When Should I Get My Next COVID-19 Vaccine? Data From the Surveillance of Responses to COVID-19 Vaccines in Systemic Immune-Mediated Inflammatory Diseases (SUCCEED) Study.

OBJECTIVE: To determine how serologic responses to coronavirus disease 2019 (COVID-19) vaccination and infection in immune-mediated inflammatory disease (IMID) are affected by time since last vaccination and other factors. METHODS: Post-COVID-19 vaccination, data, and dried blood spots or sera were collected from adults with rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis and spondylarthritis, and psoriasis and psoriatic arthritis. The first sample was collected at enrollment, then at 2 to 4 weeks and 3, 6, and 12 months after the latest vaccine dose. Multivariate generalized estimating equation regressions (including medications, demographics, and vaccination history) evaluated serologic response, based on log-transformed anti-receptor-binding domain (RBD) IgG titers; we also measured antinucleocapsid (anti-N) IgG. RESULTS: Positive associations for log-transformed anti-RBD titers were seen with female sex, number of doses, and self-reported COVID-19 infections in 2021 to 2023. Negative associations were seen with prednisone, anti-tumor necrosis factor agents, and rituximab. Over the 2021-2023 period, most (94%) of anti-N positivity was associated with a self-reported infection in the 3 months prior to testing. From March 2021 to February 2022, anti-N positivity was present in 5% to 15% of samples and was highest in the post-Omicron era, with antinucleocapsid positivity trending to 30% to 35% or higher as of March 2023. Anti-N positivity in IMID remained lower than Canada's general population seroprevalence (> 50% in 2022 and > 75% in 2023). Time since last vaccination was negatively associated with log-transformed anti-RBD titers, particularly after 210 days. CONCLUSION: Ours is the first pan-Canadian IMID assessment of how vaccine history and other factors affect serologic COVID-19 vaccine responses. These findings may help individuals personalize vaccination decisions, including consideration of additional vaccination when > 6 months has elapsed since last COVID-19 vaccination/infection.

COVID-19 Vaccine in Immunosuppressed Adults with Autoimmune rheumatic Diseases (COVIAAD): safety, immunogenicity and antibody persistence at 12 months following Moderna Spikevax primary series.

OBJECTIVE: To assess the safety, immunogenicity and cellular responses following the Moderna Spikevax primary series in rheumatic disease. METHODS: We conducted a 12-month, prospective, non-randomised, open-label, comparative trial of adults with either rheumatoid arthritis (RA, n=131) on stable treatment; systemic lupus erythematosus (SLE, n=23) on mycophenolate mofetil (MMF); other rheumatic diseases on prednisone ≥10 mg/day (n=8) or age-matched/sex-matched controls (healthy control, HC, n=58). Adverse events (AEs), humoral immune responses (immunogenicity: IgG positivity for anti-SARS-CoV-2 spike protein and its receptor binding domain, neutralising antibodies (NAbs)), cellular responses (ELISpot) and COVID-19 infection rates were assessed. RESULTS: Frequency of solicited self-reported AEs following vaccination was similar across groups (HC 90%, RA 86%, SLE 90%); among them, musculoskeletal AEs were more frequent in RA (HC 48% vs RA 66% (Δ95% CI CI 3 to 32.6)). Disease activity scores did not increase postvaccination. No vaccine-related serious AEs were reported. Postvaccination immunogenicity was reduced in RA and SLE (RA 90.2%, SLE 86.4%; for both, ΔCIs compared with HC excluded the null). Similarly, NAbs were reduced among patients (RA 82.6%, SLE 81.8%). In RA, age >65 (OR 0.3, 95% CI 0.1 to 0.8) and rituximab treatment (OR 0.003, 95% CI 0.001 to 0.02) were negative predictors of immunogenicity. ELISpot was positive in 16/52 tested RA and 17/26 HC (ΔCI 11.2-53.3). During the study, 11 HC, 19 RA and 3 SLE patients self-reported COVID-infection. CONCLUSION: In COVID-19 Vaccine in Immunosuppressed Adults with Autoimmune Diseases, the Moderna Spikevax primary series was safe. MMF, RA age >65 and rituximab were associated with reduced vaccine-induced protection.

High Frequency of COVID-19 Vaccine Hesitancy among Canadians Immunized for Influenza: A Cross-Sectional Survey.

We assessed the frequency and correlates of COVID-19 vaccine hesitancy before Canada's vaccine rollout. A cross-sectional vaccine hesitancy survey was completed by consecutive patients/family members/staff who received the influenza vaccine at McGill University affiliated hospitals. Based on the self-reported likelihood of receiving a future vaccine (scale 0-10), the following three groups were defined: non-hesitant (score 10), mildly hesitant (7.1-9.9), and significantly hesitant (0-7). Factors associated with vaccine hesitancy were assessed with multivariate logistic regression analyses and binomial logistic regression machine learning modelling. The survey was completed by 1793 people. Thirty-seven percent of participants (n = 669) were hesitant (mildly: 315 (17.6%); significantly: 354 (19.7%)). Lower education levels, opposition and uncertainty about vaccines being mandatory, feelings of not receiving enough information about COVID-19 prevention, perceived social pressure to get a future vaccine, vaccine safety concerns, uncertainty regarding the vaccine risk-benefit ratio, and distrust towards pharmaceutical companies were factors associated with vaccine hesitancy. Vaccine safety concerns and opposition to mandatory vaccinations were the strongest correlates of vaccine hesitancy in both the logistic regressions and the machine learning model. In conclusion, in this study, over a third of people immunized for influenza before the COVID-19 vaccine rollout expressed some degree of vaccine hesitancy. Effectively addressing COVID-19 vaccine safety concerns may enhance vaccine uptake.

Safety and Efficacy of Influenza Vaccination in Patients Receiving Immune Checkpoint Inhibitors. Systematic Review with Meta-Analysis.

The potential increased risk of immune-related adverse events (irAEs) post-influenza vaccine is a concern in patients receiving immune checkpoint inhibitors (ICI). We conducted a systematic review with meta-analysis of studies reporting the effects of influenza vaccination in patients with cancer during ICI treatment. We searched five electronic databases until 01/2022. Two authors independently selected studies, appraised their quality, and collected data. The primary outcome was the determination of pooled irAE rates. Secondary outcomes included determination of immunogenicity and influenza infection rates and cancer-related outcomes. Nineteen studies (26 publications, n = 4705) were included; 89.5% were observational. Vaccinated patients reported slighter lower rates of irAEs compared to unvaccinated patients (32% versus 41%, respectively). Seroprotection for influenza type A was 78%-79%, and for type B was 75%. Influenza and irAE-related death rates were similar between groups. The pooled proportion of participants reporting a laboratory-confirmed infection was 2% (95% CI 0% to 6%), and influenza-like illness was 14% (95% CI 2% to 32%). No differences were reported on the rates of laboratory-confirmed infection between vaccinated and unvaccinated patients. Longer progression-free and overall survival was also observed in vaccinated compared with unvaccinated patients. Current evidence suggests that influenza vaccination is safe in patients receiving ICIs, does not increase the risk of irAEs, and may improve survival.

Training Physicians in Motivational Communication to Address Influenza Vaccine Hesitation: A Proof-of-Concept Study.

BACKGROUND: Strategies to support health care professionals on how to address vaccine hesitancy are needed. METHODS: We developed a 4-h Motivational Communication (MC) training program tailored to help physicians address hesitancy related to influenza vaccination among patients living with rheumatoid arthritis. Five MC competencies were evaluated at baseline and post-training with a standardized patient using the Motivational Interviewing Treatment Integrity [MITI] scale. Adherence to MC during clinical consultations and changes in vaccine intentions was measured as secondary outcomes. RESULTS: Seven rheumatology physicians participated in the training. MITI scores increased in all participants, and 71% (n = 5) achieved thresholds of clinical competency (i.e., ≥3.5/5 at MITI global score and ≥3/5 on at least 3 individual competency score) post-training. Autonomy/support and empathy competencies reached competency thresholds (+2.4 ± 1.3 to +4.1 ± 0.7 and +2.1 ± 0.7 to +4.1 ± 0.7, respectively). Evocation and collaboration competencies improved but without reaching competency thresholds (+1.4 ± 0.8 to +3.1 ± 1.1; +1.4 ± 0.8 to +2.9 ± 1.1, respectively). Direction did not improve. Among 21 patient consultations post-training, 15 (71%) were MC-consistent. Of the 15 patients, 67% (10/15) intended to receive the influenza vaccine and 33% (5/15) received it. CONCLUSION: A brief MC training program targeting vaccine hesitancy increased MC competency among rheumatology physicians and promoted behavioral change among patients.

Influenza Vaccine Hesitancy and Its Determinants Among Rheumatology Patients.

OBJECTIVE: Patients with rheumatic disease (RD) have an increased risk of influenza and its complications. Despite inactivated influenza vaccine (IIV) recommendations, IIV uptake in patients with RD is suboptimal, a problem of increasing importance in the COVID-19 era. We estimated the frequency of IIV hesitancy and associated factors among Canadian patients with RD. METHODS: A cross-sectional vaccine hesitancy survey was completed by rheumatology clinic patients (November 2019 to January 2020). Patients rated their likelihood of receiving the influenza vaccine (scale of 0-10). We categorized these as follows: likely to refuse (scale of 0-2), uncertain (scale of 3-7), or likely to accept (scale of 8-10). Multivariate logistical regression was used to evaluate factors associated with vaccine hesitancy. RESULTS: A total of 282 patients (63.5% of those approached) completed the survey, with 165 (58.5%) being likely to accept, 67 (23.8%) being likely to refuse, and 50 (17.7%) uncertain. Uncertain patients were younger and more likely to be employed than those in the other two groups. No previous influenza vaccination (odds ratio [OR] 36.6, 95% confidence interval [CI] 5.3-252.9), belief that vaccination should not be mandatory (OR 0.1, 95% CI 0.0-0.7), unwillingness to take time off work to be vaccinated (OR 6.8, 95% CI 1.5-30.6), and distrust in pharmaceutical companies (OR 41.0, 95% CI 5.6-301.5) predicted likeliness to refuse. Reluctance to pay for vaccination (OR 2.8, 95% CI 1.1-7.5) and no previous influenza vaccination (OR 18.9, 95% CI 3.3-109.7) predicted uncertainty. CONCLUSION: More than 40% of rheumatology patients are either likely to refuse or uncertain about receiving IIV. This contributes to suboptimal vaccine coverage in this population. Interventions addressing these concerns are needed, particularly in the COVID-19 era.

Barriers and facilitators to influenza and pneumococcal vaccine hesitancy in rheumatoid arthritis: a qualitative study.

OBJECTIVES: Immunization is an essential component of RA care. Nevertheless, vaccine coverage in RA is suboptimal. Contextual, individual and vaccine-related factors influence vaccine acceptance. However, barriers and facilitators of vaccination in RA are not well defined. The aim of this study was to assess perspectives of RA patients and healthcare professionals (HCPs) involved in RA care of barriers and facilitators regarding influenza and pneumococcal vaccines. METHODS: Eight focus groups (four with RA patients and four with HCPs) and eight semi-structured open-ended individual interviews with vaccine-hesitant RA patients were conducted. Data were audio recorded, transcribed verbatim and imported to MAXQDA software. Analysis using the framework of vaccine hesitancy proposed by the Strategic Advisory Group of Experts on Immunization was conducted. RESULTS: RA patients and HCPs reported common and specific barriers and facilitators to influenza vaccination that included contextual, individual and/or group and vaccine- and/or vaccination-specific factors. A key contextual influence on vaccination was patients' perception of the media, pharmaceutical industry, authorities, scientists and the medical community at large. Among the individual-related influences, experiences with vaccination, knowledge/awareness and beliefs about health and disease prevention were considered to impact vaccine acceptance. Vaccine-related factors including concerns about vaccine side effects such as RA flares, the safety of new formulations, the mechanism of action, access to vaccines and costs associated with vaccination were identified as actionable barriers. CONCLUSION: Acknowledging RA patients' perceived barriers to influenza and pneumococcal vaccination and implementing specific strategies to address them might increase vaccination coverage in this population.

Systematic review of recommendations on the use of methotrexate in rheumatoid arthritis.

OBJECTIVE: Most recommendations for the use of methotrexate (MTX) in rheumatoid arthritis (RA) are issued by developed countries. It is unknown whether they are relevant globally. We reviewed existing recommendations on the use of MTX for the treatment of RA and summarized areas of agreement that could be relevant for least developed countries (LDCs). METHODS: Electronic databases and registries were searched for recommendations on MTX use in RA, duplicates were eliminated, and the most updated version adopted when there were several versions on the same recommendation. Reviewers used the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument for study quality assessment. Similarities and discrepancies of recommendations are reported. RESULTS: After deduplication, 1693 unique citations were found; 25 full texts were screened and 12 included in the narrative synthesis. Average scores for the AGREE II domains ranged from 33.3 to 83.3%. Recommendations targeted rheumatologists and health care providers involved in RA care. Most covered some but not all of the following areas: baseline "pre-MTX" assessment (7/12;58%), prescription of MTX (10/12;83.3%), management of MTX side effects (6/12;50%), and special considerations (e.g., peri-operative management) (8/12; 66.7%). Recommendations agreed on baseline tests prior to starting MTX, monitoring, and need for folic acid supplementation. These aspects can serve as the foundation for the development of MTX recommendations relevant to LDCs. Recommendations disagreed on the MTX starting dose, optimal route, titration, and intervals to monitor toxicity. CONCLUSION: Existing recommendations do not uniformly address all aspects related to the use of MTX and disagree in relevant aspects of MTX use. Adaptations to these recommendations are needed to facilitate their implementation in LDCs. Key Points • This paper summarizes current recommendations on the use of methotrexate for the treatment of rheumatoid arthritis. • Areas of agreement between recommendations include the following: pre-methotrexate patient assessment, need for folic acid supplementation, and toxicity monitoring. • Areas of disagreement relate to methotrexate starting and maximal dose, titration, and frequency of assessments.

A multimodal intervention increases influenza vaccine uptake in rheumatoid arthritis.

Annual influenza vaccination is recommended for patients with rheumatoid arthritis (RA), but coverage is suboptimal. We assessed the impact of an implementation strategy in enhancing vaccination uptake in RA. We evaluated a multimodal implementation strategy at rheumatology clinics that included 3 approaches: patient recalls, a nurse providing vaccines, and physician reminders. We compared patient-reported vaccination rates after implementation with those reported before the implementation strategy in a nonequivalent control group. In multivariate analyses, we assessed factors potentially associated with influenza vaccine uptake. One hundred and sixteen RA patients were vaccinated during the intervention. The influenza vaccination rate in RA increased from 48.5% (65/136) before implementation to 62.6% (67/107) after implementation (difference of 14.1, 95% CI 1.5, 26.1). In multivariate analyses, older age, biologics use, and physician recommendation for vaccination were associated with influenza vaccine uptake. A multimodal intervention was associated with increased influenza vaccine coverage among RA patients. Older patients and those on biologics were more likely to be immunized against influenza. Physician's recommendations are important to promote vaccine coverage. Key Points • Despite current recommendations, influenza vaccine uptake among rheumatoid arthritis (RA) patients is suboptimal. • A multimodal implementation strategy facilitating access to influenza vaccine and raising awareness through vaccination reminders improved immunization uptake in RA. • Physicians play a key role in promoting annual seasonal influenza vaccination. • The reasons for vaccine hesitancy in RA should be addressed to reach a vaccination target of 80% required to reduce the burden of this preventable infection.