Patient-reported Disease Research Articles

Kidney Stone Prevalence Based on Self-Report and Electronic Health Records: Insight into the Prevalence of Active Medical Care for Kidney Stones

ObjectiveTo compare rates of patient-reported kidney stone disease to Electronic Health Records (EHR) kidney stone diagnosis using a common dataset to evaluate for socio-demographic differences, including between those with and without active care. MethodsFrom the All of Us research database, we identified 21,687 adult participants with both patient-reported and EHR data. We compared differences in age, sex, race, education, employment status and healthcare access between patients with self-reported kidney stone history without EHR data to those with EHR-based diagnoses. ResultsIn this population, the self-reported prevalence of kidney stones was 8.6% overall (n = 1877), including 4.6% (n = 1004) who had self-reported diagnoses but no EHR data. Among those with self-reported kidney stone diagnoses only, the median age was 66. The EHR-based prevalence of kidney stones was 5.7% (n = 1231), median age 67. No differences were observed in age, sex, education, employment status, rural/urban status, or ability to afford healthcare between groups with EHR diagnosis or self-reported diagnosis only. Of patients who had a self-reported history of kidney stones, 24% reported actively seeing a provider for kidney stones. ConclusionKidney stone prevalence by self-report is higher than EHR-based prevalence in this national dataset. Using either method alone to estimate kidney stone prevalence may exclude some patients with the condition, although the demographic profile of both groups is similar. Approximately 1 in 4 patients report actively seeing a provider for stone disease.

Evaluation of Patient and Physician Assessments of Gastrointestinal Disease Activity in Systemic Sclerosis.

To assess whether patient and physician global assessment of gastrointestinal tract (GIT) disease in systemic sclerosis (SSc) are associated with a meaningful change in disease status. One hundred forty-three participants from the Australian Scleroderma Cohort Study were recruited to this study. Using logistic regression analysis, we evaluated the relationship between patient-reported and physician-assessed GIT disease status and symptoms, measures of health-related quality of life (36-item Short Form Health Survey [SF-36]) and GIT disease severity, measured by the Scleroderma Clinical Trials Consortium UCLA Gastrointestinal Tract 2.0 (GIT 2.0) score. Patient-reported worsening of GIT symptoms in the month preceding assessment was significantly associated with more severe GIT disease (odds ratio [OR] 6.14, P < 0.01) and progressive worsening GIT disease severity as measured by the GIT 2.0 score (OR 45.98, P < 0.01). The new onset of reflux was the only specific symptom associated with patient-reported GIT disease activity (OR 2.98, P = 0.04). Physician-assessed GIT disease activity was not significantly associated with higher GIT 2.0 scores or increasing severity of disease. Patient-reported and physician-assessed GIT activity was not associated with SF-36 scores. In the absence of objective measures of GIT disease activity in SSc, patient-reported symptoms of GIT disease could be used to indicate disease activity and should merit consideration for inclusion in a multisystem disease activity index.

Ocular Adverse Events in Transplant Ineligible Patients with Newly Diagnosed Multiple Myeloma Treated with Belantamab Mafodotin, Lenalidomide, and Dexamethasone in a Phase 1/2 Trial

Introduction Belantamab mafodotin (belamaf) is a B-cell maturation antigen-binding antibody-drug conjugate approved as a monotherapy in pretreated patients (pts) with relapsed/refractory multiple myeloma. In pts refractory to immunomodulatory drugs, proteasome inhibitors, and antiCD38, belamaf plus pomalidomide and dexamethasone induced a very good partial response (VGPR) or better rate of 69.2% and a median progression-free survival of 16.2 months (Trudel S, ASH 2021). Corneal examination findings (e.g., keratopathy) and visual acuity changes are common with belamaf, warranting belamaf dose modifications (dose reduction, dose holds) or treatment discontinuation. Here, we evaluate the ocular adverse effects of belamaf and their impact on daily functioning in pts participating in the phase 1/2 BelaRd study. Methods The ongoing, prospective, open-label, 2-part, phase 1/2 BelaRd study (NCT04808037) aims to enroll 66 adult pts with TI NDMM. In Part 1 of the study (dose selection), 18 pts are randomized (1:1:1) in 3 cohorts to receive belamaf 2.5, 1.9, or 1.4 mg/kg doses by intravenous infusion once every 8 weeks (Q8W) plus Rd and the safety/tolerability of the combination is evaluated for pts with ≥4 weeks of follow up. As a safety review found no unexpected findings, an additional 6 pts were enrolled in each dose cohort to select the belamaf recommended phase 2 dose (RP2D). Part 2 (dose expansion; not initiated) will further evaluate the safety and clinical activity of belamaf RP2D plus Rd. Ocular assessments include best corrected visual acuity (BCVA), using Snellen chart and manifest refraction, and corneal exam using slit lamp microscopy. Ocular symptoms are classified by Common Terminology Criteria for Adverse Events and dry eye disease severity and vision-related functioning is assessed with the patient-reported Ocular Surface Disease Index (OSDI). In Part 1 of the study, severity of corneal events is assessed with the Keratopathy Visual Acuity scale. This descriptive analysis included all Part 1 pts from the BelaRd study (data cut-off: 24 June 2022). Results Thirty-six pts were included in this analysis, who were followed up for a median of 9.5 months (range 3.2-15.4). At baseline (cycle 1 day 1), all pts had ocular comorbidities. During follow-up, most of OSDI assessments indicated that there was an impact of study treatment on activities of daily living (ADLs) 'some' or 'none of the time', while only <2.0% of OSDI assessments indicated the impact was 'all' or 'most of the time' (Table). The most common any grade (gr) ocular adverse events (OAEs) across cohorts were dry eye and visual acuity reduced. Gr 3 OAEs were observed only for visual acuity reduced, visual impairment, and cataract; no Gr 4 OAEs were observed. Belamaf doses skipped due to OAEs per the total number of planned belamaf administrations were 23/68 (33.8%), 15/73 (20.5%), and 10/69 (14.5%) in cohorts 2.5, 1.9, and 1.4 mg/kg, respectively. For the entire pt population, median times to resolution of keratopathy and BCVA change from baseline were 2.1 months (range 0.7-11.1) and 2.0 months (range 0.3-6.9), respectively; across cohorts, numerically similar median times to resolution were observed for each OAE Conclusions No new ocular safety signals were observed with belamaf plus Rd in the upfront treatment of TI pts with NDMM; the observed OAEs were within the anticipated range with the use of belamaf. Keratopathy and BCVA change from baseline were resolved by a median of ~2 months; for each of these OAEs, similar times to resolution were recorded, across dose cohorts. Belamaf plus Rd had a minor impact on ADLs, with the patients receiving 1.4 and 1.9 mg/kg doses being the least impacted. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Subcutaneous Epcoritamab in Novel Combinations with Antineoplastic Agents Among Patients with B-Cell Non-Hodgkin Lymphoma in a Phase 1b/2, Multicenter, Open-Label Study: Assessing Safety, Tolerability, and Preliminary Efficacy (EPCORE NHL-5)

Background: Novel treatment options for patients with B-cell non-Hodgkin lymphoma (B-NHL) are encouraging. Epcoritamab is a subcutaneously administered, bispecific antibody that binds to CD3+ T cells and CD20+ B cells, inducing T cells to kill CD20+ tumor cells through a unique mechanism of action (MOA). Clinically meaningful and compelling efficacy with epcoritamab was seen among patients with relapsed or refractory (R/R) B-NHL in the phase 1/2 EPCORE NHL-1 (NCT03625037) trial, including deep and durable responses (overall response rate [ORR], 63%; complete response [CR] rate, 39%; median duration of response [DOR], 12 months) in a population with highly refractory large B-cell lymphoma with a manageable safety profile (n = 157) (Thieblemont et al, EHA 2022). Investigations of agents such as polatuzumab vedotin, tafasitamab in combination with lenalidomide, and ibrutinib have shown promise in diffuse large B-cell lymphoma (DLBCL) (Goy et al, Blood 2019; Salles et al, Lancet Oncol 2020; Tilly et al, N Engl J Med 2022). Combining epcoritamab with antineoplastic agents that have different MOAs may offer enhanced clinical benefit to patients with B-NHL. The aims of this study (EPCORE NHL-5; NCT05283720) are to characterize the safety, tolerability, pharmacokinetics, and preliminary efficacy of epcoritamab and determine the recommended dose of epcoritamab when coadministered with other antineoplastic agents as novel combinations in patients with B-NHL. This open-label, global, multicenter study will evaluate epcoritamab in novel combinations with antineoplastic agents in 3 arms (arm 1: epcoritamab plus lenalidomide in R/R DLBCL; arm 2: epcoritamab, ibrutinib, and lenalidomide in R/R DLBCL [post-chimeric antigen receptor T-cell (CAR T) therapy]; arm 3: epcoritamab plus pola-R-CHP in treatment-naive DLBCL). Study Design and Methods: Each arm includes a dose-escalation/-expansion phase. The primary endpoint is dose-limiting toxicities. Secondary endpoints include best overall response, CR, DOR, progression-free survival, time to response, and overall survival. Additional endpoints are patient-reported outcomes, safety, pharmacokinetics, immunogenicity, and disease- and/or drug-related biomarkers. Patients must be at least 18 years of age with an Eastern Cooperative Oncology Group performance status of 0 to 2. Other inclusion criteria are measurable disease by positron emission tomography/computed tomography and diagnosis of CD20+ non-Hodgkin lymphoma, including DLBCL, DLBCL not otherwise specified, "double-/triple-hit" DLBCL, and grade 3B follicular lymphoma; other indications are being considered for additional novel combinations. Patients must not have prior therapy with epcoritamab or other bispecific antibodies targeting CD3 and CD20 and no autologous stem cell transplant within 3 months of screening. Enrollment is ongoing and planned in North America, Europe, and Asia.

PATIENT-REPORTED TRIGGER NUMBER IS A STRONG PREDICTOR OF UNCONTROLLED DISEASE AMONG PATIENTS WITH SEVERE ASTHMA

<h3>Introduction</h3> Severe asthma (SA) is associated with high morbidity. Numerous factors can trigger or exacerbate asthma symptoms and attacks through interactions with the airway epithelium. A better understanding of triggers among SA patients could help improve care. <h3>Methods</h3> CHRONICLE is an observational study of adults with SA receiving biologics, maintenance systemic corticosteroids (SCS), or uncontrolled on high-dosage inhaled corticosteroids and additional controllers. For patients enrolled February 2018–February 2021, this analysis examined associations between the number of patient-reported triggers (from a 17-category survey) and disease control (Asthma Control Test [ACT], work productivity, Saint George's Respiratory Questionnaire [SGRQ], HCP-reported exacerbations). Multivariate analyses further examined associations between disease control and trigger number or blood eosinophil counts [BEC]. <h3>Results</h3> Among 2847 enrolled patients, 1434 (51.3%) completed the triggers questionnaire. Median trigger number per patient was 8 (IQR: 5, 10). Most common triggers were weather/air changes, viral infections, seasonal allergies, perennial allergies, and exercise. Patients reporting more triggers experienced more poorly controlled disease, worse quality of life, reduced work productivity, and more exacerbations (<b>Figure</b>), which was confirmed by multivariate models. For all measures, trigger number was a stronger predictor than BEC. AUC-ROC for trigger number was higher than for BEC for predicting ≥1 exacerbations and ≥1 asthma hospitalizations (0.60 vs. 0.53 and 0.67 vs. 0.51, respectively). <h3>Conclusion</h3> Among US specialist-treated patients with SA, number of patient-reported triggers was a better predictor than BEC of disease morbidity across multiple measures. This highlights the importance of understanding patient-reported triggers in SA treatment.

Correspondence between patient-reported flare and disease activity score variation in axial spondyloarthritis: A 12-months web-based study.

The aims of this study were to determine thresholds of variations of BASDAI and pain associated with patient-reported outbreak or resolution of flare and to test performance of ASAS preliminary definitions of flare. SpA patients registered on the Spondy+platform were invited to fill BASDAI and global pain on numeric rating scales every week during one year and to tell if they experienced flare since last week. Performance of BASDAI and pain variations (ΔBASDAI and Δpain) to detect occurrence and resolution of flare was determined with receiver operator characteristic (ROC) curves. Ninety-one of the 99 axSpA patients included reported at least one episode of flare. Area under the ROC curve was significantly higher for ΔBASDAI than for Δpain to predict outbreak of flare (0.81 vs. 0.77, p&lt;0.05) without statically significant difference to predict flare resolution (0.78 vs. 0.80). Best sensitivity/specificity compromise was obtained for ΔBASDAI of 0.2 and 0.4 points to predict flare outbreak or resolution, respectively. All the ASAS definitions obtained a specificity higher than 95% whereas sensitivity was lower than 40%. ΔBASDAI appeared as a suitable variable to monitor occurrence and resolution of patient-reported flare in axSpA.

Switching from Adalimumab Originator to Biosimilar in Patients with Hidradenitis Suppurativa Results in Losses of Response-Data from the German HS Registry HSBest.

Since 2021, adalimumab biosimilar ABP 501 can be used alternatively to adalimumab originator (ADAO) in the treatment of hidradenitis suppurativa (HS). Effectiveness and safety data remain scarce. We investigated the impact of switching from ADAO to ABP 501 on disease severity and the occurrence of adverse events (AEs) in patients with HS. We analyzed clinical data on patients enrolled in the German HSBest registry. Evaluation outcomes were assessed at three time points (baseline of originator (t0), prior to switching to biosimilar (t1) and 12 to 14 weeks after switching (t2)) and included patient-reported AEs and disease severity using the International Hidradenitis Suppurativa Severity Score System (IHS4) score. In total, 94 patients were switched from ADAO to ABP 501. Overall, 33.3% (n = 31/94) of the patients developed AEs and/or loss of response (LoR) within 12 to 14 weeks after switching. Of these, 61.3% (n = 19/31) experienced LoR but no AEs, 22.6% (n = 7/31) LoR combined with AEs and 16.1% (n = 5/31) AEs only. Our study showed that switching HS patients from ADAO to ABP 501 does significantly affect treatment effectiveness. Switching patients who are on remission maintenance therapy should be viewed critically.

Efficacy and safety of a mobile app intervention in patients with inflammatory arthritis: a prospective pilot study

EULAR highlighted the essential role of digital health in increasing self-management and improving clinical outcomes in patients with arthritis. The objective of this study was to evaluate the efficacy and safety of the digital health application (DHA) in patients with inflammatory arthritis. We assessed demographic parameters, treatment regimen, disease activity, and other patient-reported outcomes at baseline and after 4 weeks of DHA use added to standard care treatment. Of 17 patients, who completed the study, 7 (41.2%) patients were male, ranging from 19 to 63 (40.5 ± 12.2) years. No significant change in antirheumatic treatment was observed during the study. Statistically significant improvements (p < 0.05) were noted for health-related quality of life (increase in Physical Component Summary of Short Form-36 (SF-36) by 23.6%) and disease activity (decrease of Clinical Disease Activity Index and Simple Disease Activity Index by 38.4% and 39.9%, respectively). Clinically significant improvement was demonstrated for SF-36 Total Score (+ 14.4%), disease activity (Rheumatoid Arthritis Disease Activity Index− 5 to 15.9%), and depression (Patient Health Questionnaire− 9 to 13.5%). None of the efficacy parameters showed negative trends. No adverse events were reported throughout the study. The usability level was high i.e., the mean mHealth Application Usability Questionnaire Score of 5.96 (max.: 7.0) demonstrated a high level of application usability. This suggests that using a personalized disease management program based on DHA significantly improves several measures of patient-reported outcomes and disease activity in patients with inflammatory arthritis in a timely manner. These findings highlight the potential of complementary digital therapy in patients with inflammatory arthritis.

Association between tumor response to systemic therapy and patient-reported disease symptoms.

The association of treatment-induced tumor shrinkage with symptom palliation for patients with lung cancer remains unknown. We investigated this correlation using the Edmonton Symptom Assessment System-Revised. Using the in-hospital cancer registry, we identified patients receiving chemotherapy and/or immunotherapy for newly diagnosed advanced or metastatic lung cancer. Tumor response and post-treatment Edmonton Symptom Assessment System-Revised were obtained after 2-3 treatment cycles. Patients were divided into groups with or without >30% unidirectional tumor shrinkage (objective response [OR] or non-OR [N-OR] groups, respectively). They were further classified as good-objective response (>50% unidirectional tumor shrinkage), moderate-objective response (30-50% shrinkage), progressive disease (>20% tumor growth or new lesion) or stable disease (SD; N-objective response and non-progressive disease). The primary endpoint was change in the total Edmonton Symptom Assessment System-Revised score from baseline. The Mann-Whitney U test was used for analysis. In total, 113 patients were enrolled. The total Edmonton Symptom Assessment System-Revised score was significantly more improved in the OR group versus the N-OR group (median: 5 vs. 2, respectively; P=0.013). This association was more prominent in patients with small-cell lung cancer and large-cell neuroendocrine tumor than those with other histology. Sensitivity analyses showed that the total Edmonton Symptom Assessment System-Revised score was more improved in the OR group versus the SD group (median: 5 vs. 3, respectively; P=0.029) and in the 'good-OR' group versus the 'moderate-OR and SD' group (median: 7.5 vs. 2, respectively; P=0.003), suggesting that greater tumor shrinkage led to more symptom amelioration. Tumor shrinkage was associated with Edmonton Symptom Assessment System-Revised score improvement in patients with lung cancer receiving systemic therapy.

32244 Impact of risankizumab on achieving minimal clinically important differences in patient-reported disease activity, fatigue, and pain among patients with active psoriatic arthritis: Analysis of 2 phase 3 clinical trials

Introduction: Psoriatic arthritis (PsA) is characterized by involvement of skin and joint, which greatly affects health-related quality of life. Two phase 3 clinical trials (KEEPsAKE-1 and KEEPsAKE-2) assessed the impact of risankizumab (RZB) on patient-reported outcomes (PROs). Methods: Adult patients with PsA and inadequate response or intolerance to biologic or conventional-synthetic disease-modifying antirheumatic drugs were randomized 1:1 to receive RZB (150 mg) or placebo (PBO). PROs assessed included patient pain VAS, Patient’s Global Assessment of Disease Activity (PtGA), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue). The proportion of patients achieving minimal clinically important differences (MCID) for each PRO at Week 24 was compared between study groups using logistic regression controlling for baseline PRO score and stratification factors ; results are presented as odds ratio (OR with 95% confidence interval [95% CI]) of achieving MCID relative to PBO. Results: KEEPsAKE-1 enrolled 964 patients (RZB: 481; PBO: 483). Patients receiving RZB vs PBO were more likely (OR [95% CI]) to achieve MCID in pain VAS (2.18 [1.61-2.95]), PtGA (2.06 [1.53-2.77]), and FACIT-Fatigue (1.89 [1.41-2.53]). Results from KEEPsAKE-2 (443 patients; RZB: 224; PBO: 219) in were similar to KEEPsAKE-1. RZB- vs PBO-treated patients were significantly more likely to achieve MCID in the PROs assessed (pain VAS: 2.55 [1.62-4.01], PtGA: 1.89 [1.21-2.95], and FACIT-Fatigue: 1.84 [1.17-2.90]). Conclusions: Patients with PsA receiving RZB vs PBO for 24 weeks were significantly more likely to achieve MCID in PROs assessing health-related quality of life, pain, and fatigue.

Discordance of chronic rhinosinusitis disease control between EPOS guidelines and patient perspectives identifies utility of patient-rated control assessment.

The objective of this study was to determine concordance of patient-reported chronic rhinosinusitis (CRS) disease control with CRS disease control assessed according to European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) criteria. In 421 participants, CRS disease control was determined using EPOS criteria which include the burden of 5 symptoms measured on a binary scale, use of rescue medications in the prior 6 months and presence of diseased mucosa on nasal endoscopy. Symptom severity was also assessed using a visual analogue scale (VAS). Participants rated their CRS disease control as "controlled","partly controlled" or "uncontrolled". Patient-reported and EPOS-based CRS disease control ratings agreed for 49.6% of participants. Amongst cases of disagreement, EPOS guidelines assessed worse CRS disease control relative to 92.9% of patients. Facial pain/pressure and impaired sense of smell distinctly associated with patient agreement with EPOS guidelines on having "uncontrolled" CRS. Higher VAS symptom scores were associated with worse patient-reported CRS disease control (i.e., agreeing with EPOS guidelines). Removal of the nasal endoscopy criterion improved agreement between patients' and EPOS control assessments, and replacement of this criterion with patient-reported control further aligned EPOS guidelines with patient perspectives. EPOS guidelines regularly assess worse CRS control than assessed by patients. The lack of more gradated symptom severity criteria and inclusion of nasal endoscopy may contribute to discordance of EPOS guidelines with patient-reported CRS control. Replacement of nasal endoscopy findings with a measure of patient-reported CRS disease control better aligns EPOS CRS disease control guidelines with patients' perspectives.

FIBROMYALGIA IN EARLY OSTEOARTHRITIS; A TERTIARY CARE HOSPITAL EXPERIENCE

Objectives: To find the prevalence of fibromyalgia in patients with early knee osteoarthritis. Methodology: In this observational cross-sectional study 115 patients (age 18-49) in which 65 females and 50 males were selected from the Department of Rheumatology, Lady Reading Hospital Peshawar from August 2020 and February 2021. The American College of Rheumatology 1990 criteria and American Classification Criteria 1986 were used for the diagnosis of fibromyalgia in early knee osteoarthritis. Results: Mean age of the patients was 37.38 ± 9.14 years. There were 50 patients (females= 38, males = 12) who reported fibromyalgia. Moreover, there were 41 patients with hypertension, 3 with diabetes, and 1 with ischemic heart disease. Similarly, 3 patients reported hypothyroidism while 1 patient-reported chronic kidney disease. As regards fibromyalgia, 50 patients with early OA were found to have fibromyalgia comprising 43.5% of the total patients. Conclusion: It is concluded that fibromyalgia is a commonly occurring disease among patients with early knee osteoarthritis. This condition affects both sexes, although females are far more likely to develop fibromyalgia as compared to males. The results of this study further highlighted the need for awareness, early diagnosis, and timely management of Fibromyalgia preventing patients from being over-treated for early knee OA.

The Nocebo Effect in a Non-Medical Switching Program from Originator to Biosimilar Infliximab in Inflammatory Bowel Disease.

Despite growing awareness of the nocebo effect, few studies have evaluated the nocebo effect using combined assessment of patient-reported outcome measures (PROMs), clinical indices, and objective biomarkers in inflammatory bowel disease (IBD) patients switching from originator to biosimilar medicines. This study aimed to compare these outcomes across switch and non-switch cohorts to evaluate the nocebo effect in patients with IBD. Parallel cohorts of IBD patients who (1) switched from originator to biosimilar (CT-P13) infliximab and (2) continued biosimilar (CT-P13) infliximab were evaluated over 32 weeks. Clinical disease activity, objective biomarkers and PROMs were assessed at baseline, and weeks 16 and 32 across both cohorts. The PROM of interest was patient-perceived disease activity evaluated using a 0-100 visual analogue scale (VAS) per the IBD-Control Questionnaire. Of 81 patients, 47 switched from originator to biosimilar (CT-P13) infliximab. A negative change from baseline patient-reported disease control was observed across the switch cohort compared with the non-switch cohort at week 16 (mean VAS - 8.21 vs. 1.26; p=0.03), but not at week 32 (mean VAS - 1.21 vs. 1.38; p=0.58). Corresponding clinical and objective biomarker assessments over these timepoints were comparable across both cohorts. This study demonstrated a temporary yet discernible nocebo effect in the first 16 weeks following non-medical switching that was not sustained at week 32. Negative patient perceptions may be overcome by a patient-inclusive approach to non-medical switching in conjunction with close clinical follow-up and disease monitoring.

A Patient-Reported Historical Disease Course and Flare Frequency in Adults With Moderate-to-Severe Atopic Dermatitis-A Pilot Study.

A Patient-Reported Historical Disease Course and Flare Frequency in Adults With Moderate-to-Severe Atopic Dermatitis-A Pilot Study.

Mast cells and tryptase are linked to itch and disease severity in mycosis fungoides: Results of a pilot study.

IntroductionIn mycosis fungoides (MF), the most common cutaneous T-cell lymphoma, itch is a frequent clinical symptom. Whether mast cells (MCs), eosinophils (Eos) or their mediators play a role in MF-associated itch or disease severity is controversially discussed. Here, we explored the role of MC and Eo numbers in the skin as well as blood levels of their mediators in disease severity and itch.MethodsIn 10 patients with MF and 10 matched control subjects we assessed disease severity, itch, and quality of life impairment using dedicated tools such as the mSWAT, ItchyQoL and DLQI. We analyzed skin biopsies and measured serum levels of tryptase, a mast cell mediator, as well as of the eosinophil products eosinophil cationic protein (ECP) and major basic protein (MBP).ResultsThe presence of chronic itch, in four of 10 patients, was associated with significantly higher disease severity (mSwat), larger body surface area affected, and stronger QoL impairment (Itchy-Qol, DLQI). Serum levels of tryptase, but not ECP and MBP, were linked with patient-reported disease severity, body surface area affected, and the presence of itch. Three of the four patients with chronic itch, but none of the six patients without, had tryptase levels above >6µg/l. Numbers of MCs in the papillary dermis were higher in MF skin lesions then in non-lesional skin of MF patients and skin of healthy controls.DiscussionThe MC-mediator tryptase, in MF, is linked to disease activity and impact, most prominently to itch. Our findings call for larger studies that explore the role of MCs, tryptase and other MC mediators as drivers of itch and their role in MF pathogenesis.

The Effect of Maintenance Treatment with Erdosteine on Exacerbation Treatment and Health Status in Patients with COPD: A Post-Hoc Analysis of the RESTORE Dataset.

PurposeTo explore the effect of erdosteine on COPD exacerbations, health-related quality of life (HRQoL), and subjectively assessed COPD severity.Patients and methodsThis post-hoc analysis of the RESTORE study included participants with COPD and spirometrically moderate (GOLD 2; post-bronchodilator forced expiratory volume in 1 second [FEV1] 50‒79% predicted; n = 254), or severe airflow limitation (GOLD 3; post-bronchodilator FEV1 30‒49% predicted; n = 191) who received erdosteine 300 mg twice daily or placebo added to usual maintenance therapy for 12 months. Antibiotic and oral corticosteroid use was determined together with patient-reported HRQoL (St George’s Respiratory Questionnaire, SGRQ). Patient and physician subjective COPD severity scores (scale 0‒4) were rated at baseline, 6 and 12 months. Data were analyzed using descriptive statistics for exacerbation severity, COPD severity, and treatment group. Comparisons between treatment groups used Student’s t-tests or ANCOVA as appropriate.ResultsAmong GOLD 2 patients, 43 of 126 erdosteine-treated patients exacerbated (7 moderate-to-severe exacerbations), compared to 62 of 128 placebo-treated patients (14 moderate-to-severe exacerbations). Among those with moderate-to-severe exacerbations, erdosteine-treated patients had a shorter mean duration of corticosteroid treatment (11.4 days vs 13.3 days for placebo, P = 0.043), and fewer patients required antibiotic treatment with/without oral corticosteroids (71.4% vs 85.8% for placebo, P < 0.001). Erdosteine-treated GOLD 2 patients who exacerbated showed significant improvements from baseline in SGRQ total scores and subjective disease severity scores (patient- and physician-rated), compared with placebo-treated patients regardless of exacerbation severity. Among GOLD 3 patients, there were no significant differences between treatment groups on any of these measures.ConclusionAdding erdosteine to the usual maintenance therapy of COPD patients with moderate airflow limitation reduced the number of exacerbations, the duration of treatment with corticosteroids and the episodes requiring treatment with antibiotics. Additionally, treatment with erdosteine improved HRQoL and patient-reported disease severity.

A global, cross-sectional survey of patient-reported outcomes, disease burden, and quality of life in epidermolysis bullosa simplex

BackgroundEpidermolysis bullosa simplex (EBS) comprises a group of rare, blistering genodermatoses. Prior work has been limited by small sample sizes, and much remains unexplored about the disease burden and health-related quality of life (QOL) of patients with EBS. The aim of this study was to characterize the most common patient-reported clinical manifestations and the health-related impact of QOL in EBS, and to examine differences in disease burden by age.MethodsPatients with a diagnosis of epidermolysis bullosa (EB) or their caregivers completed a one-time online survey administered by EBCare, an international online EB registry. Survey data from respondents self-reporting a diagnosis of EBS were analyzed for clinical and wound manifestations, medication use, and QOL (using Quality of Life in Epidermolysis Bullosa [QOLEB] scores). Differences across age groups were assessed using Kruskal–Wallis and Fisher’s exact tests.ResultsThere were 214 survey respondents with EBS. The mean age was 32.8 years (standard deviation = 19.2). Many respondents reported blisters (93%), recurrent wounds (89%), pain (74%), chronic wounds (59%), itch (55%), and difficulty walking (44%). Mean QOLEB score was 14.7 (standard deviation = 7.5) indicating a “moderate” impact on QOL, and 12% of respondents required regular use of opiates. Findings were consistent in subgroup analyses restricted to respondents with diagnostic confirmation via genetic testing or skin biopsy (n = 63 of 214). Age-stratified analyses revealed differences in disease burden: younger respondents were more likely to self-report severe disease (24% vs. 19% vs. 5% for respondents aged 0–9 vs. 10–17 vs. 18 + , p = 0.001), failure to thrive (9% vs. 15% vs. 3%, p = 0.02), and use of gastrostomy tubes (15% vs. 12% vs. 1%, p < 0.001) and topical antibiotics (67% vs. 69% vs. 34%, p < 0.001), while older respondents were more likely to be overweight or obese (6% vs. 0% vs. 51%, p < 0.001) and have difficulty walking (24% vs. 46% vs. 48%, p = 0.04).ConclusionsIn the largest international cross-sectional survey of EBS patients conducted, respondents reported extensive disease burden including significant wounding, pain, itch, difficulty walking, and impact on QOL. Age stratified disease manifestations. These findings suggest significant unmet need, and treatment and counseling for EBS patients should consider age-specific differences.

OP0042 LONG-TERM EFFICACY AND SAFETY OF CANAKINUMAB IN PATIENTS WITH FAMILIAL MEDITERRANEAN FEVER (FMF) - INTERIM ANALYSIS OF THE RELIANCE REGISTRY

BackgroundFamilial Mediterranean Fever (FMF) is a chronic disease characterized by recurrent attacks of fever as well as serositis and bears the risk of serious complications (e. g. amyloidosis). Treatment of FMF according to EULAR aims to control acute attacks and subclinical inflammation as well as to improve patient´s quality of life1. Clinical data indicate that the inhibition of interleukin-1β with canakinumab (CAN) is effective in controlling and preventing flares in FMF patients2.ObjectivesThe present study explores the long-term efficacy and safety of canakinumab in routine clinical practice conditions in pediatric (age ≥2 years) and adult FMF patients.MethodsRELIANCE is a prospective, non-interventional, multi-center, observational study based in Germany with a 3-year follow-up period. Patients with clinically confirmed FMF diagnosis who routinely receive canakinumab are enrolled in order to evaluate effectiveness and safety of canakinumab. Disease activity and remission by physicians´ assessment, disease activity, fatigue and impact on social life by patients’ assessment, inflammatory markers and AIDAI (Auto-Inflammatory Diseases Activity Index) score were recorded at baseline and assessed at 6-monthly intervals within the 3-year observation period of the study.ResultsThis interim analysis of FMF patients (N=74) enrolled by December 2021 includes baseline as well as 6- to 24-month data. Mean age in this cohort was 25 years (2−61 years) and the proportion of female patients was 51 % (N=38). At baseline, median duration of prior CAN treatment was 1.0 years (0−6 years).At month 24, physician ratings report around 63% of patients in disease remission and patient-reported disease activity (mean PPA) decreased from moderate (3.0) to low (2.6) during the observation period. Other disease activity parameters also decreased (Table 1). A total of 18 serious adverse events were reported, of which 2 (1 case of tonsillectomy and 1 case of tachycardia) were classified as drug - related.Table 1.Baseline characteristics and 4th interim analysis data of patients with FMFBaseline12 months24 monthsNumber of patients, N744624Number (%) of patients with days absent from work/school during last 6 months6 (8)11 (24)9 (38)Number (%) of patients in disease remission (physician assessment)22 (45)23 (72)12 (63)Patient’s assessment of current disease activity; 0–10, median (min; max)2.0 (0; 10)2.0 (0; 7)2.0 (0; 10)Patient’s assessment of current fatigue; 0–10, median (min; max)5.0 (0; 10)2.0 (0; 10)4.0 (0; 10)Number (%) of patients without impairment of social life by the disease27 (50)28 (80)8 (67)CRP (mg/dl) | SAA (mg/dl) | ESR (mm/h); median0.2 | 0.7 | 8.00.2 | 0.5 | 4.00.2 | 0.7 | 6.0Number (%) of patients with disease-related symptomsprior to inclusion into the study | at baseline12 months24 monthsFever68 (93) | 14 (29)8 (25)3 (16)Abdominal pain67 (92) | 20 (41)10 (31)4 (21)Thoracic pain45 (62) | 5 (10)3 (9)1 (5)Headache34 (47) | 11 (22)7 (22)5 (26)Myalgia23 (32) | 6 (12)4 (13)2 (11)Arthralgia/arthritis39 (54) | 16 (33)9 (28)5 (26)Dermal symptoms (urticarial, maculopapulose)15 (21) | 5 (10)3 (9)0 (0)SAENumber of eventsIncidence rate# per 100 patient yearsAll types of SAE1814.03SADR21.56Incidence rate = number of events * 36,525 / sum of observation days (=46,848).CRP, c-reactive protein; ESR, erythrocyte sedimentation rate; n. a., not annotated; SAA, serum amyloid A; SADR, serious adverse drug reaction; SAE, serious adverse events.ConclusionInterim data of FMF patients from the RELIANCE study, the longest running real-life canakinumab registry confirm efficacy and safety of long-term canakinumab treatment.

DMARD disruption, rheumatic disease flare, and prolonged COVID-19 symptom duration after acute COVID-19 among patients with rheumatic disease: A prospective study

ObjectiveTo describe disease-modifying antirheumatic drug (DMARD) disruption, rheumatic disease flare/activity, and prolonged COVID-19 symptom duration among COVID-19 survivors with systemic autoimmune rheumatic diseases (SARDs). MethodsWe surveyed people with pre-existing SARDs who had confirmed COVID-19 at Mass General Brigham to investigate post-acute sequelae of COVID-19. We obtained data on demographics, clinical characteristics, COVID-19 symptoms/course, and patient-reported measures. We examined baseline predictors of prolonged COVID-19 symptom duration (defined as lasting ≥28 days) using logistic regression. ResultsWe analyzed surveys from 174 COVID-19 survivors (mean age 52 years, 81% female, 80% White, 50% rheumatoid arthritis) between March 2021 and January 2022. Fifty-one percent of 127 respondents on any DMARD reported a disruption to their regimen after COVID-19 onset. For individual DMARDs, 56-77% had any change, except for hydroxychloroquine (23%) and rituximab (46%). SARD flare after COVID-19 was reported by 41%. Global patient-reported disease activity was worse at the time of survey than before COVID-19 (mean 6.6±2.9 vs. 7.6±2.3, p<0.001). Median time to COVID-19 symptom resolution was 25 days (IQR 11, 160). Prolonged symptom duration of ≥28 days occurred in 45%. Hospitalization for COVID-19 (OR 3.54, 95%CI 1.27-9.87) and initial COVID-19 symptom count (OR 1.38 per symptom, 95%CI 1.17-1.63) were associated with prolonged symptom duration. Respondents experiencing prolonged symptom duration had higher RAPID3 scores (p=0.007) and more pain (p<0.001) and fatigue (p=0.03) compared to those without prolonged symptoms. ConclusionDMARD disruption, SARD flare, and prolonged COVID-19 symptom duration were common in this prospective study of COVID-19 survivors, suggesting substantial impact on SARDs after acute COVID-19.

Prevalence of anxiety and depressive symptoms in ulcerative colitis patients in Jordan and its relationship to patient-reported disease activity

Inflammatory bowel disease is associated with higher rates of anxiety and depression compared to the general population. We aimed to determine the prevalence of anxiety and depressive symptoms among patients with ulcerative colitis and correlation to disease activity. In this cross-sectional study, we collected data from 70 consecutive ulcerative colitis patients over one year at our inflammatory bowel disease outpatient clinic through an interview and a questionnaire containing patient demographics and disease characteristics. Anxiety and depressive symptoms were characterized using the Generalized Anxiety Disorder-7 questionnaire and Patient Health Questionnaire-9, respectively, with ulcerative colitis disease severity assessed by the Partial Mayo scoring system. The majority of our patients were females (68.6%) and the mean age was 39.3 years. Rates of anxiety and depressive symptoms among ulcerative colitis patients were 65.7% and 58.6%, respectively. Depressive symptoms were significantly associated with patient-reported disease activity (r = 0.361; p = 0.010). Significant percentages of ulcerative colitis patients were appreciated to have anxiety and depressive symptoms, and there was a correlation between patient-reported disease activity and depressive symptoms. At this high rate of prevalence, it is justified to screen patients for the presence of psychiatric comorbidities.