ABSTRACT
BackgroundRheumatoid arthritis (RA) and spondyloarthritis, including either Psoriatic Arthritis (PsA) and Ankylosing Spondylitis (AS), are some of the most diagnosed autoimmune rheumatic diseases (AIRDs) in rheumatologists' routine clinical practice [1]. Understanding patients' health and functional status is crucial to provide personalized management strategies to optimize disease control and enhance the quality of life.ObjectivesWe aimed to compare disease burden in patients with RA, PsA or AS by assessing Patient-Reported Outcome Measurement Information System (PROMIS) Physical Health, Global Mental Health, Physical Function and Fatigue 4a together with VAS Pain.MethodsData were obtained in the international COVID vaccination in autoimmune rheumatic diseases study second e-survey (COVAD study). Demographics, AIRD diagnosis, disease activity, PROMIS Global Physical health, PROMIS Global Mental Health, PROMIS Physical Function SF10 and PROMIS Fatigue 4a score were extracted from the COVAD study database. For this study, we only included patients with self-reported RA or spondyloarthritis (either PsA or AS) undergoing active treatment with conventional synthetic disease-modifying drugs (DMARDs) and/or biologic DMARDs, who answered all the survey questions. Active disease was defined as the patient's perception of their disease as active in the four weeks before their first COVID-19 vaccine shot. Analysis of Variance with Bartlett's and Tukey's test was used to compare continuous variables between groups.ResultsFrom January to June 2022, n.1907 patients with RA, female 87.62% (1671/1907), with mean age (±SD) 50.95 ±13.67, n.311 patients with PsA, female 67.20% (209/311), with a mean age of 50.42 ±12.70, and n.336 patients with AS, male 51.31% (209/311), with a mean age of 43.13 ±12.75 years, responded to the COVAD e-survey.In those with active disease, neither physical health, global mental health, physical function, fatigue, nor pain were different among groups (Table 1, Figure 1). Patients with inactive AS had higher mean global physical health scores than RA patients (13.13 ±2.93 VS RA 12.48 ±2.90, p=0.01, Table 1). Those with inactive RA or PsA showed more severe fatigue (PsA 10.58 ±2.22, RA 10.45 ±4.08 VS 9.4 ±4.13, p =0.01 for both). Patients with inactive RA also reported poorer physical function and more residual pain than those with AS (37.79 ±8.86 VS 41.13 ±7.79, p<0.001;3.87 ±2.45 VS 3.34 ±2.39, p=0.01, respectively). Similarly, residual pain was perceived as higher in patients with inactive PsA than those with AS (4.04 ±2.50 VS 3.34 ±2.39, p=0.01)ConclusionDisease burden is roughly comparable in patients with active RA, PsA or AS. Patients with inactive RA and PsA suffer higher disease burden than those with inactive AS.Reference[1]Mease PJ, Liu M, Rebello S, Kang H, Yi E, Park Y, Greenberg JD. Comparative Disease Burden in Patients with Rheumatoid Arthritis, Psoriatic Arthritis, or Axial Spondyloarthritis: Data from Two Corrona Registries. Rheumatol Ther. 2019 Dec;6(4):529-542.Table 1.Patient-Reported Outcome Measures between groups.Inactive diseaseAS (n.185)PsA (n.179)RA (n.1167)MeanSDMeanSDMeanSDPROMIS Global Physical Health13.13*2.9512.433.2712.482.90p=0.01, VS RAPROMIS Global Mental Health13.313.3612.973.3312.843.17PROMIS Fatigue 4a9.44.1310.58*4.2210.45*4.08p=0.01, bothPROMIS Physical Function SF10 Score41.137.3939.279.0137.79*8.86p<0.001, VS ASVAS Pain3.342.394.04*2.503.87*2.45p=0.01, bothActive DiseaseAS (n.35)PsA (n.38)RA (n.189)MeanSDMeanSDMeanSDPROMIS Global Physical Health11.053.1910.102.7611.243.41PROMIS Global Mental Health11.313.2610.843.6311.893.30PROMIS Fatigue 4a12.944.8712.844.4211.754.68PROMIS Physical Function SF10 Score35.829.6233.528.7634.909.80VAS Pain4.682.775.02.544.682.61Figure 1.Violin plots showing kernel densities, quartiles and median for Patient-Reported Outcome Measures for patients with RA, PsA and AS, stratified by disease activity status.[Figure omitted. See PDF]Acknowledgements:NIL.Disclosure of InterestsVincenzo Venerito: None declared, Marc Fornaro: None declared, Florenzo Iannone: None declared, Lorenzo Cavagna: None declared, Masataka Kuwana: None declared, Vishwesh Agarwal: None declared, Naveen Ravichandran: None declared, Jessica Day Grant/research support from: JD has received research funding from CSL Limited., Mrudula Joshi: None declared, Sreoshy Saha: None declared, Syahrul Sazliyana Shaharir: None declared, Wanruchada Katchamart: None declared, Phonpen Akarawatcharangura Goo: None declared, Lisa Traboco: None declared, Yi-Ming Chen: None declared, Parikshit Sen: None declared, James B. Lilleker Speakers bureau: JBL has received speaker honoraria/participated in advisory boards for Sanofi Genzyme, Roche, and Biogen. None is related to this manuscript., Consultant of: JBL has received speaker honoraria/participated in advisory boards for Sanofi Genzyme, Roche, and Biogen. None is related to this manuscript., Arvind Nune: None declared, John Pauling: None declared, Chris Wincup: None declared, Ai Lyn Tan Speakers bureau: ALT has received honoraria for advisory boards and speaking for Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB., Nelly Ziade Speakers bureau: NZ has received speaker fees, advisory board fees, and research grants from Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, and Pierre Fabre;none are related to this manuscript, Grant/research support from: NZ has received speaker fees, advisory board fees, and research grants from Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, and Pierre Fabre;none are related to this manuscript, Marcin Milchert: None declared, Abraham Edgar Gracia-Ramos: None declared, Carlo Vinicio Caballero: None declared, COVAD Study: None declared, Vikas Agarwal: None declared, Rohit Aggarwal Speakers bureau: RA has a consultancy relationship with and/or has received research funding from the following companies: Bristol Myers-Squibb, Pfizer, Genentech, Octapharma, CSL Behring, Mallinckrodt, AstraZeneca, Corbus, Kezar, Abbvie, Janssen, Alexion, Argenx, Q32, EMD-Serono, Boehringer Ingelheim, and Roivant., Grant/research support from: RA has a consultancy relationship with and/or has received research funding from the following companies: Bristol Myers-Squibb, Pfizer, Genentech, Octapharma, CSL Behring, Mallinckrodt, AstraZeneca, Corbus, Kezar, Abbvie, Janssen, Alexion, Argenx, Q32, EMD-Serono, Boehringer Ingelheim, and Roivant., Latika Gupta: None declared.
ABSTRACT
BackgroundAlthough many studies have been conducted on COVID-19 in recent years, there are still unanswered questions regarding breakthrough infections (BTIs), particularly in patients with systemic lupus erythematosus (SLE).ObjectivesThis study aimed to determine the occurrence of breakthrough COVID-19 infections in patients with SLE versus other autoimmune rheumatic diseases (AIRDs), non-rheumatic autoimmune diseases (nrAIDs), and healthy controls (HCs).MethodsThe study was based on data from the COVAD questionnaire which amassed a total of 10,783 complete responses from patients with SLE, AIRD, or nrAIRD, and HCs. After exclusion of individuals who were unvaccinated, those who received one vaccine dose only, and those with uncertain responses regarding the vaccine doses, a total of 9,595 patients formed the study population of the present investigation. If a COVID-19 infection occurred after the initial two vaccine doses and at least one booster dose (at least three doses in total, herein termed full vaccination), it was considered a BTI. Data were analysed using multivariable regression models. Statistically significant results were denoted by p values <0.05.ResultsA total of 7,016/9,595 (73.1%) individuals were fully vaccinated. Among those, 1,002 (14.2%) reported at least one BTI, and 166 (2.3%) reported at least two BTIs. Among SLE patients, 867/1,218 (71.2%) were fully vaccinated. Among fully vaccinated SLE patients, 137 (15.8%) reported at least one BTI while 28 (3.2%) reported at least two BTIs. BTI frequencies in fully vaccinated SLE patients were comparable to those of other AIRDs (OR: 1.0;95% CI: 0.8–1.3;p=0.447) and nrAIDS (OR: 0.9;95% CI: 0.6–1.3;p=0.856) but higher compared with HCs (OR: 1.2;95% CI: 1.0–1.6;p=0.022).For SLE patients with three vaccine doses, 113/137 (82.5%) reported at least one BTI while the corresponding number for four vaccine doses was 24/137 (17.5%). Compared with HCs (OR: 10.6;95% CI: 1.2–93.0;p=0.032) and other AIRDs (OR: 3.5;95% CI: 1.08–11.5;p=0.036), SLE patients showed higher frequencies of hospitalisation.AID multimorbidity was associated with a 15-fold increased risk for a need of advanced treatment for COVID-19 (OR: 15.3;95% CI: 2.6–88.2;p=0.002).ConclusionCOVID-19 BTIs occurred in nearly 1 every 6th fully vaccinated patient with SLE, and 20% more frequently in this patient population compared with fully vaccinated HCs. Moreover, BTIs in SLE patients were more severe compared with BTIs in HCs or patients with AIRDs other than SLE, resulting in a greater need for hospitalisation. AID multimorbidity contributed to a more severe COVID-19 BTI requiring advanced management. These insights call for greater attention to vaccination in the vulnerable group of SLE patients, with appropriate risk stratification towards optimised vaccination strategies.Figure 1.Survival analysis across patients with SLE, AIRDs, or nrAIDs, and HCs. SLE: systemic lupus erythematosus;AIRD: autoimmune rheumatic disease;nrAID: non-rheumatic autoimmune disease;HC: healthy control.[Figure omitted. See PDF]AcknowledgementsThe authors thank all survey respondents, as well as patient associations and all members of the COVAD study group for their invaluable role in the data collection.Disclosure of InterestsEmelie Kihlgren Olsson: None declared, Naveen Ravichandran: None declared, Elena Nikiphorou Speakers bureau: EN has received speaker honoraria/participated in advisory boards for Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, and Lilly., Consultant of: EN has received speaker honoraria/participated in advisory boards for Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, and Lilly., Grant/research support from: EN holds research grants from Pfizer and Lilly., Julius Lindblom: None declared, Sreoshy Saha: None declared, Syahrul Sazliyana Shaharir: None declared, Wanruchada Katchamart: None declared, Phonpen Akarawatcharangura Goo: None declared, Lisa Traboco: None declared, Yi-Ming Chen: None declared, Kshitij Jagtap: None declared, James B. Lilleker Speakers bureau:
ABSTRACT
Background/Aims Post COVID-19 syndrome (PCS) is an emerging cause of morbidity and poor quality of life in COVID-19 survivors. We aimed to assess the prevalence, risk factors, outcomes, and association with disease flares of PCS in patients with autoimmune rheumatic diseases (AIRDs) and non-rheumatic autoimmune diseases (nrAIDs), both vulnerable groups understudied in the current literature using data from the 2nd COVID-19 Vaccination in Autoimmune Diseases (COVAD) global multicentre patient self-reported e-survey. Methods The survey was circulated from February to July 2022 by the international COVAD Study Group (157 collaborators from 106 countries), and demographics, comorbidities, AIRD/nrAID status, COVID-19 history, vaccination details, and PROMIS physical and mental function were recorded. PCS was defined as symptom resolution time >90 days following acute COVID-19. Predictors of PCS were analysed using regression models for the different groups. Results 7666 total respondents completed the survey. Of these, 2650 respondents with complete responses had positive COVID-19 infection, and 1677 (45.0% AIRDs, 12.5% nrAIDs, 42.5% HCs) completed the survey >90 days post acute COVID-19. Of these, 136 (8.1%) had PCS. Prevalence of PCS was higher in AIRDs (10.8%) than healthy controls HCs (5.3%) (OR: 2.1;95%CI: 1.4-3.1, p=0.002). Across the entire cohort, a higher risk of PCS was seen in women (OR: 2.9;95%CI: 1.1-7.7, p=0.037), patients with long duration of AIRDs/ nrAIDs (OR 1.01;95%CI: 1.0-1.02, p=0.016), those with comorbidities (OR: 2.8;95%CI: 1.4-5.7, p=0.005), and patients requiring oxygen supplementation for severe acute COVID-19 (OR: 3.8;95%CI: 1.1- 13.6, p=0.039). Among patients with AIRDs, comorbidities (OR 2.0;95%CI: 1.08-3.6, p=0.026), and advanced treatment (OR: 1.9;95%CI: 1.08-3.3, p=0.024), or intensive care (OR: 3.8;95%CI: 1.01-14.4, p=0.047) for severe COVID-19 were risk factors for PCS. Notably, patients who developed PCS had poorer PROMIS global physical [15 (12-17) vs 12 (9-15)] and mental health [14 (11-16) vs 11 (8-14)] scores than those without PCS. Conclusion Individuals with AIRDs have a greater risk of PCS than HCs. Associated comorbid conditions, and advanced treatment or intensive care unit admission for severe COVID-19 confer a higher risk of PCS. It is imperative to identify risk factors for PCS for immediate multidisciplinary management in anticipation of poor physical and mental health.
ABSTRACT
Background/Aims Flares following COVID-19 vaccination are an emerging concern among patients with rare rheumatic disease like idiopathic inflammatory myositis (IIMs), whereas data and understanding of this is rather limited. We aimed to study the prevalence, characteristics and determinants of IIM flares following COVID-19 vaccination. Methods CoVAD (COVID-19 Vaccination In Autoimmune Diseases) surveys are global patient self-reported e-surveys from 109 countries conducted in 2021 and 2022. Flares of IIM were defined by 4 definitions;a. patient self-reported, b. physician and immunosuppression (IS) denoted, c. sign directed (new erythematous rash, or worsening myositis or arthritis), d. MCID worsening of PROMISPF10a score between the patients who had taken both surveys. Descriptive statistics and multivariate regression were used to describe the predictors of flare. Cox-regression analysis was used to differentiate flares by IIM subtypes. Results Among the 1,278 IIM patients, aged 63 (50-71) years, 276 (21.5%) were dermatomyositis, 237 (18.5%) IBM, 899 (70.3%) were female and most were Caucasian (80.8%). Flares of IIM were seen in 123/1278 (9.6%), 163/1278 (12.7%), 112/1278 (8.7%), and 16/96 (19.6%) by definitions a-d respectively with median time to flare being 71.5 (10.7- 235) days. Muscle weakness (69.1%), and fatigue (56.9%) were the most common symptoms of flare. The predictors of self-reported flare were: inactive/disease in remission prior to first dose of vaccine (OR=4.3, 95%CI=2.4-7.6), and anxiety disorder (OR=2.2, 95%CI=1.1-4.7). Rituximab use (OR=0.3, 95%CI=0.1-0.7) and IBM (OR=0.3, 95%CI=0.1-0.7) were protective. Physician defined flares were seen more often in females, mixed ethnicity, and those with asthma, ILD, and anxiety disorder (OR ranging 1.6-7.0, all p<0.05). Notably, overlap myositis (OM) had higher HR for flare compared to polymyositis (HR=2.3, 95%CI=1.2-4.4, p=0.010). Conclusion Nearly one in ten individuals with IIM develop flares after vaccination, more so among women, those with overlap myositis, and inactive disease prior to vaccination. Formal definition of flares in IIM is needed.
ABSTRACT
Background: Patients with comorbidities and active rheumatic disease have increased morbidity and hospitalization following SARS-CoV- 2 infection. While vaccination has decreased this, many unknown factors still influence COVID-19 vaccine hesitancy. The data on predictors of vaccine hesitancy is regional and scarce. We aimed to analyze the factors influencing vaccine hesitancy in 2022 and compare them with those in 2021 through multicentre international e-surveys (The COVID-19 Vaccination in Autoimmune Diseases Studies -COVAD study 1 and 2). Method(s): COVAD 1 and 2 are multi-centre international e-survey with 152 collaborators in 106 countries including patients with idiopathic inflammatory myopathies (IIM), autoimmune rheumatic diseases (AIRDs), other autoimmune diseases (AIDs), and healthy controls (HCs) conducted in March-December 2021 and February-June 2022 (ongoing), respectively. Descriptive and multivariable regression adjusting for age, gender, ethnicity, and stratified by country of residence was performed. Result(s): Among the 18 882 (2021) and 7666 complete responses (2022), and 3109 (16.5%) and 387 (5.1%) did not receive any COVID-19 vaccine, respectively. The prevalence of vaccine hesitancy has decreased [OR 0.26 (0.24-0.3), P < 0.001]. Among the 387 vaccine non-recipients in 2022, numbers were as follows: IIM 69 (17%), AIRDs 179 (46%), other AIDs 80 (20.6%), and HC 59 (15%). The reasons for vaccine hesitancy in 2022 included: doctor advising against it 47 (12%), do not believe in the science behind the vaccine 79 (21%), long-term safety concerns 152 (39%), awaiting more safety data 105 (27%), and not recommended due to recent infection 30 (7%). Compared to AIRDs and HCs, IIM patients were more disbelievers of the science behind the vaccine [OR 1.8 (1.08-3.2), P = 0.023 AIRDs, OR 4 (1.9-8.1), P < 0.001 HC], had more long-term safety concerns [OR 1.9 (1.2-2.9), P = 0.001 AIRDs, OR 5.4 (3-9.6), P < 0.001 HC] and had more doctors recommending against the vaccine [OR 12.9 (2.8-59), P < 0.001 HC]. Vaccine non-recipients had higher pain visual analog score (VAS) (P < 0.001), lower fatigue VAS (P = 0.003), lower PROMIS10a physical health (P < 0.001), and mental health scores (P = 0.015). The factors predicting vaccine hesitancy in regression were lower PROMIS10a global physical health score [OR 0.9 (0.8-0.97), P = 0.014] and Caucasian ethnicity [OR 4.2 (1.7-10.3), P = 0.001]. Compared to 2021, doctor's advising against vaccination [OR 2.5 (1.8-3.6), P < 0.001] and long-term safety concerns [OR 3.6 (2.9-4.6), P < 0.001] were more frequent causes of vaccine hesitancy overall whereas vaccine non-availability [OR 0.05 (0.02-0.11), P < 0.001] and have scheduled the vaccination but not received [OR 0.1 (0.06-0.3), P < 0.001] were less frequent causes in 2022. Conclusion(s): Overall, the prevalence of COVID-19 vaccine hesitancy has decreased. Long-term safety concerns and the need for more safety data are now the major reasons for vaccine hesitancy. Caucasian ethnicity and lower physical health scores are predictors of vaccine hesitancy. The increase in physicians recommending against vaccination calls for more physician awareness to mitigate vaccine hesitancy.
ABSTRACT
PurposeType I IFNs and their autoantibodies are implicated in the pathogenesis of Systemic lupus erythematosus (SLE), but their incidence and importance is still unclear. Neutralizing autoantibodies against IFNα have been previously reported in patients with autoimmune polyendocrinopathy syndrome type I (APS-1), rheumatoid arthritis, thymoma and more recently life-threatening COVID-19 patients. We hypothesized that autoantibodies towards type I IFNs, that develop in some patients with SLE, are neutralizing and may interfere with the course of the disease.MethodsLuciferase immunoprecipitation (LIPS) analysis was used to screen 474 SLE patient and 312 control serum samples for the presence of IFNα binding autoantibodies and determine their subclasses. Type I IFN neutralizing capacity was tested using a reporter cell line. Circulating levels of IFNα were measured with Single Molecule Array (Simoa).Results14% of SLE patients were positive for anti-IFNα and 13% were positive for anti-IFNω. The autoantibodies against IFNα were predominantly of IgG1 subclass and neutralized IFNα bioactivity in approximately one half of the positive cases. Once developed, anti-IFNα autoantibodies were present throughout the disease course. IFNα2 and -α8 were targeted first in two informative follow-up cases. The reactivity broadened to other IFNα subtypes and IFNω within several months. Serum levels of IFNα correlated negatively with anti-IFNα neutralizing titers. Patients with high levels of autoantibodies against IFNα had significantly lower levels of circulating IFNα compared to anti-IFNα negative patients. Interestingly, patients with high IFNα neutralizing capacity displayed significantly lower disease activity than patients without these autoantibodies.ConclusionsBased on our results we suggest that autoantibodies that are able to neutralize the circulating levels of all IFNα subtypes may have a beneficial effect to SLE disease course.
ABSTRACT
Background/AimsCOVID-19 has had significant impacts upon the delivery of rheumatology care in the UK. To date, there is little data specifically addressinghow care has been disrupted and the impact upon patient attitudesand beliefs. Herein, we describe the results of a national studyinvestigating how COVID-19 has;(1) reduced access to services;(2)altered treatment and drug monitoring;(3) impacted on clinic followup;(4) changed patient beliefs regarding ongoing/future care.MethodsWe conducted an online survey of patients attending rheumatologyclinics in the UK. Questions were developed by clinicians with inputfrom patient charities and four expert patients. The survey was hostedonline between 8 September and 8 October 2020.ResultsIn total, 2, 054 patients completed the survey and the average numberof rheumatic conditions each patient reported was 1.981.38 with the most common being;rheumatoid arthritis (48%), lupus (20%), Sjogren's syndrome (19%), fibromyalgia (15%) and vasculitis (8%).More than half (57%) were told to shield, whilst 10% decided to shieldof their own accord. Compared with before the pandemic, 57% felt itwas difficult/very difficult to contact their rheumatologist. Regardingtreatment, 15% reported difficulty obtaining their usual medication.Less than half (45%) of patients continued medication as previouslyand had no problem accessing it, although 21% said their usual drugmonitoring had been discontinued. Overall, 3% stopped their treatment of their own accord. In all, 26% said their appointments inrheumatology clinics had been cancelled and they did not know whenthey would be seen again (4% reported no change in their outpatientfollow-up). Prior to the pandemic, 13% of patients had received atelephone consultation, however, since the pandemic 60% hadreceived one. Just 19% felt it was easy to be honest with theirclinician via telephone. Only 33% were satisfied with the current levelof care, 43% reported their rheumatology care was worse than prepandemic and 38% of patients felt they needed to see theirrheumatologist but could not get an appointment. Over half (57%) ofpatients expressed worries about their future care. If offered anappointment in the next few months 66% said they would prefer it beface-to-face.ConclusionTo our knowledge, this study is the largest survey of patientexperiences of the COVID-19 pandemic under rheumatological careanywhere in the world. We found more than half of patients were toldto shield and one-in-ten decided to shield without being directly told todo so. Less than half of patients maintained relatively good access totheir usual medication without necessary monitoring in many cases. Inparticular, patients express high levels of concern about their futurecare. These high levels of disruption indicate the importance ofmaintaining routine rheumatology services during the ongoingpandemic.