Changes in quality of life and disease-related symptoms in patients with polycythemia vera receiving ruxolitinib or standard therapy

Objectives Polycythemia vera (PV)-related symptoms may not be adequately controlled with conventional therapy. This current analysis of the RESPONSE trial evaluated the effects of ruxolitinib compared with standard therapy on quality of life (QoL) and symptoms in patients with PV who were hydroxyurea resistant/intolerant. Methods In the previously reported primary analysis, ruxolitinib achieved the primary composite endpoint of hematocrit control and ≥35% reduction in spleen volume at Week 32. The current analysis evaluated patient-reported outcomes using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF), the Pruritus Symptom Impact Scale (PSIS), and the Patient Global Impression of Change (PGIC). Results Compared with standard therapy, ruxolitinib was associated with greater improvements in global health status/QoL, functional subscales, and individual symptom scores of the EORTC QLQ-C30. At Week 32, more patients in the ruxolitinib arm (44%) achieved a ≥10-point improvement in global health status/QoL vs. standard therapy (9%). Improvements in MPN-SAF symptom scores were consistent with improvements in EORTC QLQ-C30, PSIS, and PGIC scores. Conclusions Ruxolitinib provides clinically relevant improvements in QoL and ameliorates symptom burden in patients with PV who are hydroxyurea resistant/intolerant

Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials

Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. Methods We did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. Findings In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo. Interpretation Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases. Funding UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology

Course of post COVID-19 disease symptoms over time in the ComPaRe long COVID prospective e-cohort

International audienceAbout 10% of people infected by severe acute respiratory syndrome coronavirus 2 experience post COVID-19 disease. We analysed data from 968 adult patients (5350 person-months) with a confirmed infection enroled in the ComPaRe long COVID cohort, a disease prevalent prospective e-cohort of such patients in France. Day-by-day prevalence of post COVID-19 symptoms was determined from patients’ responses to the Long COVID Symptom Tool, a validated self-reported questionnaire assessing 53 symptoms. Among patients symptomatic after 2 months, 85% still reported symptoms one year after their symptom onset. Evolution of symptoms showed a decreasing prevalence over time for 27/53 symptoms (e.g., loss of taste/smell); a stable prevalence over time for 18/53 symptoms (e.g., dyspnoea), and an increasing prevalence over time for 8/53 symptoms (e.g., paraesthesia). The disease impact on patients’ lives began increasing 6 months after onset. Our results are of importance to understand the natural history of post COVID-19 disease

Trajectories of the evolution of post COVID-19 condition, up to two years after symptoms onset

International audienceObjectivesWe aimed to identify trajectories of the evolution of post-COVID-19 condition, up to 2 years after symptom onset.MethodsThe ComPaRe long COVID e-cohort is a prospective cohort of patients with symptoms lasting at least 2 months after SARS-CoV2 infection. We used trajectory modeling to identify different trajectories in the evolution of post-COVID-19 condition, based on symptoms collected every 60 days using the long COVID Symptom Tool.ResultsA total of 2197 patients were enrolled in the cohort between December 2020 and July 2022 when the Omicron variant was not dominant. Three trajectories of the evolution of post-COVID-19 condition were identified: “high persistent symptoms” (4%), “rapidly decreasing symptoms” (5%), and “slowly decreasing symptoms” (91%). Participants with highly persistent symptoms were older and more likely to report a history of systemic diseases. They often reported tachycardia, bradycardia, palpitations, and arrhythmia. Participants with rapidly decreasing symptoms were younger and more likely to report a confirmed infection. They often reported diarrhea and back pain. Participants with slowly decreasing symptoms were more likely to have a history of functional diseases.ConclusionMost patients with post-COVID-19 condition improve slowly over time, while 5% have rapid improvement in the 2 years after symptom onset and 4% have a persistent condition

Cardiovascular events and change in cholesterol levels in patients with rheumatoid arthritis treated with tocilizumab: data from the REGATE Registry.

International audienceObjectives: Rheumatoid arthritis (RA) is responsible for excess mortality mainly due to cardiovascular disease. Studies have found elevated cholesterol levels in RA patients who received tocilizumab (TCZ). We studied the occurrence of major cardiovascular events in RA patients who received TCZ in current practice. We also analysed cholesterol level changes in these patients.Methods: Data were collected from the French REGATE Registry, a multicentre observational study including patients with RA treated with TCZ. All cardiovascular complications were analysed. Changes in cholesterol levels were studied. Factors associated with major adverse cardiac and cerebrovascular events were analysed by multivariate analysis, estimating odds ratios and 95% confidence intervals.Results: During an exposure time of 5591 patient-years (PYs), 35 cardiovascular events occurred in 33 patients, corresponding to an incidence of 0.63/100 PYs. The incidence of ischaemic stroke and cardiac ischaemia was 0.41 and 0.21/100 PYs. Age and personal history of cardiovascular events were identified as risk factors associated with cardiovascular events: OR=1.06 [95% CI 1.02-1.09] and 4.10 [1.90-8.83]. Female sex was a protective factor (OR=0.29 [95% CI 0.14-0.64]). Glucocorticoids may play a role but was not statistically significant. All cholesterol variables were increased in level after the third month of treatment with TCZ, with a 15.4%, 18.9% and 13.4% increase for total cholesterol, LDL-C and HDL-C, at 3 months.Conclusions: In current practice, cardiovascular events occurring under TCZ treatment is in the range of what is expected in RA patients despite a global increase in cholesterol levels

Factors associated with perceived stress in patients with vitiligo in the ComPaRe e-cohort

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Risk of diverticulitis and gastrointestinal perforation in rheumatoid arthritis treated with tocilizumab compared to rituximab or abatacept

International audienceObjective To compare the risk of diverticulitis and gastrointestinal perforation (GIP) in RA treated with tocilizumab (TCZ) compared with rituximab (RTX) and abatacept (ABA).Methods We conducted a population-based study using three observational French registries on TCZ, RTX and ABA in RA. Using a propensity score approach, we compared the risk of diverticulitis or GIP in these patients.Results With inverse probability weighting, there was an increased risk of diverticulitis in TCZ-treated patients compared with RTX- or ABA-treated patients [hazard ratio (HR)=3.1 (95% CI: 1.5, 6.3), P =0.002]. Moreover, patients treated with TCZ had also an increased risk of GIP due to diverticulitis compared with those treated with RTX or ABA [HR=3.8 (1.1–13.6), P =0.04], resulting in an overall increased risk of GIP [HR=2.9 (1.1–7.8), P =0.03], while no significant increased risk of GIP due to any other aetiology was found in TCZ treated patients. Diverticulitis and GIP occurred earlier with TCZ than other drugs after the last perfusion (P =0.01), with atypical clinical presentation (slow transit in 30%, P =0.04) and lower acute-phase reactants at the time of the event (P =0.005).Conclusion TCZ for RA was associated with increased odds of diverticulitis as well as GIP due to diverticulitis as compared with RTX and ABA. Our study confirms the increased odds of GIP in patients receiving TCZ, which might be explained by an increased risk of diverticulitis with misleading clinical presentation

Patients' perspectives on how to improve endometriosis care: A large qualitative study within the ComPaRe-Endometriosis e-cohort

International audienceEndometriosis is a chronic gynecological condition that affects about 10% of women of reproductive age. Despite its prevalence, diagnosis is often delayed, misdiagnosis is common, and treatment options are poor. This study aimed at capturing ideas to improve endometriosis care from the patients' perspectives. Materials and Methods: We analyzed cross-sectional data from 1,000 adult patients in ComPaRe-Endometriosis (a French prospective e-cohort focused on endometriosis) who answered to the open-ended question: "If you had a magic wand, what would you change about your health care?". The free-text responses were analyzed by qualitative thematic analysis using an inductive approach. Results: Patients had a mean age of 34.1 years (standard deviation = 8.1); 56% and 42% had stage IV disease or deep endometriosis, respectively. They elicited 2,487 ideas to improve the management of endometriosis, which were categorized into 61 areas of improvement, further grouped into 14 themes. The top five areas of improvement were mentioned by >10% of the patients and were to (1) train caregivers to develop their knowledge on the disease, (2) provide better management of daily pain and pain attacks, (3) take patient-reported symptoms seriously, (4) standardize diagnostic processes to improve early detection, and (5) have caregivers listen more to the patients. Conclusions: We identified 61 areas for improvement in endometriosis care. These results reflect patients' expectations in terms of management of their disease and will be useful to design a better global care for endometriosis from the patients' perspectives

Serious infusion-related reaction after rituximab, abatacept and tocilizumab in rheumatoid arthritis: prospective registry data

International audienceObjective: The aim was to evaluate the incidence of serious infusion-related reactions (SIRRs) in RA treated by non-TNF-targeted biologics. Methods: We analysed data from three independent prospective registers, namely autoimmunity and rituximab, Orencia (abatacept) and RA (ORA) and Registry RoAcTEmra (tocilizumab), promoted by the French Society of Rheumatology and including patients with RA. SIRRs were defined by an occurrence during or within 24 h of an infusion and requiring discontinuation of treatment. Characteristics of patients with SIRRs were extracted from the electronic database. Results: Among the 4145 patients, SIRRs occurred in 100 patients: 56 patients with the rituximab cohort (2.8% or 0.7/100 patient-years), 15 with the abatacept cohort (1.5% or 0.6/100 patient-years) and 29 with tocilizumab (1.9% or 1/100 patient-years). No fatal SIRR occurred. A previous mild infusion reaction to non-TNF-targeted biologics was observed in a quarter of patients with SIRRs. After pooled multivariate analysis, positive anti-CCP was associated with a higher risk of SIRR (odds ratio = 2.5; 95% CI: 1.01, 6.17). Absence of concomitant treatment with a synthetic DMARD tended to be associated with a higher risk of SIRR (odds ratio = 1.67; 95% CI: 1.00, 2.86). Conclusion: In daily practice, SIRRs are slightly more frequent than in clinical trials and rarely life threatening. In common practice, serological status (anti-CCP positivity) and absence of concomitant treatment with a synthetic DMARD increase the risk of SIRR

Safety of surgery in patients with rheumatoid arthritis treated by abatacept: data from the French Orencia in Rheumatoid Arthritis Registry

International audienceObjective:To investigate the frequency and risk factors of postoperative complications in RA patients treated with abatacept (ABA).Methods:The Orencia RA registry recruited 1012 patients receiving ABA for RA in routine care. Data from patients treated with ABA who underwent surgery were reviewed to describe the frequency of postoperative complications. Characteristics of patients and surgeries with and without complications were compared to identify factors associated with complications.Results:We identified 205 (20.3%) patients who underwent 263 surgeries, including 176 (66.9%) orthopaedic surgeries. Nineteen (7.2%) surgeries, in 19 patients (9.3%), entailed complications, including 7 delayed wound healing (2.7% of surgeries) and 6 surgical site infections (2.3% of surgeries). The median time between the last infusion of ABA and surgery was 5.9 weeks (range: 0.3-12.0 weeks), with no significant difference between patients with and without complications. The median corticosteroids daily dosage was higher in the group with complications [10.0 (6.25-15.0) vs 6.0 (5.0-10.0) mg/day, P = 0.042]. In multivariate analysis, only the duration of ABA treatment was significantly associated with postoperative complications [adjusted odds ratio (aOR) = 0.94 (95% CI: 0.89, 0.99) for each month of treatment], as were orthopaedic surgeries compared with other kinds of surgery [aOR = 4.45 (95% CI: 1.01, 20.2)].Conclusion:In RA patients treated with ABA, the rate of surgical complications was low: 7.2% and higher in case of orthopaedic procedure and a more recent initiation of ABA. The median time between surgery and the last infusion of ABA was short and did not influence the rate of postoperative complications