The persistence of anti-Spike antibodies following two SARS-CoV-2 vaccine doses in patients on immunosuppressive therapy compared to healthy controls—a prospective cohort study

The durability of vaccine-induced humoral immunity against SARS-CoV-2 in patients with immune mediated inflammatory diseases (IMIDs) on immunosuppressive therapy is not known. The aim of this study was to compare the persistence of anti-Spike antibodies following two-dose SARS-CoV-2 vaccination between IMID patients and healthy controls and to identify factors associated with antibody decline.publishedVersio

Criterion validity of The International Physical Activity Questionnaire-Short Form (IPAQ-SF) for use in clinical practice in patients with osteoarthritis

Background To tailor physical activity treatment programs for patients with osteoarthritis, clinicians need valid and feasible measurement tools to evaluate habitual physical activity. The widely used International Physical Activity Questionnaire-Short Form (IPAQ-SF) is not previously validated in patients with osteoarthritis. Purpose To assess the concurrent criterion validity of the IPAQ-SF in patients with osteoarthritis, using an accelerometer as a criterion-method. Method Patients with osteoarthritis (n = 115) were recruited at The Division of Rheumatology and Research at Diakonhjemmet Hospital (Oslo, Norway). Physical activity was measured by patients wearing an accelerometer (ActiGraph wGT3X-BT) for seven consecutive days, followed by reporting their physical activity for the past 7 days using the IPAQ-SF. Comparison of proportions that fulfilled physical activity recommendations as measured by the two methods were tested by Pearson Chi-Square analysis. Differences in physical activity levels between the IPAQ-SF and the accelerometer were analyzed with Wilcoxon Signed-Rank Test and Spearman rank correlation test. Bland-Altman plots were used to visualize the concurrent criterion validity for total- and intensity-specific physical activity levels. Results In total, 93 patients provided complete physical activity data, mean (SD) age was 65 (8.7) years, 87% were women. According to the IPAQ-SF, 57% of the patients fulfilled the minimum physical activity recommendations compared to 31% according to the accelerometer (p = 0.043). When comparing the IPAQ-SF to the accelerometer we found significant under-reporting of total physical activity MET-minutes (p = < 0.001), sitting (p = < 0.001) and walking (p < 0.001), and significant over-reporting of moderate-to-vigorous physical activity (p < 0.001). For the different physical activity levels, correlations between the IPAQ-SF and the accelerometer ranged from rho 0.106 to 0.462. The Bland-Altman plots indicated an increased divergence between the two methods with increasing time spent on moderate-to-vigorous intensity physical activity. Conclusion Physical activity is a core treatment of osteoarthritis. Our finding that patients tend to over-report activity of higher intensity and under-report low-intensity activity and sitting-time is of clinical importance. We conclude that the concurrent criterion validity of the IPAQ-SF was weak in patients with osteoarthritis

Osteoarthritis-related walking disability and arterial stiffness-results from a cross-sectional study

OBJECTIVES: To compare 6 minute walking distance (6MWD) in a population-based osteoarthritis (OA) cohort with matched peers from the general population, and to explore the associations between walking ability and CVD risk (arterial stiffness) in the OA cohort.DESIGN: This cross-sectional study included participants (40-80 years) who self-reported OA (n=500) in a population-based study and age- and gender-matched peers from the general population (n=235). Clinical examinations of the OA participants included classification according to the American College of Rheumatology criteria, blood samples and measuring arterial stiffness (pulse wave velocity, PWV). Group differences in 6MWD were calculated with t-tests. The association between walking ability and CVD risk in the OA cohort was explored in multivariate regression models.RESULTS: In age stratified analyses, the largest mean difference in 6MWD was observed in the youngest age groups (40-49 years); the OA group walked 84.6 meters (female; 579.4 m vs 663.9 m, p<0.001) and 88.3 meters (male; 619.9 m vs 708.3 m, p=0.001) shorter than the reference groups, respectively. In the OA group, the 6MWD was significantly associated to PWV in adjusted analysis (p=0.001); 100 m longer walking distance corresponded to 0.3 m/s reduction in arterial stiffness.CONCLUSION: Already from the age of forty, people with OA have significantly shorter mean walking distance compared to matched peers, underlining the importance of early clinical approach to OA. Further, in the OA-group, the 6MWD was significantly associated with arterial stiffness, suggesting that walking ability is important for the CVD risk profile in OA. This article is protected by copyright. All rights reserved

The AktiWeb study: feasibility of a web-based exercise program delivered by a patient organisation to patients with hip and/or knee osteoarthritis

Background Patient organisations may be an under-utilised resource in follow-up of patients requiring long-term exercise as part of their disease management. The purpose of this study was to explore the feasibility of a web-based exercise program delivered by a patient organisation to patients with hip and/or knee osteoarthritis (OA). Methods In this pre–post feasibility study, patients aged 40–80 years with hip and/or knee OA were recruited from Diakonhjemmet Hospital. The 12-week intervention was delivered through a patient organisation’s digital platform. Feasibility was evaluated by proportion of eligible patients enrolled, proportion of enrolled patients who provided valid accelerometer data at baseline, and proportion completing the cardiorespiratory exercise test according to protocol at baseline and completed follow-up assessments. Patient acceptability was evaluated for website usability, satisfaction with the initial exercise level and comprehensibility of the exercise program. Change in clinical outcomes were assessed for physical activity, cardiorespiratory fitness and patient-reported variables. Results In total, 49 eligible patients were identified and 35 were enrolled. Thirty (86%) of these attended baseline assessments and provided valid accelerometer data and 18 (51%) completed the maximal cardiorespiratory exercise test according to protocol. Twenty-two (63%) patients completed the follow-up questionnaire, and they rated the website usability as ‘acceptable’ [median 77.5 out of 100 (IQR 56.9, 85.6)], 19 (86%) reported that the initial exercise level was ‘just right’ and 18 (82%) that the exercise program was ‘very easy’ or ’quite easy’ to comprehend. Improvement in both moderate to vigorous physical activity (mean change 16.4 min/day; 95% CI 6.9 to 25.9) and cardiorespiratory fitness, VO2peak (mean change 1.83 ml/kg/min; 95% CI 0.29 to 3.36) were found in a subgroup of 8 patients completing these tests. Across all patient-reported outcomes 24–52% of the patients had a meaningful improvement (n = 22). Conclusion A web-based exercise program delivered by a patient organisation was found to be feasible and acceptable in patients with hip and/or knee OA. Trial registration ClinicalTrials.gov, NCT04084834 (registered 10 September 2019). The Regional Committee for Medical and Health Research Ethics south-east, 2018/2198. URL: Prosjekt #632074 - Aktiv med web-basert støtte. - Cristin (registered 7 June 2019)

The persistence of anti-Spike antibodies following two SARS-CoV-2 vaccine doses in patients on immunosuppressive therapy compared to healthy controls—a prospective cohort study

Background The durability of vaccine-induced humoral immunity against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressive therapy is not known. The aim of this study was to compare the persistence of anti-Spike antibodies following two-dose SARS-CoV-2 vaccination between IMID patients and healthy controls and to identify factors associated with antibody decline. Methods IMID patients on immunosuppressive medication enrolled in the prospective observational Nor-vaC study were included. Participants received two-dose SARS-CoV-2 vaccination. Serum collected at two time points following vaccination (first assessment within 6–48 days, second within 49–123 days) were analyzed for antibodies binding the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein. Multivariable regression models estimated percent reduction in anti-RBD over 30 days and factors associated with reduction. Results A total of 1108 patients (403 rheumatoid arthritis, 195 psoriatic arthritis, 195 spondyloarthritis, 124 ulcerative colitis, 191 Crohn’s disease) and 134 controls provided blood samples within the defined intervals (median 19 days [IQR 15–24] and 97 days [87–105] after second vaccine dose). Antibody levels were lower in patients compared to controls at both time points, with median anti-RBD 2806 BAU/ml [IQR 1018–6068] in patients and 6187 BAU/ml [4105–7496] in controls (p<0.001) at first assessment, and 608 BAU/ml [IQR 58–1053] in patients and 1520 BAU/ml [979–3766] in controls (p<0.001) at second assessment. At second assessment, low anti-RBD antibody levels (defined as <200 BAU/ml) were found in 449 (41%) patients, and 6 (5%) controls (p<0.001). The change was − 83% in patients and − 66% in controls (p<0.001). Patients had a greater estimated 30 days percent reduction in anti-RBD levels compared to controls − 4.9 (95% CI − 7.4 to − 2.4), (p<0.05). Among therapies, mono- or combination treatment with tumor necrosis factor inhibitors was associated with the greatest decline. Conclusions Within 4 months after vaccination, antibody levels declined considerably in both IMID patients and controls. Patients had lower initial antibody levels and a more pronounced decline compared to healthy controls and were therefore more likely to decline to low antibody levels. These results support that IMID patients need additional vaccine doses at an earlier stage than healthy individuals

Humoral and cellular immune responses to two and three doses of SARS-CoV-2 vaccines in rituximab-treated patients with rheumatoid arthritis: a prospective, cohort study

Background In rituximab-treated patients with rheumatoid arthritis, humoral and cellular immune responses after two or three doses of SARS-CoV-2 vaccines are not well characterised. We aimed to address this knowledge gap. Methods This prospective, cohort study (Nor-vaC) was done at two hospitals in Norway. For this sub-study, we enrolled patients with rheumatoid arthritis on rituximab treatment and healthy controls who received SARS-CoV-2 vaccines according to the Norwegian national vaccination programme. Patients with insufficient serological responses to two doses (antibody to the receptor-binding domain [RBD] of the SARS-CoV-2 spike protein concentration <100 arbitrary units [AU]/mL) were allotted a third vaccine dose. Antibodies to the RBD of the SARS-CoV-2 spike protein were measured in serum 2–4 weeks after the second and third doses. Vaccine-elicited T-cell responses were assessed in vitro using blood samples taken before and 7–10 days after the second dose and 3 weeks after the third dose from a subset of patients by stimulating cryopreserved peripheral blood mononuclear cells with spike protein peptides. The main outcomes were the proportions of participants with serological responses (anti-RBD antibody concentrations of ≥70 AU/mL) and T-cell responses to spike peptides following two and three doses of SARS-CoV-2 vaccines. The study is registered at ClinicalTrials.gov, NCT04798625, and is ongoing. Findings Between Feb 9, 2021, and May 27, 2021, 90 patients were enrolled, 87 of whom donated serum and were included in our analyses (69 [79·3%] women and 18 [20·7%] men). 1114 healthy controls were included (854 [76·7%] women and 260 [23·3%] men). 49 patients were allotted a third vaccine dose. 19 (21·8%) of 87 patients, compared with 1096 (98·4%) of 1114 healthy controls, had a serological response after two doses (p<0·0001). Time since last rituximab infusion (median 267 days [IQR 222–324] in responders vs 107 days [80–152] in non-responders) and vaccine type (mRNA-1273 vs BNT162b2) were significantly associated with serological response (adjusting for age and sex). After two doses, 10 (53%) of 19 patients had CD4+ T-cell responses and 14 (74%) had CD8+ T-cell responses. A third vaccine dose induced serological responses in eight (16·3%) of 49 patients, but induced CD4+ and CD8+ T-cell responses in all patients assessed (n=12), including responses to the SARS-CoV-2 delta variant (B.1.617.2). Adverse events were reported in 32 (48%) of 67 patients and in 191 (78%) of 244 healthy controls after two doses, with the frequency not increasing after the third dose. There were no serious adverse events or deaths. Interpretation This study provides important insight into the divergent humoral and cellular responses to two and three doses of SARS-CoV-2 vaccines in rituximab-treated patients with rheumatoid arthritis. A third vaccine dose given 6–9 months after a rituximab infusion might not induce a serological response, but could be considered to boost the cellular immune response