Autoimmune Inflammatory Rheumatic Diseases Patients Research Articles

Impact of Immunomodulatory Therapy on COVID-19 Vaccine Response in Patients with Autoimmune Inflammatory Rheumatic Diseases.

Coronavirus disease 2019 (COVID-19) vaccination is essential for patients with autoimmune inflammatory rheumatic diseases (AIIRD) to reduce the risk of morbidity and mortality associated with serious COVID-19 infection. With endemicity, waning of vaccine- and infection-acquired immunity, and development of SARS-CoV-2 variants, the need for additional doses of vaccines against serious illness in high-risk immunocompromised persons remains imperative. This review examines how immunomodulatory therapies affect vaccine-induced immune response in patients with AIIRD. Glucocorticoids, methotrexate, azathioprine, calcineurin inhibitors, mycophenolate mofetil, tumor necrosis factor inhibitors, and abatacept have been shown to variably attenuate both humoral and cellular immune responses to vaccination. Janus kinase inhibitors reduce humoral immune response. In contrast, sulfasalazine, leflunomide, belimumab, interleukin (IL)-17, IL-12/23, IL-6, and IL-1 inhibitors appear favorable, with mild or no impact on vaccine response. Although rituximab is known to profoundly diminish humoral immune response, cellular immunity is relatively preserved. Administering a third and subsequent vaccine dose or temporally coordinating the dosing of immunomodulatory drugs may improve vaccine effectiveness. Further research is needed to personalise vaccination strategies for AIIRD patients, considering their specific immunomodulatory treatments.

Biological and glucocorticoids treatment impair the medium-term immunogenicity to SARS-CoV-2 mRNA vaccines in autoimmune inflammatory rheumatic diseases

BackgroundThis study aims to assess the sustained immunological response to the SARS-CoV-2 vaccine in patients with autoimmune inflammatory rheumatic diseases (AIRD) undergoing different treatment regimens.MethodsWe conducted a prospective observational study involving 157 AIRD patients without prior COVID-19 infection. Treatment regimens included non-treatment or glucocorticoid-only (not-treated/GCs), non-biological drugs, biological therapy, and JAK inhibitors. All participants completed the two-dose vaccine schedule, and 110 of them received an additional booster dose. Serum samples were collected approximately 3–6 months after the second and third vaccine doses to measure antibodies against the Spike protein (antiS-AB) and neutralizing antibodies (nAB) targeting six SARS-CoV-2 variants.ResultsFollowing the third dose, all patients exhibited a significant increase in antiS-AB (FC = 15, p < 0.0001). Patients under biological therapy had lower titres compared to the non-biological (66% decrease, p = 0.038) and the not-treated/GCs group (62% decrease, p = 0.0132), with the latter persisting after the booster dose (86% decrease, p = 0.0027). GC use was associated with lower antiS-AB levels in the biological group (87% decrease, p = 0.0124), although not statistically significant after confounders adjustment. nABs showed the highest positivity rates for the wild-type strain before (50%) and after the booster dose (93%), while the Omicron variant exhibited the lowest rates (11% and 55%, respectively). All variants demonstrated similar positivity patterns and good concordance with antiS-AB (AUCs from 0.896 to 0.997).ConclusionsThe SARS-CoV-2 vaccine booster strategy effectively elicited a sustained antibody immune response in AIRD patients. However, patients under biological therapies exhibited a reduced response to the booster dose, particularly when combined with GCs.

CD4/CD8 Ratio: An Independent Predictor of Herpes Zoster in Patients With Autoimmune Inflammatory Rheumatic Diseases.

A higher incidence of herpes zoster (HZ) was found in people with decreased cell-mediated immunity. However, the relationship between cellular immunity and HZ infection in patients with autoimmune inflammatory rheumatic diseases (AIRD) remains elusive. To investigate the role of CD4/CD8 ratio in patients with AIRD and HZ. This case-control study compared AIRD patients with and without HZ. We chose 70 AIRD patients with HZ as the experimental group and 140 AIRD patients without HZ as the control group. The clinical and laboratory findings were assessed in each trial participant. The CD4/CD8 ratio (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.10-0.49) was independently associated with the occurrence of HZ after adjusting for various confounders. Nonlinear analysis has unveiled a more profound nonlinear relationship between the CD4/CD8 ratio and the occurrence of HZ in patients with AIRD. The OR of HZ increased with a decreasing CD4/CD8 ratio before the turning point of 2. The adjusted regression coefficient was 0.14 (95% CI, 0.05-0.37, p<0.0001) for CD4/CD8 ratio less than 2. The CD4/CD8 ratio was expected to be a very promising quantitative biomarker for predicting the risk of developing HZ in patients with AIRD.

A review on cytomegalovirus in patients with autoimmune inflammatory rheumatic diseases: Prevalence, clinical spectrum, treatment, and antiviral prophylaxis

Human cytomegalovirus (CMV) is a highly infectious virus that is prevalent among adults worldwide. In immunocompetent individuals, CMV infection rarely causes complications. Following initial infection, however, CMV remains latent in the body and can be reactivated especially in immunocompromised patients, such as those with autoimmune inflammatory rheumatic diseases (AIIRDs), leading to tissue-invasive, life-threatening diseases, such as colitis, vascular thrombosis, and pneumonitis. Although there are standard treatment recommendations for symptomatic CMV disease, there is paucity of consensus in the role of primary and secondary antiviral prophylaxis to prevent CMV reactivation, especially in AIIRDs patients undergoing immunosuppressive therapy. Therein, this review aimed to provide an overview of the prevalence, clinical disease, risk factors, and treatment for CMV infection, as well as on the role of primary and secondary antiviral prophylaxis in AIIRDs patients. The emerging novel techniques that measure CMV-specific T-cell immunity as a guide to initiate prophylaxis in high-risk patients were also discussed.

Do Not Leave Your Patients in the Dark-Using American College of Rheumatology and European Alliance of Associations for Rheumatology Recommendations for Vaccination in Polish Adult Patients with Autoimmune Inflammatory Rheumatic Diseases.

(1) Introduction: Patients with autoimmune inflammatory rheumatic diseases (AIIRD) face a higher infectious risk compared to the general population. As per the ACR and EULAR recommendations, vaccinations against influenza, COVID-19, pneumococci, and tetanus are recommended for most patients with AIIRD. (2) Objectives: This study aimed to assess vaccination coverage among Polish AIIRD patients and identify factors influencing it. (3) Patients and Methods: This study was conducted at the reference rheumatological center in Poland between May 2023 and October 2023. The study participants completed a questionnaire covering their knowledge of vaccination recommendations, actual vaccination status, factors affecting their decision to vaccinate, and their perspectives on immunization. (4) Results: This study involved 300 AIIRD patients and 60 controls. Both groups exhibited comparably low vaccination rates for all diseases (the highest for COVID-19-52% in both groups and the lowest for pneumococci-7.7% and 10%, respectively). Knowledge about recommended vaccinations was limited among patients in both groups. AIIRD patients were also not aware that they should avoid live vaccines. The primary motivators for vaccination among AIIRD patients were fear of infection (up to 75%) and medical advice (up to 74.6%). Conversely, the predominant reasons for non-vaccination were a lack of knowledge that vaccination is recommended (up to 74.7%) and concerns about potential adverse effects (up to 48.6%). Many patients reported not receiving vaccination recommendations from either primary care physicians or rheumatologists. (5) Conclusions: To enhance vaccination coverage among AIIRD patients in Poland, it is essential to educate them about vaccinations during routine medical consultations, emphasizing the increased risk of infection, informing them about recommended vaccinations, and clarifying doubts about adverse effects.

Vaccination in the Era of Immunosuppression.

Patients with autoimmune inflammatory rheumatic diseases (AIIRDs) are at increased risk for severe infections. Vaccine responses and safety profiles may differ between AIIRD patients and the general population. While patients with autoimmune inflammatory rheumatic diseases (AIIRDs) often experience diminished humoral responses and reduced vaccine efficacy, factors such as the type of immunosuppressant medications used and the specific vaccine employed contribute to these outcomes. Notably, individuals undergoing B cell depletion therapy tend to have poor vaccine immunogenicity. However, despite these considerations, vaccine responses are generally considered clinically sufficient. Ideally, immunosuppressed AIIRD patients should receive vaccinations at least two weeks before commencing immunosuppressive treatment. However, it is common for many patients to already be on immunosuppressants during the immunization process. Vaccination rarely triggers flares in AIIRDs; if flares occur, they are typically mild. Despite the heightened infection risk, including COVID-19, among AIIRD patients with rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, and other diseases on immunosuppressants, the vaccination rates remain suboptimal. The future directions of vaccination in the era of immunosuppression will likely involve customized vaccines with enhanced adjuvants and alternative delivery methods. By addressing the unique challenges faced by immunosuppressed individuals, we may improve vaccine efficacy, reduce the risk of infections, and ultimately enhance the health outcomes. Additionally, clinical trials to evaluate the safety and efficacy of temporarily discontinuing immunosuppressants during vaccination in various AIIRDs are crucial.

Immunogenicity and safety of the BBIBP-CorV vaccine in patients with autoimmune inflammatory rheumatic diseases undergoing immunosuppressive therapy in a monocentric cohort.

Vaccination plays a fundamental role in mastering the COVID-19 pandemic and protecting vulnerable groups. Persons with autoimmune inflammatory rheumatic diseases (AIIRD) requiring immunosuppressive therapies are prioritized for vaccination. However, data concerning immunogenicity and safety of the BBIBP-CorV vaccine in immunosuppressed patients are not found. This study presents data on the efficacy and safety of the BBIBP-CorV vaccine in immunosuppressed patients compared to healthy controls. Study population consisted of 100 healthy controls and 100 patients with AIIRD. Vaccination was performed according to national guidelines with the BBIBP-CorV vaccine. SARS-CoV-2 neutralizing antibody titers were quantified by enzyme-linked immunosorbent assay before initial vaccination and 1-3 months after secondary vaccination. Adverse events were assessed before study initiation and 7 days after the second dose. Disease activity was studied before entering the study and 3-8 weeks after the second dose. Vaccination-induced positive immunogenic response rates and SARS-CoV-2 neutralizing antibody titers were significantly lower in the AIIRD patients than healthy subjects (p < .05). There are significant differences in neutralizing antibody titers among patients suffering from rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis, and ankylosing spondylitis (p < .01-.05). The rates of seropositive vaccine responses were similarly distributed across all diseases. Healthy and AIIRD individuals had a similar profile in adverse events. No significant difference was observed in SARS-CoV-2 antibody titers between subjects suffering from side effects and those who did not have. SARS-CoV-2 neutralizing antibody levels were significantly higher in subjects with a history of COVID-19 infection than seronegative individuals (p < .01-0.05). Seropositive subjects had a significant increase in the percentage of vaccine-related adverse events compared to seronegative persons (p < .05). Despite a minor change in the disease activity of patients with RA and SLE, disease activity indices were overall stable in the AIIRD patients. These findings revealed that the BBIBP-CorV vaccine is effective in the development of neutralizing antibodies in immunosuppressed patients without considerable reactogenicity or induction of disease flares.

Influenza, Pneumococcal and Herpes Zoster Vaccination Rates in Patients with Autoimmune Inflammatory Rheumatic Diseases.

Vaccination rates are known to be low in patients with autoimmune inflammatory rheumatic diseases (AIIRD). We therefore aimed to determine current vaccination rates against influenza, Streptococcus pneumoniae and herpes zoster in a cohort of patients with AIIRD in Germany. Consecutive adult patients with an AIIRD were recruited from our outpatient clinic during their regular consultations. The individual vaccination status regarding influenza, Streptococcus pneumoniae and herpes zoster was obtained by reviewing the vaccination documents. A total of 222 AIIRD patients (mean age 62.9 ± 13.9 years) were included. In total, 68.5% were vaccinated against influenza, 34.7% against Streptococcus pneumoniae and 13.1% against herpes zoster (HZ). The pneumococcal vaccination was outdated in 29.4% of the vaccinated patients. Vaccination rates were significantly higher in patients ≥60 years old (odds ratio (OR) 2.167, 95% confidence interval (CI) 1.213-3.870, p = 0.008 for influenza, OR 4.639, 95% CI 2.555-8.422, p < 0.0001 for pneumococcal and OR 6.059, 95% CI 1.772-20.712, p = 0.001 for HZ vaccination). Ages > 60 years, female sex, glucocorticoid use and influenza vaccination were all independently associated with a pneumococcal vaccination. Regarding influenza vaccination, only a positive pneumococcal vaccination history remained independently associated. In patients with HZ vaccination, glucocorticoid use and a preceding pneumococcal vaccination were independently associated with HZ protection. The frequencies of vaccinations against influenza, Streptococcus pneumoniae and HZ have increased during recent years. While this can be partly explained by continuous efforts in patient education during the outpatient visits, the COVID-19 pandemic might also have contributed. Nevertheless, the persistently high incidence and mortality of these preventable diseases in patients with AIIRDs mandates further efforts to increase vaccination coverage, particularly in SLE patients.

CovAID: Identification of factors associated with severe COVID-19 in patients with inflammatory rheumatism or autoimmune diseases.

Autoimmune/inflammatory rheumatic diseases (AIRDs) patients might be at-risk of severe COVID-19. However, whether this is linked to the disease or to its treatment is difficult to determine. This study aimed to identify factors associated with occurrence of severe COVID-19 in AIRD patients and to evaluate whether having an AIRD was associated with increased risk of severe COVID-19 or death. Two databases were analyzed: the EDS (Entrepôt des Données de Santé, Clinical Data Warehouse), including all patients followed in Paris university hospitals and the French multi-center COVID-19 cohort [French rheumatic and musculoskeletal diseases (RMD)]. First, in a combined analysis we compared patients with severe and non-severe COVID-19 to identify factors associated with severity. Then, we performed a propensity matched score case-control study within the EDS database to compare AIRD cases and non-AIRD controls. Among 1,213 patients, 195 (16.1%) experienced severe COVID-19. In multivariate analysis, older age, interstitial lung disease (ILD), arterial hypertension, obesity, sarcoidosis, vasculitis, auto-inflammatory diseases, and treatment with corticosteroids or rituximab were associated with increased risk of severe COVID-19. Among 35,741 COVID-19 patients in EDS, 316 having AIRDs were compared to 1,264 Propensity score-matched controls. AIRD patients had a higher risk of severe COVID-19 [aOR = 1.43 (1.08-1.87), p = 0.01] but analysis restricted to rheumatoid arthritis and spondyloarthritis found no increased risk of severe COVID-19 [aOR = 1.11 (0.68-1.81)]. In this multicenter study, we confirmed that AIRD patients treated with rituximab or corticosteroids and/or having vasculitis, auto-inflammatory disease, and sarcoidosis had increased risk of severe COVID-19. Also, AIRD patients had, overall, an increased risk of severe COVID-19 compares general population.

Inflammatory rheumatic diseases developed after COVID-19 vaccination: presentation of a case series and review of the literature.

An increasing number of new on-set autoimmune-inflammatory rheumatic diseases (AIRD) after COVID-19 vaccination has begun to be reported in the literature. In this article, we present our patients with new-onset AIRD after vaccination for COVID-19 and review the literature on the subject. We investigated the clinical characteristics and laboratory parameters of previously described "newly developed AIRD in individuals recently vaccinated for COVID-19", in 22 cases vaccinated with one of the COVID-19 vaccines (BNT162b2 or CoronaVac) approved in our country. We collected 22 cases (14 female, 63.6%) that developed an AIRD after COVID-19 vaccination. Mean age was 53±14.4 (24-87) years. The interval between the last dose of vaccination and the development of the first complaint was 23.9±19.5 (4-90) days. CoronaVac was administered to four patients, and the BNT162b2 to 18 patients. AIRD-related symptoms developed in 12 patients after the first dose, in 8 patients after the second dose, and in two patients after the third dose. Twelve out of the 22 (54.5%) cases were diagnosed with rheumatoid arthritis, two with SLE, and the remaining eight patients each with leukocytoclastic vasculitis, Sjogren's syndrome, psoriatic arthritis, ankylosing spondylitis, systemic sclerosis, mixed connective tissue disease, eosinophilic granulomatosis with polyangiitis, and inflammatory myositis, respectively. Six patients had a history of documented antecedent COVID-19 infection. Autoimmune/inflammatory rheumatic diseases may develop after COVID-19 vaccinations. In the era of the COVID-19 pandemic, vaccination should be questioned carefully in newly diagnosed AIRD patients.

Development of Autoantibodies Following BNT162b2 mRNA COVID-19 Vaccination and Their Association with Disease Flares in Adult Patients with Autoimmune Inflammatory Rheumatic Diseases (AIIRD) and the General Population: Results of 1-Year Prospective Follow-Up Study.

Development of autoantibodies following BNT162b2 mRNA COVID-19 vaccination and their association with disease flares in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) and the general population: results of 1-year prospective follow-up study. We conducted a prospective study aimed at investigating the incidence of appearance of autoantibodies (antinuclear, antiphospholipid, and rheumatoid factor) in the sera of 463 adult patients with AIIRD compared to 55 controls from the general population prior to, and following the second and third vaccine doses, and at 1-year of follow-up. Pre- and post-vaccination disease activity indices and the association of autoantibodies with rheumatic disease flares and new onset AIIRD were examined. Autoantibody development of any type in AIIRD patients vs. the controls was 4.0% (vs. 6.7%, p = 0.423) following two vaccine doses and 7.6% (vs. 0%, p = 0.152) after three doses. There was no significant difference in sex, age, or disease-type among individuals with and without autoantibody development, regardless of the immunosuppressant use. More patients developed autoantibodies following the third than the second vaccine dose (p = 0.004). Disease flares occurred in 5.8% and 7.2% of AIIRD patients following second and third vaccine doses, respectively, with autoantibody production increasing the risk of flares following the second (p = 0.002) and third (p = 0.004) vaccine doses. BNT162b2 vaccination resulted in the development of autoantibodies in a minority of AIIRD patients and controls. Autoantibody development was associated with disease flares in patients, but no new-onset autoimmunity was observed.

Post-mRNA vaccine flares in autoimmune inflammatory rheumatic diseases: Results from the COronavirus National Vaccine registry for ImmuNe diseases SINGapore (CONVIN-SING)

BackgroundStudies of flares of autoimmune inflammatory rheumatic diseases (AIIRD) after COVID-19 mRNA vaccination are limited by small sample size, short follow up or at risk of selection bias. MethodsA national retrospective cohort study of consecutive AIIRD patients ≥12 years old, across 8 hospitals who received at least one dose of a COVID-19 mRNA vaccine. Patients were included from the date of 1st vaccine dose and censored at the time of flare or on the date of the clinic visit at least 3 months from cohort entry, whichever came first. Predictors of flare were determined by Cox proportional hazards analysis. Findings4627 patients (73% Chinese, 71% female) of median (IQR) age 61 (48, 70) years were included; 42% Rheumatoid arthritis, 14% Systemic lupus erythematosus and 11% Psoriatic arthritis. 47% were in remission, 41% low disease activity, 10% moderate disease activity and 1% in high disease activity. 18% patients flared, of which 11.7% were within the 3-month period of interest. 11.8% patients improved. Median (IQR) time-to-flare was 60 (30, 114) days. 25% flares were self-limiting, 61% mild-moderate and 14% severe. Older patients (53–65 years and >66 years) had a lower risk of flare [HR 0.6 (95% CI 0.5–0.8) and 0.7 (0.6–0.8) respectively]. Patients with inflammatory arthritis and with active disease had a higher risk of flare [HR 1.5 (1.2–2.0) and 1.4 (1.2–1.6), respectively]. Treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), immunosuppression and prednisolone was also associated with an increased risk of flare [HR 1.5 (1.1–2), 1.2 (1.1–1.4) and 1.5 (1.2–1.8) for prednisolone ≤7.5 mg respectively]. InterpretationThere was a moderately high rate of AIIRD flares after mRNA vaccination but also improvement in several patients. Severe flares and hospitalisation were rare. Thus, vaccination remains safe and highly recommended.

Varicella zoster virus reactivation following COVID-19 vaccination in patients with autoimmune inflammatory rheumatic diseases: A cross-sectional Chinese study of 318 cases.

Recently, varicella-zoster virus (VZV) reactivation has been observed after the administration of coronavirus disease 2019 (COVID-19) vaccines. Autoimmune inflammatory rheumatic diseases (AIIRDs) patients are at a higher risk for VZV reactivation for immunocompromised status. The study aimed to investigate the adverse events (AEs), especially VZV reactivation, following vaccination against severe acute respiratory syndrome coronavirus-2in a Chinese cohort of AIIRD patients. A cross-sectional survey using an online questionnaire was conducted among AIIRD patients and healthy controls (HCs). Multivariate logistic regression was used to identify potential factors associated with VZV reactivation. 318 AIIRD patients and 318 age and sex-matched HCs who got COVID-19 inactivated vaccines were recruited. The main AIIRDs are rheumatoid arthritis (31.8%) and systemic lupus erythematous (23.9%). Most of patients (85.5%) had stable disease and 13.2% of them had aggravation after vaccination. Compared to HCs, patients had higher rates of rash (p = 0.001), arthralgia (p < 0.001) and insomnia (p = 0.007). In addition, there were 6 (1.9%) AIIRD patients and 5 (1.6%) HCs reported VZV reactivation after the COVID-19 vaccination (p = 0.761). Multivariate logistic regression analysis illustrated that diabetes mellitus (odd ratio [OR], 20.69; 95% confidence interval [CI], 1.08-396.79; p = 0.044), chronic hepatitis B virus infection (OR, 24.34; 95%CI, 1.27-466.74; p = 0.034), and mycophenolate mofetil (OR, 40.61; 95%CI, 3.33-496.15; p = 0.004) independently identified patients with VZV reactivation. Our findings showed that the inactivated COVID-19 vaccination was safe for AIIRD patients though some patients could suffer from VZV reactivation.

Myocarditis and pericarditis following mRNA vaccination in autoimmune inflammatory rheumatic disease patients: A single-center experience.

IntroductionThe mRNA vaccines Comirnaty (Pfizer/BioNTech) and Spikevax (Moderna) are considered safe and highly effective against SARS‐COV2. However, they are also associated with a small increased risk of pericarditis and myocarditis. There is concern about an increased risk of these complications in patients with autoimmune inflammatory rheumatic diseases (AIRD).Case ReportWe describe three patients with pre‐existing AIRD who developed myocarditis or pericarditis shortly after receiving their first dose of the Pfizer‐BioNTech vaccine. The first case is a 31‐year‐old female with systemic lupus erythematosus (SLE) and anti‐phospholipid syndrome (APLS) who presented 7 days after receiving the Pfizer‐BioNTech vaccine and was diagnosed with myopericarditis following a positive troponin and abnormal transthoracic echocardiogram (TTE). The second case is a 29‐year‐old man with seronegative inflammatory arthritis and APLS who presented 7 days after receiving the first dose of the Pfizer‐BioNTech vaccine. His troponin and TTE were unremarkable however his ECG showed widespread ST elevation. Lastly, the third case is a 34‐year‐old man with Behcet's disease with a history of recurrent pericarditis. He developed a recurrence of symptoms approximately 7 days after his Pfizer‐BioNTech vaccine and self‐commenced prednisolone at home. He had normal laboratory and radiological findings. All patients received prednisolone resulting in a quick recovery and resolution of symptoms.DiscussionIn this review we discuss the association between myocarditis, pericarditis and mRNA COVID‐19 vaccines, those who are at greatest risk and current clinical considerations. We also discuss the possible increased risk in AIRD patients and the current research supporting this.

OP0177 IMMUNOGENICITY INDUCED BY TWO AND THREE DOSES OF THE BNT162B2 mRNA VACCINE IN PATIENTS WITH AUTOIMMUNE INFLAMMATORY RHEUMATIC DISEASES AND IMMUNOCOMPETENT CONTROLS: A LONGITUDINAL MULTI-CENTER STUDY

BackgroundData on the kinetics of the immune response to SARS-CoV-2 vaccination in patients with autoimmune inflammatory rheumatic diseases (AIIRD) are limited.ObjectivesTo evaluate the kinetics of the immune response induced by two and three doses of the BNT162b2 mRNA vaccine in adult patients with AIIRD and immunocompetent controls.MethodsA prospective multicenter study investigated the antibody response to the BNT162b2 vaccine by serial measurement of serum anti-SARS-CoV-2 S1/S2 IgG titers at the following time points: 2-6 weeks (AIIRD n=720, controls n=122) and six months (AIIRD n=628, controls=116) after the second vaccine dose, and 2-6 weeks after the third vaccine dose (AIIRD n=169, controls n=45). A seropositive response was defined as a detectable anti-S1/S2 IgG titer ≥ 15 BAU/ml. T-cell immune response was evaluated in a sample of patients (n=28) and controls (n=9) by intracellular staining of S-stimulated CD4+ T-cells for TNFα and IFNγ production.ResultsThe two-dose vaccine regimen induced a higher humoral response in controls compared to patients, as reflected by the post-vaccination seropositivity rates of 100% vs 84.72%, p&lt;0.0001, and 96.55% vs 74.26%, p&lt;0.0001 at 2-to-6 weeks and at 6 months, respectively. The decline of S1/S2 IgG titers within six months was similar in controls and patients. Following the 3rd vaccine, the seropositivity rate increased to 80.47% and 100% in AIIRD and control groups, p=0.0028, with a significantly higher increase of S1/S2 IgG titers in controls compared with AIIRD patients, 284.09±76.58 vs 219.39±151.55 BAU/ml, p=0.0016. At all-time points, S1/S2 IgG titers were significantly lower in AIIRD patients compared with controls (Figure 1).We further investigated the impact of therapies on the vaccine‘s immunogenicity (Figure 1). Glucocorticoids (GC) were associated with a significantly lower seropositivity rate and lower S1/S2 IgG titers compared to controls at all time points. Monotherapy with methotrexate (MTX) was associated with a comparable to controls humoral response at all time points. Anti-cytokine biologics (TNFi, IL6i, IL17i) were associated with an initial high seropositivity rate, similar to controls, followed by a steeper decline at 6 months, 79.82% vs 96.55%, p=0.0001, and restoration of seropositivity after the 3rd vaccine dose in all patients. JAKi were associated with a mildly decreased seropositivity rate after the 2nd vaccine dose and similar to controls response after the 3rd vaccine dose. Abatacept was associated with a reduced immunogenicity after the 2nd vaccine dose, but was restored to 100% seropositivity after the 3rd vaccine dose. Rituximab (RTX) significantly blunted the humoral response at all time points, with a seropositivity rate of 42% after the 2nd vaccine dose, 29% at 6 months, and with increase to 40% after the 3rd vaccine dose. A third of the RTX-treated patients who were seronegative after two vaccine doses, seroconverted after the 3rd dose. The multivariate model for predicting the seropositive response to vaccination found that higher S1/S2 IgG titers after the 2nd vaccine dose was associated with a higher seropositivity rate following the 3rd vaccine dose, OR 1.026 (1.008-1.045), p=0.0027, and that treatment with RTX was associated with a 14.3-fold risk for a negative humoral response, p≤0.0001. Cellular immune response, evaluated mainly in RTX treated patients, was preserved prior to and after the 3rd vaccine dose and was similar to controls.ConclusionOver a six-month period, the two dose BNTb262 vaccination was associated with a similar extent of waning of the humoral immune response in AIIRD patients and controls. The 3rd vaccine dose restored the response in all controls and in patients treated with MTX monotherapy, anti-cytokine biologics, abatacept, and JAKi. Treatment with GC and RTX was associated with an impaired humoral response at all time points.AcknowledgementsWe would like to thank the statistician Mr Yishai Friedlander and Mr Yoram Neufeld for their valuable assistance.Disclosure of InterestsNone declared

POS0200 POST-mRNA VACCINE FLARES IN AUTOIMMUNE INFLAMMATORY RHEUMATIC DISEASES: INTERIM RESULTS FROM THE CORONAVIRUS NATIONAL VACCINE REGISTRY FOR IMMUNE DISEASES SINGAPORE (CONVIN-SING)

POS0200 POST-mRNA VACCINE FLARES IN AUTOIMMUNE INFLAMMATORY RHEUMATIC DISEASES: INTERIM RESULTS FROM THE CORONAVIRUS NATIONAL VACCINE REGISTRY FOR IMMUNE DISEASES SINGAPORE (CONVIN-SING)

COVID-19 susceptibility and clinical outcomes in autoimmune inflammatory rheumatic diseases (AIRDs): a systematic review and meta-analysis.

This meta-analysis aims to assess the susceptibility to and clinical outcomes of COVID-19 in autoimmune inflammatory rheumatic disease (AIRD) and following AIRD drug use. We included observational and case-controlled studies assessing susceptibility and clinical outcomes of COVID-19 in patients with AIRD as well as the clinical outcomes of COVID-19 with or without use of steroids and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Meta-analysis including three studies showed that patients with AIRD are not more susceptible to COVID-19 compared to patients without AIRD or the general population (OR: 1.11, 95% CI: 0.58 to 2.14). Incidence of severe outcomes of COVID-19 (OR: 1.34, 95% CI: 0.76 to 2.35) and COVID-19 related death (OR: 1.21, 95% CI: 0.68 to 2.16) also did not show significant difference. The clinical outcomes of COVID-19 among AIRD patients with and without csDMARD or steroid showed that both use of steroid (OR: 1.69, 95% CI: 0.96 to 2.98) or csDMARD (OR: 1.35, 95% CI: 0.63 to 3.08) had no effect on clinical outcomes of COVID-19. AIRD does not increase susceptibility to COVID-19, not affecting the clinical outcome of COVID-19. Similarly, the use of steroids or csDMARDs for AIRD does not worsen the clinical outcome.

The COVID-19 vaccine: Attitudes and vaccination in patients with autoimmune inflammatory rheumatic diseases.

BackgroundWe examined attitudes toward the COVID‐19 vaccine, potential factors underlying these attitudes, and ways to increase vaccination willingness in autoimmune inflammatory rheumatic diseases (AIIRD) patients.MethodsA multicenter, web‐based, observational survey using an online questionnaire was conducted among AIIRD patients aged ≥18 years from May 24, 2021, to June 3, 2021. Participants were 3104 AIIRD patients (2921 unvaccinated and 183 vaccinated).ResultsOf the unvaccinated patients, 32.9% were willing to receive the COVID‐19 vaccine, 45.0% were uncertain, and 14.8% were unwilling. When vaccination was recommended by physicians, patients' willingness increased to 93.8%. Participants' main concerns were that the vaccine may aggravate AIIRD disease (63.0%) and may cause vaccine‐related adverse events (19.9%). Female patients were less likely to be vaccinated. However, patients who had children aged ≤18 years were more willing to be vaccinated. In addition, vaccination willingness was higher in patients with trust in the safety and efficacy of the COVID‐19 vaccine. Notably, 183 (5.9%) patients were vaccinated. The major vaccination side effects were injection reaction, myalgia, and fatigue. At a median follow‐up of 88 (38, 131) days, patients' disease activities were stable.ConclusionsThe findings show that AIIRD patients were unwilling to receive the COVID‐19 vaccine because of fears of potential disease exacerbation and additional adverse events. Sociodemographic characteristics and concerns about COVID‐19 disease and vaccines had a significant effect on vaccination willingness.

Humoral and cellular response to COVID-19 vaccination in patients with autoimmune inflammatory rheumatic diseases under real-life conditions.

ObjectivesSuccessful vaccination is key to overcoming the COVID-19 pandemic. Immunosuppressive medication is known to potentially compromise vaccination responses, and expansion of our knowledge on vaccination efficacy in patients with autoimmune inflammatory rheumatic diseases (AIIRD) is therefore of utmost importance.MethodsWe conducted a single-centre observational study and evaluated the efficacy of approved COVID-19 vaccines in 303 adult AIIRD patients. Serum levels of IgG antibodies against the S1 subunit of SARS-CoV-2 spike proteins (anti-S IgG) were measured at least two weeks after vaccination. In a subgroup of patients without humoral response, T-cell responses were determined using an interferon-γ gamma release assay.ResultsOverall seropositivity rate was 78.5% and was significantly lower in patients under immunosuppressive therapy (75.7 vs 93.2%, P = 0.009). No difference regarding the vaccination type was observed. Glucocorticoids, mycophenolate-mofetil, TNF inhibitors, tocilizumab, abatacept and rituximab were all associated with non-response after proper vaccination. The risk was highest under RTX therapy (OR 0.004, 95% CI 0.001, 0.023, P < 0.0001). A strong negative correlation was observed between time since vaccination with an mRNA vaccine and anti-S antibody levels (r=–0.6149, P < 0.0001). In patients without humoral response, a T-cell response was found in 50%.ConclusionsCOVID-19 vaccination in patients with AIIRD is effective using any approved vaccine. Humoral response might be impaired depending on the individual immunosuppressive medication. The risk of non-response is highest under rituximab therapy. Anti-S IgG antibody levels wane over time after mRNA vaccination. Importantly, 50% of humoral non-responders showed a T-cellular response, suggesting T-cell-mediated protection to a certain extent.

Comparable long-term retention rates and effects on bone mineral density of denosumab treatment in patients with osteoporosis with or without autoimmune inflammatory rheumatic diseases: real-life data.

Objectives:To investigate whether concomitant autoimmune inflammatory rheumatic diseases (AIIRDs) represent a risk factor for denosumab discontinuation and to explore other possible predictors.Design:This is a real-life retrospective study conducted at our centre on consecutive patients who started treatment with denosumab from January 2014 to October 2021.Methods:Data on patients’ characteristics, denosumab prescriptions and reason for discontinuation were collected from their medical electronic records. A log-rank test was run to assess differences in the denosumab retention rate between the not AIIRD and AIIRD patients. A backward stepwise logistic regression was used to identify possible predictors of denosumab discontinuation. When available, BMD data of the lumbar spine and total hip were collected.Results:Three hundred and sixty-three patients were included (265 not AIIRD and 98 AIIRD; median follow-up, 44 months). Sixty-nine patients discontinued denosumab at any time point (4 due to patient’s decision, 3 due to medical decision, 62 were lost in follow-up). The log-rank test did not find a statistically significant difference for denosumab persistence between the two subgroups. In the binary logistic regression analysis, only older age at initiation and lower baseline serum 25-hydroxy vitamin D were confirmed as predictors for discontinuation. BMD significantly increased from baseline to the last prescription visit at both the lumbar spine and the total hip, without statistically significant differences in the not AIIRD and AIIRD patients.Conclusion:The present data seem to suggest that AIIRDs do not represent a risk factor for denosumab discontinuation. Furthermore, the presence of AIIRDs does not seem to impair its effectiveness in terms of BMD.