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Glucocorticoids (prednisone) are essential in the treatment of RA and other autoimmune diseases. They are widely used, but treatment guidelines advise against. This viewpoint article explains why and suggests a way forward. [ABSTRACT FROM AUTHOR]

Objectives Self-monitoring and patient-initiated care (PIC) leads to fewer outpatient clinic visits in patients with established RA with low disease activity (LDA) while healthcare outcomes are similar. This study assesses the cost-effectiveness of PIC with self-monitoring. Methods A 12-month randomized controlled trial was performed with 49 patients in the PIC with self-monitoring group (app-group) and 53 in usual care. The usual care group continued with preplanned visits. The app group had one planned follow-up visit after 12 months and monitored their RA disease activity in a smartphone app. Both groups could make additional appointments at liberty. We included adult RA patients with a disease duration of over 2 years, a disease activity score 28 (DAS28) below 3.2 that were stable on medication for at least 6 months. The effect measure, the DAS28, was measured at 12 months and healthcare resource usage and productivity losses were measured at 3, 6, 9 and 12 months. Results There was no significant difference in mean change of DAS28 (-0.04 mean difference, 95% CI: -0.39, 0.30), nor a statistically significant difference in total costs (mean difference €514, 95% CI:-€266, €3690) in the app group compared with the usual care group. The probability that the app was cost-effective was 0.37 and 0.57 at a willingness-to-pay threshold of 0 and 50 000 €/point improvement DAS28, respectively. Conclusion Although rheumatic care costs were significantly lower in the app group, total costs and effects of PIC with self-monitoring were not different from usual care in RA patients with LDA. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to assess the safety and efficacy of long-term low-dose glucocorticoids (GCs) in RA. Methods A protocolised systematic review and meta-analysis (PROSPERO No. CRD42021252528) of double-blind, placebo-controlled randomised trials (RCTs) comparing a low dose of GCs (≤ 7.5mg/day prednisone) to placebo over at least 2 years was performed. The primary outcome investigated was adverse events (AEs). We performed random-effects meta-analyses and used the Cochrane RoB tool and GRADE to assess risk of bias and quality of evidence (QoE). Results Six trials with 1078 participants were included. There was no evidence of an increased risk of AEs (incidence rate ratio 1.08; 95% CI 0.86, 1.34; P  = 0.52); however, the QoE was low. The risks of death, serious AEs, withdrawals due to AEs, and AEs of special interest did not differ from placebo (very low to moderate QoE). Infections occurred more frequently with GCs (risk ratio 1.4; 1.19–1.65; moderate QoE). Concerning benefit, we found moderate to high quality evidence of improvement in disease activity (DAS28: −0.23; −0.43 to −0.03), function (HAQ −0.09; −0.18 to 0.00), and Larsen scores (–4.61; −7.52 to −1.69). In other efficacy outcomes, including Sharp van der Heijde scores, there was no evidence of benefits with GCs. Conclusion There is very low to moderate QoE for no harm with long-term low dose GCs in RA, except for an increased risk of infections in GC users. The benefit-risk ratio might be reasonable forusing low-dose long-term GCs considering the moderate to high quality evidence for disease-modifying properties. [ABSTRACT FROM AUTHOR]

Objectives To identify highly ranked features related to clinicians' diagnosis of clinically relevant knee OA. Methods General practitioners (GPs) and secondary care physicians (SPs) were recruited to evaluate 5–10 years follow-up clinical and radiographic data of knees from the CHECK cohort for the presence of clinically relevant OA. GPs and SPs were gathered in pairs; each pair consisted of one GP and one SP, and the paired clinicians independently evaluated the same subset of knees. A diagnosis was made for each knee by the GP and SP before and after viewing radiographic data. Nested 5-fold cross-validation enhanced random forest models were built to identify the top 10 features related to the diagnosis. Results Seventeen clinician pairs evaluated 1106 knees with 139 clinical and 36 radiographic features. GPs diagnosed clinically relevant OA in 42% and 43% knees, before and after viewing radiographic data, respectively. SPs diagnosed in 43% and 51% knees, respectively. Models containing top 10 features had good performance for explaining clinicians' diagnosis with area under the curve ranging from 0.76–0.83. Before viewing radiographic data, quantitative symptomatic features (i.e. WOMAC scores) were the most important ones related to the diagnosis of both GPs and SPs; after viewing radiographic data, radiographic features appeared in the top lists for both, but seemed to be more important for SPs than GPs. Conclusions Random forest models presented good performance in explaining clinicians' diagnosis, which helped to reveal typical features of patients recognized as clinically relevant knee OA by clinicians from two different care settings. [ABSTRACT FROM AUTHOR]

Objective To determine the effect of a multidisciplinary lifestyle program in patients with RA with low–moderate disease activity. Methods In the 'Plants for Joints' (PFJ) parallel-arm, assessor-blind randomized controlled trial, patients with RA and 28-joint DAS (DAS28) ≥2.6 and ≤5.1 were randomized to the PFJ or control group. The PFJ group followed a 16-week lifestyle program based on a whole-food plant-based diet, physical activity and stress management. The control group received usual care. Medication was kept stable 3 months before and during the trial whenever possible. We hypothesized that PFJ would lower disease activity (DAS28). Secondary outcomes included anthropometric, metabolic and patient-reported measures. An intention-to-treat analysis with a linear mixed model adjusted for baseline values was used to analyse between-group differences. Results Of the 83 people randomized, 77 completed the study. Participants were 92% female with mean (s. d.) age of 55 (12) years, BMI of 26 (4) kg/m2 and mean DAS28 of 3.8 (0.7). After 16 weeks the PFJ group had a mean 0.9-point greater improvement of DAS28 vs the control group (95% CI 0.4, 1.3; P  < 0.0001). The PFJ intervention led to greater decreases in body weight (difference –3.9 kg), fat mass (–2.8 kg), waist circumference (–3 cm), HbA1c (–1.3 mmol/mol) and low-density lipoprotein (–0.32 mmol/l), whereas patient-reported outcome measures, blood pressure, glucose and other lipids did not change. Conclusion The 16-week PFJ multidisciplinary lifestyle program substantially decreased disease activity and improved metabolic status in people with RA with low–moderate disease activity. Trial Registration International Clinical Trials Registry Platform; https://www.who.int/clinical-trials-registry-platform ; NL7800. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to investigate the effect of treat-to-target combination therapy with intensification at 13 weeks in early RA. Methods Early RA patients were classified as being at high or low risk of worsening RA based on disease activity and prognostic factors. High-risk patients received COBRA-light (prednisolone 30 mg/day tapered to 7.5 mg/day, MTX increasing to 25 mg/week), and low-risk patients received MTX monotherapy increasing to 25 mg/week. The primary outcome (target) was DAS44 < 1.6 or EULAR good response at 26 weeks. At 13 weeks, non-responders were randomized to (open-label) intensification [high-risk patients: prednisolone 60 mg/day tapered to 7.5 mg/day, addition of SSZ (2 g/day) and HCQ (400 mg/day); low-risk patients: prednisolone 30 mg/day tapered to 7.5 mg/day] or continuation. Results In the high-risk group (n  = 150), 110 patients (73%) reached the target at 13 weeks, and 9 dropped out. Non-responders were randomized to intensification (n  = 15) or continuation (n  = 16), and after 26 weeks, 12 (80%) vs 7 (44%) of these, respectively, reached the target [difference: 36%, (95% CI 2%, 71%); P  = 0.04]. In the low-risk group (n  = 40), 17 (43%) reached the target. Non-responders were randomized to intensification (n  = 8) or continuation (n  = 7); 4 vs 3, respectively, reached the target. Adverse event rates were higher in the high-risk group, and higher in the intensification subgroup of that group. Serious adverse events were rare. Protocol violations were frequent and mostly led to mitigation of actual treatment intensification. Conclusion Initial combination therapy was very successful in high-risk RA, and early intensification was beneficial in patients not reaching the strict target. The low-risk group was too small for drawing conclusions. In routine practice, adherence to early intensification based on strict targets is difficult. Trial registration Netherlands Trial Register (NTR), NL4393, https://www.trialregister.nl/. [ABSTRACT FROM AUTHOR]

Objective To develop prediction models for individual patient harm and benefit outcomes in elderly patients with RA and comorbidities treated with chronic low-dose glucocorticoid therapy or placebo. Methods In the Glucocorticoid Low-dose Outcome in Rheumatoid Arthritis (GLORIA) study, 451 RA patients ≥65 years of age were randomized to 2 years 5 mg/day prednisolone or placebo. Eight prediction models were developed from the dataset in a stepwise procedure based on prior knowledge. The first set of four models disregarded study treatment and examined general predictive factors. The second set of four models was similar but examined the additional role of low-dose prednisolone. In each set, two models focused on harm [the occurrence of one or more adverse events of special interest (AESIs) and the number of AESIs per year) and two on benefit (early clinical response/disease activity and a lack of joint damage progression). Linear and logistic multivariable regression methods with backward selection were used to develop the models. The final models were assessed and internally validated with bootstrapping techniques. Results A few variables were slightly predictive for one of the outcomes in the models, but none were of immediate clinical value. The quality of the prediction models was sufficient and the performance was low to moderate (explained variance 12–15%, area under the curve 0.67–0.69). Conclusion Baseline factors are not helpful in selecting elderly RA patients for treatment with low-dose prednisolone given their low power to predict the chance of benefit or harm. Trial registration https://clinicaltrials.gov ; NCT02585258. [ABSTRACT FROM AUTHOR]

The article reports a response after switching from prednisole to dexamethasone in three D2T-RA patients with active disease despite prednisolone. Topics discussed include possible mechanisms why response to different glucocorticoids (GCs) may vary, pharmacodynamic differences between GCs, and characteristics of 3 ACPA-positive patients switched from prednisolone to dexamethasone.

Objectives Glucocorticoids (GCs) increase the risk of fracture through reduction in BMD; they may also reduce bone quality, but recent supporting data are scarce. We aimed to confirm these effects in a large population-based cohort. Methods We used data from patients referred for first hip and lumbar spine BMD estimation by the sole DXA scanner in the north-west of England between June 2004 and September 2016. We compared the history of fractures and BMD between patients currently on GCs and patients never exposed to GC. A logistic model adjusted for possible confounders. Results More than 20 000 subjects were included, 82% female, with mean age 63 (s. d. 13) years; 19% were currently on GCs. The patients on GCs were more often male, with higher BMI, but their age was similar to those not exposed to GC. Surprisingly, patients receiving GCs had ∼2% higher BMD at both sites (P  < 0.001) and lower prevalence of (history of) fractures (22% vs 34%; P  < 0.001). The corresponding odds ratio was 0.53 (95% CI: 0.49, 0.58); adjustment for age, sex, BMI and the number of indications for scanning did not alter the association. Conclusion In this large population-based cohort, current GC use compared with never use was associated with higher bone mass and fewer rather than more fractures after adjusting for confounders. These results might be subject to unmeasured confounding, but for now they do not lend support to a detrimental effect of GCs on bone. [ABSTRACT FROM AUTHOR]

Objectives To investigate the dynamics of response of synovitis to IL-17A inhibition with secukinumab in patients with active PsA using Power Doppler ultrasound. Methods The randomized, placebo-controlled, Phase III ULTIMATE study enrolled PsA patients with active ultrasound synovitis and clinical synovitis and enthesitis having an inadequate response to conventional DMARDs and naïve to biologic DMARDs. Patients were randomly assigned to receive either weekly subcutaneous secukinumab (300 or 150 mg according to the severity of psoriasis) or placebo followed by 4-weekly dosing thereafter. The primary outcome was the mean change in the ultrasound Global EULAR and OMERACT Synovitis Score (GLOESS) from baseline to week 12. Key secondary endpoints included ACR 20 and 50 responses. Results Of the 166 patients enrolled, 97% completed 12 weeks of treatment (secukinumab, 99%; placebo, 95%). The primary end point was met, and the adjusted mean change in GLOESS was higher with secukinumab than placebo [−9 (0.9) vs −6 (0.9), difference (95% CI): −3 (−6, −1); one-sided P= 0.004] at week 12. The difference in GLOESS between secukinumab and placebo was significant as early as one week after initiation of treatment. All key secondary endpoints were met. No new or unexpected safety findings were reported. Conclusion This unique ultrasound study shows that apart from improving the signs and symptoms of PsA, IL-17A inhibition with secukinumab leads to a rapid and significant reduction of synovitis in PsA patients. Trial registration ClinicalTrials.gov; NCT02662985. [ABSTRACT FROM AUTHOR]

Objectives Although there is a general focus on early diagnosis and treatment of hip OA, there are no validated diagnostic criteria for early-stage hip OA. The current study aimed to take the first steps in developing diagnostic criteria for early-stage hip OA, using factors obtained through history taking, physical examination, radiography and blood testing at the first consultation in individuals presenting with hip pain, suspicious for hip OA, in primary care. Methods Data of the 543 individuals with 735 symptomatic hips at baseline who had any follow-up data available from the prospective CHECK cohort study were used. A group of 26 clinical experts [general practitioners (GPs), rheumatologists and orthopaedic surgeons] evaluated standardized clinical assessment forms of all subjects on the presence of clinically relevant hip OA 5–10 years after baseline. Using the expert-based diagnoses as reference standard, a backward selection method was used to create predictive models based on pre-defined baseline factors from history taking, physical examination, radiography and blood testing. Results Prevalence of clinically relevant hip OA during follow-up was 22%. Created models contained four to eight baseline factors (mainly WOMAC pain items, painful/restricted movements and radiographic features) and obtained area under the curve between 0.62 (0.002) and 0.71 (0.002). Conclusion Based on clinical and radiographic features of hip OA obtained at first consultation at a GP for pain/stiffness of the hip, the prediction of clinically relevant hip OA within 5–10 years was 'poor' to 'fair'. [ABSTRACT FROM AUTHOR]

Background older people remain underrepresented in clinical trials, and evidence generated in younger populations cannot always be generalized to older patients. Objective to identify key barriers and to discuss solutions to specific issues affecting recruitment and retention of older participants in clinical trials based on experience gained from six current European randomised controlled trials (RCTs) focusing on older people. Methods a multidisciplinary group of experts including representatives of the six RCTs held two networking conferences and compiled lists of potential barriers and solutions. Every item was subsequently allocated points by each study team according to how important it was perceived to be for their RCTs. Results the six RCTs enrolled 7,612 older patients. Key barriers to recruitment were impaired health status, comorbidities and diverse health beliefs including priorities within different cultural systems. All trials had to increase the number of recruitment sites. Other measures felt to be effective included the provision of extra time, communication training for the study staff and a re-design of patient information. Key barriers for retention included the presence of severe comorbidities and the occurrence of adverse events. Long study duration, frequent study visits and difficulties accessing the study site were also mentioned. Solutions felt to be effective included spending more time maintaining close contact with the participants, appropriate measures to show appreciation and reimbursement of travel arrangements. Conclusion recruitment and retention of older patients in trials requires special recognition and a targeted approach. Our results provide scientifically-based practical recommendations for optimizing future studies in this population. [ABSTRACT FROM AUTHOR]