Objective. To establish the test–retest reproducibility of performance measures of physical function based on the Bath Ankylosing Spondylitis Functional Index (BASFI) questionnaire in patients with AS. Methods. Data were obtained from 65 AS patients. They were tested on two occasions by one assessor with a 1-week interval. Physical function was assessed via eight performance measures based on items used in the BASFI questionnaire, representing activities of daily life, which AS patients frequently report to be problematic. For each activity, a performance score was determined. Pain and exertion were measured using a 10-cm horizontal visual analogue scale (VAS) and Borg's modified scale, respectively. Test–retest reproducibility was assessed for all measurements using intraclass correlation coefficients (ICCs) and by calculating the standard error of measurement (SEM). Results. Adequate intrarater reliability was found. For performance scores, ICCs ranged from 0.73 to 0.96. Measurements of exertion and pain also showed adequate intrarater reliability, with the exception of one performance measure, namely the test for the ability to look over one's shoulder. For this test, the ICCs were 0.66 and 0.69 for exertion and pain, respectively. The remaining ICCs for exertion ranged from 0.71 to 0.88 and for pain from 0.74 to 0.83. The SEM for performance scores ranged from 4 to 9% of the observed score. The SEM for exertion ranged from 8 to 11% and for pain from 10 to 15%. Conclusions. Performance measures of physical function based on the BASFI questionnaire have adequate to excellent test–retest reproducibility. Due to the presence of measurement error, measurements are accurate for group assessment; repeated measurements are advised for an adequate assessment of individual patients.
Summary In the Netherlands, four low molecular weight heparins (dalteparin, enoxaparin, nadroparin and tinzaparin) are available on the market. This strengthens the need for a rational selection of the best low molecular weight heparin for formulary purposes. The available low molecular weight heparins were evaluated by means of the System of Objectified Judgement Analysis (SOJA) method. Separate scores were made for prophylaxis in orthopaedic surgery, non-orthopaedic surgery and for the treatment of deep venous thrombosis (DVT). The following selection criteria were used (relative weight): approved indications (20); number of formulations (60); variability of the AUC (20); drug interactions (60); clinical efficacy (295); side effects (220); dosage frequency (115); acquisition cost (110); and documentation (100). Despite many differences in their physicochemical properties, few major clinically relevant differences are observed between the various low molecular weight heparins. Overall, dalteparin shows the highest scores for all indications, mainly due to its good documentation and the large number of available formulations. The differences are small in comparison with other SOJA scores. No relevant differences between the drugs are apparent for the major criteria, such as clinical efficacy, tolerability and drug interactions; the only major differences between the drugs are observed in the extent of clinical documentation. In general, dalteparin and enoxaparin are better documented than nadroparin or tinzaparin. The differences in acquisition cost are generally limited.
We thank Marotte et al for their interest in our study and for presenting their own recent study. The Spacing of TNF-blocker injections in Rheumatoid ArthritiS Study (STRASS) results on drug concentrations are highly valuable, as this is a large, pragmatic, randomised trial. Marotte et al found that high drug concentrations were related to lower relapse rates after 6 months of tapering.1 This is in line with our study, where we found that patients with high adalimumab concentrations could safely reduce the dose.2
In the STRASS study, 39% of the patients discontinued the biologic disease-modifying antirheumatic drugs (bDMARDs) successfully.3 These patients, apparently, did not need the drug anymore, suggesting that …
Abstract Background The type I interferon (IFN) gene signature is present in a subgroup of patients with early rheumatoid arthritis (RA). Protein levels of IFNα have not been measured in RA and it is unknown whether they associate with clinical characteristics or treatment effect. Methods Patients with early untreated RA (n = 347) were randomized to methotrexate combined with prednisone, certolizumab-pegol, abatacept, or tocilizumab. Plasma IFNα protein levels were determined by single molecular array (Simoa) before and 24 weeks after treatment initiation and were related to demographic and clinical factors including clinical disease activity index, disease activity score in 28 joints, swollen and tender joint counts, and patient global assessment. Results IFNα protein positivity was found in 26% of the patients, and of these, 92% were double-positive for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). IFNα protein levels were reduced 24 weeks after treatment initiation, and the absolute change was similar irrespective of treatment. IFNα protein positivity was associated neither with disease activity nor with achievement of CDAI remission 24 weeks after randomization. Conclusion IFNα protein positivity is present in a subgroup of patients with early RA and associates with double-positivity for autoantibodies but not with disease activity. Pre-treatment IFNα positivity did not predict remission in any of the treatment arms, suggesting that the IFNα system is distinct from the pathways of TNF, IL-6, and T-cell activation in early RA. A spin-off study of the NORD-STAR randomized clinical trial, NCT01491815 (ClinicalTrials), registered 12/08/2011, https://clinicaltrials.gov/ct2/show/NCT01491815 .
### Learning objectives
Immune-mediated inflammatory diseases (IMIDs) comprise a wide range of conditions of which rheumatoid arthritis (RA), spondyloarthritis (SpA) and inflammatory bowel disease (IBD; ie, Crohn’s disease and ulcerative colitis) are most common (table 1, table 2). SpA consists of a range of diseases, including ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, spondylitis associated with IBD and undifferentiated SpA.1 As data regarding cardiovascular disease (CVD) risk are mainly available for RA, AS, PsA, severe psoriasis and IBD, we will focus on these conditions.
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Table 1
Main characteristics of the most common immune-mediated inflammatory diseases
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Table 2
Glossary
IMIDs are associated with increased mortality when compared with the general population (table 1). Reported standardised mortality ratios (SMRs) range from 0.9 to 2.7 for RA, from 1.6 to 1.9 for SpA, and from 1.2 to 1.5 for IBD.2 3 Majority of these excess deaths are caused by CVD, at least in patients with RA and SpA.4 A meta-analysis of 14 observational studies, including 40 000 patients with RA, showed an age-adjusted and sex-adjusted relative risk (RR) of 1.48 (95% CI 1.36 to 1.62) for a first CVD event, mainly driven by an increased risk of myocardial infarction (MI) and stroke.5 The available studies report an HR of 1.36 (95% CI 1.13 to 1.65) in patients with AS and 1.24 (95% CI 1.03 to 1.49) in patients with PsA for major atherosclerotic events after adjustment for traditional cardiovascular (CV) risk factors.6 …
Background: Research on the disease severity of COVID-19 in patients with rheumatic immune-mediated inflammatory diseases (IMIDs) has been inconclusive, and long-term prospective data on the development of SARS-CoV-2 antibodies in these patients are lacking. We conducted an investigator-driven prospective cohort study to compare the disease severity of COVID-19, and the development of SARS-CoV-2 antibodies over time between patients with rheumatic IMIDs and healthy controls.Methods: Adult patients with rheumatic IMIDs from the Amsterdam Rheumatology & immunology Center, Amsterdam were invited to participate. All patients were asked to recruit their own sex- and age-matched control subject. We developed a new platform for collecting clinical data in large patient groups with online questionnaires (at baseline, and after 1-4 and 5-9 months of follow-up). Serum samples were collected two times during follow-up; after completing the follow-up questionnaires and prior to COVID-19 vaccination. All serum samples were analyzed for the presence of SARS-CoV-2 specific antibodies with a total-antibody bridging ELISA. IgG titers were quantified in samples with a positive test result in the bridging assay. Logistic regression analyses, and linear and logistic mixed model analyses were used to compare COVID-19 related hospitalization rates, proportions of SARS-CoV-2 seropositivity and IgG antibody titers between patients and controls, and between patients stratified for major immunosuppressive drug categories (i.e. biological [b] or conventional synthetic [cs] disease modifying anti-rheumatic drugs [DMARDs]).Findings: In total, 3080 consecutive patients and 1102 healthy controls with comparable age and sex distribution were included for analyses. The incidence of COVID-19 was slightly lower in patients compared to controls (14.7% vs. 16.0% had detectable SARS-CoV-2 antibodies), but patients were more frequently hospitalized compared to controls; 23 of 347 (7%) patients vs. 1 of 134 (0.7%) controls (adjusted OR: 7.33, 95% CI: 0.96 – 55.77, P 0.055). Three (13%) of 23 patients were admitted to the intensive care unit (ICU), and one of these died. Only treatment with B-cell targeting therapy was independently associated with an increased risk of COVID-19 related hospitalization (adjusted OR: 14.62, 95% CI: 2.31 – 92.39, P 0.004). Proportions of SARS-CoV-2 seropositivity in participants with a PCR confirmed COVID-19 diagnosis were similar for patients and controls ( P 0.73), and did not significantly decrease during the first twelve months after infection ( P 0.10). IgG antibody titers were higher in hospitalized patients compared to non-hospitalized patients, and slowly declined with time (rate per month: 0.86, 95% CI: 0.81 – 0.91, P < 0.0001) in similar patterns for patients in all treatment subgroups and controls.Interpretation: We observed that patients with rheumatic IMIDs, especially those treated with B-cell targeting therapy, were more likely to be hospitalized when infected with SARS-CoV-2, although subsequent ICU admissions and/or death were infrequent. In addition, treatment with cs- or bDMARDs other than B-cell targeting agents is unlikely to have negative effects on the development of long-lasting humoral immunity against SARS-CoV-2.Funding Information: ZonMw and Reade Foundation.Declaration of Interests: None to declare. Ethics Approval Statement: The research protocol was approved by the medical ethical committee of the VU University medical center (registration number 2020.169). All participants gave written informed consent.
Objective To assess the effects of treatment with antitumour necrosis factor (TNF) agents, methotrexate, or other non-biological disease-modifying antirheumatic drugs (DMARDs) on cardiovascular event risks among patients with rheumatoid arthritis (RA). Methods We conducted a retrospective study using data from the MarketScan claims database. Patients with RA with ≥1 prescription for an index drug were included. Each patient's use of an index drug was calculated cumulatively as a time-varying exposure. The incidence of cardiovascular events among patients with RA was determined. Associations between drug exposures and occurrence of cardiovascular events were assessed with Cox proportional hazards models. Results Of 113 677 patients identified, 35.8%, 41.1% and 23.1% received anti-TNF agents, methotrexate and other DMARDs, respectively. Patients were treated for an average of 7.6 months; 2138 patients (1.9%) had a cardiovascular event following their index prescription. Each additional 6 months of anti-TNF therapy use versus non-use reduced the risk (HR; 95% CI) for any cardiovascular event by 12% (0.88; 0.81 to 0.95, p=0.002). Anti-TNF therapy was associated with a 13% and 12% reduction in cardiovascular events in patients aged ≥50 years (0.87; 0.80 to 0.95, p=0.002) and in those without prior methotrexate use (0.88; 0.78 to 0.99, p=0.04), respectively. Cumulative use of 1, 2 or 3 years of anti-TNF therapy versus non-use is expected to reduce cardiovascular event risks by 21%, 38% and 51%, respectively. Conclusions Anti-TNF therapy was associated with a significantly lower risk of cardiovascular events among patients with RA, older patients with RA and patients without prior exposure to methotrexate.
Objective To establish the 3-year outcome and course of physical functioning and spinal mobility impairments in patients routinely treated with tumor necrosis factor inhibitors (TNFi) and to find predictors of physical functioning and spinal mobility impairments. Methods Ankylosing spondylitis (AS) patients eligible for TNFi were followed in a 3-year prospective observational study. Prediction models were developed with linear mixed modeling. Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI) were used as outcome measures for physical functioning and spinal mobility. Results A total of 257 patients were included and treated with etanercept (n = 174) or adalimumab (n = 83). Physical functioning improved significantly during the first 6 months after the start of TNFi. The BASFI score decreased from mean ± SD 5.4 ± 2.4 to 3.3 ± 2.6 at 6 months, and stabilized thereafter (BASFI third year score mean ± SD 3.6 ± 2.5). The BASMI showed no significant changes over time. Lower baseline BASFI and BASMI scores predicted a better level of physical functioning and spinal mobility after 3 years of TNFi therapy. Other predictors for a better 3-year outcome and course of physical functioning included absence of comorbidity, physical activity, younger age, and lower body mass index at baseline. Conclusion Physical functioning in routinely TNFi-treated AS patients improved up to 6 months and stabilized thereafter. Therefore, it would be better to extend the period of evaluation of TNFi treatment to 6 months rather than the 3 months currently used. The risk factors of long-term physical functioning found in this study might help to identify patients at risk at an earlier stage and improve treatment strategy.
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