Effectiveness of bDMARDs in ankylosing spondylitis patients by biologic use: experience from the CorEvitas PsA/SpA Registry.

OBJECTIVE: To describe bDMARD initiators by biologic experience among ankylosing spondylitis (AS) patients and change in disease activity and patient-reported outcomes (PROs) in real-world US patients. METHODS: We included patients ≥18 years with AS based on physician diagnosis enrolled between 3/2013 and 11/2019 in the CorEvitas Psoriatic Arthritis (PSA)/Spondyloarthritis Registry (NCT02530268). Patients concurrently diagnosed with PSA were excluded. Baseline (bDMARD initiation) demographics, comorbidities, disease characteristics, treatment, and PROs were collected. Response rates and changes in disease activity and PROs between baseline and 6- and 12- month follow-up visits were calculated. RESULTS: Of the 489 AS patients in the PsA/SpA Registry, 254 AS (52.0%) patients initiated a bDMARD at enrollment or during follow-up (total initiations: AS = 313). Of the 313 AS initiations, 179 (57.2%) had a 6-month follow-up, 122 (39.0%) had a 12-month follow-up, and 94 (30.0%) had a 6- and 12-month follow-up visit. For those AS initiators with a 6-month follow-up, the mean age was 49.1 years, 44.4% were female, and 70.4%, 47.5%, 96.1%, and 46.9% had never used cDMARDs, TNFis, non-TNFis, and bDMARDs, respectively. Of these 179 AS initiators, 20.1% and 14.0% achieved ASAS20/40, respectively. Further, only 34% achieved low disease activity (ASDAS <2.1). When stratified by biologic-naivete and biologic-experience, the ASAS 20/40 achievement rates were 26.2% and 14.7%, and 21.4% and 7.4%, respectively, for this cohort. CONCLUSION: Although AS patients initiate bDMARDs, many do not achieve optimal treatment responses. Future research is needed to investigate the aspects associated with inadequate improvement and treatment response to bDMARDs.

Clinical profiles and outcomes in patients with inflammatory bowel disease receiving standard and escalated doses of targeted therapies: findings from a global real-world study.

OBJECTIVE: Although dosing regimens of targeted therapies (TT) for ulcerative colitis (UC) and Crohn's disease (CD) are guided by market authorizations and clinical guidelines, little is known about clinical guideline adherence or outcomes in patients receiving escalated doses of TT due to lack of response. This real-world study explored the prevalence of dose escalation and compared outcomes between patients receiving standard and escalated TT doses. METHODS: Data were from the 2020-2021 Adelphi Disease Specific Programme for inflammatory bowel disease, a cross-sectional survey of gastroenterologists and their UC and CD patients across five European countries and the US. Physicians provided retrospective data collection of patient demographics, clinical characteristics, treatment history, and satisfaction; patients reported quality-of-life and work productivity. Patients were grouped by TT maintenance dose; standard and escalated dose groups were compared. Outcomes were adjusted for time on current TT and severity at current TT initiation using regression analyses. RESULTS: Of 1,241 UC and 1,477 CD patients, 19.1% and 24.1%, respectively, received escalated TT doses. Despite escalation, a substantial proportion of patients had not achieved remission, had moderate or severe disease activity, or were flaring. Most physicians were not fully satisfied with treatment in the escalated dose group and were more likely to switch patients to another treatment regimen than patients on standard dose. CONCLUSION: Dose escalation is not always an effective approach to resolve inadequate or loss of response in UC and CD, highlighting a need for more therapeutic options or alternative treatment strategies in patients unresponsive to TT.

Validation of the bowel urgency numeric rating scale in patients with Crohn's disease: results from a mixed methods study.

PURPOSE: Bowel urgency (BU) is an important symptom of Crohn's disease (CD), however there is no patient-reported outcome (PRO) scale validated in this population to assess BU severity. Here we evaluated the content validity and psychometric properties of the Urgency Numeric Rating Scale (NRS). METHOD: Qualitative interviews were conducted with moderate-to-severe CD participants to confirm importance and relevance of BU in this population, cognitively debrief the Urgency NRS, and explore score interpretation and CD remission. A quantitative web survey study was conducted to explore the measurement properties of the urgency NRS. RESULTS: Qualitative Interview: 34 of 35 participants reported BU. It was most bothersome for 44%, 47% reported it daily, 18% with every bowel movement. BU had a severe impact on daily activities, causing many participants to stay home more than preferred. Patients confirmed the relevance, appropriateness, comprehensibility of the item, recall period, response options, and instructions of the Urgency NRS. Small reductions on the Urgency NRS score reflected meaningful improvements. Quantitative survey: The study sample comprised 76 participants (65.8% female). Mean Urgency NRS score was 4.7 (SD 2.26; N = 76) at Week 1, with no floor/ceiling effect. Test-retest reliability was acceptable. Construct and known-groups validity against selected PROs were overall strong and within ranges hypothesized a priori. CONCLUSION: The Urgency NRS is a valid and reliable instrument to assess BU severity in CD.

Experience and measurement of fatigue in adults with Crohn's disease: results from qualitative interviews and a longitudinal 2-week daily diary pilot study.

BACKGROUND: Fatigue has a detrimental impact on health-related quality of life and functioning in patients with Crohn's disease (CD). We aimed to confirm the relevance and importance of fatigue, establish the content validity of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), qualitatively explore meaningful change in fatigue experience, and assess the measurement properties of the FACIT-F in patients with moderate-to-severe CD. METHODS: This was a mixed-methods observational study consisting of a cross-sectional qualitative interview (Part A) and a longitudinal 2-week daily diary pilot study (Part B) in participants aged ≥ 18 years with a clinical diagnosis of moderate-to-severe CD. Part A included open-ended questions related to the participant's overall experiences with CD, fatigue, and impact on daily activities and a cognitive debriefing of several patient-reported outcomes (PROs), including the FACIT-F. Part B consisted of participants completing an electronic daily diary that included the FACIT-F and other PROs for 14 days. Item performance, test-retest reliability, and construct validity were assessed at baseline (Day 1), Day 7, and Day 14. RESULTS: Thirty-five participants (mean age 45.1 years; 65.7% female) completed an interview (Part A). Ninety-one percent of the interview participants reported fatigue as a symptom attributed to CD. Participants indicated that fatigue had a major impact on their daily activities (e.g., recreation/ hobbies, work/school, yard work and housework), social activities, and emotional health. The FACIT-F was well understood by the interview participants. Seventy-six participants (mean age 41.9 years; 66% female) completed at least the Day 1 diary entry (Part B). Potential floor and ceiling effects were observed for several FACIT-F items, but test-retest reliability and construct validity were all strong and within the ranges hypothesized a priori. CONCLUSIONS: The interviews indicate that fatigue is a frequent and bothersome symptom experienced by most patients with moderate-to-severe CD and support the content validity of the FACIT-F in this population. Daily diary study results indicate that the FACIT-F scale demonstrates adequate reliability and validity among patients with CD. These study findings suggest that the FACIT-F would be a reliable, valid, and useful measure of fatigue in patients with moderate-to-severe CD.

Neoantigen-targeted CD8+ T cell responses with PD-1 blockade therapy.

Neoantigens are peptides derived from non-synonymous mutations presented by human leukocyte antigens (HLAs), which are recognized by antitumour T cells1-14. The large HLA allele diversity and limiting clinical samples have restricted the study of the landscape of neoantigen-targeted T cell responses in patients over their treatment course. Here we applied recently developed technologies15-17 to capture neoantigen-specific T cells from blood and tumours from patients with metastatic melanoma with or without response to anti-programmed death receptor 1 (PD-1) immunotherapy. We generated personalized libraries of neoantigen-HLA capture reagents to single-cell isolate the T cells and clone their T cell receptors (neoTCRs). Multiple T cells with different neoTCR sequences (T cell clonotypes) recognized a limited number of mutations in samples from seven patients with long-lasting clinical responses. These neoTCR clonotypes were recurrently detected over time in the blood and tumour. Samples from four patients with no response to anti-PD-1 also demonstrated neoantigen-specific T cell responses in the blood and tumour to a restricted number of mutations with lower TCR polyclonality and were not recurrently detected in sequential samples. Reconstitution of the neoTCRs in donor T cells using non-viral CRISPR-Cas9 gene editing demonstrated specific recognition and cytotoxicity to patient-matched melanoma cell lines. Thus, effective anti-PD-1 immunotherapy is associated with the presence of polyclonal CD8+ T cells in the tumour and blood specific for a limited number of immunodominant mutations, which are recurrently recognized over time.

Treatment and biologic maintenance-dosing patterns among pediatric patients with ulcerative colitis or Crohn's disease.

OBJECTIVES: To assess treatment patterns and initial and maintenance dosing of biologics over 3 years in pediatric patients with ulcerative colitis (UC) or Crohn's disease (CD), utilizing data from the ImproveCareNow registry. METHODS: Pediatric patients diagnosed with UC or CD and aged 2-17 years were included in the study. Descriptive statistics were employed to summarize baseline demographics. The proportion of patients on medication for UC or CD were analyzed at the baseline visit, 1-year, and 3-year time points (Cohort 1). Biologic maintenance dosage was calculated only for patients who had data for dose and weight at all-time points (Cohort 2). RESULTS: In Cohort 1 (UC = 1784; CD = 4720), baseline treatment in UC included corticosteroid, 5-ASA, and 6-MP/AZA; at 1-year and 3-year time points, treatment with 5-ASA and corticosteroid decreased, whereas 6-MP/AZA and anti-TNFs increased. In CD, baseline treatment included corticosteroid, anti-TNF, 6-MP/AZA, and methotrexate; use of corticosteroids decreased, whereas the use of methotrexate and anti-TNFs increased over 3 years. In Cohort 2 (UC = 350; CD = 1537), at first maintenance dose, UC patients on infliximab received a mean dose of 10.5 mg/kg/8 wk, adalimumab (weight < 40 kg and ≥40 kg) 1.3 mg/kg/2 wk and 0.8 mg/kg/2 wk, and vedolizumab 6.9 mg/kg/8 wks. At the first maintenance dose, CD patients on infliximab received a mean dose of 8.1 mg/kg/8 wk, adalimumab (weight < 40 kg) 1.1 mg/kg/2 wk, adalimumab (weight ≥ 40 kg) 0.8 mg/kg/2 wk, and vedolizumab 10.5 mg/kg/8 wks. CONCLUSION: The use of corticosteroids was common at the initial visit in patients. Anti-TNFs remain the most used class of biologics, however, reported doses in our study were substantially higher than the standard dosing guidelines.

Burden of Fatigue Among Patients with Ulcerative Colitis and Crohn's Disease: Results from a Global Survey of Patients and Gastroenterologists.

INTRODUCTION: To assess the prevalence of fatigue and its association with disease activity and patient-reported outcomes among patients with ulcerative colitis (UC) or Crohn's disease (CD). METHODS: Data from a cross-sectional survey conducted with gastroenterologists and their consulting adult patients with UC or CD were analyzed. Data were collected via gastroenterologist-completed patient record forms and patient-self completion forms. Patient demographics, clinical characteristics, disease activity and medication use were reported by the gastroenterologist, while current symptoms (fatigue, rectal urgency, abdominal pain, sleep disturbance), work productivity and the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) were reported by the patient. Logistic regression models were used to identify measures associated with fatigue and expressed as odds ratio (OR) with 95% confidence interval. p < 0.05 was considered statistically significant. RESULTS: A total of 1057 patients with UC and 1228 patients with CD were included in this analysis. Fatigue was reported in 22.6% of UC and 26.0% of patients with CD. Higher proportion of patients with UC and fatigue had moderate/severe disease activity (p = 0.0001), had a higher Mayo score (5.0 vs. 4.0, p < 0.0001) and were unemployed (5.6% vs. 3.9%, p = 0.0149) compared to those without fatigue. In patients with CD reporting fatigue, a higher proportion were female (55.9% vs. 48.2%, p = 0.0193), were unemployed (5.8% vs. 4.9%, p = 0.0069), had moderate/severe disease (p < 0.0001) and had a higher mean Crohn's Disease Activity Index score (145.0 vs. 96.2, p < 0.0001) than patients without fatigue. Patients with UC and fatigue had higher mean level of pain (p < 0.0001) and sleep disturbance (p < 0.0001), whereas patients with CD and fatigue had lower SIBDQ scores (p < 0.0001) and greater work impairment (p = 0.0015) than patients without fatigue. Abdominal pain (OR: 2.01, p = 0.001) and use of immunomodulators (OR: 1.69, p = 0.006) increased the odds of having fatigue in patients with UC. In patients with CD, abdominal pain (OR: 2.29, p < 0.001) and use of biologics or biosimilars (OR: 2.02, p = 0.003) increased the odds of having fatigue. CONCLUSION: Fatigue is a common symptom among patients with UC or CD that is associated with higher levels of disease activity and decreased work productivity and is driven by various factors. A multidisciplinary approach may be needed to manage fatigue.

Non-viral precision T cell receptor replacement for personalized cell therapy.

T cell receptors (TCRs) enable T cells to specifically recognize mutations in cancer cells1-3. Here we developed a clinical-grade approach based on CRISPR-Cas9 non-viral precision genome-editing to simultaneously knockout the two endogenous TCR genes TRAC (which encodes TCRα) and TRBC (which encodes TCRß). We also inserted into the TRAC locus two chains of a neoantigen-specific TCR (neoTCR) isolated from circulating T cells of patients. The neoTCRs were isolated using a personalized library of soluble predicted neoantigen-HLA capture reagents. Sixteen patients with different refractory solid cancers received up to three distinct neoTCR transgenic cell products. Each product expressed a patient-specific neoTCR and was administered in a cell-dose-escalation, first-in-human phase I clinical trial ( NCT03970382 ). One patient had grade 1 cytokine release syndrome and one patient had grade 3 encephalitis. All participants had the expected side effects from the lymphodepleting chemotherapy. Five patients had stable disease and the other eleven had disease progression as the best response on the therapy. neoTCR transgenic T cells were detected in tumour biopsy samples after infusion at frequencies higher than the native TCRs before infusion. This study demonstrates the feasibility of isolating and cloning multiple TCRs that recognize mutational neoantigens. Moreover, simultaneous knockout of the endogenous TCR and knock-in of neoTCRs using single-step, non-viral precision genome-editing are achieved. The manufacture of neoTCR engineered T cells at clinical grade, the safety of infusing up to three gene-edited neoTCR T cell products and the ability of the transgenic T cells to traffic to the tumours of patients are also demonstrated.

Exploring Disease Remission and Bowel Urgency Severity Among Adults with Moderate to Severe Ulcerative Colitis: A Qualitative Study.

Purpose: Achieving and maintaining symptom control is a key treatment goal in ulcerative colitis (UC). Bowel urgency is an important symptom of UC, thus measurement of urgency is critical. This research explored the patient experience of UC and "remission" in UC, with a focus on urgency, and cognitively debriefed the Urgency Numeric Rating Scale (NRS), including score interpretation and examination of meaningful improvement. Patients and Methods: Semi-structured hybrid concept elicitation and cognitive debriefing interviews with adults with moderately-severely active UC were conducted to explore experiences of UC and urgency, as well as examine meaningful improvement and score interpretation of the Urgency NRS. Purposive sampling was used to identify 20 eligible adult participants with UC. Concept elicitation data were analyzed using thematic analysis, and a deductive approach was used to analyze cognitive debriefing data. Thematic analysis was also applied to meaningful change-related data. Results: Twenty participants were interviewed (average age = 42.6 years old, 50% male); 14 with moderately active (70.0%) and 6 with severely active UC (30.0%). Disease remission was not consistently defined by participants and description varied in terms of definition (absence vs not complete absence of symptoms), duration (months vs days) and key symptoms to consider. Urgency was a prominent symptom for all participants, with 8 (40.0%) identifying it as the most bothersome aspect of UC. No issues were identified with the Urgency NRS. Participants were able to define different levels of urgency severity, describe how they relate to daily life impacts, and score them differently on the Urgency NRS. Participants were also able to reflect urgency improvement on the NRS and discuss how small changes in numeric ratings of urgency can reflect meaningful change in the symptom burden of their UC. Conclusion: The Urgency NRS is a content valid and interpretable measure to assess bowel urgency severity.

Psychometric evaluation of the Urgency NRS as a new patient-reported outcome measure for patients with ulcerative colitis.

BACKGROUND: The Urgency Numeric Rating Scale (NRS) was developed as a content-valid single-item patient-reported outcome measure to assess severity of bowel urgency. Here, we evaluated the psychometric properties of the Urgency NRS. METHODS: Data were from a multicenter, randomized, placebo-controlled phase 3 trial in adults with moderately to severely active ulcerative colitis (NCT03518086). Patients completed the Urgency NRS using a daily electronic diary, from which weekly average Urgency NRS scores were calculated. Test-retest reliability, known-groups validity, construct validity, responsiveness, and score interpretation were assessed using the modified Mayo score, Inflammatory Bowel Disease Questionnaire (IBDQ), Patient Global Rating of Severity (PGRS), Patient Global Rating of Change (PGRC), and Geboes score. RESULTS: The study sample comprised 1,162 participants (40.2% female). Mean Urgency NRS score was higher (worse) at baseline than at week 12 (6.2 vs. 3.7). Test-retest reliability was strong, with intra-class correlation coefficients of 0.76-0.89. Baseline least-square mean Urgency NRS score was higher for participants with a PGRS score greater than the median (worse symptoms) than for those with a PGRS score less than or equal to the median (7.5 vs. 5.4; p < 0.0001), indicating good known-groups validity. Urgency NRS score was moderately correlated with IBDQ total and domain scores, PGRS, PGRC, and modified Mayo stool frequency, establishing its convergent validity. Correlations were weak for Geboes score and weak to moderate for modified Mayo endoscopic subscore and modified Mayo rectal bleeding, indicating that the Urgency NRS also had discriminant validity. Patients achieving clinical remission, clinical response, IBDQ remission, and PGRS score improvement showed significantly greater improvement on the Urgency NRS (p < 0.0001 for all), demonstrating responsiveness to change. A ≥ 3-point improvement in Urgency NRS score represented a meaningful improvement in bowel urgency and an Urgency NRS score of ≤ 1 point represented a bowel urgency remission threshold that was closely associated with clinical, endoscopic, and histologic remission. CONCLUSIONS: The Urgency NRS is a valid and reliable patient-reported outcome measure that is suitable for evaluating treatment benefits in clinical trials in patients with moderately to severely active ulcerative colitis.

Medication use among patients with Crohn's disease or ulcerative colitis before and after the initiation of advanced therapy.

BACKGROUND: Although various treatments help reduce abdominal pain, real-world pain medication utilization among patients with Crohn's disease (CD) or ulcerative colitis (UC) receiving advanced therapies is poorly understood. The aim is to understand the utilization of pain medication 12 months before and after the initiation of advanced therapies among patients with newly diagnosed CD or UC. METHODS: This retrospective, observational cohort study used administrative medical and pharmacy claims data of patients with CD or UC from HealthCore Integrated Research Database (HIRD®). The data from patients with use of pain medication over 12 months follow-up (after the initiation date of advanced therapies) were collected and analyzed. Differences in the use of pain medication 12 months before and after the initiation of advanced therapies were assessed using McNemar's and Wilcoxon signed-rank test. RESULTS: Prior to initiating advanced therapies, 23.1% of patients with CD (N = 540) received nonsteroidal anti-inflammatory drugs (NSAIDs), 78.1% glucocorticoids, 49.4% opioids, and 29.3% neuromodulators; similarly, 20.9% of patients with UC (N = 373) received NSAIDs, 91.4% glucocorticoids, 40.8% opioids, and 29.5% neuromodulators. After receiving advanced therapies for 12 months, patients reported a reduction in the use of steroids (78.1% vs. 58.9%, P < 0.001 in CD; 91.4% vs. 74.3%, P < 0.001 in UC), opioids (49.4% vs. 41.5%, P = 0.004 in CD; 40.8% vs. 36.5%, P = 0.194 in UC), and NSAIDs (23.1% vs. 15.0%, P < 0.001 in CD; 20.9% vs. 15.8%, P = 0.035 in UC), while the use of neuromodulators significantly increased (29.3% vs. 33.7%, P = 0.007 in CD; 29.5% vs. 35.7%; P = 0.006 in UC). CONCLUSIONS: The use of pain medications such as NSAIDs, glucocorticoids, opioids, and neuromodulators was common among patients with CD or UC. These results highlight that patients with CD or UC continued to receive pain medications even after initiating advanced therapies.

Early identification of axial psoriatic arthritis among patients with psoriasis: a prospective multicentre study.

OBJECTIVES: To evaluate a dermatologist-centred screening tool followed by a structured rheumatological examination including MRI of sacroiliac joints and spine for the recognition of psoriatic arthritis with axial involvement (axPsA). METHODS: This was a prospective multicentre study. Adult patients with a confirmed diagnosis of psoriasis who had chronic back pain (≥3 months), onset <45 years and had not been treated with any biologic or targeted synthetic disease-modifying antirheumatic drug in the 12 weeks before screening were referred to a specialised rheumatology clinic. A rheumatological investigation including clinical, laboratory and genetic assessments as well as imaging with conventional radiography and MRI of sacroiliac joints and spine was performed. The primary outcome of the study was the proportion of patients diagnosed with axPsA among all referred patients with PsO. RESULTS: Rheumatologists examined 100 patients of those who qualified for referral. 14 patients (including 3 with both axial and peripheral involvement) were diagnosed with axPsA and 5 were diagnosed with peripheral PsA solely. All patients diagnosed with axPsA had active inflammatory and/or structural (post)inflammatory changes in the sacroiliac joints and/or spine on imaging. In five patients, MRI changes indicative of axial involvement were found only in the spine. All but one patient with PsA (13/14 with axPsA and 5/5 with pPsA) fulfilled the Classification Criteria for Psoriatic Arthritis criteria for PsA. The Assessment of SpondyloArthritis International Society criteria for axSpA were fulfilled in 9 (64.3%) patients diagnosed with axPsA. CONCLUSIONS: Applying a dermatologist-centred screening tool may be useful for the early detection of axPsA in at-risk patients with psoriasis .

Identifying inadequate response among patients with ankylosing spondylitis and psoriatic arthritis prescribed advanced therapy in a real-world, commercially insured adult population in the USA.

OBJECTIVE: This study aimed to assess treatment patterns and frequency of inadequate response associated with advanced therapy initiation among patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) in the USA. METHODS: Adult patients with AS or PsA who initiated advanced therapy were identified from the HealthCore Integrated Research Database®. Inadequate response to advanced therapies (tumour necrosis factor inhibitors [TNFi] and non-TNFi biologics) was identified using a claims-based algorithm. Factors influencing inadequate response were assessed using multivariable logistic regression. RESULTS: In total, 646 patients with AS, and 1433 patients with PsA were evaluated. Among patients with AS (mean age, 43 years; male, 58%), 93% patients initiated TNFi, and 69% of patients had inadequate response. In patients with PsA (mean age, 49 years; male, 47%), 67% initiated TNFi, and 77% had inadequate response. Low adherence was the main predictor of inadequate response in patients with AS (56%) and PsA (63%). Inadequate responders were more likely to be female (odds ratio [OR] 2.05 for AS and 1.37 for PsA). Prior exposure to TNFi was associated with 3.89- and 2.14-fold greater odds of inadequate response in both AS and PsA patients, respectively, while patients using methotrexate were less likely to have inadequate response (OR 0.48 for AS and 0.72 for PsA; all p < 0.05). CONCLUSIONS: Over 69% of patients with AS and 77% of patients with PsA had inadequate response to their index advanced therapy during 1 year after initiation. Health plan claims data appear useful to classify inadequate responders in AS and PsA. Key Points • Estimating inadequate response to advanced therapies and identifying factors associated with this outcome using claims data could improve treatment outcomes in AS and PsA. • In a sample of commercially insured US patients, over 69% of patients with AS and 77% of patients with PsA had inadequate response to their index advanced therapy during 1 year after initiation. Patient characteristics such as sex and prior therapy use were predictive of inadequate response to advanced therapies. • Health plan claims data appear useful to classify inadequate responders in AS and PsA and identify factors associated with this outcome.

Baseline Characteristics and Treatment Response to Ixekizumab Categorised by Sex in Radiographic and Non-radiographic Axial Spondylarthritis Through 52 Weeks: Data from Three Phase III Randomised Controlled Trials.

OBJECTIVES: Assess baseline characteristics and treatment response to ixekizumab (IXE) categorised by sex in patients with radiographic axial spondyloarthritis (r-axSpA) and non-radiographic axSpA (nr-axSpA) up to 52 weeks. METHODS: Data were analysed from three randomised controlled trials of IXE through 52 weeks. Patients fulfilled ASAS classification criteria for r-axSpA or nr-axSpA and were randomised to receive 80 mg subcutaneous administration of IXE every 2 weeks (Q2W) or 4 weeks (Q4W), or placebo (16 weeks COAST-V/W; 52 weeks COAST-X). Baseline characteristics and treatment outcomes were assessed. Patients were categorised by sex; methods included non-responder imputation for categorical variables, and modified baseline observation carried forward for continuous efficacy variables. RESULTS: At presentation, female patients had higher disease burden as reflected by significantly higher spinal pain at night, fatigue scores and pain/swelling in joints other than the neck, back or hip. ASAS40 response rate with the approved label dose, IXEQ4W, was achieved in 39% of male patients with r-axSpA by week 16, and 44% by week 52. For female patients, 16.7% and 33.3% achieved ASAS40 at week 16 and 52, respectively. In nr-axSpA, 46% of male patients achieved ASAS40 at week 16 and 30% at week 52. In total, 23.9% of female patients achieved ASAS40 at week 16, and 30.4% at week 52. CONCLUSIONS: This analysis demonstrates that for the axSpA disease spectrum, female patients present with higher disease burden. Following treatment with IXE, there is a higher proportion of male responders up to 16 weeks, while female patients show less robust responses for the first 16 weeks but larger responses from weeks 16 through 52. TRIAL REGISTRATION NUMBERS: NCT02696785, NCT02696798 and NCT02757352.

The impact of symptom severity on the humanistic and economic burden of inflammatory bowel disease: a real-world data linkage study.

OBJECTIVE: Few studies have examined the association between inflammatory bowel disease (IBD) severity, and humanistic, and economic burden. We addressed this gap using a unique real-world data source that links self-reported patient data from the US National Health and Wellness Survey (NHWS) to claims data. METHODS: This cross-sectional study linked the 2015-2018 US NHWS data with medical, and pharmacy claims. Patients (≥18 years) who self-reported a physician diagnosis of IBD (ulcerative colitis [UC], or Crohn's disease [CD]) in the NHWS, and had a medical or pharmacy claim indicating a possible diagnosis of IBD were included. Disease symptom severity was defined by a weighted symptom score and main outcomes include health-related quality of life (HRQoL), work productivity (WPAI), healthcare resource use (HRU), and associated costs. RESULTS: Overall, 687 patients with IBD were included, of which 347 were identified with UC and 340 with CD. Validation analysis showed that 94.7% of UC and 88.7% of patients with CD who self-reported diagnosis of CD or UC in NHWS had evidence of diagnosis and/or treatment patterns in claims. Patients with both UC and CD with moderate or severe symptoms had significantly lower HRQoL, increased work productivity loss, greater HRU, and associated costs compared with patients with mild symptoms. CONCLUSIONS: Patients with moderate/severe UC or CD experience substantial humanistic, and economic burden compared with patients with mild UC or CD. These factors should be considered within treatment goals for patients in order to provide holistic care beyond the treatment of objective markers or disease severity and symptoms alone.

Employment, Work Productivity, and Biologic Treatments in Self-Reported Axial Spondyloarthritis: a Cross-Sectional Study in a Female Predominant Population from the ArthritisPower Registry.

INTRODUCTION: The aim of this study was to characterize employment, work productivity, and biologic disease-modifying anti-rheumatic drug (bDMARD) treatment in a predominantly female population of axial spondyloarthritis (axSpA) patients in a real-world setting. METHODS: This was a cross-sectional study of axSpA participants within the ArthritisPower registry. Outcomes were assessed with surveys (Work Productivity and Activity Impairment [WPAI], Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], and Patient-Reported Outcomes Measurement Information System instruments) and compared between subgroups (employed vs. not employed; taking vs. not taking a bDMARD). RESULTS: Among the 195 participants, 117 (60.0%) were employed and 78 (40.0%) were not employed entirely or partially due to axSpA. The mean age of the participants was 47.6 years and 86.7% were female. Current bDMARD use was reported by 57.4% of those surveyed (59.8% employed vs. 53.9% not employed; p = 0.408). Compared to not employed participants, employed participants had more favorable disease activity (BASDAI 6.0 vs. 7.6; p < 0.001) and overall health (self-rated health 2.5 vs. 1.8; p < 0.001). Employed participants, compared to not employed participants, were diagnosed at an earlier age (36.0 vs. 42.5 years, respectively) and experienced a shorter time between symptom onset and diagnosis (9.5 vs. 13.6 years, respectively). Employed participants reported missing on average 6.5 days of work and experienced a 52.7% impairment on work productivity due to axSpA over a 3-month period. Absenteeism and presenteeism were statistically similar between participants taking a bDMARD versus those not taking a bDMARD. CONCLUSIONS: Although bDMARD treatment rates were similar between employed and not employed participants, disease activity and overall health were better in employed than non-employed participants. Employed participants experienced substantial work productivity impairment due to axSpA.

Patient Perspectives on Biologics for Axial Spondyloarthritis in a Cross-sectional Study in a Predominantly Female Population: Treatment Satisfaction, Wear-off Between Doses, and Use of Supplemental Medication.

INTRODUCTION: There is limited information regarding treatment experience of patients with axial spondyloarthritis/ankylosing spondylitis (axSpA/AS) receiving biological disease-modifying antirheumatic drugs (bDMARDs). Here we characterize patient experiences and perspectives, including satisfaction among those currently treated with bDMARD therapy for axSpA/AS. We also assess the use of supplemental medication during perceived wear-off between doses. METHODS: Adult participants from the United States within the ArthritisPower registry with physician-diagnosed axSpA/AS were invited to complete electronic patient-reported outcome measures and an online survey about their perspectives of treatment. Analysis compared patient characteristics and treatment satisfaction by whether wear-off in axSpA/AS between bDMARD doses was reported. RESULTS: Of 128 patients currently taking a DMARD, the mean age was 46.9 (10.3) years, 82.0% were female, and 93.8% were White. A total of 78 (60.9%) perceived wear-off with their current bDMARD before the next dose, 19 (14.8%) did not experience wear-off and 31 (24.2%) were unsure about wear-off. Mean (standard deviation [SD]) Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score indicated poor disease control in all patients receiving bDMARDs (6.4 [1.8]); worse for those perceiving wear-off between doses versus those who did not perceive wear-off or were unsure (6.8 [1.6] vs. 5.9 [2.0], p = 0.011). Patients experiencing wear-off reported being 'very satisfied' or 'somewhat satisfied' with their treatment less frequently than patients without wear-off (73.1 vs. 89.5%, respectively). Of patients reporting wear-off, 82.1% (n = 64) used supplemental medications during wear-off (non-steroidal anti-inflammatory drugs [68.8%, n = 44], muscle relaxants [42.2%, n = 27], and/or opioids [37.5%, n = 24]). CONCLUSIONS: In a predominantly female sample of bDMARD-treated patients with axSpA/AS and high disease activity, the majority expressed treatment satisfaction. However, most experienced wear-off between doses and relied on supplemental medications, including opioids, to manage symptoms.

Improvement of Functioning and Health With Ixekizumab in the Treatment of Active Nonradiographic Axial Spondyloarthritis in a 52-Week, Randomized, Controlled Trial.

OBJECTIVE: To evaluate the effect of ixekizumab on self-reported functioning and health in patients with active nonradiographic axial spondyloarthritis (SpA). METHODS: COAST-X was a randomized, controlled trial conducted in patients with nonradiographic axial SpA over 52 weeks. Participants were randomized at a ratio of 1:1:1 to receive 80 mg of ixekizumab subcutaneously every 4 weeks or 2 weeks or placebo for 52 weeks. Self-reported functioning and health end points included the Medical Outcomes Study Short Form 36 (SF-36) health survey, Assessment of Spondyloarthritis International Society (ASAS) health index, and European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) health-utility descriptive system. RESULTS: Compared to placebo, ixekizumab treatment resulted in improvement of SF-36 physical component summary scores from baseline, with a score of 4.7 improving to 8.9 with ixekizumab therapy every 4 weeks (P < 0.05) and a score of 9.3 with ixekizumab therapy every 2 weeks (P < 0.01); the greatest improvements were observed in the domains of physical functioning, role-physical, and bodily pain at weeks 16 and 52. A higher proportion of patients receiving ixekizumab therapy every 2 weeks reported ≥3 improvements based on the ASAS health index from baseline to weeks 16 and 52 (P < 0.05). Significantly more patients receiving ixekizumab every 4 weeks reported improvements in "good health status" on the ASAS health index (ASAS score of ≤5) at weeks 16 and 52 (P < 0.05). Patients receiving ixekizumab reported improvements on the EQ-5D-5L compared to those who received placebo at week 16 (0.11 versus 0.17 for patients receiving treatment every 4 weeks and 0.19 for patients receiving treatment every 2 weeks; P < 0.05), which remained consistent at week 52. There were no clinical meaningful differences in responses based on the ixekizumab dosing regimen for patients who received ixekizumab therapy every 2 weeks or every 4 weeks. CONCLUSION: In patients with nonradiographic axial SpA, therapy with ixekizumab was superior to placebo in the improvement of self-reported functioning and health at weeks 16 and 52.

Identifying trajectories of radiographic spinal disease in ankylosing spondylitis: a 15-year follow-up study of the PSOAS cohort.

OBJECTIVES: Little is known with certainty about the natural history of spinal disease progression in ankylosing spondylitis (AS). Our objective was to discover if there were distinct patterns of change in vertebral involvement over time and to study associated clinical factors. METHODS: Data were analysed from the Prospective Study of Outcomes in Ankylosing Spondylitis (PSOAS) observational cohort. All patients met modified New York Criteria for AS and had ≥2 sets of radiographs scored by modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) by two independent readers between 2002 and 2017. Group-based trajectory modelling (GBTM) was used to classify patients into distinct groups of longitudinal mSASSS considering sociodemographic and clinical covariables. The optimal trajectory model and number of trajectories was selected using Nagin's Bayesian information criterion (BIC). RESULTS: A total of 561 patients with 1618 radiographs were analysed. The optimum number of trajectory groups identified was four (BIC -4062). These groups were subsequently categorized as: non-progressors (204 patients), late-progressors (147 patients), early-progressors (107 patients) and rapid-progressors (103 patients). Baseline predictors associated with higher spinal disease burden groups included: baseline mSASSS, male gender, longer disease duration, elevated CRP and smoking history. In addition, time-varying anti-TNF use per year was associated with decreased mSASSS progression only in the rapid-progressor group. CONCLUSIONS: GBTM identified four distinct patterns of spinal disease progression in the PSOAS cohort. Male gender, longer disease duration, elevated CRP and smoking were associated with higher spinal disease groups. Independent confirmation in other AS cohorts is needed to confirm these radiographic patterns.

Treatment Satisfaction and Decision-making from the Patient Perspective in Axial Spondyloarthritis: Real-World Data from a Descriptive Cross-sectional Survey Study from the ArthritisPower Registry.

OBJECTIVE: Aims were to 1) to characterize patient decision-making with treatment for axial spondyloarthritis (axSpA) and 2) to explore relationships among decision-making, treatment satisfaction, and biologic disease modifying antirheumatic drugs (bDMARDs). METHODS: ArthritisPower participants with physician-diagnosed axSpA were invited to complete an online survey about their treatment and their most recent physician visit. Analysis compared treatment decision by satisfaction and bDMARD status. RESULTS: Among the 274 participants, 87.2% were female, and the mean age was 50 years. Of participants, 79.5% had researched treatment before their most recent physician visit, and 56.9% discussed treatment change at their most recent physician visit. Of treatment-change discussions, 69.2% of them were related to escalation, compared with deescalation (27.6%) and/or switching (39.1%). Among those participants who discussed a change, 73.7% agreed to it because they felt that their disease was not being controlled (54.9%) or felt that it could be better controlled on new treatment (20.3%). Top symptoms prompting change were back/buttock pain (63.3%), other joint pain (55.1%), and fatigue (54.1%). Among bDMARD-treated participants (n = 128), important factors for treatment decisions were prevention of long-term axSpA consequences (92.9%) and doctor's advice (87.5%). Among 43.4% of participants reporting treatment dissatisfaction, 37% did not discuss treatment change. Current bDMARD use was more common in satisfied (61.9%) than dissatisfied participants (26.9%). CONCLUSION: In this cross-sectional study of a predominantly female axSpA population, patients frequently researched treatment options and discussed escalation with their providers. Under two-thirds of participants who were dissatisfied with treatment discussed changes at their most recent visit. Current bDMARD use was associated with higher satisfaction, and bDMARD users considered prevention of long-term consequences and doctor's advice to be very important for decision-making.