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Patients might have musculoskeletal manifestations—ie, peripheral or axial arthritis, enthesitis, dactylitis, and tendinitis—but non-musculoskeletal involvement is also prevalent—eg, nails, gut, and eyes, in addition to latent or manifest psoriasis.1 Additionally, patients with psoriatic arthritis have increased risk of cardiovascular, psychological, and metabolic comorbidities.2 Psoriatic arthritis was thought to be rare, but occurs in up to 30% of patients with psoriasis.3 Initially considered a benign disease, it is now recognised that disease burden is high and patients have severely reduced quality of life and increased mortality.4 Treatment of patients with psoriatic arthritis aims to maximise health-related quality of life through control of symptoms, prevention of structural damage, and normalisation of function and social participation.5 A cornerstone to achieving these goals is control of the inflammatory process using disease-modifying antirheumatic drugs (DMARDs). Head-to-head studies of different drugs are needed to guide clinical decision making regarding the best choice of treatment.5 Cid - Ism/Science Photo Library In The Lancet, Iain McInnes and colleagues6 report the results of the double-blind, multicentre EXCEED study. 853 biological-naive patients (437 [51%] men and 416 [49%] women; mean age 49·0 years [SD 12·41]) with active psoriatic arthritis and inadequate response or intolerance to csDMARDs and NSAIDs were randomly assigned to receive the IL-17A inhibitor secukinumab (300 mg monthly after loading dose) or the TNF inhibitor adalimumab (40 mg every other week). Bearing in mind that the recommended secukinumab dose in biological-naive patients treated in clinical practice would be 150 mg rather than the 300 mg used in this trial, it would have been interesting to see the performance of the lower dose. [...]moderate to severe psoriasis, which would have justified the choice of the higher dose, was not present in all patients.

ObjectivesTo provide an update of the European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) management recommendations to account for the most recent developments in the field.MethodsAn international task force considered new evidence supporting or contradicting previous recommendations and novel therapies and strategic insights based on two systematic literature searches on efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) since the last update (2016) until 2019. A predefined voting process was applied, current levels of evidence and strengths of recommendation were assigned and participants ultimately voted independently on their level of agreement with each of the items.ResultsThe task force agreed on 5 overarching principles and 12 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, sarilumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib). Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering on sustained clinical remission is provided. Cost and sequencing of b/tsDMARDs are addressed. Initially, MTX plus GCs and upon insufficient response to this therapy within 3 to 6 months, stratification according to risk factors is recommended. With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD or JAK inhibitor should be added to the csDMARD. If this fails, any other bDMARD (from another or the same class) or tsDMARD is recommended. On sustained remission, DMARDs may be tapered, but not be stopped. Levels of evidence and levels of agreement were mostly high.ConclusionsThese updated EULAR recommendations provide consensus on the management of RA with respect to benefit, safety, preferences and cost.

ObjectiveNew modes of action and more data on the efficacy and safety of existing drugs in psoriatic arthritis (PsA) required an update of the EULAR 2019 recommendations for the pharmacological treatment of PsA.MethodsFollowing EULAR standardised operating procedures, the process included a systematic literature review and a consensus meeting of 36 international experts in April 2023. Levels of evidence and grades of recommendations were determined.ResultsThe updated recommendations comprise 7 overarching principles and 11 recommendations, and provide a treatment strategy for pharmacological therapies. Non-steroidal anti-inflammatory drugs should be used in monotherapy only for mild PsA and in the short term; oral glucocorticoids are not recommended. In patients with peripheral arthritis, rapid initiation of conventional synthetic disease-modifying antirheumatic drugs is recommended and methotrexate preferred. If the treatment target is not achieved with this strategy, a biological disease-modifying antirheumatic drug (bDMARD) should be initiated, without preference among modes of action. Relevant skin psoriasis should orient towards bDMARDs targeting interleukin (IL)-23p40, IL-23p19, IL-17A and IL-17A/F inhibitors. In case of predominant axial or entheseal disease, an algorithm is also proposed. Use of Janus kinase inhibitors is proposed primarily after bDMARD failure, taking relevant risk factors into account, or in case bDMARDs are not an appropriate choice. Inflammatory bowel disease and uveitis, if present, should influence drug choices, with monoclonal tumour necrosis factor inhibitors proposed. Drug switches and tapering in sustained remission are also addressed.ConclusionThese updated recommendations integrate all currently available drugs in a practical and progressive approach, which will be helpful in the pharmacological management of PsA.

DANBIO is a research register and a data source for rheumatologic diseases (rheumatoid arthritis [RA], axial spondyloarthritis, and psoriatic arthritis) for monitoring clinical quality at the national, regional, and hospital levels. The register includes patients with rheumatologic diseases who are treated at a hospital or a private rheumatologic clinic. Registration is mandatory for all patients with RA regardless of treatment and also for patients with other diagnoses if treated with biological disease-modifying antirheumatic drugs. Since 2006, the registration has been done electronically, including patient-reported outcome measures registered electronically by the patients with the use of touch screens. Core variables such as diagnosis, year of diagnosis, age, and sex are registered at the beginning. Data entered at later visits included the following: patient-reported outcomes for disease activity, pain, fatigue, functional status, and physician-reported objective measures of disease activity, treatment, C-reactive protein, and, when indicated, imaging. For subgroups of patients, the variables such as quality of life, sociodemographic factors, lifestyle, and comorbidity are also registered. The DANBIO cohort comprised ∼26,000 patients with RA, 3,200 patients with axial spondyloarthritis, and 6,200 patients with psoriatic arthritis in 2015. DANBIO has high nationwide coverage and completeness on key data variables. More than 60 original papers as well as annual reports of clinical quality (since 2005) have been published. DANBIO is a powerful register for research in rheumatologic diseases and furthermore serves as a Clinical Quality Register with the aim of monitoring treatment quality in patients with RA in Denmark.

Pneumatic transportation systems (PTSs) are increasingly used for transportation of blood samples to the core laboratory. Many studies have investigated the impact of these systems on different types of analyses, but to elucidate whether PTSs in general are safe for transportation of blood samples, existing literature on the subject was systematically assessed. A systematic literature review was conducted following the preferred reporting items for systematic reviews and metaanalyses (PRISMA) Statement guidelines to gather studies investigating the impact of PTS on analyses in blood samples. Studies were extracted from PubMed and Embase. The search period ended November 2016. A total of 39 studies were retrieved. Of these, only 12 studies were conducted on inpatients, mainly intensive care unit patients. Blood gases, hematology, and clinical chemistry were well investigated, whereas coagulation, rotational thromboelastometry, and platelet function in acutely ill patients were addressed by only 1 study each. Only a few parameters were affected in a clinically significant way (clotting time parameter in extrinsic system thromboelastometry, pO in blood gas, multiplate analysis, and the hemolysis index). Owing to their high degree of heterogeneity, the retrieved studies were unable to supply evidence for the safety of using PTSs for blood sample transportation. In consequence, laboratories need to measure and document the actual acceleration forces in their existing PTS, instituting quality target thresholds for these measurements such as acceleration vector sums. Computer modeling might be applied to the evaluation of future PTS installations. With the increasing use of PTS, a harmonized, international recommendation on this topic is warranted.

ObjectivesReal-world evidence on effectiveness of switching to biosimila r etanercept is scarce. In Denmark, a nationwide guideline of mandatory switch from 50 mg originator (ETA) to biosimilar (SB4) etanercept was issued for patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA) in 2016. Clinical characteristics and treatment outcomes were studied in ETA-treated patients, who switched to SB4 (switchers) or maintained ETA (non-switchers). Retention rates were compared with that of a historic cohort of ETA-treated patients. Switchers who resumed ETA treatment (back-switchers) were characterised.MethodsObservational cohort study based on the DANBIO registry. Treatment retention was explored by Kaplan-Meier plots and Cox regression (crude, adjusted).Results1621 (79%) of 2061 ETA-treated patients switched to SB4. Disease activity was unchanged 3 months’ preswitch/postswitch. Non-switchers often received 25 mg ETA (ETA 25 mg pens/syringes and powder solution were still available). One-year adjusted retention rates were: non-switchers: 77% (95% CI: 72% to 82%)/switchers: 83% (79% to 87%)/historic cohort: 90% (88% to 92%). Patients not in remission had lower retention rates than patients in remission, both in switchers (crude HR 1.7 (1.3 to 2.2)) and non-switchers (2.4 (1.7 to 3.6)). During follow-up, 120 patients (7% of switchers) back-switched to ETA. Back-switchers’ clinical characteristics were similar to switchers, and reasons for SB4 withdrawal were mainly subjective.ConclusionSeventy-nine per cent of patients switched from ETA to SB4. After 1 year, adjusted treatment retention rates were lower in switchers versus the historic ETA cohort, but higher than in non-switchers. Withdrawal was more common in patients not in remission. The results suggest that switch outcomes in routine care are affected by patient-related factors and non-specific drug effects.

ObjectivesTo compare the 1-year, 2-year and 5-year incidences of acute coronary syndrome (ACS) in patients with rheumatoid arthritis (RA) starting any of the biologic disease-modifying antirheumatic drugs (bDMARDs) currently available in clinical practice and to anchor these results with a general population comparator.MethodsObservational cohort study, with patients from Denmark, Finland, Norway and Sweden starting a bDMARD during 2008–2017. Time to first ACS was identified through register linkages. We calculated the 1-year, 2-year and 5-year incidence rates (IR) (on drug and ever since treatment start) and used Cox regression (HRs) to compare ACS incidences across treatments taking ACS risk factors into account. Analyses were further performed separately in subgroups defined by age, number of previous bDMARDs and history of cardiovascular disease. We also compared ACS incidences to an individually matched general population cohort.Results24 083 patients (75% women, mean age 56 years) contributing 40 850 treatment courses were included. During the maximum (5 years) follow-up (141 257 person-years (pyrs)), 780 ACS events occurred (crude IR 5.5 per 1000 pyrs). Overall, the incidence of ACS in RA was 80% higher than that in the general population. For all bDMARDs and follow-up definitions, HRs were close to 1 (etanercept as reference) with the exception of the 5-year risk window, where signals for abatacept, infliximab and rituximab were noted.ConclusionThe rate of ACS among patients with RA initiating bDMARDs remains elevated compared with the general population. As used in routine care, the short-term, intermediate-term and longer-term risks of ACS vary little across individual bDMARDs.

To determine whether baseline CD4+ T helper (Th) cell subset proportions in blood may serve as predictive biomarkers for achieving remission 48 weeks after initiating CTLA-4Ig, anti-tumor necrosis factor (TNF), or anti-interleukin 6 receptor (IL6R) treatment in patients with early rheumatoid arthritis (eRA). This study included 60 untreated eRA patients from the larger randomized treatment trial NORD-STAR. They were treated with methotrexate (MTX) combined with either CTLA-4Ig (n = 17), anti-TNF (n = 22), or anti-IL6R (n = 21). Disease activity was assessed by clinical disease activity index (CDAI), C-reactive protein, and erythrocyte sedimentation rate. The primary outcome was remission (CDAI ≤ 2.8) at week 48, and the secondary outcomes were time to reach remission or sustained remission during the 48-week follow-up. CD4+ T cell subset proportions were analyzed fresh by flow cytometry at baseline and at 24 and 48 weeks. In CTLA-4Ig + MTX-treated patients, baseline Th2 together with PD1+ T follicular helper (TFh) cell proportions predicted CDAI remission at week 48 (AUC: 0.986, 95% CI 0.94-1.0). Survival analysis revealed that patients with Th2 proportions below 16.8% or PD1+ TFh proportions above 7.6% at baseline were more likely to achieve remission (log-rank p = 0.002 and p = 0.007, respectively), and sustained remission (log-rank p = 0.01 and p = 0.001, respectively), over the 48-week follow-up. CD4+ T cell subset proportions did not predict remission in patients treated with anti-TNF + MTX or anti-IL6R + MTX. Only CTLA-4Ig treatment reduced PD1+ TFh and PD1neg TFh fractions after 48 weeks. Circulating Th2 and PD1+ TFh cell proportions at baseline may serve as predictive biomarkers for achieving CDAI remission after 48 weeks of CTLA-4Ig treatment in eRA.

Background Patients with rheumatoid arthritis (RA) have an increased risk of developing serious infections (SIs) vs. individuals without RA; efforts to predict SIs in this patient group are ongoing. We assessed the ability of different machine learning modeling approaches to predict SIs using baseline data from the tofacitinib RA clinical trials program. Methods This analysis included data from 19 clinical trials (phase 2, n  = 10; phase 3, n  = 6; phase 3b/4, n  = 3). Patients with RA receiving tofacitinib 5 or 10 mg twice daily (BID) were included in the analysis; patients receiving tofacitinib 11 mg once daily were considered as tofacitinib 5 mg BID. All available patient-level baseline variables were extracted. Statistical and machine learning methods (logistic regression, support vector machines with linear kernel, random forest, extreme gradient boosting trees, and boosted trees) were implemented to assess the association of baseline variables with SI (logistic regression only), and to predict SI using selected baseline variables using 5-fold cross-validation. Missing values were handled individually per prediction model. Results A total of 8404 patients with RA treated with tofacitinib were eligible for inclusion (15,310 patient-years of total follow-up) of which 473 patients reported SIs. Amongst other baseline factors, age, previous infection, and corticosteroid use were significantly associated with SI. When applying prediction modeling for SI across data from all studies, the area under the receiver operating characteristic (AUROC) curve ranged from 0.656 to 0.739. AUROC values ranged from 0.599 to 0.730 in data from phase 3 and 3b/4 studies, and from 0.563 to 0.643 in data from ORAL Surveillance only. Conclusions Baseline factors associated with SIs in the tofacitinib RA clinical trial program were similar to established SI risk factors associated with advanced treatments for RA. Furthermore, while model performance in predicting SI was similar to other published models, this did not meet the threshold for accurate prediction (AUROC > 0.85). Thus, predicting the occurrence of SIs at baseline remains challenging and may be complicated by the changing disease course of RA over time. Inclusion of other patient-associated and healthcare delivery-related factors and harmonization of the duration of studies included in the models may be required to improve prediction. Trial registration ClinicalTrials.gov: NCT00147498; NCT00413660; NCT00550446; NCT00603512; NCT00687193; NCT01164579; NCT00976599; NCT01059864; NCT01359150; NCT02147587; NCT00960440; NCT00847613; NCT00814307; NCT00856544; NCT00853385; NCT01039688; NCT02187055; NCT02831855; NCT02092467.

The HOPE cohort is a Danish nationwide cohort with ongoing follow-up, holding information on postpartum depression (PPD) symptoms and diagnoses on 170,218 childbirths (142,795 unique mothers). These data have been linked with extensive register data on health and socioeconomic information on the mothers, their partners, parents, and children. This cohort profile aimed to provide an overview of the data collection and content, describe characteristics, and evaluate potential selection bias. PPD screenings, using the Edinburgh Postnatal Depression Scale, were collected from 67 of the 98 Danish municipalities, covering the period January 2015 to December 2021. This data was linked with register data on PPD diagnoses (identified through medication prescriptions and hospital contacts) as well as background information. Cohort characteristics were compared to the source population, defined as all childbirths by women residing in Denmark during the same period (452,207 childbirths). Potential selection bias was evaluated by comparing odds ratios of five well-established associations between the cohort and the source population. The HOPE cohort holds information on 170,218 childbirths (38% of the source population) involving 142,795 unique mothers. The HOPE cohort only differed slightly from the source population on most characteristics examined, but larger differences were observed on specific characteristics with an underrepresentation of the youngest and oldest age groups, women with more than three children or twins/triplets, and women born outside Denmark. Similar associations were identified across the two populations within the five well-established associations. There was no indication of selection bias on the five examined associations, and the HOPE cohort is representative of the source population on important perinatal characteristics.