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BackgroundVaccination remains essential in preventing morbidity of SARS-CoV-2 infections. We previously showed that >10mg/day prednisolone and methotrexate use were associated with reduced antibody concentrations four weeks after primary vaccination in patients with giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) [1].ObjectivesHere, we performed a follow-up study to measure the decay of antibody concentrations over time and the immunogenicity of SARS-CoV-2 booster vaccination.MethodsGCA/PMR patients included in the primary vaccination (BNT162b2 or ChAdOx1) study were asked again to donate blood samples six months after primary vaccination (n=24) and one month after booster vaccination (n=46, BNT162b2 or mRNA1273). Data were compared to that of age-, sex-, and vaccine-matched controls (n=58 and n=42, respectively).ResultsAntibody concentrations decreased faster over time in GCA/PMR patients than in controls, but this decrease was not associated with treatment during primary vaccination. Post-booster antibody concentrations were comparable between patients and controls. Antibody concentrations post booster vaccination associated strongly with antibody concentrations post primary vaccination, but not with treatment during booster vaccination. However, the fold-change of post-booster vaccination showed a slight negative correlation with the post-primary vaccine antibodies.ConclusionThese results indicate that patients with impaired vaccine responses after primary vaccination, have slightly stronger increases in humoral immunity after booster vaccination, but this is not enough to reach a similar protection. The decrease in humoral immunity, and subsequent increase after booster vaccination, is likely not impacted by prednisolone or methotrexate treatment. Rather, these treatments put the patients at an immunogenic disadvantage during primary SARS-CoV-2 vaccination, which is not fully repaired by a single booster vaccination. This longitudinal study in GCA/PMR patients stresses the importance of repeat booster vaccination for patients that used >10mg/day prednisolone or methotrexate during primary vaccination.Reference[1]van Sleen Y, van der Geest, Kornelis SM, Reitsema RD, Esen I, Terpstra JH, Raveling-Eelsing E, et al. Humoral and cellular SARS-CoV-2 vaccine responses in patients with giant cell arteritis and polymyalgia rheumatica. RMD open 2022;8(2):e002479.Figure 1.Acknowledgements:NIL.Disclosure of InterestsYannick van Sleen: None declared, Kornelis van der Geest Speakers bureau: Speaker fees from Roche, Grant/research support from: Grant support from Abbvie, Annemarie Buisman: None declared, Maria Sandovici: None declared, Debbie van Baarle: None declared, Elisabeth Brouwer: None declared.
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Background: People with multiple sclerosis (MS) are a vulnerable group for severe COVID-19, particularly those taking immunosuppressive disease-modifying therapies (DMTs). Objective(s): To assess characteristics of COVID-19 severity in an international sample of people with MS, including hospitalisation, ICU admission, requiring artificial ventilation, and death. Method(s): Data from 12 data-sources in 28 countries were aggregated. Demographic and clinical covariates were queried, alongside COVID-19 clinical severity outcomes, hospitalisation, admission to ICU, requiring artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/ confirmed COVID-19 using multilevel mixed-effects logistic regression. Result(s): 657 (28.1%) with suspected and 1,683 (61.9%) with confirmed COVID-19. Older age, progressive MS-phenotype, and higher disability associated with worse COVID-19 outcomes. Ocrelizumab and rituximab associated with hospitalisation (aOR=1.75,95%CI=1.29-2.38;aOR=2.76,95%CI=1.87-4.07) and ICU admission (aOR=2.55,95%CI=1.49-4.36;aOR=4.32, 95%CI=2.27-8.23) vs pooled-other-DMTs but only rituximab with artificial ventilation (aOR=6.15,95%CI=3.09-12.27). Similar associations seen compared to dimethyl fumarate and to natalizumab. No associations observed between DMTs and death. Conclusion(s): Using the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of rituximab and ocrelizumab with worse COVID-19, suggesting their use may be a risk factor for more severe COVID-19.
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Objectives Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are overlapping autoinflammatory diseases affecting people over 50 years. The diseases are treated with immunosuppressive drugs such as prednisolone, methotrexate, leflunomide and tocilizumab. In this study, we assessed the immunogenicity and safety of SARS-CoV-2 vaccinations in these diseases (based on humoral and cellular immunity). Methods Patients (n=45 GCA, n=33 PMR) visited the outpatient clinic twice: pre-vaccination and 4 weeks after the second dose (BNT162b2 or ChAdOx1 vaccine). Patients with previous SARS-CoV-2 infection were excluded. In both pre-vaccination and post-vaccination samples, anti-Spike antibody concentrations were assessed and compared with age-, sex-and vaccine-matched control groups (n=98). In addition, the frequency of SARS-CoV-2 Spike-specific T-cells was assessed by IFN-gammaELIspot assay, and side effects and disease activity were recorded. Results GCA/PMR patients did not have reduced antibody concentrations compared with controls. However, linear regression analysis revealed a significant association of methotrexate and >10 mg/day prednisolone use with lower antibody concentrations in GCA/PMR patients. Evidence of cellular immunity, as assessed by ELIspot assay, was found in 67% of GCA/PMR patients. Patients using >10 mg/day prednisolone had reduced cellular immunity. Importantly, vaccination did not lead to significant side effects or changes in disease activity. Conclusions SARS-CoV-2 vaccination was safe for GCA/PMR patients and immunogenicity was comparable to other older individuals. However, patients using methotrexate and particularly >10 mg/day prednisolone did show lower vaccine responses, which corroborates findings in other autoinflammatory patient populations. These patients may therefore be at higher risk of (potentially even severe) breakthrough SARS-CoV-2 infection. Copyright ©
ABSTRACT
Background: Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are overlapping autoinfammatory diseases affecting people over 50 years. The diseases are treated with immunosuppressive drugs such as prednisolone, metho-trexate, lefunomide and tocilizumab. Even though GCA and PMR patients have a substantially higher risk for infections, little is known about humoral and cellular immune responses after vaccination in these patients. Objectives: In this study we assessed the immunogenicity and safety of SARS-CoV-2 vaccinations in these diseases. Methods: Patients (n=45 GCA, n=33 PMR) visited the outpatient clinic twice: pre-vaccination and 4 weeks post-vaccination (BNT162b2 or ChAdOx1 vaccine). Patients with previous SARS-CoV-2 infection were excluded. In both pre-and post-vaccination samples, anti-Spike antibody concentrations were assessed and compared to age-, sex-and vaccine-matched control groups (n=98). In addition, the frequency of SARS-CoV-2 Spike-specifc T-cells was assessed by IFN-γ ELIspot assay, and side-effects and disease activity were recorded. Results: The GCA/PMR patients, as a group, did not have reduced antibody concentrations compared to controls. However, linear regression analysis revealed a signifcant association of methotrexate and >10mg/day prednisolone use with lower antibody concentrations in GCA/PMR patients. Evidence of cellular immunity, as assessed by ELIspot assay, was found in 67% of GCA/PMR patients, and was correlated with humoral immunity (Figure 1). Patients using >10mg/day prednisolone had reduced cellular immunity. Importantly, vaccination did not lead to signifcant side-effects or changes in disease activity. Conclusion: SARS-CoV-2 vaccination was safe for GCA/PMR patients and immunogenicity was comparable to other older individuals. However, patients using methotrexate and particularly >10mg/day prednisolone did show lower vaccine responses, which corroborates fndings in other autoinfammatory patient populations. These patients may therefore be at higher risk of (potentially even severe) breakthrough SARS-CoV-2 infection.
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Background: As the COVID-19 pandemic continues, evidencebased clinical guidance for managing the care of people with multiple sclerosis (MS) is an ongoing concern. In recent months, data from cohorts of people with MS has indicated that certain demographic and clinical characteristics, including use of some disease- modifying therapies (DMTs), leads to worse outcomes from SARS-CoV-2 infection. The COVID-19 in MS global data sharing initiative, which now includes over 4,500 confirmed COVID- 19 cases in people with MS, gives the opportunity to corroborate previous findings with greater certainty. Methods: Clinician-reported data from 32 countries were aggregated into a dataset of 5,543 patients who had suspected or confirmed COVID-19. Demographic and clinical covariates were queried, alongside COVID-19 clinical severity outcomes. These outcomes (hospitalisation, admission to ICU, requiring artificial ventilation, and death) were assessed in patients with suspected/ confirmed COVID-19 using multilevel mixed-effects logistic regression. All models were corrected for age, sex, EDSS, and MS type. DMTs were individually compared to glatiramer acetate (GA), as well as to pooled other DMTs and natalizumab. Results: Of 5,543 patients in the clinician-reported dataset, 909 with suspected and 4,634 with confirmed COVID-19 were included in the analysis. Previous demographic findings were confirmed: male sex, older age, progressive MS, and higher disability were associated with worse outcomes from SARS-CoV-2 infection. Use of anti-CD20 DMTs (ocrelizumab and rituximab) was associated with worse COVID-19 outcomes. Compared to GA, ocrelizumab and rituximab were associated with increased risk of hospitalisation (aOR=1.61(95%CI=1.06-2.43);aOR=2.42(95%CI=1.54-3.81) and ICU admission (aOR=3.13(95%CI=1.22-8.00);aOR=4.46 (95%CI=1.64-12.09)). Rituximab was associated with increased risk of artificial ventilation (aOR=3.57(95%CI=1.38-9.20));ocrelizumab showed a positive trend (aOR=1.86(95%CI=0.76-4.55). Rituximab showed a positive trend with increased risk of death (aOR=2.74(95%CI=0.68-11.09). Associations persisted on restriction to confirmed COVID-19 cases. Conclusions: Analysing the largest international real world dataset of people with MS who have suspected or confirmed COVID- 19 confirms previous findings that male sex, older age, progressive MS, higher disability, the use of anti-CD20 medication (ocrelizumab and rituximab) are associated with worse COVID-19 outcomes.
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Background: Early diagnosis and management of patients with inflammatory arthritis(IA) are critical to improve long-term patient-outcomes. Assessment of joint swelling at joint examination is the reference of IA-identification;early access clinics are constructed to promote this early recognition of IA. However, due to the COVID-19 pandemic the face-to-face capacity of such services is severely reduced. The accuracy of patient-reported swelling in comparison to joint examination has been extensively evaluated in established RA (ρ 0.31-0.67), but not in patients suspected for IA.[1] Objectives: To promote evidence based care in the era of telemedicine, we determined the accuracy of patient-reported joint swelling for actual presence of IA in persons suspected of IA by general practitioners(GP). Methods: Data from two Dutch Early Arthritis Recognition Clinics were studied. These are screening clinics (1.5-lines-setting) where GPs send patients in case of doubt on IA. At this clinic patients were asked to mark the presence of swollen joints on a mannequin with 52 joints. For this study the DIP joints and the metatarsal joints were excluded and, therefore, a total of 42 joints were assessed for self-reported joint swelling. Clinically apparent IA of ≥1 joint determined by the physician was the reference to calculate sensitivity, specificity, positive and negative likelihood ratios (LR+,LR-), and positive and negative predictive values (PPV, NPV) on patient-level. Pearson correlation coefficients(ρ) were determined. Predictive values depend on the prevalence of a disease in a population. Because the prevalence of IA in a 1.5-lines-setting will differ from a primary care setting, post-test probabilities of IA were estimated for two lower prior-test probabilities as example, namely 20% (estimated probability in patients GPs belief IA is likely) and 2% (prior-test probability with less preselection by GPs), using likelihood ratios and nomograms. Results: A total of 1637 consecutive patients were studied. Median symptom duration was 13 weeks. 76% of patients marked ≥1swollen joint at the mannequin. 41% of patients had ≥1swollen joint at examination by rheumatologists. ρ was 0.20(patient-level)-0.26(joint-level). The sensitivity of patients-reported joint swelling was high, 87%, indicating that the majority of patients with IA had marked swelling on the mannequin. However the specificity was 31%, indicating that 69% of persons without IA had also done so. The LR+ was 1.25;the LR-0.43. The PPV was 46%, the NPV 77%. Thus the PPV increased hardly (from 41% to 46%) and the NPV somewhat (from 59% to 77%). Also in settings with prior-test probabilities of 20% and 2%, estimated PPVs (from respectively 20% and 2% to 24% and 2%) and NPVs (from respectively 80% and 98% to 90% and 99%) hardly increased. Conclusion: Patient-reported joint swelling had little value in distinguishing patients with/without IA for different prior-test probabilities, and is less valuable in comparison to self-reported flare detection in established RA.