The three monoclonal antibodies ustekinumab, guselkumab and risankizumab targeting the p 40 or the 19 subunit of interleukin -23 have now been approved for the indication psoriasis and the former two ...also for psoriatic arthritis (PsA). Ustekinumab and risankizumab have appeared ineffective in randomised controlled trials with patients with axial spondyloarthritis (axSpA), but post-hoc analyses of PsA trials have now suggested that they may improve back pain symptoms potentially induced by axial inflammation based on PsA. Here we argue that, based on the absence of efficacy in axSpA, this is unlikely and more probably due to generic, non-specific effects, which are not adequately covered by the tools developed for the assessment of inflammation in axSpA.
Perform a systematic literature review (SLR) on risk and prognosis of SARS-CoV-2 infection and vaccination against SARS-CoV-2 in patients with rheumatic and musculoskeletal diseases (RMDs).
...Literature was searched up to 31 May 2021, including (randomised) controlled trials and observational studies with patients with RMD. Pending quality assessment, data extraction was performed and risk of bias (RoB) was assessed. Quality assessment required provision of (1) an appropriate COVID-19 case definition, and (2a) a base incidence (for incidence data) or (2b) a comparator, >10 cases with the outcome and risk estimates minimally adjusted for age, sex and comorbidities (for risk factor data).
Of 5165 records, 208 were included, of which 90 passed quality assessment and data were extracted for incidence (n=42), risk factor (n=42) or vaccination (n=14). Most studies had unclear/high RoB. Generally, patients with RMDs do not face more risk of contracting SARS-CoV-2 (n=26 studies) or worse prognosis of COVID-19 (n=14) than individuals without RMDs. No consistent differences in risk of developing (severe) COVID-19 were found between different RMDs (n=19). Disease activity is associated with worse COVID-19 prognosis (n=2), possibly explaining the increased risk seen for glucocorticoid use (n=13). Rituximab is associated with worse COVID-19 prognosis (n=7) and possibly Janus kinase inhibitors (n=3). Vaccination is generally immunogenic, though antibody responses are lower than in controls. Vaccine immunogenicity is negatively associated with older age, rituximab and mycophenolate.
This SLR informed the July 2021 update of the European Alliance of Associations for Rheumatology recommendations for the management of RMDs in the context of SARS-CoV-2.
Overdiagnosis is a term coined by experts in cancer screening to point to indolent cancers detected by screening that would have never led to manifest health problems. Overdiagnosis leads to ...unnecessary medical care (overtreatment), anxiety and cost. In rheumatology overdiagnosis and overtreatment are hardly discussed but likely present. This viewpoint examines how our prevailing views on the management of inflammatory rheumatic diseases may relate to overdiagnosis and overtreatment. Six paradigms of modern rheumatology will be discussed: early diagnosis, intensive treatment, remission, prognosis and risk stratification, evidence-based rheumatology, and precision medicine. It is concluded that, in spite of the enormous progress that they have brought, all paradigms bear the intrinsic dangers of overdiagnosis and overtreatment. So a little caution is in order.
To assess the safety of synthetic (s) and biological (b) disease-modifying antirheumatic drugs (DMARDs) for the management of rheumatoid arthritis (RA) to inform the European League Against ...Rheumatism recommendations for the management of RA.
Systematic literature review (SLR) of observational studies comparing any DMARD with another intervention for the management of patients with RA. All safety outcomes were included. A comparator group was required for the study to be included. Risk of bias was assessed with the Hayden's tool.
Twenty-six observational studies addressing diverse safety outcomes of therapy with bDMARDs met eligibility criteria (15 on serious infections, 4 on malignancies). Substantial heterogeneity precluded meta-analysis. Together with the evidence from the 2013 SLR, based on 15 studies, 7 at low risk of bias, patients on bDMARDs compared with patients on conventional sDMARDs had a higher risk of serious infections (adjusted HR (aHR) 1.1 to 1.8)-without differences across bDMARDs-a higher risk of tuberculosis (aHR 2.7 to 12.5), but no increased risk of infection by herpes zoster. Patients on bDMARDs did not have an increased risk of malignancies in general, lymphoma or non-melanoma skin cancer, but the risk of melanoma may be slightly increased (aHR 1.5).
These findings confirm the known safety pattern of bDMARDs, including both tumour necrosis factor-α inhibitor (TNFi) and non-TNFi, for the treatment of RA.
To update the evidence on efficacy and safety of biological disease-modifying antirheumatic drugs (bDMARDs) in patients with axial spondyloarthritis (axSpA) to inform the 2022 update of the ...Assessment of SpondyloArthritis international Society/European Alliance of Associations for Rheumatology (ASAS-EULAR) recommendations for the management of axSpA.
Systematic literature review (2016-2021) on efficacy and safety of bDMARDs in axSpA (radiographic axSpA (r-axSpA)/non-radiographic axSpA (nr-axSpA)). Eligible study designs included randomised controlled trials (RCTs), strategy trials and observational studies (the latter only for safety and extra-musculoskeletal manifestations). All relevant efficacy/safety outcomes were included.
In total, 148 publications were included. Efficacy of golimumab and certolizumab was confirmed. Tumour necrosis factor inhibitor (TNFi) biosimilar-originator equivalence was demonstrated. RCT (n=15) data on efficacy of interleukin-17 inhibitors (IL-17i) demonstrated clinically relevant effects (risk ratio vs placebo to achieve ASAS40 response 1.3-15.3 (r-axSpA, n=9), 1.4-2.1 (nr-axSpA, n=2)). Efficacy of secukinumab/ixekizumab was demonstrated in TNFi-naïve and TNFi-inadequate responders. IL-23 and IL-12/23 inhibitors (risankizumab/ustekinumab) failed to show relevant benefits. Tapering of TNFi by spacing was non-inferior to standard-dose treatment. The first axSpA treat-to-target trial did not meet its primary endpoint, but showed improvements in secondary outcomes. No new risks were identified with TNFi use in observational studies (data lacking for IL-17i). Secukinumab (n=1) and etanercept (n=2) were associated with increased risk of uveitis in observational studies compared to monoclonal TNFi.
New evidence supports the efficacy and safety of TNFi (originators/biosimilars) and IL-17i in r-axSpA and nr-axSpA, while IL-23i failed to show relevant effects. Observational studies are needed to confirm long-term IL-17i safety.
CRD42021257588.
Although gender differences have been observed in the severity of axial spondyloarthritis (axSpA), gender differences in disease presentation of early axSpA have not been thoroughly investigated. In ...particular, their impact on the diagnostic process is unknown.
Baseline data from the SPondyloArthritis Caught Early cohort, which includes patients with chronic back pain (CBP; duration ≥ 3 months and ≤ 2 years, age of onset < 45 years), were analysed. Patients underwent a full diagnostic work-up, including MRI and radiograph of the sacroiliac joints (MRI-SIJ and X-SIJ), to establish a diagnosis of axSpA. Characteristics of male and female patients with a certain diagnosis of axSpA (confidence level by the physician ≥ 7 on a 0-10 rating scale) were compared. Regression models were built for: the whole CBP cohort stratified by gender, to study which SpA features were associated most with diagnosis in each gender; and for axSpA patients, to test whether gender was associated with imaging positivity (MRI-SIJ
and/or X-SIJ
).
Of the 719 CBP patients, 275 were male. With 146/275 males and 155/444 females diagnosed as axSpA, males were more likely to be diagnosed with axSpA (OR 2.1, 95% CI 1.5-2.9). Despite similar symptom duration, male axSpA patients were younger at diagnosis (27.4 ± 7.5 vs 29.5 ± 7.8 years; p = 0.02). Presence of SpA features was similar in male and female axSpA patients, except for HLA-B27 and imaging positivity that were more common in male axSpA patients (80% vs 60%; p < 0.01 and 78% vs 64%; p = 0.01). Nevertheless, these SpA features were still more prevalent in female axSpA patients than in no-axSpA patients, both females (HLA-B27
23%, positive imaging 7%) and males (HLAB27
34%, positive imaging 11%) (all p < 0.01). Moreover, in multivariable models with diagnosis of axSpA as outcome, HLA-B27 and imaging positivity were associated with the diagnosis in both sexes. In models with imaging positivity as outcome, male gender and HLA-B27 were both independently associated with MRI
and/or X-SI
.
While our data show clear gender differences in early axSpA, they highlight that HLA-B27 and imaging are still key elements for diagnosis in both genders. Our study does not suggest that separate diagnostic strategies for men and women are required.
During the transition to rheumatoid arthritis (RA) many patients pass through a phase characterised by the presence of symptoms without clinically apparent synovitis. These symptoms are not ...well-characterised. This taskforce aimed to define the clinical characteristics of patients with arthralgia who are considered at risk for RA by experts based on their clinical experience.
The taskforce consisted of 18 rheumatologists, 1 methodologist, 2 patients, 3 health professionals and 1 research fellow. The process had three phases. In phase I, a list of parameters considered characteristic for clinically suspect arthralgia (CSA) was derived; the most important parameters were selected by a three-phased Delphi approach. In phase II, the experts evaluated 50 existing patients on paper, classified them as CSA/no-CSA and indicated their level of confidence. A provisional set of parameters was derived. This was studied for validation in phase III, where all rheumatologists collected patients with and without CSA from their outpatient clinics.
The comprehensive list consisted of 55 parameters, of which 16 were considered most important. A multivariable model based on the data from phase II identified seven relevant parameters: symptom duration <1 year, symptoms of metacarpophalangeal (MCP) joints, morning stiffness duration ≥60 min, most severe symptoms in early morning, first-degree relative with RA, difficulty with making a fist and positive squeeze test of MCP joints. In phase III, the combination of these parameters was accurate in identifying patients with arthralgia who were considered at risk of developing RA (area under the receiver operating characteristic curve 0.92, 95% CI 0.87 to 0.96). Test characteristics for different cut-off points were determined.
A set of clinical characteristics for patients with arthralgia who are at risk of progression to RA was established.
Telemedicine is increasingly used in rheumatology. While telemedicine guaranteed care of patients during the COVID-19 pandemic, it is now increasingly used to facilitate triage of patients, ...monitoring of disease activity, and patients' education. In addition, tele-visits as well as remote physio- and psychotherapy are replacing traditional face-to-face contacts between patients and their healthcare provider. While this may save resources in a world in which the gap between the demand and the provision of healthcare increases, there is also a danger of losing essential information, for example by non-verbal communication, that can only be retrieved during face-to-face contact in the office. In addition, it may be challenging to build a trusting relationship between patients and healthcare professionals by virtual means only. Globally acting companies that see market opportunities already amply offer 'simple' technical solutions for telemedicine. While such solutions may seem (economically) interesting at first glance, there is a risk of monopolization, leaving the most valuable parts of healthcare to a small number of profit-seeking companies. In this article, the opportunities and threats of telemedicine in rheumatology are debated. A possible way forward is to complement traditional face-to-face visits with information gained by telemedicine, in order to render these consultations more efficient rather than replacing personal contact by technology.
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