Explore the vast range of titles available.

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.

ObjectiveTo 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.MethodsSystematic 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.ResultsIn 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.ConclusionsNew 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.PROSPERO registration numberCRD42021257588

ObjectivesPerform 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).MethodsLiterature 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).ResultsOf 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.ConclusionThis 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.

ObjectiveTo update the evidence of non-biological treatments for axial spondyloarthritis (axSpA), as a basis for the 2022 Assessment of SpondyloArthritis international Society-European Alliance of Associations for Rheumatology (ASAS-EULAR) recommendations for the management of axSpA.MethodsA systematic literature review (2016–2021) on efficacy and safety of non-pharmacological and non-biological pharmacological treatments was performed, up to 1 January 2022. The research question was formulated according to the PICO format: Population: adult patients with r-axSpA and nr-axSpA; Intervention: non-pharmacological and non-biological pharmacological treatments; Comparator: active comparator or placebo; Outcomes: all relevant efficacy and safety outcomes. Type of studies included were: randomised controlled trials (RCTs), observational studies (for efficacy of non-pharmacological treatments, and safety), qualitative studies. Cohen’s effect size (ES) was calculated for non-pharmacological and risk ratio (RR) for pharmacological treatments.ResultsOf 107 publications included, 63 addressed non-pharmacological interventions, including education (n=8) and exercise (n=20). The ES for education on disease activity, function, mobility was small to moderate (eg. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), ES: 0.06–0.59). Exercise had moderate to high ES on these outcomes (eg. BASDAI, ES: 0.14–1.43). Six RCTs on targeted synthetic disease-modifying antirheumatic drugs (DMARDs) showed efficacy of tofacitinib, upadacitinib and filgotinib (phase 2 only) in r-axSpA (range RR vs placebo for ASAS20: 1.91–3.10), while apremilast and nilotinib were not efficacious. Studies on conventional synthetic DMARDs (n=3), non-steroidal anti-inflammatory drugs (NSAIDs, n=8) and other drugs (n=12) did not provide new evidence on efficacy/safety (efficacy of NSAIDs confirmed; limited efficacy of short-term glucocorticoids in one RCT).ConclusionsEducation, exercise and NSAIDs confirmed to be efficacious in axSpA. JAKi were proved efficacious in r-axSpA.

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.

ObjectivesTo perform a systematic literature review (SLR) concerning the safety of synthetic(s) and biological (b) disease-modifying antirheumatic drugs (DMARDs) to inform the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis (RA).MethodsSLR of observational studies comparing safety outcomes of any DMARD with another intervention in RA. A comparator group was required for inclusion. For treatments yet without, or limited, registry data, randomised controlled trials (RCTs) were used.ResultsFifty-nine observational studies addressed the safety of DMARDs. Two studies (unclear risk of bias (RoB)) showed an increased risk of serious infections with bDMARDs compared with conventional synthetic (cs)DMARDs. Herpes zoster infections occurred more with JAKi than csDMARDs (adjusted HR (aHR): 3.66) and bDMARDs (aHR: 1.9–2.3) (four studies, two low RoB). The risk of malignancies was similar across bDMARDs (five studies) and with tofacitinib compared with bDMARDs (one study, low RoB). The risk of major adverse cardiovascular events (MACE) was similar with bDMARDs and tofacitinib (two studies, one low RoB). Thirty studies reported safety from RCTs, with one, designed to evaluate safety, showing that malignancies (HR (95% CI): 1.48 (1.04 to 2.09)) and MACE (HR (95% CI): 1.33 (0.91 to 1.94)) occurred numerically more frequently with tofacitinib (5 mg and 10 mg doses combined) than with TNFi in patients with cardiovascular risk factors. In this study, the risk of venous thromboembolism (VTE) was higher with tofacitinib 10 mg than with TNFi.ConclusionThe safety profile of bDMARDs was further demonstrated. Whether the difference in incidence of malignancies, MACE and VTE between tofacitinib and TNFi applies to other JAKi needs further evaluation.

Correspondence to Dr Pedro M Machado, Centre for Rheumatology and MRC Centre for Neuromuscular Diseases, University College London, London WC1B 5EH, UK; p.machado@ucl.ac.uk The Ankylosing Spondylitis Disease Activity Score (ASDAS) is a measure of axial spondyloarthritis (axSpA) disease activity with validated cut-offs endorsed by the Assessment of SpondyloArthritis international Society (ASAS) and Outcome Measures in Rheumatology (OMERACT).1 2 In the 2016 update of the ASAS-European League Against Rheumatism (EULAR) management recommendations for axSpA, it is recommended that biological disease-modifying antirheumatic drugs should be considered in patients with persistently high disease activity despite conventional treatments, and that the preferred measure to define active disease should be the ASDAS (ASDAS of at least 2.1, ie, high disease activity).3 The 2017 update of treat-to-target recommendations in axial and peripheral SpA recommends that the treatment target should be inactive disease/clinical remission and that low/minimal disease activity may be an alternative treatment target. The compelling argument is the fact that the majority of patients in this ASDAS category have indeed mild disease activity, an observation that is in line with the external constructs that were used to derive the ASDAS cut-off of 2.1: patient and physician global assessments <3 using the 90% specificity criterion to determine the optimal cut-off.1 5 Furthermore, recent publications have shown that the majority of patients with ASDAS values in the ‘moderate disease activity’ category consider themselves as being in a patient-acceptable symptom state (PASS), which can be defined as the maximum level of symptoms with which patients consider themselves to be well. [...]the nomenclature of ASDAS disease activity states was updated by ASAS.

ObjectivesTo update the evidence on efficacy of DMARDs (disease-modifying antirheumatic drugs) and inform the taskforce of the 2022 update of the European Alliance of Associations for Rheumatology (EULAR) recommendations for management of rheumatoid arthritis (RA).MethodsThis systematic literature review (SLR) investigated the efficacy of conventional synthetic (cs), biological (b), biosimilar and targeted synthetic (ts)DMARDs in patients with RA. Medline, EMBASE, Cochrane CENTRAL and Web of Science were used to identify all relevant articles published since the previous update in 2019 to 14 January 2022.ResultsOf 8969 search results, 169 articles were selected for detailed review and 47 were finally included. Trials investigated the efficacy of csDMARDs, bDMARDs and tsDMARDs, DMARD switching, tapering and trials investigating different treatment strategies. The compounds investigated were csDMARDs (methotrexate (MTX), leflunomide, sulfasalazine, hydroxychloroquine), bDMARDs (abatacept, adalimumab, certolizumab-pegol, denosumab, etanercept, infliximab, levilimab, olokizumab, opineracept, rituximab, sarilumab, tocilizumab) and tsDMARDs (baricitinib, filgotinib, tofacitinib, upadacitinib). The efficacy of csDMARDs+ short-term glucocorticoids in early RA was confirmed and similar to bDMARD+MTX combination therapy. Interleukin-6 pathway inhibition was effective in trials on olokizumab and levilimab. Janus kinase inhibitor (JAKi) was efficacious in different patient populations. After insufficient response to JAKi, patients could respond to TNFi treatment. Tapering of DMARDs was feasible for a proportion of patients, who were able to taper therapy while remaining in low disease activity or remission.ConclusionThe results of this SLR, together with one SLR on safety of DMARD and one on glucocorticoids, informed the taskforce of the 2022 update of the EULAR recommendations for pharmacological management of RA.

Background 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. Methods 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 + ). Results 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 + . Conclusions 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.