. The main variable evaluated was the percentage of patients under remission and low disease activity, assessed through DAPSA and MDA. RESULTS: 313 patients with PsA were included: 54.3% male; with mean age of 54.1±12.2 years and mean disease duration of 10.5±9.0 years. Mean C-reactive protein (CRP) serum levels were 4.9±7.3mg/L. At the study visit, 58.5% of patients were in monotherapy (17.6% biological and 40.9% non-biological) and 41.2% were receiving biological and non-biological therapy. 59.4% of patients showed low disease activity (DAPSA≤14) and 19.8% were on remission (DAPSA≤4). Moreover, 51.4% of the patients reached an MDA status (≥5 MDA). CONCLUSIONS: Around 40% of PsA patients presented uncontrolled disease, highlighting the need to improve the management of these patients in clinical practice.

Using natural language processing to explore characteristics and management of patients with axial spondyloarthritis and psoriatic arthritis treated under real-world conditions in Spain: SpAINET study.

Background: Spondyloarthritis (SpA) is a group of related but phenotypically distinct inflammatory disorders that include axial SpA (axSpA) and psoriatic arthritis (PsA). Information on the characteristics and management of these patients in the real world remains scarce. Objectives: To explore the characteristics and management [disease activity assessment and treatment with secukinumab (SEC) or other biologic disease-modifying antirheumatic drugs (bDMARDs)] of axSpA and PsA patients using natural language processing (NLP) in Electronic Health Records (EHRs). Design: National, multicenter, observational, and retrospective study. Methods: We analyzed free-text and structured clinical information from EHR at three hospitals. All adult patients with axSpA, PsA or non-classified SpA from 2018 to 2021 with minimum follow-up of three months were included when starting SEC or other bDMARDs. Clinical variables were extracted using EHRead® technology based on Systemized Nomenclature of Medicine-Clinical Terms (SNOMED CT) terminology. Results: Out of 887,735 patients, 758 were included, of which 328 had axSpA [58.5% male; mean (SD) age of 50.7 (12.7) years], 365 PsA [54.8% female, 53.9 (12.4) years], and 65 non-classified SpA. Mean (SD) time since diagnosis was 36.8 (61.0) and 24.1 (35.2) months for axSpA and PsA, respectively. Only 116 axSpA patients (35.3%) had available Ankylosing Spondylitis Disease Activity Score (ASDAS) or Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at bDMARD onset, of which 61 presented active disease. Disease Activity in PSoriatic Arthritis (DAPSA) or Disease Assessment Score - 28 joints (DAS-28) values at bDMARD onset were available for only 61 PsA (16.7%) patients, with 23 of them having active disease. The number of patients with available tender joint count or swollen joint count assessment was 68 (20.7%) and 59 (18%) for axSpA, and 115 (31.5%) and 119 (32.6%) for PsA, respectively. SEC was used in 63 (19.2%) axSpA patients and in 63 (17.3%) PsA patients. Conclusion: Using NLP, the study showed that around one-third of axSpA and one-sixth of PsA patients have disease activity assessments with ASDAS/BASDAI or DAPSA/DAS-28, respectively, highlighting an area of improvement in these patients' management.

Investigating axial spondyloarthritis and psoriatic arthritis patients using natural language processing We conducted a study in Spain to better understand patients with specific rheumatic conditions known as axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). To analyze their characteristics, we used a computer technology called EHRead, which uses Natural Language Processing (NLP) to analyze free text from electronic health records. Out of a large group of patients, we focused on 758 individuals who had axSpA or PsA. Most of the axSpA patients were men, and they were around 51 years old on average. For the PsA patients, most were women, and their average age was about 54 years. We analyzed outcomes and treatments of these patients. Our findings showed that we can describe and assess a cohort of patients from real world using NLP. Besides, only about one-third of axSpA patients and one-sixth of PsA patients had their respective outcomes completely assessed, which indicates that there is potential room for improvement in the management of axSpA and PsA. The most promising feature in our study is the use of NLP, an artificial intelligence technology that helps us understand information in medical records written in free text. This can help us explore the characteristics of patients and their management in the real world, bringing an opportunity to enhance the care of patients with axSpA and PsA.

Evidence for the Use of Secukinumab in Patients with Radiographic and Non-radiographic Axial Spondyloarthritis in the Last 5 Years.

Axial spondyloarthritis (axSpA) is an inflammatory rheumatic disorder that causes chronic pain, primarily in the spine and sacroiliac joints. It is characterized by the presence of type 1 major histocompatibility complex HLA-B27 genetic marker, arthritis in peripheral joints, enthesitis and/or dactylitis and extra-articular manifestations. Current guidelines recommend biological therapy when first-line therapy is not sufficiently effective. The finding that the interleukin (IL)-17 axis is vital for the pathogenesis of axSpA propelled the development of secukinumab, a fully human monoclonal antibody directed against IL-17A. The present review provides evidence on the efficacy and safety of secukinumab in the treatment of radiographic and non-radiographic axSpA from nine randomized controlled phase III trials, as well as evidence from real-world observational analyses. The primary endpoint in six clinical trials was the proportion of patients meeting the Assessment of SpondyloArthritis international Society criteria for either 20% or 40% improvement (ASAS20, ASAS40) at week 16. Significantly more patients achieved the primary endpoint with secukinumab compared with placebo in all the studies except MEASURE 4. Both clinical trials and real-world studies showed significant improvements in the secondary endpoints of disease activity, quality of life, and pain and fatigue relative to placebo. The benefits of secukinumab were generally sustained during longer-term (up to 5 years) treatment. Overall, secukinumab was well tolerated with a low frequency of adverse events and treatment persistence was high in the real-world setting. Although indirect comparisons suggest that secukinumab and adalimumab have comparable efficacy and safety, they are being directly compared in the ongoing SURPASS study. During the current coronavirus disease 2019 (COVID-19) pandemic, it is advisable to continue biological therapy in patients who do not have severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection, but interrupt treatment during an infection, reinitiating once the patient has recovered from the infection. In conclusion, secukinumab is a largely safe and effective treatment for radiographic and non-radiographic axSpA.

Similarities and differences between non-radiographic and radiographic axial spondyloarthritis: The patient perspective from the Spanish atlas.

AIM: Although non-radiographic axial spondyloarthritis (EspAax-nr) is well understood within health institutions, being considered along with radiographic EspAax (EspAax-r) as part of the same disease spectrum, patient understanding is unknown. The aim is to describe the patient's knowledge of the EspAax-nr entity. METHODS: Atlas 2017, promoted by the Spanish Federation of Spondylarthritis Associations (CEADE), aims to comprehensively understand the reality of EspAax patients from a holistic approach. A cross-sectional on-line survey of unselected patients with self-reported EspAax diagnosis from Spain was conducted. Participants were asked to report their diagnosis. Socio-demographic, disease characteristics and patient-reported outcomes (PROs) were compared between those patients self-reporting as EspAax-nr and EspAax-r. RESULTS: 634 EspAax patients participated. Mean age 45.7±10.9 years, 50.9% female and 36.1% university-educated. 35 (5.2%) self-reported as EspAax-nr. Compared to EspAax-r patients, those with EspAax-nr were more frequently women (48.6% vs 91.4%, p<0.001), had longer diagnostic delay (10.1±8.9 vs 8.5±7.6 years), higher psychological distress (GHQ-12: 7.5±4.9 vs 5.6±4.4) and similar degree of disease activity (BASDAI: 5.7±2.1 vs 5.7±2.0), and unemployment rates (20.0% vs 21.6%). 20.0% of EspAax-nr received biologics vs 36.9% of EspAax-r, p=0.043. Visits to the rheumatologist in the past year were similar in both groups (3.8±4.5 vs 3.2±3.8), while GP visits were much higher within EspAax-nr (8.0±10.7 vs 4.9±13.3 p=0.003). CONCLUSION: For the first time, EspAax-nr characteristics and PROs have been analyzed from the patient's perspective. Both groups reported similar trends with the exception of EspAax-nr being more frequently women, younger, having longer diagnostic delay and lower use of biologic therapy.

Understanding the Disease Burden of Unemployed Patients With Axial Spondyloarthritis: Results From the Spanish Atlas 2017.

OBJECTIVE: To evaluate differences in sociodemographic factors and patient-reported outcomes (PROs) between unemployed and employed patients with axial spondyloarthritis (axSpA), and to explore work-related issues (WRIs). METHODS: Data from an online survey of 680 unselected patients of the Atlas of Axial Spondyloarthritis in Spain 2017 were analyzed. Active workforce participants were divided into employed and unemployed groups according to International Labour Organization definitions. Sociodemographic characteristics, PROs (Bath Ankylosing Spondylitis Disease Activity Index [0-10], Spinal Stiffness Index [3-12], Functional Limitation Index [0-54], and psychological distress through the 12-item General Health Questionnaire [0-12]) were assessed. Logistic regression analysis was used to evaluate the association with unemployment status. RESULTS: Four hundred fifteen (63.6%) patients with axSpA were categorized in the active population, of which 325 (78.3%) were employed and 90 (21.7%) unemployed. Of the unemployed patients, 62.8% (n = 54) declared that their joblessness was due to axSpA. Of the employed patients, 170 (54.3%) reported WRIs in the year prior to the survey, the most frequent being difficulty fulfilling working hours (44.1%), missing work for doctor appointments (42.9%), and taking sick leave (37.1%). Being unemployed was associated with lower educational level (OR = 2.92), disease activity (OR = 1.37), spinal stiffness (OR = 1.21), functional limitation (OR = 1.05), worse mental health (OR = 1.15), anxiety (OR = 2.02), and depression (OR = 2.69) in the univariable models; and with lower educational level (OR = 2.76) and worse mental health (OR = 1.15) in the multivariable analysis. CONCLUSION: Results show significant differences between employed and unemployed patients with axSpA. Employed patients with axSpA endure many problems at work related to their condition, whereas unemployed patients present worse disease outcomes associated with greater psychological distress.

Disease activity indexes might not capture the same disease aspects in males and females with ankylosing spondylitis: A real-world nationwide analysis.

Background: To evaluate gender differences in disease activity and health status (HS) in patients with radiographic axial spondyloarthritis (r-axSpA)/ankylosing spondylitis (AS). Methods: Ancillary analysis of the MIDAS study, an observational, non-interventional, cross-sectional and retrospective multicenter nationwide study to assess disease activity and its relationship with HS in clinical practice. Adult patients with AS diagnosis, fulfilling ASAS and modified New York criteria, treated for ≥3 months upon study inclusion according to clinical practice were included. The primary outcome was "disease control" assessed by the percentage of patients in remission and low disease activity (BASDAI and ASDAS-CRP scores). HS was evaluated using the ASAS health index (ASAS-HI). Patients' responses and characteristics were analyzed by gender. Results: We analyzed 313 patients with AS, 237 (75.7%) males and 76 (24.3%) females. A total of 202 (64.5%) patients had adequate disease control (BASDAI < 4); 69.2% of males [mean (SD) BASDAI 2.9 (2.1)] and 50.0% of females [mean (SD) BASDAI 3.8 (2.4); p = 0.01]. According to ASDAS-CRP, 57.5% of patients were adequately controlled (ASDAS-ID +ASDAS-LDA); 138 (58.2%) males and 42 (55.3%) females. The mean (SD) ASDAS-CRP was 1.9 (1.1); being 1.9 (1.0) in males and 2.0 (1.1) in females. Overall, the impact of AS on HS was low to moderate [mean (SD) ASAS-HI 5.8 (4.4)]; being 5.5 (4.4) for males and 6.8 (4.2) for females (p = 0.02). Conclusion: This study showed a higher proportion of females with AS and active disease using the BASDAI definition. When using the ASDAS-CRP definition these differences by gender were less pronounced. The impact of disease activity on HS appears to be higher in females than males.

Real-World Effectiveness and Treatment Retention of Secukinumab in Patients with Psoriatic Arthritis and Axial Spondyloarthritis: A Descriptive Observational Analysis of the Spanish BIOBADASER Registry.

Rheumatic diseases are extensively managed with biological disease-modifying antirheumatic drugs (bDMARDs), but a notable proportion of patients withdraw in the long term because of lack of effectiveness, adverse events, or the patient's decision. The present real-world analysis showed the effectiveness, retention, and safety data collected in the Spanish BIOBADASER registry for patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA, including ankylosing spondylitis (AS) and non-radiographic axSpA) treated with secukinumab, a human antibody against interleukin-17A (IL-17A), for more than 12 months. Six hundred and thirty-nine patients were analysed (350, 262, and 27 PsA, AS, and nr-axSpA patients, respectively). The results showed an improvement in the disease activity after 1 year of treatment, in terms of decreases of the mean Disease Activity Score 28 using C-reactive protein (DAS28-CRP), the mean Disease Activity Psoriatic Arthritis (DAPSA) score, swollen joint counts (SJC), and tender joint counts (TJC) in PsA patients and decreases in the mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the mean Ankylosing Spondylitis Disease Activity Score (ASDAS) in axSpA patients. This improvement was maintained or increased after 2 and 3 years of treatment, indicating that secukinumab is effective in both naïve and non-responder patients. Retention rates were higher when secukinumab was used as the first-line biological treatment, although they were also adequate in the second and third lines of treatment. Collected safety data were consistent with previous reports.

The journey of the non-radiographic axial spondyloarthritis patient: the perspective of professionals and patients.

OBJECTIVE: Explore the perspective of patients and professionals regarding non-radiographic axial spondyloarthritis (nr-axSpA) and to define the patient's journey from diagnosis to treatment in order to identify unmet needs during the process. METHODS: A qualitative study was carried out in two phases. In the first part, five focus groups were held with rheumatologists, orthopaedist, physiotherapists, primary care physicians (PCP), radiologists and six narrative interviews with nr-axSpA patients. In the second part, a nominal group meeting was held to detect which needs were not covered in the nr-axSpA (all of whom had collaborated in the previous phase). RESULTS: The topics discussed with professional groups and patients were the appropriateness of the term and concept of nr-axSpA, the management of low back pain and inflammatory back pain in routine clinical practice, complementary test and the problem of waiting lists and finally the unmet needs both from a practitioner's and a patient's perspective. The final group explored solutions to the problems based on what was discussed in the first part of the project. Some of these solutions were strengthening relations between specialties, implementing high resolution consultations, rethinking the disability scales, offering better information to patients, designing resource maps and using different strategies to promote knowledge of the disease. CONCLUSION: Many different perspectives on the same disease have revealed the difficult journey of the patient with suspected nr-axSpA, while identifying problems and solutions. Key Points • Diagnosis of nr-AxSpA among health professionals outside rheumatology may lead to numerous turns and difficulties in the patient's journey. • The impact of delays and complications in the journey to diagnosis is not quantified but directly affects the state of well-being and health of patients. • Multidisciplinary care is far from a reality. Primary care (key specialists in any chronic condition), radiologists, orthopaedists, and non-physicians such as physiotherapists and psychologists are generally excluded from dealing with these patients, and often have to do their work outside of physicians, rather than working together in a truly patient-centred medicine.

A Benchmarking Study Evaluating Axial Spondyloarthritis Burden in Spain and Other European Countries. Results from the Spanish Atlas and the European Map of Axial Spondyloarthritis (EMAS) Studies.

AIM: To compare the burden of disease in Spanish patients with axial spondyloarthritis (axSpA) vs other European countries (OEC). METHODS: Data from 2846 unselected patients from the European Map of Axial Spondyloarthritis (EMAS) and the Atlas of Axial Spondyloarthritis in Spain (Atlas) were collected through online surveys. Comparative analysis was carried out between Spanish patients (2016) and patients from 12 OEC ( 2017-2018). Socio-demographic characteristics, life habits, and patient-reported outcomes (Bath Ankylosing Spondylitis Disease Activity Index 0-10, spinal stiffness 3-12, functional limitation 0-54, the 12-Item General Health Questionnaire [GHQ-12] for psychological distress 0-12) were compared. Chi-square and Mann-Whitney tests were used for qualitative and quantitative variables respectively. RESULTS: 680 (23.9%) Spanish axSpA patients were compared to 2166 axSpA patients (76.1%) from OEC. Compared to Spain, the OEC group had a higher percentage of females (64.1% vs 52.5%; P < .001) and university-educated participants (51.7% vs 36.9%; P < .001). Spanish patients showed a greater diagnostic delay (8.5 ± 7.7 vs 7.2 ± 8.6 years; P < .001), visits to orthopedic specialists before diagnosis (56.9% vs 25.3%; P < .001), human leukocyte antigen-B27 carriership (77.1% vs 70.1%; P = .003), disease activity (5.7 ± 2.0 vs 5.4 ± 2.0; P = .024), and higher unemployment rates (21.7% vs 9.2%; P < .001). Despite lower rates of diagnosed anxiety and depression, Spanish patients were at higher risk of psychological distress according to the GHQ-12 (5.7 ± 4.5 vs 4.8 ± 4.0; P < .001). CONCLUSION: Compared to European axSpA patients, Spanish patients experience a longer diagnostic delay and greater psychological distress. Being wrongly referred to orthopedic specialists and facing a more precarious labor scenario appear as possible causal factors, highlighting the need to increase the number of rheumatologists, the training of healthcare professionals, and improving axSpA patients' working conditions.

Similarities and differences between non-radiographic and radiographic axial spondyloarthritis: The patient perspective from the Spanish atlas.

AIM: Although non-radiographic axial spondyloarthritis (EspAax-nr) is well understood within health institutions, being considered along with radiographic EspAax (EspAax-r) as part of the same disease spectrum, patient understanding is unknown. The aim is to describe the patient's knowledge of the EspAax-nr entity. METHODS: Atlas 2017, promoted by the Spanish Federation of Spondylarthritis Associations (CEADE), aims to comprehensively understand the reality of EspAax patients from a holistic approach. A cross-sectional on-line survey of unselected patients with self-reported EspAax diagnosis from Spain was conducted. Participants were asked to report their diagnosis. Socio-demographic, disease characteristics and patient-reported outcomes (PROs) were compared between those patients self-reporting as EspAax-nr and EspAax-r. RESULTS: 634 EspAax patients participated. Mean age 45.7±10.9 years, 50.9% female and 36.1% university-educated. 35 (5.2%) self-reported as EspAax-nr. Compared to EspAax-r patients, those with EspAax-nr were more frequently women (48.6% vs 91.4%, p<0.001), had longer diagnostic delay (10.1±8.9 vs 8.5±7.6 years), higher psychological distress (GHQ-12: 7.5±4.9 vs 5.6±4.4) and similar degree of disease activity (BASDAI: 5.7±2.1 vs 5.7±2.0), and unemployment rates (20.0% vs 21.6%). 20.0% of EspAax-nr received biologics vs 36.9% of EspAax-r, p=0.043. Visits to the rheumatologist in the past year were similar in both groups (3.8±4.5 vs 3.2±3.8), while GP visits were much higher within EspAax-nr (8.0±10.7 vs 4.9±13.3 p=0.003). CONCLUSION: For the first time, EspAax-nr characteristics and PROs have been analyzed from the patient's perspective. Both groups reported similar trends with the exception of EspAax-nr being more frequently women, younger, having longer diagnostic delay and lower use of biologic therapy.