Immune-mediated Inflammatory Diseases Patients Research Articles

Clinical and molecular characterization of steatotic liver disease in the setting of immune-mediated inflammatory diseases

Background and aimsGrowing evidence suggest an increased prevalence of metabolic associated steatotic liver disease (MASLD) in the context of immune-mediated inflammatory diseases (IMIDs). We aimed to characterize clinically and mechanistically a prospective cohort of steatotic liver disease (SLD) in IMID patients compared to controls. MethodsCross-sectional, case‒control study including a subset of IMID patients. Controls from the general population were age-, sex-, type 2 diabetes-, and BMI-matched at a 1:2 ratio. SLD was established using controlled attenuation parameter. Liver biopsies were obtained when significant liver fibrosis was suspected. Total RNA was extracted from freshly frozen cases and analyzed by RNA-seq. Differential gene expression was performed with ‘limma-voom’. Gene set enrichment analysis was performed using the fgsea R package with a preranked “limma t-statistic” gene list. Results1456 IMID patients and 2945 controls were included. Advanced-SLD (LSM ≥9.7 kPa) (13.46% vs. 3.79%; p<0.001) and advanced-MASLD (12.8% vs. 2.8%; p<0.001) prevalence were significantly higher among IMID patients than controls. In multivariate analysis, concomitant IMID was an independent and the strongest predictor of advanced-SLD (Adjusted OR 3.318 [2.225-4.947]; p < 0.001). Transcriptomic data was obtained in 109 patients and showed 87 significant genes differentially expressed between IMID-MASLD and control-MASLD. IMID-MASLD cases displayed an enriched expression of genes implicated in pro-tumoral activities or the control of the cell cycle concomitant with a negative expression of genes related to metabolism. ConclusionsThe prevalence of advanced SLD and MASLD is disproportionately elevated in IMID cohorts. Our findings suggest that IMIDs may catalyse a distinct MASLD pathway, divergent from classical metabolic routes, highlighting the need for tailored clinical management strategies. Impact and implicationsThe prevalence of advanced fibrosis SLD is increased in patients with immune-mediated inflammatory diseases, independent of classic metabolic risk factors or high-risk alcohol consumption. The transcriptomic analysis reveals a unique gene expression signature associated with cellular activities that can be compatible with a liver condition leading to an accelerated and aggressive form of SLD. Our findings underscore the importance of heightened screening for advanced liver disease risk across various medical disciplines overseeing IMID patients.

The Effect of Exposure to SARS-CoV-2 Vaccination and Infection on Humoral and Cellular Immunity in a Cohort of Patients with Immune-Mediated Diseases: A Pilot Study.

Immunization against COVID-19 is needed in patients with immune-mediated inflammatory diseases (IMIDs). However, data on long-term immunity kinetics remain scarce. This study aimed to compare the humoral and cellular response to COVID-19 in patients with immune-mediated inflammatory diseases (IMIDs) compared to healthy controls. We compared the humoral and cellular response to SARS-Cov-2 elicited by vaccination and/or infection in a prospective cohort of 20 IMID patients compared with a group of 21 healthcare workers (HCWs). We assessed immunity before and after the third and fourth dose of BNT162b2 or after COVID-19 infection using quantitative IgG anti-SARS-CoV-2 Spike antibody (anti-S-IgG), neutralization assay, and specific interferon-gamma (IFN-g) release assay (IGRA). The responses were compared with those of healthy controls. The two groups were similar in age and total exposure, becoming infected for the first time, mainly after the third dose. Neutralizing antibodies and IGRA were negative in 9.5% of IMID patients but not in any HCWs. No significant difference was found between neutralization titers to BA.1 in the IMID and the HCW groups. The study highlights the SARS-CoV-2 immunological responses in healthy controls and IMID patients, suggesting that the combined stimuli of vaccination and infection in IMID patients could promote a more profound immunological response.

Biosimilars and access to biologic therapy in immune-mediated diseases

ABSTRACT Background The rise of biologic agents has been a major breakthrough in treating immune-mediated inflammatory diseases (IMIDs). However, their high cost underscores the need for strategies to optimize treatment efficiency. Biosimilars offer cost-effective alternatives to biologics. This study aimed to assess biosimilar drug availability’s impact on biologic therapy access for IMIDs. Research design and methods A retrospective observational study in 15 Spanish hospitals analyzed IMID patients (arthropathies, inflammatory bowel disease and psoriasis) initiating biologic therapy with originator or biosimilar drugs (infliximab, etanercept, adalimumab). Time to availability and initiation of biologic therapy were assessed. Results 267 patients were included, with 58.4% starting on biosimilars. The mean time to availability of the biologic drugs in the hospitals was 15.9 ± 6.7 months, (20.0 ± 12.4 for originator and 11.8 ± 5.2 for biosimilars). Mean time to biologic treatment was 7.7 ± 9.0 years (8.6 ± 8.9 for originators and 7.0 ± 9.0 for biosimilars). Showing statistically significant differences among conditions. Conclusion The emergence of biosimilar drugs has enhanced market competition and accelerated their adoption into hospitals’ therapeutic regimens over original reference drugs. This has significantly improved access to biologic therapy for patients with IMIDs, evidenced by a notable 1.6-year reduction in access time for biosimilar drugs.

P021 Uptake, safety, and effectiveness of pneumococcal vaccination in adults with immune mediated inflammatory diseases: a UK wide study using data from the Clinical Practice Research Datalink

Abstract Background/Aims The safety and effectiveness of pneumococcal vaccine in people with immune mediated inflammatory diseases (IMIDs) is not known, which may contribute to suboptimal uptake. We investigated UK wide pneumococcal vaccine uptake in adults with IMIDs, the association between pneumococcal vaccination and disease flares, and the effectiveness of pneumococcal vaccine in preventing pneumonia in this at-risk population. Methods Adults with incident rheumatoid arthritis (RA), inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE) and spondyloarthritis (SpA) prior to 31st August 2018 in the Clinical Practice Research Datalink (CPRD) Gold were included. The study was approved by CPRD research data governance (Reference 21_000614). We calculated the proportion of patients vaccinated against pneumococcal pneumonia. To investigate the association between vaccination and IMID flare, we employed a self-controlled case series analysis, adjusted for season. The study period was up-to six-month before and six-month after the date of pneumococcal vaccination. This period was partitioned into induction (14 days pre-vaccination) and exposed periods (up-to 90 days post vaccination) with the remaining time considered unexposed. Incidence rate ratios (IRR) and 95% CI were calculated. We conducted a multivariable nested case-control study to assess vaccine effectiveness. Cases were patients hospitalised with pneumonia and were matched to up to ten controls for age and sex. Multivariable conditional logistic regression was used to calculate odds ratio (OR) and 95% CI. Results We included 32,277 IMID patients: 14,151 with RA, 13,631 with IBD, 3,804 with SpA and 691 with SLE. Overall uptake of pneumococcal vaccination was 50% (95% CI 49.4% -50.5%). Vaccination uptake was significantly lower in the under 45-year-olds, in patients with IBD and in those without additional indication for vaccination at 29.7%, 38.4%, 42.7% respectively. In the safety study, data for 1001, 854, 424 vaccinated patients with primary care consultations for joint pain, AIRD flare, and IBD flare respectively were included. Vaccination against pneumococcal pneumonia was not associated with AIRD flare (IRR (95% CI) 1.07 (0.93-1.22)), primary care consultations for joint pain (IRR (95% CI) 0.95 (0.83-1.10)), and IBD flare (IRR (95% CI) 0.82 (0.64-1.06)) in the 90-days post vaccination. The vaccine effectiveness study included 25,707 patients, either with (n = 2,771) or without (n = 22,936) a hospitalisation record for pneumonia after IMID diagnosis. Patients hospitalised for pneumonia compared with their matched controls, had higher odds of current smoking, deprivation, corticosteroid prescriptions, additional indication for vaccination, primary care consultations, hospital admissions and prescriptions. In the multivariable adjusted model, pneumococcal vaccination was associated with reduced odds of hospitalisation for pneumonia (OR (95% CI) 0.88 (0.78-0.98). Conclusion The uptake of pneumococcal vaccine is low in IMID patients. Pneumococcal vaccination is not associated with IMID flare and is protective against pneumonia. These findings call for promotion of pneumococcal vaccination in IMID by health professionals. Disclosure G. Nakafero: None. M.J. Grainge: None. C.D. Mallen: Grants/research support; NIHR, MRC, Versus Arthritis and BMS. T. Card: None. J.S. Nguyen Van-Tam: Consultancies; CSL Seqirus and Moderna. Royalties; AstraZeneca and Sanofi Pasteur. A. Abhishek: Consultancies; NGM Bio, Limbic and Inflazome.. Royalties; UpToDate, Springer, Cadilla Pharmaceuticals.. Grants/research support; AstraZeneca and Oxford Immunotech..

The effect of colchicine on cancer risk in patients with immune-mediated inflammatory diseases: a time-dependent study based on the Taiwan’s National Health Insurance Research Database

BackgroundTo determine the effect of colchicine on cancer risk in patients with the immune-mediated inflammatory diseases (IMIDs)-related to colchicine use.MethodsThis is a time-dependent propensity-matched general population study based on the National Health Insurance Research Database (NHIRD) of Taiwan. We identified the IMIDs patients (n = 111,644) newly diagnosed between 2000 and 2012 based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)—274,712, 135, 136.1, 279.49, 518.3, 287.0, 696.0, 696.1, 696.8, 420, 429.4, 710.0, 710.1, 710.3, 710.4, 714.0, 720, 55.0, 55.1, 55.9, 556. Inclusion criteria: aged ≧ 20 years, if a patient had at least these disease diagnosis requirements within 1 year of follow-up, and, these patients had at least two outpatient visits or an inpatient visit. After propensity-matched according to age, sex, comorbidities, medications and index date, the IMIDs patients enter into colchicine users (N = 16,026) and colchicine nonusers (N = 16,026). Furthermore, time-dependent Cox models were used to analyze cancer risk in propensity-matched colchicine users compared with the nonusers. The cumulative cancer incidence was analyzed using Cox proportional regression analysis. We calculated adjusted hazard ratios (aHRs) and their 95% confidence intervals (95% CIs) for cancer after adjusting for sex, age, comorbidities, and use of medicine including acetylcysteine, medication for smoking cessation such as nicotine replacement medicines (the nicotine patch) and pill medicines (varenicline), anti-inflammatory drugs and immunosuppressant drugs.ResultsComparing the colchicine nonusers, all cancer risk were mildly attenuated, the (aHR (95% CI)) of all cancer is (0.84 (0.55, 0.99)). Meanwhile, the colchicine users were associated with the lower incidence of the colorectal cancer, the (aHRs (95% CI)) is (0.22 (0.19, 0.89)). Those aged < 65 years and male/female having the colchicine users were associated with lower risk the colorectal cancer also. Moreover, the colchicine > 20 days use with the lower aHR for colorectal cancer.ConclusionColchicine was associated with the lower aHR of the all cancer and colorectal cancer formation in patients with the IMIDs.

Symptoms and Severity of COVID-19 in Patients with Immune-Mediated Inflammatory Diseases: Experience of a University Medical Center.

The pandemic situation of the novel coronavirus (severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) and its associated disease (coronavirus disease 2019 (COVID-19)) represents a challenging condition with a plethora of aspects. The course of COVID-19 in patients with immune-mediated inflammatory diseases (IMID) such as inflammatory bowel disease (IBD) and rheumatic diseases (RD) is not well known. Our study is one step toward closing this gap by collecting data on vaccination rates, infection-free survival, and individual symptom severity. We conducted a prospective questionnaire-based study between April 2022 and October 2022 at our university hospital. Outward patients over the age of 18 years were screened for participation and reported about their infection/infection-free survival since the start of the pandemic. Finally, 156 patients were included in the study, 117 (75.0%) of which had inflammatory bowel disease and 39 (25.0%) patients with rheumatic disease. Altogether, 143 (91.7%) persons had received at least one vaccination against SARS-CoV-2. A total of 153 patients provided information regarding their COVID-19 history: 81 patients (52.0%) self-reported about their SARS-CoV-2 infection. In general, courses of infection were mild: only two patients (2.5% of patients with reported COVID-19) were hospitalized due to COVID-19 with one (1.2%) of the two needing intensive care. Asymptomatic COVID-19 had been described by 7 persons (8.6% of patients with reported COVID-19). Acute COVID-19 was accompanied by fatigue/tiredness in 58 persons (71.6% of patients with history of COVID-19) as the most frequent symptom. Other complaints were common cold (55 patients = 67.9%), cough (51 patients = 63.0%), headache (44 patients = 54.3%), and fever (35 patients = 43.2%). Stratified by vaccination status (unvaccinated vs. at least once vaccinated), the time to infection differed significantly (logrank test: p = 0.04, Chi2 4.1). At least once vaccinated people had a median COVID-19-free survival of 28.5 months (confidence interval (CI): 23.6 months-not reached). Without any vaccination, the estimated time to infection was 25.1 months (CI: 23.6 months-not reached). Our IMID patients have a high rate of vaccination against SARS-CoV-2. Data show a significantly longer infection-free survival in vaccinated IMID patients as compared to unvaccinated patients. Discrimination between symptoms of COVID-19 and a concomitant inflammatory disease is difficult as complaints might be overlapping. This trial is registered with DRKS00028880.

P325 Post-COVID general health symptoms in patients with Immune Mediated Inflammatory Diseases

Abstract Background Post-COVID entails persistent symptoms following a presumed or confirmed SARS-CoV-2 infection and has a prevalence of 12.5% in the general population in The Netherlands. The aim of this study is to evaluate post-COVID general health symptoms reported by patients with Immune Mediated Inflammatory Diseases (IMIDs), given the unclear prevalence. Methods An online questionnaire was distributed to IMID patients at dermatology, rheumatology and gastroenterology departments in an academic and teaching hospital in Rotterdam, the Netherlands. Only patients on systemic therapy were included. General health symptoms were compared between patients with and without prior SARS-CoV-2 infection. Multivariable logistic regression, adjusted for disease-related factors and known post-COVID risk factors, was performed to assess the association between SARS-CoV-2 infection and symptom occurrence. Additionally, the self-reported prevalence of post-COVID symptoms was assessed by asking patients if they linked their symptoms to the previous SARS-CoV-2 infection. Results The final study population comprised 1,518 patients, of whom 58% (n=877) reported ≥ 1 SARS-CoV-2 infections (table 1). More patients with a prior SARS-CoV-2 infection reported general health symptoms compared to those without (56% vs 44%; P&amp;lt;0.001) (figure 1). After adjusting for potential risk factors, including age, sex, smoking, diagnosis, SARS-CoV-2 vaccination status, and immunosuppressive therapy, a consistent significant association was found between SARS-CoV-2 infection and symptoms (OR 1.53; 95%CI 1.23-1.91; P&amp;lt;0.001). Sub-analysis showed a significant association between self-reported COVID-19 severity and symptoms, while presumed SARS-CoV-2 variant (based on date of reported infection) and number of infections were not associated. Fatigue was the most common symptom in both patients with and without a previous SARS-CoV-2 infection, with significantly higher prevalence among patients with previous SARS-CoV-2 infection (42% vs 32%; P&amp;lt;0.001). After adjusting for the potential risk factors, a previous SARS-CoV-2 infection remained significantly associated with fatigue (OR 1.31; 95%CI 1.04-1.64; P=0.021). Of the patients with a prior SARS-CoV-2 infection, 14% (122 out of 877) reported post-COVID symptoms, with fatigue as the most common complaint (78%). Conclusion The self-reported prevalence of post-COVID general health symptoms among IMID patients on systemic therapy (14%) aligns with that of the general population. The prevalence of symptoms, particularly fatigue, is elevated in patients with a history of a SARS-CoV-2 infection. Our findings emphasize the importance of incorporating SARS-CoV-2 infection history when evaluating fatigue in IMID patients during outpatient visits.

P1117 Molecular and clinical characterization of metabolic associated steatotic liver disease in the setting of immune-mediated inflammatory diseases: a link with cancer risk in IBD?

Abstract Background Growing evidence suggests an increased prevalence of metabolic associated steatotic liver disease (MASLD) in the context of immune-mediated inflammatory diseases (IMIDs). The risk of incident extrahepatic cancers is higher in MASLD. We aimed to clinically and mechanistically characterize IMID-MASLD patients compared to classic-MASLD, and its relation to cancer risk in IBD. Methods Ambidirectional, case‒control study including a prospective cohort of IMID patients (IBD, psoriasis, hidradenitis, and spondyloarthritis). MASLD and advanced-MASLD was established by the controlled attenuation parameter and transient elastography, respectively. Controls from the general population were age-, sex-, type 2 diabetes-, and BMI-matched in a 1:2 ratio. Liver biopsies were collected when significant liver fibrosis was suspected. Total RNA was obtained from freshly frozen cases and analyzed by RNA-seq. Differential gene expression was performed with‘limma-voom’. Gene set enrichment analysis was performed using the fgsea R package with a preranked “limma t-statistic” gene list. Data on global cancer prevalence was retrospectively collected on a multicenter IBD cohort. Results 1435 IMID patients and 2918 controls were initially included. Advanced-MASLD prevalence was significantly higher among IMID patients than controls(p&amp;lt;0.0001). In multivariate analysis, concomitant IMID was an independent and the strongest predictor of advanced-MASLD (adjusted OR 2.587; &amp;lt; 0.001).Transcriptomic data was obtained in 109 patients and showed 87 significant genes differentially expressed between IMID- and classic-MASLD. IMID-MASLD cases displayed an enriched expression of genes implicated in pro-tumoral activities or the control of the cell cycle concomitant with a negative expression of genes related to metabolism (figure 1). A comparable transcriptomic signature was observed in IBD-MASLD, involving genes as IGFBP2, PLEKHA4, or metallothioneins, all of them associated to pour prognosis in renal cell carcinoma (RCC). In the multicentre IBD cohort (n=1905; female 50.5%; mean age 50.7 years, mean follow up: 13.3 years) we observed a global cancer prevalence of 9.0%, with a higher-than-expected RCC prevalence (table 1). Whereas RCC represents 3.2% of all cancers in the general population, it accounts for 8.7% in our IBD cohort, in agreement with our molecular data. Conclusion Advanced MASLD has a disproportionately high prevalence in IMID populations. Both conditions can trigger a protumoral condition that can lead to an accelerated form of MASLD independent of classic metabolic pathways and a higher cancer risk, as is the case of RCC in the IBD population.

Characteristics and Prognosis Factors of Pneumocystis jirovecii Pneumonia According to Underlying Disease: A Retrospective Multicenter Study

Pneumocystis jirovecii pneumonia (PcP) remains associated with high rates of mortality, and the impact of immunocompromising underlying disease on the clinical presentation, severity, and mortality of PcP has not been adequately evaluated. Does the underlying disease and immunosuppression causing PcP impact the outcome and clinical presentation of the disease? In this multicenter retrospective observational study, conducted from January 2011 to December 2021, all consecutive patients admitted with a proven or probable diagnosis of PcP according to The European Organisation for Research and Treatment of Cancer consensus definitions were included to assess the epidemiology and impact of underlying immunosuppressive diseases on overall and 90-day mortality. Overall, 481 patients were included in the study; 180 (37.4%) were defined as proven PcP and 301 (62.6%) were defined as probable PcP. Patients with immune-mediated inflammatory diseases (IMIDs) or solid tumors had a statistically poorer prognosis than other patients with PcP at day 90. In multivariate analysis, among the HIV-negative population, solid tumor underlying disease (OR, 5.47; 95%CI, 2.16-14.1; P< .001), IMIDs (OR, 2.19; 95%CI, 1.05-4.60; P= .037), long-term corticosteroid exposure (OR, 2.07; 95%CI, 1.03-4.31; P= .045), cysts in sputum/BAL smears (OR, 1.92; 95%CI, 1.02-3.62; P= .043), and SOFA score at admission (OR, 1.58; 95%CI, 1.39-1.82; P< .001) were independently associated with 90-day mortality. Prior corticotherapy was the only immunosuppressant associated with 90-day mortality (OR, 1.67; 95%CI, 1.03-2.71; P= .035), especially for a prednisone daily dose≥ 10mg (OR, 1.80; 95%CI, 1.14-2.85; P= .010). Among patients who were HIV-negative, long-term corticosteroid prior to PcP diagnosis was independently associated with increased 90-day mortality, specifically in patients with IMIDs. These results highlight both the needs for PcP prophylaxis in patients with IMIDs and to early consider PcP curative treatment in severe pneumonia among patients with IMIDs.

COVID-19 vaccination of patients with chronic immune-mediated inflammatory disease

ObjectiveThis study aimed to analyze the safety and efficacy of COVID-19 vaccines among patients with chronic immune-mediated inflammatory disease (IMID) in China.MethodsParticipants who were diagnosed with a chronic IMID were eligible for inclusion in this study. Age- and sex-matched healthy vaccinated individuals were set as the control group. All participants received two doses of the inactivated CoronaVac vaccine or three doses of the recombinant protein subunit vaccine ZF2001. Adverse events, IMID activity after vaccination, and the rate of COVID-19 in the two groups were compared.ResultsThere were 158 patients in the IMID group, with an average age of 40 ± 14 years old, and 98 female subjects. In the IMID group, 123 patients received the inactivated CoronaVac vaccine, and 35 patients received the recombinant protein subunit vaccine ZF2001. There were 153 individuals in the control group, including 122 who received the CoronaVac vaccine and 31 who received the recombinant protein subunit vaccine ZF2001. The frequency of vaccine-related adverse events in the IMID group was less than that in the control group, all of which were mild local effects, and no serious events occurred. Of note, no disease flares occurred in the IMID group. No participants in either group subsequently got COVID-19, so the incidence rate was 0% in both groups.ConclusionCOVID-19 vaccination was found to be safe for IMID subjects, any adverse events were mild, and vaccination did not increase the risk of disease activity. Meanwhile, vaccination could effectively reduce the incidence of COVID-19 in IMID patients. In the future, studies with a larger sample size and a longer duration are needed.

Comparison of the first and sixth waves of the SARS-COV-2 coronavirus pandemic in patients with immune-mediated disease.

Recent evidence shows that COVID-19 infection does not have a worse prognosis in patients with immune-mediated inflammatory diseases (IMID), although they develop a worse response to vaccination.Objective To compare the incidence of COVID-19 and clinical features in patients with IMID between the first and sixth waves.Method Prospective observational study of two cohorts of IMID patients diagnosed with COVID-19. First cohort March to May 2020, and second cohort December/2021 to February/2022.Sociodemographic and clinical variables were collected and, in the second cohort, COVID-19 vaccination status. Statistical analysis established differences in characteristics and clinical course between the two cohorts.Results In total, 1627 patients were followed up, of whom 77 (4.60%) contracted COVID-19 during the first wave and 184 in the sixth wave (11.3%). In the sixth wave, there were fewer hospitalisations, intensive care unit admissions, and deaths than in the first wave (p=.000) and 180 patients (97.8%) had at least one dose of vaccine.Conclusion Early detection and vaccination have prevented the occurrence of serious complications.

The Real-World Study of Immunogenicity and Safety of the Adjuvant Recombinant Vaccine against Varicella Zoster Virus in Patients with Immune-Mediated Inflammatory Diseases Treated with Janus Kinase Inhibitors.

Background. The risk of herpes zoster reactivation is increased in immunocompromised patients, especially in those with immune-mediated inflammatory diseases (IMIDs) on Janus kinase inhibitor (JAKi) treatment. The recombinant subunit herpes zoster vaccine (RZV) is a non-live vaccine, recently approved for this subgroup of patients, which shows high rates of vaccine effectiveness, with few adverse effects reported in clinical trials. Purpose. The aim of this real-world study was to determine the immunogenicity and safety of RZV in IMID patients on JAKi treatment. Methods. The increase in the concentration of anti-gE antibody for varicella zoster virus post-vaccination, compared to the pre-vaccination concentration, was analyzed to test the humoral immune response. Adverse effects after the first and second vaccine doses were registered. Results. In total, 49 patients were analyzed, and a fourfold increase in antibody concentration was achieved in almost 40% of subjects, with only one serious local adverse effect. Discussion. The resulting immunogenicity was lower than that observed in clinical trials, probably due to the presence of immune disease and immunosuppressive treatment, and to the fact that this was a real-world study. No differences in response according to age, previous virus zoster reactivation, or concomitant treatments were found. Conclusions. RZV was well tolerated and reached the immune response objective in 40% of patients. These results reinforce the importance of including RZV vaccination for immunosuppressed patients. Real-world studies regarding vaccine effectiveness are still needed in order to gain a full understanding of the response to RZV in this group of patients.

COVID-19 vaccine confidence in the post-vaccination era: Perceptions among adults with immune-mediated inflammatory diseases

ObjectiveAssess the perceived protection afforded by a range of COVID-19 vaccines in immune-mediated inflammatory diseases patients previously vaccinated against SARS-CoV-2. Study designSurvey. MethodsOn-line cross-sectional survey aimed at evaluating the perceived protection (and its determinants) afforded by a range of COVID-19 vaccines among immune-mediated inflammatory diseases previously vaccinated for COVID-19. ResultsOut of 493 eligible respondents who lived in Brazil, 397 (80.5%) were confident that their primary vaccination series would protect them against severe COVID-19. In multivariate analysis, only overlapping immune-mediated inflammatory diseases remained (negatively) associated with the perception of protection. ConclusionsNo influence was found between COVID-19 vaccine types and the perception of protection after initial vaccinations.

Tixagevimab/cilgavimab for the prevention of COVID-19 in vaccine-refractory patients with autoimmune diseases: a prospective cohort study.

To investigate the effects of passive immunization with the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies tixagevimab/cilgavimab on humoral responses and on coronavirus disease 2019 (COVID-19) outcomes in vaccine-refractory patients with immune-mediated inflammatory diseases (IMIDs) at high risk of severe COVID-19. A prospective cohort study was performed on a cohort of high-risk vaccine-refractory IMID patients treated with a single dose of tixagevimab/cilgavimab (150 mg/150 mg). COVID-19 outcomes as well as serum and salivary anti-SARS-CoV-2 IgG were assessed at baseline and for at least 6 months. Results were compared with an untreated high-risk vaccine-refractory IMID population. Standardized incidence ratios (SIRs) of COVID-19 compared with the general population were calculated for both groups. A total of 38 high-risk IMID patients received tixagevimab/cilgavimab and were compared with 114 untreated high-risk IMID controls. Serum anti-spike IgG increased to 6.6 OD (s.d. 0.8) at day 1 and remained positive up to month 6 [6.3 OD (s.d. 1.4)]. Salivary anti-spike IgG peaked at month 2 [1.6 OD (s.d. 1.1)] and decreased from month 3 [0.8 OD (s.d. 0.3)]. No severe or extended infection was observed in the tixagevimab/cilgavimab group. Compared with the general population, the SIR of COVID-19 in treated patients was 0.76 (95% CI 0.24, 1.58) despite the increased risk profile. The SIR of the control group was 1.51 (95% CI 1.07, 2.02), corresponding to a significantly increased incidence. Passive immunization with tixagevimab/cilgavimab is safe and effective in inducing anti-SARS-CoV-2 immunity and potentially in preventing COVID-19 in high-risk vaccine-refractory IMID patients. These data provide a proof of concept for the use of monoclonal antibodies as a preventative strategy against SARS-CoV-2 in vulnerable populations.

Patient preferences in chronic immune-mediated inflammatory diseases potentially treated with biological drugs: discrete choice analysis using real-world data analysis

ABSTRACT Objectives Immune-mediated inflammatory diseases (IMIDs) represent a high burden due to their chronicity, high prevalence, and associated comorbidities. Chronic patients’ preferences must be considered in IMIDs treatment and follow-up. The objective of this study was to further understand patient’s preferences in private settings. Methods A literature review was performed to choose the most relevant criteria for patients. A D-efficient discrete choice experiment was designed to elicit preferences of adult patients with IMIDs and potential biological treatment prescription. Participants were collected from private practices (rheumatology, dermatology, and gastroenterology) from February to May 2022. Patients chose between option pairs, characterized by six health-care attributes, as well as monthly out-of-pocket drug price. Responses were analyzed through a conditional logit model. Results Eighty-seven patients answered the questionnaire. The most frequent pathologies were Rheumatoid Arthritis (31%) and Psoriatic Arthritis (26%). The most relevant criteria were choosing the preferred physician (OR 2.25 [SD0.26]); reducing time until visit with specialist (OR 1.79 [SD0.20]), access through primary care (OR 1.60 [SD0.08]), and an increase in monthly out-of-pocket price from 100€ to 300€ (OR 0.55 [SD0.06]) and to 600€ (OR 0.08 [SD0.02]). Conclusions Chronic IMIDs patients showed a preference toward a faster, personalized service, even with a trade-off in terms of out-of-pocket price

Third and Fourth Vaccine Doses Broaden and Prolong Immunity to SARS-CoV-2 in Adult Patients with Immune-Mediated Inflammatory Diseases.

Previous studies have reported impaired humoral responses after SARS-CoV-2 mRNA vaccination in patients with immune-mediated inflammatory diseases (IMIDs), particularly those treated with anti-TNF biologics. We previously reported that IMID patients diagnosed with inflammatory bowel disease, psoriasis, psoriatic arthritis, ankylosing spondylitis, or rheumatoid arthritis exhibited greater waning of Ab and T cell responses than healthy control subjects after SARS-CoV-2 vaccine dose 2. Fewer data are available on the effects of third and fourth doses. This observational cohort study collected plasma and PBMCs from healthy control subjects and untreated or treated patients with IMIDs prevaccination and after one to four doses of SARS-CoV-2 mRNA vaccine (BNT162b2 or mRNA-1273). SARS-CoV-2-specific Ab levels, neutralization, and T cell cytokine release were measured against wild-type and Omicron BA.1 and BA.5 variants of concern. Third vaccine doses substantially restored and prolonged Ab and T cell responses in patients with IMIDs and broadened responses against variants of concern. Fourth-dose effects were subtle but also prolonged Ab responses. However, patients with IMIDs treated with anti-TNF, especially patients with inflammatory bowel disease, exhibited lower Ab responses even after the fourth dose. Although T cell IFN-γ responses were maximal after one dose, IL-2 and IL-4 production increased with successive doses, and early production of these cytokines was predictive of neutralization responses at 3-4 mo postvaccination. Our study demonstrates that third and fourth doses of the SARS-CoV-2 mRNA vaccines sustain and broaden immune responses to SARS-CoV-2, supporting the recommendation for three- and four-dose vaccination regimens in patients with IMIDs.

Comparison of the first and sixth waves of the SARS-COV-2 coronavirus pandemic in patients with immune-mediated disease

IntroductionRecent evidence shows that COVID-19 infection does not have a worse prognosis in patients with immune-mediated inflammatory diseases (IMID), although they develop a worse response to vaccination. ObjectiveTo compare the incidence of COVID-19 and clinical features in patients with IMID between the first and sixth waves. MethodProspective observational study of two cohorts of IMID patients diagnosed with COVID-19. First cohort March to May 2020, and second cohort December/2021 to February/2022.Sociodemographic and clinical variables were collected and, in the second cohort, COVID-19 vaccination status. Statistical analysis established differences in characteristics and clinical course between the two cohorts. ResultsIn total, 1627 patients were followed up, of whom 77 (4.60%) contracted COVID-19 during the first wave and 184 in the sixth wave (11.3%). In the sixth wave, there were fewer hospitalisations, intensive care unit admissions, and deaths than in the first wave (p=.000) and 180 patients (97.8%) had at least one dose of vaccine. ConclusionEarly detection and vaccination have prevented the occurrence of serious complications.

Venous and arterial thromboembolic risk of Janus kinase inhibitors: a systematic review with meta-analysis.

Preliminary data led licencing authorities to alert clinicians of an increased venous thrombotic risk associated to the use of Janus kinase (JAK) inhibitors (JAKi). We performed a systematic review to estimate the risk of venous and arterial thrombosis associated to JAKi for the treatment of immune-mediated inflammatory diseases (IMIDs). Randomized controlled trials (RCTs) on JAKi in patients with IMIDs were identified by the MEDLINE and EMBASE databases until October 2021. Risk of bias was assessed according to Cochrane criteria. The beta-binomial model was applied to calculate pooled odds ratio (OR) and corresponding 95% CI. The PROSPERO registration number is CRD42022324143. We have included one phase I, 21 phase II, three phase II-III and 36 phase III RCTs for a total of 19 443 patients in the JAKi group and 6354 in the control group. Thirty-one (unweighted rate 0.16%; 95% CI: 0.10, 0.21) events were reported in the JAKi group and 20 (unweighted rate 0.22%; 95% CI: 0.12, 0.32) in the control group in a mean follow-up of 16.8 weeks. IMID patients treated with JAKi did not have an increased thromboembolic risk compared with those treated with placebo (OR 0.82; 95% CI: 0.43, 1.56). No statistically different results were seen in subanalyses for each investigated IMID, drug and dosage. JAKi do not increase thromboembolic risk compared with placebo in IMID patients enrolled in selected RCTs.

Primary SARS-CoV-2 infection in patients with immune-mediated inflammatory diseases: long-term humoral immune responses and effects on disease activity

BackgroundPatients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressants (ISPs) may have impaired long-term humoral immune responses and increased disease activity after SARS-CoV-2 infection. We aimed to investigate long-term humoral immune responses against SARS-CoV-2 and increased disease activity after a primary SARS-CoV-2 infection in unvaccinated IMID patients on ISPs.MethodsIMID patients on active treatment with ISPs and controls (i.e. IMID patients not on ISP and healthy controls) with a confirmed SARS-CoV-2 infection before first vaccination were included from an ongoing prospective cohort study (T2B! study). Clinical data on infections and increased disease activity were registered using electronic surveys and health records. A serum sample was collected before first vaccination to measure SARS-CoV-2 anti-receptor-binding domain (RBD) antibodies.ResultsIn total, 193 IMID patients on ISP and 113 controls were included. Serum samples from 185 participants were available, with a median time of 173 days between infection and sample collection. The rate of seropositive IMID patients on ISPs was 78% compared to 100% in controls (p < 0.001). Seropositivity rates were lowest in patients on anti-CD20 (40.0%) and anti-tumor necrosis factor (TNF) agents (60.5%), as compared to other ISPs (p < 0.001 and p < 0.001, respectively). Increased disease activity after infection was reported by 68 of 260 patients (26.2%; 95% CI 21.2–31.8%), leading to ISP intensification in 6 out of these 68 patients (8.8%).ConclusionIMID patients using ISPs showed reduced long-term humoral immune responses after primary SARS-CoV-2 infection, which was mainly attributed to treatment with anti-CD20 and anti-TNF agents. Increased disease activity after SARS-CoV-2 infection was reported commonly, but was mostly mild.Trial registrationNL74974.018.20, Trial ID: NL8900. Registered on 9 September 2020.

P037 The NIHR IMID Bioresource: a descriptive analysis of the first 5000 participants

Abstract Background/Aims The NIHR Immune-mediated inflammatory diseases (IMID)-Bioresource is a recallable resource of patients with an IMID, pre-disease states and unaffected first-degree relatives. Here, we report on the recruited cohort to date, focusing on co-existent comorbidities. Methods Patients are categorised into one of three primary IMID groups: rheumatoid arthritis (RA), axial-spondyloarthropathy-psoriasis spectrum (AxSpA-PsO: AxSpA, PsO, psoriatic arthritis [PsA], reactive arthritis) and systemic autoimmune rheumatic diseases (SARDs: systemic lupus erythematosus [SLE], mixed and undifferentiated connective tissue disease). Data were collected on clinical phenotype, secondary IMIDs, medications and key co-morbidities. Results 5028 participants (4965 IMIDs, 46 pre-disease, 17 relatives) have been enrolled to the IMID-Bioresource Sept-2020-Aug-2022 from 63 UK-centres. Of those with a diagnosed IMID, RA (N = 2472) was the largest group, then AxSpA-PsO (N = 2012) and SARDs (n = 479). Two-thirds (N = 3210, 64.7%) female, median (IQR) age 57.9 (47.3-67.6) years. 1544 (62.5%) patients with primary IMID RA were seropositive. The commonest AxSpA-PsO diseases included PsO (N = 1232, 24.8%), PsA (N = 1116, 22.5%) and AxSpA (N = 467, 9.4%). SLE was the commonest SARD (N = 376, 7.6%), a third (N = 133, 35.4%) reported previous lupus nephritis. 1241 (25.0%) patients reported &amp;gt;1 IMID diagnoses. The commonest overlaps were PsO and RA (N = 108, 2.2%), PsO and AxSpA (N = 72, 1.5%) and RA and Sjögren’s syndrome (N = 65, 1.3%). 2880 (58.0%) reported minimum one (range 1-11) co-morbidity, the commonest, hypertension (N = 1201, 24.2%), depression (N = 820, 16.5%) and asthma (N = 580, 11.7%). 274 (5.5%) patients reported ischaemic heart disease, commonest in RA (N = 152, 6.2%). Interstitial lung disease was reported by 75 (1.5%) patients, again most frequent in RA (N = 48, 1.9%). Overall, 696 (14.0%) IMID patients had ≥3 co-morbidities. Oral steroid use was highest in SARD (N = 166, 34.7%). The commonest DMARD in all groups was methotrexate, followed by sulfasalazine in RA (N = 379, 15.3%) and AxSpA-PsO (N = 189, 9.4%) and mycophenolate mofetil in SARDs (N = 69, 14.4%). Overall, 2079 (41.9%) IMID patients were receiving a biological DMARD. Conclusion A high proportion of IMID patients have more than one IMID diagnoses. Significant multi-morbidity with cardiovascular, respiratory and mood disorders was observed and considerable ongoing glucocorticoid usage. The IMID-Bioresource aims to refine patient subsets based on shared immune mechanisms to ultimately, improve precision medicine and patient outcomes. Disclosure S. Dyball: Grants/research support; MRC. Other; GSK, UCB. E. Vital: None. S. Plein: None. D. McGonagle: None. A.G. Pratt: None. J. Isaacs: None. B. Griffiths: None. W. Ng: None. J. McBeth: None. C.E.M. Griffiths: None. B. Parker: Honoraria; Fresenius-Kabi, AbbVie. Grants/research support; GSK, Genzyme/Sanofi. Other; Eli Lilly, Roche. M.H. Buch: None. I. Bruce: Consultancies; ILTOO, AstraZeneca, Eli Lilly, GSK, Merck Serono, UCB. Grants/research support; Genzyme/Sanofi, GSK, UCB, Roche. Other; AstraZeneca, GSK, UCB.