Using a Single Irb for Nih-Funded Multisite Trials

As clinical trials evolve, the oversight by Institutional Review Boards (IRBs) has also evolved to meet everexpanding needs for both efficiency and changing regulatory requirements in the protection of human subjects. The most significant regulatory change to occur was the change to the Revised Common Rule Research Provision (45 CFR 46.114(b)) that went into effect on 20 January 2020, requiring all cooperative research subject to the Common Rule to use a single Institutional Review Board (sIRB) to review the research. Since the Common Rule affects all federally funded research, clinical trialists performing multicenter trials using federal grants are now required to use an sIRB instead of individual IRBs at each research site in their trials. For those multicenter trialists, using an sIRB offers efficiencies in time and effort which can aid in bringing trial results to fruition both faster and at a lower cost while still providing protection to human subjects. While commercial sIRBs have been available for many years, sIRBs placed at academic institutions and health care systems are relatively new. They can offer the benefit of lower cost for trialists within an institution, and better overall trial management by having more frequent communication and discussion regarding trial issues as well as improved safety management through aggregate safety review. They can also offer increased speed of research review with cooperative planning between trialist and the sIRB representatives. This session will focus on the use of sIRBs from various perspectives to give the view from an academic sIRB, from end users of both an academic sIRB and a health system IRB, and guidance from a clinical regulatory specialist regarding maintaining a trial master file while using an sIRB. Mr. Jarrod Feld from the University of Iowa will present from his perspective as the External IRB Coordinator at the University of Iowa. Mr. Feld coordinates reliance and compliance for University of Iowa human research studies which use the University of Iowa Institutional Review Board as their sIRB, and studies where Iowa relies on another institutional IRB. Mr. Feld also provides guidance to investigators on using an sIRB. Using his experience, Mr. Feld will outline the nature of reliance agreements, discuss working with a range of local IRBs to develop understanding regarding the reliance program and outline best practices for using an sIRB, and discuss enhanced safety management oversight when using an sIRB for large multisite trial. Ms. Tina Neill-Hudson from the University of Iowa will present from her experience as the sIRB Liaison for both the Acute to Chronic Pain Signature (A2CPS) Consortium, an NIH (National Institutes of Health)- funded multisite observational trial, and the Fibromyalgia and TENS in Physical Therapy Study (FM TIPS) study, an NIH-funded embedded pragmatic clinical trial. Ms. Neill-Hudson works with relying sites on completing the necessary regulatory documents needed for reliance agreements and sIRB approval. Ms. Neill-Hudson will discuss the process for obtaining reliance for institutions who may or may not have local IRB oversight and provide examples of specific steps and procedures for obtaining sIRB approval in a timely manner. Ms. Neill-Hudson will speak to the importance of having an sIRB liaison on the study team and the use of SMART IRB. Ms. Catherine Gladden from MassGeneral Brigham will present on using an sIRB for multicenter NIHfunded trials. Ms. Gladden will discuss the use of a Consortium-level reliance agreement and role of the local IRBs. Ms. Gladden oversees the sIRB liaison team at the Coordinating Center for the NeuroNEXT Network and works with the sIRB and local IRBs to ensure local policies and requirements are followed while maintaining compliance with the sIRB and the NeuroNEXT reliance agreement. Ms. Gladden will be discussing best practices for using an sIRB in a multicenter trial and discuss the experience of using an sIRB in the safety management plan. Ms. Cynthia Diltz from the University of Iowa wi l present on the topic of managing a trial master file while using an sIRB. Ms. Diltz will speak on her experience with electronic trial master files versus hard copy master files, and in using commercial software for trial master file management. Using an electronic trial master file is a necessity in the scheme of using an sIRB to assist sponsors and individual clinical research sites to view Institutional Review Board documents in real time and to provide a single storage location for documentation of Institutional Review Board approvals and activities such as continuing review. This session is timely due to the change to the Common Rule mandating the use of an sIRB for all research subject to the Common Rule, which has the most significant impact on trialists at academic institutions and health care systems. In an era of the need for timely study results for use in addressing urgent public health policy concerns, using an sIRB is becoming a necessity. The speed with which clinical trials need to be managed by an IRB has accelerated during recent public health care crises, notably the COVID-19 pandemic. In addition, it is likely that there will be changes to local IRBs as the norm becomes using an sIRB for any research subject to the Common Rule. Investigators and clinical site staff will require education on the evolution of human subject's protection and research review happening at an sIRB instead of within their local IRBs, and assistance in understanding the process and planning for success will be crucial.

RISK FACTORS for SEVERE COVID-19 INFECTION among PATIENTS with AUTOIMMUNE INFLAMMATORY RHEUMATIC DISEASES (AIRD) and the IMPACT of VACCINATIONS-AN ISRAELI, MULTICENTER EXPERIENCE

Background: AIRD patients (pts) may be more susceptible to severe COVID19. Objectives: To determine the risk factors for severe COVID19 and the effect of vaccinations among AIRD pts followed at dedicated rheumatology clinics. Methods: At the onset of the pandemic, we established a national registry of AIRD pts, diagnosed with COVID19, based on voluntary reporting by the treating rheumatologist. 12 centers from Israel participated in the study. COVID19 was confrmed by a positive SARS CoV2 PCR. The indications for PCR testing were clinical symptoms or close contact with an infected person. Severe illness was defned by SpO2 <94% in room air, respiratory rate of >30 breaths/min, PaO2/FiO2 <300 mm Hg, or lung infltrates >50% on imaging. The registry included demographic data, AIRD diagnosis and duration, visceral involvement, co-morbidities, immunomodulatory treatment, date of diagnosis and severity of COVID19 disease, management, complications, duration of hospitalization, the dates of the mRNA vaccinations, lab results and outcome. We analyzed data from 1.3.2020 to 30.11.2021 Results: During the study period we experienced 4 outbreaks of COVID19 infection. Initially social distancing, followed by a lockdown were imposed. The low number of cases led to relaxation of the measures. Two more severe outbreaks followed, which triggered 2 new lockdowns. The 3rd outbreak ended almost 2 months after vaccination started (BNT162b2 mRNA COVID19 vaccine). From March 1st 2020 to April 30, 2021, 298 AIRD pts (70.8% females, mean (SD) age 53.3(15.3)) with confrmed COVID19 infection were included. 43.3%(129) had visceral involvement due to the AIRD. 58.7%(175 pts) were on conventional synthetic disease modifying drugs (csDMARDs), 44.6% (133) on biologic/targeted DMARDs and 40% (120) on prednisone. Almost 2/3 of pts had at least one comorbidity. In a multivariate logistic regression analysis age, AIRD with pulmonary involvement, diabetes and treatment with prednisone, mycophenolate mofetil or JAK inhibitors were associated with hospitalization. Older age, renal and vascular involvement due to the AIRD, and congestive heart failure were associated with higher mortality. The 4th outbreak occurred 6 months after the introduction of vaccines, with spreading of the delta variant: 110 AIRD pts with COVID19 were recorded. Demographic data, clinical AIRD's characteristics, immunomodulatory treatment and comorbidities were similar to the previous outbreaks. However, during the 4th outbreak, the proportion of pts with severe COVID19, the hospitalization and mortality rate were signifcantly lower as compared to the frst 3 outbreaks (15% vs 24%, 27% vs 53%, 6.7% vs 9.1%, respectively). Among COVID19 pts, 25% received a 3rd vaccine dose (booster), 56% contracted infection more than 5 months after the 2nd vaccine dose and 24% were unvaccinated. Most of the pts who received the booster contracted the disease within a week of vaccination. The odds ratio for hospitalization in vaccinated pts compared to unvaccinated was 0.11 (0.01-0.63 95% CI, p=0.041) in those vaccinated within the previous 1-5 months, and 0.38 (0.21-0.67 95% CI, p=0.001) in those vaccinated more than 6 months ago. 9 pts died, 5 were more than 6 months after the 2nd mRNA vaccine, 2 were unvaccinated and 1 patient received the booster on the same day of COVID19 diagnosis. Conclusion: Before the vaccination campaign, the hospitalization and mortality rate in our cohort were similar to the data reported by other registries. COVID19 tends to be more severe, with increased mortality in patients with active AIIRD and visceral involvement (pulmonary, cardiac, renal), advanced age and co-morbidities. The delta outbreak occured 6 months after the implementation of vaccinations and was associated with signifcantly lower hospitalization and mortality rates, despite the increased aggressiveness of the variant. Vaccination of AIIRD pts with 3 doses of mRNA vaccines protects from severe COVID19 disease, hospitalization, and death.

THE EFFECT of SECUKINUMAB on the HUMORAL RESPONSE FOLLOWING TWO and THREE DOSES of the BNT162B2 MRNA VACCINE in PATIENTS with SPONDYLOARTHRITIS

Background: Data on the effect of secukinumab on the humoral response to the BNT162b2 mRNA vaccine are limited. Objectives: We aimed to assess prospectively the humoral response to the BNT162b2 mRNA vaccine in patients with spondyloarthritis (SpA) treated with secukinumab in comparison to immunocompetent controls. Methods: Patients with psoriatic arthritis (PsA) or ankylosing spondylitis (AS) treated with secukinumab for at least 3 months and immunocompetent controls were vaccinated with two-dose regimen of the BNT162b2 mRNA vaccine. Clinical and laboratory assessments were performed at 2-8 weeks [SpA: 37 on secukinumab, (median age 53% female), 122 controls (median age 53, 51% female)], and 6 months [SpA: 27 on secukinumab, 116 controls] after the second vaccine dose. A subgroup of patients (22 SpA on secukinumab, 45 controls) were evaluated after the third vaccine dose. The seropositive response was defned as a detectable S1/S2 IgG ≥15 binding antibody units (BAU)/ml. Results: The two-dose vaccine regimen induced a similar immunogenic response in patients and controls refected by the seropositivity rates of 100% in both groups. After six months, the rate of seropositivity remained as high as 96% in both secukinumab-treated patients and immunocompetent controls. The decline of S1/S2 IgG titer within six months was similar in controls and secukinumab-treated patients,-66.4 (95% CI {-70.9,-39.9}) and-55 BAU/ml (95% CI {-95.42,-36.87)). Following the third vaccine, the seropositivity rate increased to 100 % in both groups. At all-time points, S1/S2 IgG titers were similar in secukinumab treated patients and immunocompetent controls (Figure 1). Conclusion: SpA patients treated with secukinumab consistently demonstrated an adequate humoral response to the BNT162b2 mRNA vaccination similar to immunocompetent controls, both short-term and within six months after two vaccine doses and after the third vaccine dose.

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

Background: Data on the kinetics of the immune response to SARS-CoV-2 vaccination in patients with autoimmune infammatory rheumatic diseases (AIIRD) are limited. Objectives: To 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. Methods: A 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 defned 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. Results: The two-dose vaccine regimen induced a higher humoral response in controls compared to patients, as refected by the post-vaccination seroposi-tivity rates of 100% vs 84.72%, p<0.0001, and 96.55% vs 74.26%, p<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 signifcantly 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 signifcantly lower in AIIRD patients compared with controls (Figure 1). We further investigated the impact of therapies on the vaccine's immuno-genicity (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 seroposi-tivity 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. Conclusion: Over 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 biolog-ics, abatacept, and JAKi. Treatment with GC and RTX was associated with an impaired humoral response at all time points.

Timing of elimination of hepatitis C virus in Canada's provinces

BACKGROUND: Infection with chronic hepatitis C virus is a global public health concern. A recent study concluded that Canada is on track to achieve hepatitis C elimination goals set by the World Health Organization if treatment levels are maintained. However, recently a falling temporal trend in treatments in Canada was observed, with most provinces seeing a decrease before the global coronavirus pandemic. This study assesses the timing of elimination of hepatitis C in the 10 provinces of Canada. METHODS: Previously published disease and economic burden model of hepatitis C infection was populated with the latest epidemiological and cost data for each Canadian province. Five scenarios were modelled: maintaining the status quo, decreasing diagnosis and treatment levels by 10% annually, decreasing diagnosis and treatment levels by 20% annually, increasing them by 10% annually, and assuming a scenario with no post-coronavirus pandemic recovery in treatment levels. Year of achieving hepatitis C elimination, necessary annual treatments for elimination, and associated disease and economic burden were determined for each province. RESULTS: If status quo is maintained, Manitoba, Ontario, and Quebec are off track to achieve hepatitis C elimination by 2030 and would require 540, 7,700, and 2,800 annual treatments, respectively, to get on track. Timely elimination would save 170 lives and CAD$122.6 million in direct medical costs in these three provinces. CONCLUSIONS: Three of Canada's provinces-two of them most populous in the country-are off track to achieve the hepatitis C elimination goal. Building frameworks and innovative approaches to prevention, testing, and treatment will be necessary to achieve this goal.

Oncology clinical trial disruption during the COVID-19 pandemic: a COVID-19 and cancer outcomes study.

BACKGROUND: COVID-19 disproportionately impacted patients with cancer as a result of direct infection, and delays in diagnosis and therapy. Oncological clinical trials are resource-intensive endeavors that could be particularly susceptible to disruption by the pandemic, but few studies have evaluated the impact of the pandemic on clinical trial conduct. PATIENTS AND METHODS: This prospective, multicenter study assesses the impact of the pandemic on therapeutic clinical trials at two large academic centers in the Northeastern United States between December 2019 and June 2021. The primary objective was to assess the enrollment on, accrual to, and activation of oncology therapeutic clinical trials during the pandemic using an institution-wide cohort of (i) new patient accruals to oncological trials, (ii) a manually curated cohort of patients with cancer, and (ii) a dataset of new trial activations. RESULTS: The institution-wide cohort included 4756 new patients enrolled to clinical trials from December 2019 to June 2021. A major decrease in the numbers of new patient accruals (-46%) was seen early in the pandemic, followed by a progressive recovery and return to higher-than-normal levels (+2.6%). A similar pattern (from -23.6% to +30.4%) was observed among 467 newly activated trials from June 2019 to June 2021. A more pronounced decline in new accruals was seen among academically sponsored trials (versus industry sponsored trials) (P < 0.05). In the manually curated cohort, which included 2361 patients with cancer, non-white patients tended to be more likely taken off trial in the early pandemic period (adjusted odds ratio: 2.60; 95% confidence interval 1.00-6.63), and substantial pandemic-related deviations were recorded. CONCLUSIONS: Substantial disruptions in clinical trial activities were observed early during the pandemic, with a gradual recovery during ensuing time periods, both from an enrollment and an activation standpoint. The observed decline was more prominent among academically sponsored trials, and racial disparities were seen among people taken off trial.

Disruption to care of patients with thoracic malignancies: A COVID-19 and cancer outcomes study

Introduction: Patients with thoracic malignancies are susceptible to severe outcomes from coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the disruption to care of patients with thoracic malignancies during the COVID-19 pandemic. Methods: The COVID-19 and Cancer Outcomes Study (CCOS) is a multicenter prospective cohort study comprised of adult patients with a current or past history of hematological malignancy or invasive solid tumor who had an outpatient medical oncology visit on the index week between March 2 and March 6, 2020 at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai in New York, NY (MSSM) or the Dana-Farber Cancer Institute in Boston, MA (DFCI). An electronic data capture platform was used to collect patient-, cancer-, and treatment-related variables during the three months prior to the index week (the baseline period) and the following three months (the pandemic period). Two-by-three contingency tables with Fisher's exact tests were computed. All tests were two-tailed and considered statistically significant for p<0.05. All analyses were done in the R statistical environment (v3.6.1). Results: The overall cohort included 2365 patients, of which 313 had thoracic malignancies, 1578 had other solid tumors, and 474 had hematological malignancies. At a median follow-up of 84 days (95% confidence interval, 82-84), 13 patients with thoracic malignancies (4.1%) had developed COVID-19 (vs. other solid: 63 [4.0%] and hematological: 52 [11.0%];p<0.001). When comparing data from the pandemic period to the baseline period, patients with thoracic malignancies had a decrease in the number of in-person outpatient visits (thoracic: 209 [66.8%] vs. other solid: 749 [47.5%] vs. hematological: 260 [54.9%];p<0.001) and an increase in the number of telehealth visits (thoracic: 126 [40.3%] vs. other solid: 465 [29.5%] vs. hematological: 168 [35.4%];p<0.001). During the pandemic period, 33 (10.5%) patients with thoracic malignancies experienced treatment delays due to the pandemic (vs. other solid: 127 [8.0%] and hematological: 79 [16.7%];p<0.001), and 26 (8.3%) patients with thoracic malignancies experienced delays in cancer imaging or diagnostic procedures (vs. other solid: 63 [4.0%] and hematological: 26 [5.5%];p=0.003). Discussion: In this prospective cohort study, patients with thoracic malignancies were not at increased risk of developing COVID-19 compared to patients with other cancers, but experienced significant cancer care disruption during the COVID-19 pandemic with a higher likelihood of decreased in-person visits and increased telehealth visits compared to patients with other malignancies. Focused efforts to ensure continuity of care for this vulnerable patient population are warranted.

Leveraging COVID-19 vaccination to enhance hcv testing in priority populations

Background: Intersecting priority populations are disproportionately affected by HCV and COVID-19;including people who use drugs, those with mental health issues, and those who are homeless/street-involved. COVID-19 vaccine clinics present an opportunity for co-localization of HCV testing by leveraging resources and infrastructure that promote COVID-19 vaccination among these populations. Methods: HHCV Ab point-of-care testing (POCT) was offered at two COVID-19 vaccination sites: the Centre for Addiction and Mental Health (CAMH) in Toronto, ON and the Ontario Addiction Treatment Centre (OATC) in North Bay, ON. Vaccine recipients (VRs) were staff, community members, or patients (CAMH);or patients and household members (OATC). HCV outreach workers approached VRs for testing, which was promoted by clinic staff. At OATC, VRs received a $5 coffee card incentive to undergo testing. At both sites, Ab POCT was done by fingerprick (OraQuick) during or after a 15-minute post-vaccine observation period. Results were provided after 5 minutes based on prior data showing this approach detects all viremic individuals (VIRCAN 5-Minute Rule). Dried blood spot (DBS) samples were collected by fingerprick for HCV RNA testing following Ab+ results. Results: CAMH - 2759 individuals received vaccine over 12 days (mean 230/day, range 102-350). 621 (23%) underwent Ab POCT (mean 52/day, range 16-106). The mean age was 46 yrs (range 12-87) and 307 (49%) were male. Staff constituted 55% of tested VRs with a positivity rate of 0% compared to 2.2% in patients/community members. Of 6 Ab+ individuals, 5 DBS samples were collected and 2 were RNA+. One Ab+ individual was counseled by phone to follow up for RNA testing due to a late Ab+ result (20'). OATC - 150 individuals received vaccine over 9 days (mean 17/day, range 11-33). 27 (18%) were recruited for Ab POCT (mean 3/day, range 0-10). The mean age was 37 yrs (range 25-56) and 14 (52%) were male. Seven individuals were known to be Ab+ and DBS samples were collected from each, of which 4 were RNA+. The remaining 20 individuals were all Ab- by POCT. Outreach and linkage to care is ongoing at both sites. Conclusion: Co-localization of HCV testing with COVID-19 vaccination enables reaching and re-engaging populations with a tenuous link to the healthcare system. HCV Ab POCT with the VIRCAN 5-Minute Rule followed by DBS sample collection is a quick, low-barrier approach that enables high throughput and ensures complete diagnosis of HCV.

Immunogenicity and safety of the BNT162B2 mRNA COVID-19 vaccine in adult patients with autoimmune inflammatory rheumatic diseases and general population: A multicenter study

Background: Vaccination represents a cornerstone in mastering the COVID-19 pandemic. Data on immunogenicity, efficacy, and safety of the novel BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases (AIIRD) are limited. Objectives: To investigate the immunogenicity, efficacy, and safety of the BNT162b2 mRNA vaccine in patients with AIIRD compared to the general population. Methods: A prospective multicenter study investigated immunogenicity, efficacy, and safety of the two-dose regimen BNT162b2 mRNA vaccine in adult patients with AIIRD including rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthropathy (axSpA), systemic lupus erythematosus (SLE), connective tissues diseases (CTD), systemic vasculitides, and idiopathic inflammatory myositis (IIM), compared to control subjects without rheumatic diseases or immunosuppressive therapies. Serum IgG antibody levels against SARS-CoV-2 spike S1/S2 proteins were measured 2 -6 weeks after the second vaccine dose. Seropositivity was defined as IgG ≥15 binding antibody units (BAU)/ml. Post-vaccination efficacy defined as post-vaccination COVID-19 infection and safety were assessed. Preand post-vaccination disease activity indices were assessed as appropriate for each disease. Results: A total of 686 AIIRD patients and 121 controls participated into the study. AIIRD patients were significantly older than controls, mean age±SD 56.76±14.88 vs 50.76±14.68, respectively, p<0.0001. A total of 95.2% (n=653) AIIRD patients were treated with immunomodulatory medications. The seropositivity rate was 86% (n=590) in patients with AIIRD compared to 100% in controls (p <0.0001) The level of the S1/S2 antibodies was significantly reduced in AIIRD patients compared to controls (mean± SD 132.9±91.7 vs 218.6±82.06, P<0.0001). In patients with PsA, AxSpA, SLE, and LVV, the seropositive rate was above 90%. In RA, the seropositive rate was 82.1% and the lowest seropositive rate (<40%) was observed in patients with AAV and IIM. Anti-CD20 significantly impaired the vaccine's immunogenicity, with the lowest seropositivity rate of 39%. The use of GC, mycophenolate mofetil (MMF), and abatacept was associated with a significantly lower rate of seropositivity (Figure 1). MTX significantly reduced the seropositivity in patients treated with MTX monotherapy and in combinations with other treatments (92% and 84%, respectively), although at a lesser magnitude than anti-CD20, MMF, and abatacept. More than 97% of patients treated with anti-cytokine therapies including TNFi, interleukin-17 and interleukin-6 inhibitors had an appropriate immunogenic response when used as monotherapy. The combination of TNFi with MTX significantly reduced the rate of seropositivity to 93%, p=0.04. Age over 65 years, a diagnosis of RA, IIM, ANCA-associated vascilitis, and treatment with GC, MMF, anti-CD20, and abatacept were associated with a reduced likelihood of seropositivity. There were no post-vaccination symptomatic cases of COVID-19 among AIIRD patients and one mild case in the control group. Major adverse events in AIIRD patients included death (n=2) several weeks after the second vaccine dose, non-disseminated herpes zoster (n=6), uveitis (n=2), and pericarditis (n=1). Post-vaccination disease activity remained stable in the majority of patients. Conclusion: Vaccination with the BNTb262 vaccine resulted in an adequate immunogenic response with an acceptable safety profile in the majority of patients with AIIRD. Treatment with GC, rituximab, MMF, and abatacept may impair BNT162b2-induced immunogenicity. Postponing administration of rituximab, when clinically feasible, seems to be reasonable to improve vaccine-induced immunogenicity. Holding treatment with abatacept and MMF may be considered on an individual basis.

Disparities in cancer during the COVID-19 pandemic: COVID-19 and cancer outcomes study (CCOS)

Background: The COVID-19 pandemic has rapidly altered cancer care. However, the ways in which it has done so and the associated impact at the individual and societal levels remains poorly defined. Methods: CCOS is a multicenter prospective cohort study designed to define the impact of the pandemic on cancer care delivery and outcomes. The CCOS cohort comprised consecutive outpatients with cancer seen at two US cancer centers from March 2 to March 6, 2020 (index visit). Data was collected at baseline, retrospectively from the preceding 3 months, and prospectively at 3-month follow up. Per patient changes in numbers of visits were compared using Wilcoxon signed rank tests. Correlates of increases in telehealth visits and decreases in in-person visits were evaluated using multivariable logistic regression models. Adjusted Odds ratios [aOR] and 95% confidence intervals (CI) were reported. Results: Of 2365 included patients, 1219 (51.6%) had a decrease in in-person visit frequency during the pandemic period relative to the preceding 3 months. Conversely, 760 (32.2%) had an increased frequency of telehealth visits (decrease in in-person and increase in telehealth visits;both p<0.01). 128 (5.4%) patients developed COVID-19. Compared to White patients, Black and Hispanic patients were less likely to have telehealth visits, had no significant change in frequency of in-person visits, and were more likely to develop COVID-19 (Table). [Formula presented] Conclusions: Significant disruptions to routine cancer care were observed during the pandemic period relative to the prior 3 months. Racial and ethnic barriers to the adoption of telehealth, and related socioeconomic factors, place these vulnerable populations simultaneously at disproportionate risk for decreased cancer-related visits and COVID infection, thereby exacerbating existing racial and ethnic health disparities. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: D. Doroshow: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen;Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim;Honoraria (self), Advisory/Consultancy: Athenaeum Partners;Honoraria (self), Advisory/Consultancy: Boston Healthcare Associates. A.L. Schmidt: Travel/Accommodation/Expenses: Pfizer;Travel/Accommodation/Expenses: Astellas. Z. Bakouny: Non-remunerated activity/ies: Bristol Myers Squibb;Research grant/Funding (self): Genentech/ImCore. M.M. Awad: Advisory/Consultancy, Research grant/Funding (self): Bristol Myers Squibb;Advisory/Consultancy, Research grant/Funding (self): Lilly;Advisory/Consultancy, Research grant/Funding (self): AstraZeneca;Advisory/Consultancy, Research grant/Funding (self): Genentech;Advisory/Consultancy: Merck;Advisory/Consultancy: Achilles;Advisory/Consultancy: AbbVie. R. Haddad: Advisory/Consultancy, Research grant/Funding (self): Bristol Myers Squibb;Advisory/Consultancy, Research grant/Funding (self): Merck;Advisory/Consultancy, Research grant/Funding (self): Pfizer;Advisory/Consultancy, Research grant/Funding (self): Genentech;Advisory/Consultancy, Research grant/Funding (self): AstraZeneca;Advisory/Consultancy, Research grant/Funding (self): GlaxoSmithKline. M.D. Galsky: Shareholder/Stockholder/Stock options: Rappta Therapeutics;Honoraria (self): BioMotiv;Honoraria (self): Janssen;Honoraria (self): Dendreon;Honoraria (self): Merck;Honoraria (self): GlaxoSmithKline;Honoraria (self): Lilly;Honoraria (self): Astellas Pharma;Honoraria (self): Genentech;Honoraria (self): Bristol-Myers Squibb;Honoraria (self): Novartis;Honoraria (self): Pfizer;Honoraria (self): EMD Serono;Honoraria (self): AstraZeneca;Honoraria (self): Seattle Genetics;Honoraria (self): Incyte;Honoraria (self): Alleron Therapeutics;Honoraria (self): Dracen;Honoraria (self): Inovio Pharmaceuticals;Honoraria (self): NuMab;Honoraria (self): Dragonfly Therapeutics;Honoraria (institution): Janssen Oncology;Honoraria (institution): Dendreon;Honoraria (institution): Novartis;Honoraria (institu ion): Bristol-Myers Squibb;Honoraria (institution): Merck;Honoraria (institution): AstraZeneca;Honoraria (institution): Genentech/Roche. T.K. Choueiri: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): AstraZeneca;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Alexion;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Bayer;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): BristolMyersSquibb;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Cerulean;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Eisai;Honoraria (self), Research grant/Funding (self): Foundation Medicine;Honoraria (self), Research grant/Funding (self): Exelixis;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Ipsen;Research grant/Funding (self): 16 Tracon;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Genentech;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Roche;Honoraria (self), Research grant/Funding (self): Roche Products Limited;Honoraria (self), Research grant/Funding (self): Hoffman-LaRoche;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): GlaxoSmithKline;Advisory/Consultancy, Research grant/Funding (self): Lilly;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Merck;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Novartis;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Peloton;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Pfizer;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Prometheus labs;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Corvus;Research grant/Funding (self): Calithera;Research grant/Funding (self): Analysis Group;Honoraria (self), Research grant/Funding (self): Sanofi/Aventis;Research grant/Funding (self): Takeda;Honoraria (self), Advisory/Consultancy: EMD Serono;Honoraria (self), Advisory/Consultancy: UpToDate;Honoraria (self): NCCN;Honoraria (self), Advisory/Consultancy, Dr. Choueiri reports research support from AstraZeneca, Alexion, Bayer, Bristol Myers Squibb/ER Squibb and sons LLC, Cerulean, Eisai, Foundation Medicine Inc., Exelixis, Ipsen, 16 Tracon, Genentech, Roche, Roche Products Limited, F. Hoffmann-La Roche, GlaxoSmithKline, Lilly, Merck, Novartis, Peloton, Pfizer, Prometheus Labs, Corvus, Calithera, Analysis Group, Sanofi/Aventis, Takeda;Honoraria: AstraZeneca, Alexion, Sanofi/Aventis, Bayer, Bristol Myers-Squibb/ER Squibb and sons LLC, Cerulean, Eisai, Foundation Medicine Inc., Exelixis, Genentech, Roche, Roche Products Limited, F. Hoffmann-La Roche, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, EMD Serono, Prometheus Labs, Corvus, Ipsen, Up-to-Date, NCCN, Analysis Group, NCCN, Michael J. Hennessy (MJH) Associates, Inc (Healthcare Communications Company with several brands such as OnClive, PeerView and PER), Research to Practice, L-path, Kidney Cancer Journal, Clinical Care Options, Platform Q, Navinata Healthcare, Harborside Press, American Society of Me: Analysis Group. All other authors have declared no conflicts of interest.