Rheumatologistadherence to Vaccine Recommendation in Patients with Immune-Mediated Inflammatory Diseases

Objectives: Backgroud: Patients with immune-mediated inflammatory diseases (IMID), have an increased risk of presenting infections, this arises from immunosuppression related to the disease and its treatments. Vaccination in patients with autoimmune diseases is highly recommended by various clinical practice guidelines(1). Studies in Latin America show low rates of adherence, both in patients vaccine application and doctor's recommendations. One study shows that the lack of vaccination in 43% of their patients was due to their rheumatologist not recommending it (2). This is an eye opener on the key role physicians play in the overall outcome. Objective(s): To determine the adherence rate rheumatologists have, when it comes to recommending their patients vaccinations, suggested by clinical practice guidelines. Method(s): A descriptive study was performed, with previous authorization by the research department of the Colombian rheumatology association (ASOREUMA). A survey was sent via email to all its members asking about general knowledge about the subject and percentages on recommendations in their daily practice. Result(s): The survey was sent to 214 rheumatologist members of ASOREUMA, 34 (16%) of whom responded. In clinical practice there is a universal knowledge on the vaccination requirements for patients with IMID, nevertheless just 38.2% of clinicians tell patients to vaccinate against influenza of the 80%-100% of patients they see. For pneumococcus its 26.5%, hepatitis B 20.6%, human papilloma virus 8.8%, herpes zoster 2.9%. When it comes to SARS CoV2 vaccines it's by far the most recommended with 79.4%, and most physicians consider its mechanism of action before prescribing it. In table 1 we are summarizing the primary results. Conclusion(s): Despite the fact that rheumatologists are widely aware of the indications for vaccination in patients with IMID, these recommendations are not transmitted to all patients, due to the limited care time for each patient;in addition to the fact that the vast majority consider that the health system does not allow quick and timely access to these services.

The effects of methotrexate on the immune responses to the COVID-19 vaccines in the patients with immune-mediated inflammatory disease: A systematic review of clinical evidence.

COVID-19 vaccines exhibit high levels of immunogenicity in the overall population. Data on the effects of immunomodulators on the consequences of COVID-19 in patients with Immune-mediated inflammatory diseases (IMIDs) remains scarce. This systematic review aimed to evaluate the immune responses to the COVID-19 vaccines in IMID patients receiving methotrexate (MTX) compared to healthy individuals. A comprehensive literature search was carried out using electronic databases such as PubMed, Web of Science, Scopus, Google Scholar, and Embase up to August 2022 to identify eligible RCTs evaluating the effect of MTX on immune responses in patients with COVID-19. The PRISMA checklist protocol was applied for the quality assessment of the selected trials. Our findings demonstrated that MTX lowered the responses of T cells and antibodies in IMID patients compared to healthy controls. We also discovered that young age (<60 years) was the main parameter influencing the antibody response after vaccination, while MTX had little effect. Following vaccination, MTX-hold and age were considered the main factors influencing the antibody response. In patients older than 60 years of age, the time point of 10 days of MTX discontinuation was critical to boosting the humoral response to anti-SARS-CoV-2 IgG. Because many IMID patients did not have adequate humoral and cellular responses, our findings highlighted the importance of second or booster doses of vaccine and temporary MTX discontinuation. As a result, it implies that individuals with IMIDs should be subjected to more research, particularly humoral and cellular immunity efficiency trials after COVID-19 vaccination, until credible information is achieved.

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

BACKGROUND: Patients 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. METHODS: IMID 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. RESULTS: In 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%). CONCLUSION: IMID 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 REGISTRATION: NL74974.018.20, Trial ID: NL8900. Registered on 9 September 2020.

Immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in patients receiving secukinumab: a literature review.

Purpose: There is a paucity of evidence on the impact of immune-mediated inflammatory disease (IMID) treatments on the immunogenicity of SARS-CoV-2 vaccination. The purpose of this literature review is to address the question of whether patients with IMIDs receiving secukinumab, a fully human anti-interleukin-17A monoclonal antibody, have an adequate immune response after SARS-CoV-2 vaccination. Materials and Methods: Clinical studies that evaluated the effect of secukinumab on immune responses in patients with IMIDs after SARS-CoV-2 vaccination were searched in publication databases, including Medline and Embase, until May 2022. Results: From the 53 articles identified, a total of 11 articles were included. Overall, the majority of the patients treated with secukinumab elicited an adequate immune response to SARS-CoV-2 vaccines. Patients receiving secukinumab for IMIDs developed cellular immune responses following vaccination with the BNT162b2 vaccine, and there were no significant differences in the overall humoral and cellular immune responses between patients and healthy individuals. The third dose of the BNT162b2 mRNA vaccine resulted in a positive antibody response in secukinumab-treated patients. Conclusion: The available data provide no evidence of impairment in immunological response to SARS-CoV-2 vaccines by secukinumab in patients with IMIDs.

Impact of the First SARS-CoV-2 Lockdown on Adherence to Biological Treatment in Patients with Immune-Mediated Inflammatory Diseases in the Netherlands.

Purpose: During the SARS-CoV-2 pandemic, national and international societies have recommended continuing biological agents in patients with immune-mediated inflammatory diseases (IMID) in the absence of SARS-CoV-2 symptoms. However, adherence to biological treatment might decrease, because these recommendations contradict patients' beliefs. Especially an increased concern about side effects could have influenced the adherence to biological treatment during the first lockdown. The primary objective was to investigate the impact of the first SARS-CoV-2 lockdown on adherence to biological treatment in IMID patients. Patients and Methods: In this prospective cohort study, IMID patients who received a biological agent before and during the first SARS-CoV-2 lockdown (March 2020- June 2020) were included. Patients were excluded if they did not complete the medication adherence report scale-5 (MARS-5) questionnaire at ≥1 visit before the lockdown and ≥1 visit during the lockdown. Adherence to biological treatment was measured with the MARS-5 and Medication Possession Ratio (MPR). Results: We included 157 IMID patients. The percentage of adherent patients, defined as MARS-5 score >21, was significantly lower during the lockdown compared to the period before the lockdown (88.5% vs 84.1%, p<0.001). Additionally, the overall percentage of adherent patients during the lockdown based on the MPR ≥90% was significantly lower compared to adherence based upon the MARS-5 (65.1% vs 84.1%, p<0.001). Conclusion: This study showed that the first SARS-CoV-2 lockdown negatively impacts adherence to biological treatment in IMID patients. Therefore, treating physicians should be aware of this problem to minimize the potential harmful effects of non-adherence.

Characteristics of patients with immune-mediated inflammatory diseases hospitalized for SARS-CoV-2 infection.

BACKGROUND: Immune-mediated inflammatory diseases (IMID) predispose to a higher infection risk by modifying the host's immune response, which acts as a key factor in SARS-CoV-2 infection resolution. Recent publications show that IMID patients and its treatments do not worsen the outcome of SARS-CoV-2 infection. OBJECTIVES: To describe the clinical characteristics and outcomes of patients with IMID who required hospital admission due to SARS-CoV-2 infection. Secondly, to compare clinical characteristics and outcomes between patients who required hospital admission due to SARS-CoV-2 infection with IMID and those who were not affected. METHODS: We performed an observational retrospective cohort study, including admitted patients with suspected SARS-CoV-2 infection, treated according to medical criteria and local protocols based on the best available scientific evidence. Clinical data were collected from their electronical clinical history. Statistical analysis determined the differences in the characteristics and clinical outcome of the infection in IMID patients. RESULTS: Of a total number of 612 revised patients, 23 had an IMID and 9 of them were positive for the SARS-CoV-2 infection. We did not observe a correlation between these two disorders. There was a higher frequency of obesity and cardiovascular disease among IMID patients, but without statistical significance. The clinical outcomes were no different between hospitalized IMID and non IMID patients. CONCLUSION: IMID and its treatments do not determine the outcome of patients admitted with SARS-CoV-2 infection.

Impact of COVID-19 Pandemic on Initiation of Immunosuppressive Treatment in Immune-Mediated Inflammatory Diseases in Austria: A Nationwide Retrospective Study.

OBJECTIVE: Conventional immunosuppressive and advanced targeted therapies, including biological medications and small molecules, are a mainstay in the treatment of immune-mediated inflammatory diseases (IMID). However, the COVID-19 pandemic caused concerns over these drugs' safety regarding the risk and severity of SARS-CoV-2 infection. Thus, we aimed to assess the impact of the COVID-19 pandemic on the initiation of these treatments in 2020. STUDY DESIGN AND SETTING: We conducted a population-based retrospective analysis of real-world data of the Austrian health insurance funds on the initiation of conventional immunosuppressive and advanced targeted therapies. The primary objective was to compare the initiation of these medications in the year 2020 with the period 2017 to 2019. Initiation rates of medication were calculated by comparing a certain unit of time with an average of the previous ones. RESULTS: 95,573 patients were included. During the first lockdown in Austria in April 2020, there was a significant decrease in the initiations of conventional immunosuppressives and advanced targeted therapies compared to previous years (p < 0.0001). From May 2020 onwards, numbers rapidly re-achieved pre-lockdown levels despite higher SARS-CoV-2 infection rates and subsequent lockdown periods at the end of 2020. Independent from the impact of the COVID-19 pandemic, a continuous increase of starts of advanced targeted therapies and a continuous decrease of conventional immunosuppressants during the observation period were observed. CONCLUSIONS: In IMID patients, the COVID-19 pandemic led to a significant decrease of newly started conventional immunosuppressive and advanced targeted therapies only during the first lockdown in Austria.

Booster COVID-19 Vaccines for Immune-Mediated Inflammatory Disease Patients: A Systematic Review and Meta-Analysis of Efficacy and Safety.

BACKGROUND: Seroconversion and longevity of vaccine-induced immune response is blunted in immune-mediated inflammatory disease (IMID) patients owing to immunosuppressive regimens. COVID-19 booster vaccines after a primary series have been proposed with inconclusive evidence on efficacy to date. METHODS: This PROSPERO-registered systematic review (CRD42022302534) was conducted according to PRISMA guidelines. PubMed, EMBASE, CENTRAL, Web of Science, CORD-19, WHO ICTRP, and medRxiv were searched up to 28 February 2022 for eligible studies. Risk of bias was assessed using the Joanna Briggs Institute critical appraisal tools. RESULTS: From 6647 records, 17 prospective studies were included for systematic review and 12 in meta-analysis of primary series non-responders. The risk of bias was low. Pooling 340 non-responders, a booster dose proved effective with 0.47 seroconverting (95% CI: 0.32-0.63, I2 = 82%). Rituximab therapy was associated with significant impairment, with risks of 0.25 (95% CI: 0.17-0.36, I2 = 50.7%) versus 0.81 (95% CI: 0.72-0.87, I2 = 0.0%) for those without rituximab therapy. A systematic review of antibody levels against COVID-19 showed several-fold increases across studies. Incidence of local and systemic adverse events, including disease flares, were either comparable or slightly increased after the booster dose compared to primary series. No major events such as myocarditis or death were reported. CONCLUSION: Our results show that booster doses are effective in eliciting seroconversion in non-responders, bolstering immunity to COVID-19. It has also not been associated with major adverse events.

The Immunogenicity and Safety of Three Types of SARS-CoV-2 Vaccines in Adult Patients with Immune-Mediated Inflammatory Diseases: A Longitudinal Cohort Study.

Patients with immune-mediated inflammatory diseases (IMID) were seldom enrolled in the studies of SARS-CoV-2 vaccines, and real-world data regarding the immunogenicity of different types of vaccines is limited. We aimed to assess the immunogenicity and safety of three types of vaccines (AZD1222, mRNA-1273, and BNT162b2) in 253 patients with IMID and 30 healthcare workers (HCWs). Plasma levels of IgG-antibody against SARS-CoV-2 targeting the receptor-binding domain of spike protein (anti-S/RBD-IgG) were determined by chemiluminescent immunoassay 3-4 weeks after the first-dose and second-dose vaccination. The positive rate and titers of anti-S/RBD-IgG were significantly higher in mRNA-1273 or BNT162b2 than in the AZD1222 vaccine. Immunogenicity was augmented after the second dose of any vaccine type in all IMID patients, suggesting that these patients should complete the vaccination series. Anti-S/RBD-IgG titers after first-dose vaccination were significantly lower in RA patients than pSS patients, but there was no significant difference after second-dose vaccination among five groups of IMID patients. The positive rate and titers of anti-S/RBD-IgG were significantly lower in patients receiving abatacept/rituximab therapy than in those receiving other DMARDs. All three SARS-CoV-2 vaccines showed acceptable safety profiles, and the common AEs were injection site reactions. We identified SLE as a significant predictor of increased autoimmunity and would like to promote awareness of the possibility of autoimmunity following vaccination.

Chilblains in immune-mediated inflammatory diseases: a review.

Chilblains were first described over a hundred years ago as cutaneous inflammatory lesions, typically on the digits, occurring on cold exposure. Chilblains can be primary, or secondary to a number of conditions such as infections, including COVID-19, and immune-mediated inflammatory disorders (IMIDs) with SLE being the commonest. Chilblain lupus erythematosus (CHLE) was first described in 1888 as cold-induced erythematous lesions before the terms 'chilblains' or 'perniosis' were coined. Diagnostic criteria exist for both chilblains and CHLE. Histopathologically, CHLE lesions show interface dermatitis with perivascular lymphocytic infiltrate. Immunofluorescence demonstrates linear deposits of immunoglobulins and complement in the dermo-epidermal junction. This narrative review focuses on chilblains secondary to immune-mediated inflammatory disorders, primarily the epidemiology, pathogenesis and treatment of CHLE.

Response to Vaccines in Patients with Immune-Mediated Inflammatory Diseases: A Narrative Review.

Patients with immune-mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis and inflammatory bowel disease, are at increased risk of infection. International guidelines recommend vaccination to limit this risk of infection, although live attenuated vaccines are contraindicated once immunosuppressive therapy has begun. Biologic therapies used to treat IMIDs target the immune system to stop chronic pathogenic process but may also attenuate the protective immune response to vaccines. Here, we review the current knowledge regarding vaccine responses in IMID patients receiving treatment with biologic therapies, with a focus on the interleukin (IL)-12/23 inhibitors. B cell-depleting therapies, such as rituximab, strongly impair vaccines immunogenicity, and tumor necrosis factor (TNF) inhibitors and the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) fusion protein abatacept are also associated with attenuated antibody responses, which are further diminished in patients taking concomitant immunosuppressants. On the other hand, integrin, IL-6, IL-12/23, IL-17, and B-cell activating factor (BAFF) inhibitors do not appear to affect the immune response to several vaccines evaluated. Importantly, treatment with biologic therapies in IMID patients is not associated with an increased risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or developing severe disease. However, the efficacy of SARS-CoV-2 vaccines on IMID patients may be reduced compared with healthy individuals. The impact of biologic therapies on the response to SARS-CoV-2 vaccines seems to replicate what has been described for other vaccines. SARS-CoV-2 vaccination appears to be safe and well tolerated in IMID patients. Attenuated but, in general, still protective responses to SARS-CoV-2 vaccination in the context of certain therapies warrant current recommendations for a third primary dose in IMID patients treated with immunosuppressive drugs.

Influence of chronic use of corticosteroids and calcineurin inhibitors on COVID-19 clinical outcomes: analysis of a nationwide registry.

OBJECTIVES: The aim of this study was to analyze whether subgroups of immunosuppressive (IS) medications conferred different outcomes in COVID-19. METHODS: The study involved a multicenter retrospective cohort of consecutive immunosuppressed patients (ISPs) hospitalized with COVID-19 from March to July, 2020. The primary outcome was in-hospital mortality. A propensity score-matched (PSM) model comparing ISP and non-ISP was planned, as well as specific PSM models comparing individual IS medications associated with mortality. RESULTS: Out of 16 647 patients, 868 (5.2%) were on chronic IS therapy prior to admission and were considered ISPs. In the PSM model, ISPs had greater in-hospital mortality (OR 1.25, 95% CI 0.99-1.62), which was related to a worse outcome associated with chronic corticoids (OR 1.89, 95% CI 1.43-2.49). Other IS drugs had no repercussions with regard to mortality risk (including calcineurin inhibitors (CNI); OR 1.19, 95% CI 0.65-2.20). In the pre-planned specific PSM model involving patients on chronic IS treatment before admission, corticosteroids were associated with an increased risk of mortality (OR 2.34, 95% CI 1.43-3.82). CONCLUSIONS: Chronic IS therapies comprise a heterogeneous group of drugs with different risk profiles for severe COVID-19 and death. Chronic systemic corticosteroid therapy is associated with increased mortality. On the contrary, CNI and other IS treatments prior to admission do not seem to convey different outcomes.

Serologic Response to Coronavirus Disease 2019 (COVID-19) Vaccination in Patients With Immune-Mediated Inflammatory Diseases: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Patients with immune-mediated inflammatory diseases (IMIDs) have an increased risk of coronavirus disease 2019 (COVID-19), primarily attributed to the use of immunosuppressive drugs such as glucocorticoids, which may attenuate the response to vaccines. This meta-analysis assessed the serologic response to COVID-19 vaccination in patients with IMIDs. METHODS: Electronic databases were searched on August 1, 2021, for observational studies. Data extracted included reference population, medications, vaccination, and proportion of patients achieving a serologic response. RESULTS: The analysis included 25 observational studies (5360 patients). Most of the studies used messenger RNA (mRNA) vaccines (BNT162b2, mRNA-1273), with a small number of studies including other types of vaccines (AZD1222, CoronaVac, BBV152, Ad26.COV2.S). Serologic response after 1 dose (6 studies) and 2 doses (17 studies) of mRNA vaccine were 73.2% (95% confidence interval [CI], 65.7%-79.5%) and 83.4% (95% CI, 76.8%-88.4%), respectively. On meta-regression, anti-CD20 therapy was associated with lower response rates (P < .001) and anti-tumor necrosis factor therapy also showed a trend toward lower response rates (P = .058). Patients with IMIDs were less likely to achieve a serologic response compared with controls after 2 doses of mRNA vaccine (6 studies; odds ratio, 0.086; 95% CI, 0.036-0.206; P < .001). There were not enough studies to assess response to the adenoviral or inactivated vaccines. CONCLUSIONS: Our meta-analysis demonstrated that patients with IMIDs have a reduced response to mRNA COVID-19 vaccines. These results suggest that IMID patients receiving mRNA vaccines should complete the vaccine series without delay and support the strategy of providing a third dose of the vaccine.

Characteristics associated with COVID-19 vaccine hesitancy: A nationwide survey of 1000 patients with immune-mediated inflammatory diseases.

OBJECTIVES: To identify potential predictors of COVID-19 vaccine hesitancy (C19-VH) in adults with immune-mediated inflammatory diseases (IMID). METHODS: A total of 1000 IMID patients were enrolled in this web-based cross-sectional study. A standardised and self-administered survey was designed by members of the Brazilian Society of Rheumatology Steering Committee for Infectious and Endemic diseases and distributed to IMID patients spread across Brazil. RESULTS: Of the 908 (90.8%) respondents eligible for analysis, 744 (81.9%) were willing to get vaccinated against COVID-19. In our multivariable logistic regression model, concurrent malignancy, fibromyalgia, hydroxychloroquine use, and recent corticosteroid pulse therapy were independently associated with higher odds of C19-VH. The short duration of COVID-19 vaccine clinical trials was the main reason for C19-VH. CONCLUSION: We identified novel characteristics potentially associated with C19-VH among adults with IMID. Greater awareness on the safety and efficacy of COVID-19 vaccines is needed for both IMID patients and attending physicians.

Characteristics of Patients With Immune-Mediated Inflammatory Diseases Hospitalized for SARS-CoV-2 Infection. / Características de pacientes con enfermedades inflamatorias inmunomediadas hospitalizados por infección por SARS-CoV-2.

BACKGROUND: Immune-mediated inflammatory diseases (IMID) predispose to a higher infection risk by modifying the host's immune response, which acts as a key factor in SARS-CoV-2 infection resolution. Recent publications show that IMID patients and its treatments do not worsen the outcome of SARS-CoV-2 infection. OBJECTIVES: To describe the clinical characteristics and outcomes of patients with IMID who required hospital admission due to SARS-CoV-2 infection. Secondly, to compare clinical characteristics and outcomes between patients who required hospital admission due to SARS-CoV-2 infection with IMID and those who were not affected. METHODS: We performed an observational retrospective cohort study, including admitted patients with suspected SARS-CoV-2 infection, treated according to medical criteria and local protocols based on the best available scientific evidence. Clinical data were collected from their electronical clinical history. Statistical analysis determined the differences in the characteristics and clinical outcome of the infection in IMID patients. RESULTS: Of a total number of 612 revised patients, 23 had an IMID and 9 of them were positive for the SARS-CoV-2 infection. We did not observe a correlation between these two disorders. There was a higher frequency of obesity and cardiovascular disease among IMID patients, but without statistical significance. The clinical outcomes were no different between hospitalized IMID and non IMID patients. CONCLUSION: IMID and its treatments do not determine the outcome of patients admitted with SARS-CoV-2 infection.

Direct and Indirect Impact of COVID-19 for Patients with Immune-Mediated Inflammatory Diseases: A Retrospective Cohort Study.

IMPORTANCE: Since the beginning of the Coronavirus Disease-19 (COVID-19) pandemic, Severe Acute Respiratory Syndrome-CoV-2 (SARS-CoV-2) infection has been a serious challenge for immune-compromised patients with immune-mediated inflammatory diseases (IMIDs). OBJECTIVE: Our aim was to investigate the impact of COVID-19 in terms of risks of infection, hospitalization and mortality in a cohort of patients with rheumatoid arthritis (RA), psoriasis (PSO) or inflammatory bowel disease (IBD). Furthermore, we studied the impact of SARS-CoV-2 infection on the prescribed drug regimen in these patients. METHODS: Through the record linkage between health information systems, a cohort of patients, ≥18 years old, assisted in the Lazio region and who had suffered from immune-mediated inflammatory diseases (RA, PSO, IBD) between 2007 and 2019, was identified. The risk of infection, hospitalization or mortality for COVID-19, was assessed by logistic regression models, and reported in an Odds Ratio (ORs; CI 95%), adjusting for sex, age and the Charlson Comorbidity Index. We also estimated these risks separately by IMID and in the subgroup of prevalent biologic drug users. We investigated deferral of biological treatments in the study population by comparing the prevalence of weekly use of biologicals (2019-2020) before and during the pandemic periods. FINDINGS: Within the 65,230 patients with IMIDs, the cumulative incidence for COVID-19 was 303/10,000 ab. In this cohort of patients, we observed a significantly higher risk of SARS-CoV-2 infection than the general population: OR = 1.17 (95% CI 1.12-1.22). The risk was higher even considering separately each disease and in the subgroup of prevalent biologic drug users. This last subgroup of patients showed a higher risk of death related to COVID-19 (OR 1.89; 95% CI 1.04-3.33) than the general population. However, no differences in terms of risks of hospitalization or death related to COVID-19 were recorded in patients with the IMIDs. Comparing the 2019-2020 prevalence of weekly biological drug treatments in prevalent biologic drug users, we found a decrease (-19.6%) during the lockdown, probably due to pandemic restrictions. CONCLUSIONS AND RELEVANCE: Patients with IMIDs seem to have a higher risk of SARS-CoV2 infection. However, other than for patients with prevalent biologic drug treatment, no significant differences in terms of hospitalization and mortality were reported compared to the general populations; further investigation is warranted on account of unmeasured confounding. In addition, during the lockdown period, the COVID-19 emergency highlighted a lower use of biologic drugs; this phenomenon requires strict pharmacological monitoring as it could be a proxy of forthcoming long-term clinical progression.

Coronavirus disease 2019, immune-mediated inflammatory diseases and immunosuppressive therapies - A Danish population-based cohort study.

BACKGROUND: Limited data exist regarding the disease course of coronavirus disease 2019 (COVID-19) and its relationship with immunosuppressants among patients with immune-mediated inflammatory diseases (IMIDs). Therefore, this study aims to investigate the association between COVID-19, frequent rheumatological, dermatological, gastrointestinal, and neurological IMIDs and immunosuppressants. METHODS: We conducted a Danish population-based cohort study including all residents living within Capital Region of Denmark and Region Zealand from January 28th, 2020 until September 15th, 2020 with the only eligibility criterion being a test for SARS-CoV-2 via reverse transcription-polymerase chain-reaction. Main outcomes included development of COVID-19, COVID-19-related hospitalization and mortality. RESULTS: COVID-19 was less common among patients with IMIDs than the background population (n = 328/20,513 (1.60%) and n = 10,792/583,788(1.85%), p < 0.01, respectively). However, those with IMIDs had a significantly higher risk of COVID-19-related hospitalization (31.1% and 18.6%, p < 0.01, respectively) and mortality (9.8% and 4.3%, p < 0.01, respectively), which were associated with patients older than 65 years, and presence of comorbidities. Furthermore, systemic steroids were independently associated with a severe course of COVID-19 (Odds ratio (OR) = 3.56 (95%CI 1.83-7.10), p < 0.01), while biologic therapies were associated with a reduced risk hereof (OR = 0.47 (95%CI 0.22-0.95), p = 0.04). Patients suspending immunosuppressants due to COVID-19 had an increased risk of subsequent hospitalization (OR = 3.59 (95%CI 1.31-10.78), p = 0.02). CONCLUSION: This study found a lower occurrence, but a more severe disease course, of COVID-19 among patients with IMIDs, which was associated with the use of systemic steroids for IMIDs and suspension of other immunosuppressants. This study emphasizes the importance of weighing risks before suspending immunosuppressants during COVID-19.

Prevalence and Outcomes of COVID-19 Among Patients With Inflammatory Bowel Disease-A Danish Prospective Population-based Cohort Study.

BACKGROUND AND AIMS: As no population-based study has investigated the susceptibility and disease course of COVID-19 among patients with inflammatory bowel diseases [IBD], we aimed to investigate this topic in a population-based setting. METHODS: Two cohorts were investigated. First, a nationwide cohort of all IBD patients diagnosed with COVID-19 was prospectively followed to investigate the disease courses of both diseases. Second, within a population-based cohort of 2.6 million Danish citizens, we identified all individuals tested for SARS-CoV-2 to determine the occurrence of COVID-19 among patients with and without IBD and other immune-mediated inflammatory diseases [IMIDs]. RESULTS: Between January 28, 2020 and June 2, 2020, a total of 76 IBD patients with COVID-19 were identified in the national cohort and prospectively followed for 35 days (interquartile range [IQR]: 25-51). A large proportion [n = 19: 25%] required a COVID-19-related hospitalisation for 7 days [IQR: 2-8.5] which was associated with being 65 years or older (odds ratio [OR] = 23].80, 95% confidence interval [CI] 6.32-89.63, p <0.01) and presence of any non-IMID comorbidity [OR = 8.12, 95% CI 2.55-25.87, p <0.01], but not use of immunomodulators [p = 0.52] or biologic therapies [p = 0.14]. In the population-based study, 8476 of 231 601 [3.7%] residents tested positive for SARS-CoV-2; however, the occurrence was significantly lower among patients with IBD [62 of the 2486 patients = 2.5%, p <0.01] and other IMIDs [531 of 16 492 patients = 3.2%, p <0.01] as compared with patients without IMIDs. CONCLUSIONS: Patients with IMIDs, including IBD, had a significantly lower susceptibility to COVID-19 than patients without IMIDs, and neither immunosuppressive therapies nor IBD activity were associated with the disease course of COVID-19.

Antecedent immunosuppressive therapy for immune-mediated inflammatory diseases in the setting of a COVID-19 outbreak.

BACKGROUND: Finite clinical data and understanding of COVID-19 immunopathology has led to limited, opinion-based recommendations for the management of patients with immune-mediated inflammatory disease (IMID) receiving immunosuppressive (IS) therapeutics. OBJECTIVE: To determine if IS therapeutic type affects COVID-19 risk among patients with IMID. METHODS: We conducted a retrospective cohort analysis of Henry Ford Health System patients tested for COVID-19 between February 1 and April 18, 2020, treated with IS medication for IMID. Therapeutic class of IS medication, comorbidities, and demographic factors were combined into multivariate models to determine predictors of COVID-19 infection, admission, ventilation, and mortality. RESULTS: Of 213 patients with IMID, 36.2% tested positive for COVID-19, and they had no greater odds of being hospitalized or requiring ventilation relative to the general population. No IS therapeutic worsened the course of disease after multivariate correction, although multidrug regimens and biologics predicted an increased and decreased rate of hospitalization, respectively, with the latter driven by tumor necrosis factor α inhibitors. LIMITATIONS: A single-center study somewhat limits the generalization to community-based settings. Only patients tested for COVID-19 were analyzed. CONCLUSION: IS therapies for IMIDs are not associated with a significantly greater risk of SARS-CoV-2 or severe sequelae when controlling for other factors, and tumor necrosis factor α inhibitors may decrease the odds of severe infection.