Background: Up to one-third of people living with psoriasis develop psoriatic arthritis (PsA), and the majority have active psoriasis prior to the development of arthritis. Clinical risk factors, such as nail involvement, in conjunction with novel blood biomarkers, could improve PsA risk monitoring and early diagnosis. Objectives: The aim of the HIPPOCRATES Prospective Observational Study (HPOS— www.hpos.study ) is to follow a cohort living with psoriasis and identify risk factors for the development of PsA. Design: HPOS is a patient-driven online prospective European observational cohort. Methods: Adult participants with psoriasis but with no prior diagnosis of PsA are eligible. Participants are invited to provide consent and join the study online. They complete a semi-structured questionnaire to collect data on demographics, psoriasis, comorbidities, risk factors for PsA, and the Psoriasis Epidemiology Screening Tool screening questionnaire. Follow-up is conducted through a questionnaire every 6 months. The primary outcome is the new onset of PsA confirmed by a diagnosis from their doctor. The study will also collect peripheral blood samples from a subset of participants for biomarker identification. Ethics: This study follows the principles of the Declaration of Helsinki. To date, ethical approval has been granted by independent ethical committees in 10 countries. Discussion: Studying a cohort of individuals with psoriasis will allow us to identify risk factors for arthritis development and to develop a risk calculator. This can support focused efforts on screening, patient education, and even studies looking to delay or prevent the onset of arthritis. This study, run via remote online data collection, provides an efficient way to recruit a large cohort (25,000) across multiple countries. However, challenges have had to be addressed with some key changes in study design, ethical review, and recruitment strategies required for each individual country. Trial registration: HPOS, Clinicaltrials.gov ID: NCT05858528, IRAS number 325080; https://clinicaltrials.gov/study/NCT05858528?locStr=United%20Kingdom&country=United%20Kingdom&cond=Psoriasis&term=HPOS&aggFilters=status%3Anot%20rec&rank=1 .

Objective: To describe determinants of persisting humoral and cellular immune response to the second COVID-19 vaccination among patients with myeloma.Methods: This is a prospective, observational study utilising the platform. Participants reported their second and third COVID-19 vaccination dates. Myeloma patients had an Anti-S antibody level sample taken at least 21 days after their second vaccination and a repeat sample before their third vaccination.Results: 60 patients provided samples at least 3 weeks (median 57.5 days) after their second vaccination and before their third vaccination (median 176.0 days after second vaccine dose). Low Anti-S antibody levels (<50 IU/mL) doubled during this interval (p = .023) and, in the 47 participants with T-spot data, there was a 25% increase negative T-spot tests (p = .008). Low anti-S antibody levels prior to the third vaccination were predicted by lower Anti-S antibody level and negative T-spot status after the second vaccine. Independent determinants of a negative T-spot included increasing age, previous COVID infection, high CD4 count and lower percentage change in Anti-S antibody levels.Conclusions: Negative T-spot results predict low Anti-S antibody levels (<50 IU/mL) following a second COVID-19 vaccination and a number of biomarkers predict T cell responses in myeloma patients.

Hereditary angioedema (HAE) adversely affects patients’ social and daily life significantly, and the disease burden is high. We recruited study participants from a patient-participatory registry, Rare and Undiagnosed Diseases Study (RUDY) Japan, to better understand the broader effect of HAE on patients’ lives. Thirteen patients with HAE who registered between January 2019 and March 2021 completed an online questionnaire to record details of episodes and the angioedema quality of life (AE-QoL) questionnaire, in which they described the degree to which QoL was impaired. In all, 58 episodes were recorded, and self-reported data were accumulated from 24 returned AE-QoL questionnaires. The episodes peaked between approximately 06:00 and 07:00 h and between approximately 16:00 and 20:00 h. Of the 58 episodes, 38 (65.5%) were treated; 24 (63.2%) were treated at patients’ homes. The drugs used in treatment were hospital-administered human C1-inhibitor preparations for 14 episodes and home-administered icatibant for 26 episodes. Time between episode onset and treatment initiation and between episode onset and full recovery tended to be shorter with icatibant treatment at home. The total AE-QoL score was 37.1 ± 22.9, indicating great impairment of QoL, with particularly high scores in the fatigue/mood and fears/shame domains. Most previous studies of real-world HAE episodes have been retrospective, based on patients’ memories. Collaboration between patients and researchers revealed the location of episodes, the time of day they appeared, treatments for episodes, and the degree to which patients’ QoL was impaired by HAE in this prospective study.

Objectives:Rituximab is used for remission induction and the prevention of relapse in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). This study evaluated the incidence of safety events and compared time to first serious adverse event (SAE) between a rituximab cohort and a cohort treated with non-rituximab therapies in a real-life setting. Methods:Rituximab surveillance study in vasculitis was a retrospective observational study of patients with AAV who received rituximab (MabThera) or other treatments between 2003 and 2017 at a specialist vasculitis clinic. The primary endpoint was time to first SAE. Results:392 patients were enrolled: 247 in the rituximab and 145 in the control cohorts with a total follow up of 2217 person-years (mean study duration 5.7 years). Mean age was 61 years, 77% had granulomatosis with polyangiitis (GPA). There were differences in baseline characteristics (disease duration and prior immunosuppressive use) between groups. 134/247 patients (54%) in the rituximab and 58/145 (40%) of controls experienced at least one SAE. Time to first SAE was shorter in the rituximab group (hazard ratio (HR) 1.55, 95% CI 1.07-2.26, P = 0.022). Predictors of first SAE were higher vasculitis damage index and the presence of chronic pulmonary or kidney disease. The risk of serious infection was higher in the rituximab group (relative risk (RR) 2.12, 95% CI 1.31-3.43). Conclusion:Over 40% of patients with AAV experienced at least one SAE. Although shorter time to first SAE and higher risk of infection were observed in the rituximab group, baseline imbalances necessitate a careful interpretation of these results.

strong rational to develop Tra-based immunotherapies for treating RAS-driven hrMM and ultra hrMM.

Myeloma patients frequently respond poorly to bacterial and viral vaccination. A few studies have reported poor humoral immune responses in myeloma patients to COVID-19 vaccination. Using a prospective study of myeloma patients in the UK Rudy study cohort, we assessed humoral and interferon gamma release assay (IGRA) cellular immune responses to COVID-19 vaccination post second COVID-19 vaccine administration. We report data from 214 adults with myeloma (n = 204) or smouldering myeloma (n = 10) who provided blood samples at least three weeks after second vaccine dose. Positive Anti-spike antibody levels (> 50 iu/ml) were detected in 189/203 (92.7%), positive IGRA responses were seen in 97/158 (61.4%) myeloma patients. Only 10/158 (6.3%) patients were identified to have both a negative IGRA and negative anti-spike protein antibody response. In all, 95/158 (60.1%) patients produced positive results for both anti-spike protein serology and IGRA. After adjusting for disease severity and myeloma therapy, poor humoral immune response was predicted by male gender. Predictors of poor IGRA included anti-CD38/anti-BCMA (B-cell maturation antigen) therapy and Pfizer-BioNTech vaccination. Further work is required to understand the clinical significance of divergent cellular response to vaccination.

OBJECTIVE:COVID-19 is a novel infectious disease with a broad spectrum of clinical severity. Patients with systemic vasculitis have an increased risk of serious infections and may be at risk of severe outcomes following COVID-19. We undertook this study to establish the risk factors for severe COVID-19 outcomes in these patients, including the impact of immunosuppressive therapies. METHODS:A multicenter cohort was developed through the participation of centers affiliated with national UK and Ireland vasculitis registries. Clinical characteristics and outcomes are described. Logistic regression was used to evaluate associations between potential risk factors and a severe COVID-19 outcome, defined as a requirement for advanced oxygen therapy, a requirement for invasive ventilation, or death. RESULTS:The cohort included 65 patients with systemic vasculitis who developed COVID-19 (median age 70 years, 49% women), of whom 25 patients (38%) experienced a severe outcome. Most patients (55 of 65 [85%]) had antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Almost all patients required hospitalization (59 of 65 [91%]), 7 patients (11%) were admitted to intensive care, and 18 patients (28%) died. Background glucocorticoid therapy was associated with severe outcomes (adjusted odds ratio [OR] 3.7 [95% confidence interval 1.1-14.9]; P = 0.047), as was comorbid respiratory disease (adjusted OR 7.5 [95% confidence interval 1.9-38.2]; P = 0.006). Vasculitis disease activity and nonglucocorticoid immunosuppressive therapy were not associated with severe outcomes. CONCLUSION:In patients with systemic vasculitis, glucocorticoid use at presentation and comorbid respiratory disease were associated with severe outcomes in COVID-19. These data can inform clinical decision-making relating to the risk of severe COVID-19 in this vulnerable patient group.

ABSTRACTObjectiveMultiple myeloma (MM)-related morbidity has a profound effect on quality of life (QoL), and immune function, but few studies have prospectively examined the impact of COVID-19 pandemic and attendant vaccination on both immunity and QoL of patients with MM. We aimed to characterise these effects in a prospective cohort study.DesignWe initiated a prospective national cohort study of patients with MM from start of the second wave of SARS CoV-2 infections in December 2020 and resultant COVID lockdown in the United Kingdom. We assessed current myeloma status, history of COVID19 symptoms, testing and vaccination including response using the rudystudy.org platform. In addition, healthcare resource use, mental and social well being and loneliness (Lubben scale) from the start of the COVID-19 pandemic were assessed.ParticipantsWe report data from the first one hundred and nine adults with MM who completed the questionnaires and the first round of blood testing in the cohort.ResultsFive patients (4.5%) had COVID-19 infection confirmed by history and/or testing (Nucleocapsid antibody). Up to 98% of patients shielded completely or partially during both waves of the pandemic, with 18% of patients consequently changing antimyeloma therapy in the shielding period. Using the Lubben scale, 21/99 (21.2 %) reported social isolation. Using HADS scale 23.1% of patients reported symptoms of mild to moderate anxiety or mild to moderate depression during this period. Humoral immune response (spike ab) tested 3 weeks after first vaccination was detected in 17/28 (60%) patients.ConclusionMyeloma patients shielded during waves of the pandemic with significant change to therapy, low level natural COVID-19 infection (4%) and social isolation. Humoral response following the first dose of COVID-19 vaccine is lower than that reported in non-myeloma cohorts.What is already known on this topicLimited published data exist on the effect of the COVID-19 pandemic on myeloma patients. Post first vaccine response in myeloma patients has been reported in a small number of patients from two studies ranging from 25 % to 56%.What this study addsThis study reports myeloma patients shielded during waves of the pandemic and demonstrates consequent significant social isolation and changes to therapy. Low level natural COVID-19 infection (4%) was noted in the study and humoral response following first dose of COVID-19 vaccine was lower than that reported in non-myeloma cohorts.

Background The role of patients in medical research is changing, as more emphasis is being placed on patient involvement, and patient reported outcomes are increasingly contributing to clinical decision-making. Information and communication technology provides new opportunities for patients to actively become involved in research. These trends are particularly noticeable in Europe and the US, but less obvious in Japan. The aim of this study was to investigate the practice of active involvement of patients in medical research in Japan by utilizing a digital platform, and to analyze the outcomes to clarify what specific approaches could be put into practice. Methods We developed the RUDY JAPAN system, an ongoing rare disease medical research platform, in collaboration with the Rare and Undiagnosed Diseases Study (RUDY) project in the UK. After 2 years of preparation, RUDY JAPAN was launched in December 2017. Skeletal muscle channelopathies were initially selected as target diseases, and hereditary angioedema was subsequently added. Several approaches for active patient involvement were designed through patient-researcher collaboration, namely the Steering Committee, questionnaire development, dynamic consent, and other communication strategies. We analyzed our practices and experiences focusing on how each approach affected and contributed to the research project. Results RUDY JAPAN has successfully involved patients in this research project in various ways. While not a part of the initial decision-making phase to launch the project, patients have increasingly been involved since then. A high level of patient involvement was achieved through the Steering Committee, a governance body that has made a major contribution to RUDY JAPAN, and the process of the questionnaire development. The creation of the Patient Network Forum, website and newsletter cultivated dialogue between patients and researchers. The registry itself allowed patient participation through data input and control of data usage through dynamic consent. Conclusions We believe the initial outcomes demonstrate the feasibility and utility of active patient involvement in Japan. The collaboration realized through RUDY JAPAN was enabled by digital technologies. It allowed busy patients and researchers to find the space to meet and work together for the Steering Committee, questionnaire development and various communication activities. While the practice of active patient involvement in Japan is still in its early stages, this research confirms its viability if the right conditions are in place. (331 words).

on behalf of the Czech Registry of ANCA-

BACKGROUND:Health-related quality of life of adults with osteogenesis imperfecta (OI), fibrous dysplasia (FD) and X-linked hypophosphatemia (XLH) remains poorly described. The aim of this study was to describe the HRQoL of adults with osteogenesis imperfecta, fibrous dysplasia and X-linked hypophophataemia and perform a cost-utility simulation to calculate the maximum cost that a health care system would be willing to pay for a hypothetical treatment of a rare bone disease. RESULTS:Participants completed the EQ-5D-5 L questionnaire between September 2014 and March 2016. For the economic simulation, we considered a hypothetical treatment that would be applied to OI participants in the lower tertile of the health utility score. A total of 109 study participants fully completed the EQ-5D-5 L questionnaire (response rate 63%). Pain/discomfort was the most problematic domain for participants with all three diseases (FD 31%, XLH 25%, OI 16%). The economic simulation identified an expected treatment impact of +2.5 QALYs gained per person during the 10-year period, which led to a willing to pay of £14,355 annually for a health care system willing to pay up to £50,000 for each additional QALY gained by an intervention. CONCLUSIONS:This is the first study to quantitatively measure and compare the HRQoL of adults with OI, FD and XLH and the first to use such data to conduct an economic simulation leading to healthcare system willingness-to-pay estimates for treatment of musculoskeletal rare diseases at various cost-effectiveness thresholds.